Download Free Medical Drug Induced Nephrotoxicity PowerPoint Presentation

Drug Induced Nephrotoxicity PowerPoint Presentation

DOWNLOAD MEDICAL POWERPOINT PRESENTATION

About This Presentation

Description : Check out this medical PowerPoint presentation titled "Drug induced nephrotoxicity” by Naser Hadavand.

This medical PowerPoint presentation is about drug-induced nephrotoxicity, kidney damage caused by medications or other substances. The kidneys are responsible for filtering the blood and removing waste products, excess fluid, and toxins from the body. When certain drugs are metabolized in the kidneys, they can produce toxic byproducts that can damage the kidneys.

Common drugs that can cause nephrotoxicity include Nonsteroidal anti-inflammatory drugs (NSAIDs), Antibiotics, Chemotherapy drugs, Contrast dyes and Antiviral drugs.

Symptoms of nephrotoxicity can include decreased urine output, swelling of the legs or feet, fatigue, nausea, vomiting, and confusion. Treatment may involve stopping the use of the offending drug, managing symptoms, and providing supportive care to the kidneys.

Prevention of nephrotoxicity involves avoiding drugs known to cause kidney damage in individuals who are at risk of kidney disease or have preexisting kidney conditions. It is also important to closely monitor kidney function and adjust medication dosages accordingly in individuals with kidney disease.

Tags : Drug induced nephrotoxicity, kidney damage, Nonsteroidal anti-inflammatory drugs, NSAIDs, Antibiotics, Chemotherapy drugs, Contrast dyes, Antiviral drugs, Nephrology, Nephrology PowerPoint presentation

Published on : Jun 07, 2023 | Views : 1343 | Downloads : 0

Shareable Url :

Embed Code :

Comment

Transcript

Slide 1-

25/11/1444 Drug induced nephrotoxicity Naser Hadavand
Slide 2-

ppt slide no 2 content not found
Slide 3-

Definitions Type Onset Severity Classification of Drug Induced Disordres
Slide 4-

Definition and Classifications of Adverse Reaction Terms Adverse Event: Adverse Drug Reaction: Side Effect:
Slide 5-

Definition and Classifications of Adverse Reaction Terms Adverse Event: Any untoward medical occurrence that may present during treatment with pharmaceutical product but which does not necessarily have a causal relationship with treatment.
Slide 6-

Definition and Classifications of Adverse Reaction Terms Adverse Event: Any untoward medical occurrence that may present during treatment with pharmaceutical product but which does not necessarily have a causal relationship with treatment. Adverse Drug Reaction: A response to a drug that is noxious and unintended and occurs at doses normally used in man for the prophylaxis, diagnosis or therapy of disease, or for modification of physiological function.
Slide 7-

Definition and Classifications of Adverse Reaction Terms Adverse Event: Any untoward medical occurrence that may present during treatment with pharmaceutical product but which does not necessarily have a causal relationship with treatment. Adverse Drug Reaction: A response to a drug that is noxious and unintended and occurs at doses normally used in man for the prophylaxis, diagnosis or therapy of disease, or for modification of physiological function. Side Effect: Any unintended effect of a pharmaceutical product occurring at doses normally used in man which is related to the pharmacological properties of drug.
Slide 8-

Examples Adverse Event: Adverse Drug Reaction: Side Effect:
Slide 9-

Adverse Drug Reaction vs. Adverse Event Adverse Drug Reaction (event attributed to drug) Adverse Event All Spontaneous reports Events not attributed to drug Diseases Other Drugs Environment Diet Genetics Compliance Other factors
Slide 10-

Definitions Type Onset Severity Classification
Slide 11-

Comparison Type A and Type B
Slide 12-

Adverse Drug Reactions Unwanted effects of drugs are separated into those represent: Augmented pharmacological effects of a substance but qualitatively normal (Type A) Qualitatively bizarre pharmacological effects (Type B) Long term effects (Type C) Delayed effects (Type D) End of use (Type E) Failure (Type F) * Most long term effects are Type A reactions.
Slide 13-

Introduction Occurs frequently in patients treated with diagnostic and therapeutic agents Manifestation Decrease in renal function(often reversible) Is seen in which patients? Drug induced nephrotoxicity
Slide 14-

Incidence 5% بیماران بستری در بیمارستان دچار نارسایی حاد کلیوی می شوند. 25% موارد نارسایی حاد کلیوی حاصل از مصرف دارو می باشد. که در 8% موارد منجر به مرگ می شود. نارسایی کلیوی حاصل از دارو 7% کل مسمومیت های دارویی را شامل می شود.
Slide 15-

Incidence Frequent adverse event in hospitalized patients - 7% of all drugs toxicity - 1/5 of all ARF induced by drugs Mortality: 8% Drugs induced nephrotoxicity in general: Aminoglycosides, Cisplatin, Radiographic contrast media Drugs induced ARF: AG, Pentamidine,Cephalosporins, NSAIDs, ACEIs, Diuretics(29%)
Slide 16-

Risk factors: Idiosyncratic Direct cumulative toxicity No generalizable risk factors are applicable to all drug classes and patient situation ,Exception: ARF due to NSAIDs & ACEIs The risk factors are: Preexisting renal insufficiency & decrease effective renal blood flow from volume depletion and HF, liver dx.
Slide 17-

Recognition and assessment of renal toxicity: Hospitalized patients: 1-recognized quickly 2-by lab test: BUN,Cr 3-decrease in urine out put(ACEIs,NSAIDs, Radiographic contrast) Out patients recognized by advanced renal dysfunction Signs
Slide 18-

Classification of drug induced renal disease: Based on mechanism of toxicity Presenting of renal manifestations: CRF,ARF,Pyuria,Hematuria, Proteinuria Therapeutic use and the various types of nephropathies they may produced Renal structural and functional alterations(produced by drugs)
Slide 19-

Definitions: Pseudo Renal Failure Interstitial Nephritis Acute interstitial nephritis Chronic interstitial nephritis Acute Glomerulonephritis Acute Tubular Necrosis Crystal nephropathy Rhabdomyolysis Nephrotic Syndrome minimal-change nephropathy
Slide 20-

Pseudo Renal Failure (Normal GFR) ↑ BUN due to protein catabolism , Normal Cr 􀂄 Steroids, tetracyclines ↑ SCr due to competitive inhibition of creatinine secretion, Normal BUN 􀂄 Trimethoprim, Cimetidine, Triamterene - 15-35% rise SCr fully expressed after 3 days - More sig in pts with pre-existing renal dysfunction - Can occur with normal doses - Completely reversible when drug is discontinued (J Int Med 1999l246:247-52; TDM 1987;9:161-5)
Slide 21-

Definitions: Interstitial Nephritis Interstitial nephritis (or Tubulo-interstitial nephritis) is a form of nephritis affecting the interstitium of the kidneys surrounding the tubules. This disease can be either acute, meaning it occurs suddenly, or chronic, meaning it is ongoing and eventually ends in kidney failure.
Slide 22-

Definitions: Interstitial Nephritis When caused by an allergic reaction, the symptoms of acute tubulointerstitial nephritis are: - fever (27% of patients) - rash (15% of patients) - enlarged kidneys. Other: Dysuria, and lower back pain. In chronic tubulointerstitial nephritis: nausea, vomiting, fatigue, and weight loss. hyperkalemia, metabolic acidosis, and kidney failure. Blood tests: Eosinophilia, ↑ Cr & BUN Urinary findings: Eosinophiluria, Isosthenuria, hematuria, Sterile pyuria: white blood cells and no bacteria
Slide 23-

Acute interstitial nephritis Symptoms and Signs Classic triad (Methicillin induced hypersensitivity) Low grade fever (>70% of cases) Rash (>30% of cases) Arthralgia (>15% of cases) Acute Renal Failure Oliguria Malaise Nausea or Vomiting Labs: General Urinalysis Eosinophiluria Proteinuria Fractional Excretion of Sodium >1% Renal Function tests with renal insufficiency Cr & BUN increased Miscellaneous Hyperchloremic Metabolic Acidosis
Slide 24-

Acute interstitial nephritis Causes Infection Diphtheria , Group A beta hemolytic Streptococcus (classic) Legionella , Yersinia , Staphylococcus or Streptococcus infection Mycobacterium , Toxoplasmosis , Mycoplasma , Leptospira Rickettsia , Syphilis , Herpes viruses (e.g. CMV, EBV, HSV) Human Immunodeficiency Virus (HIV),Hantavirus Hepatitis C , Mumps Medications (AIN occurs >2 weeks after drug started) Penicillins and Cephalosporins Hypersensitivity (fever, rash, arthralgia) Sulfonamides Vasculitis reaction NSAIDs Nephrotic Syndrome type reaction Rifampin , Diuretics (Thiazides and Lasix), Allopurinol , Cimetidine , Ciprofloxacin Dilantin Other medications have caused AIN to a lesser extent Miscellaneous conditions Glomerulonephritis , Necrotizing Vasculitis, Systemic Lupus Erythematosus Acute kidney transplant rejection Symptoms and Signs Classic triad (Methicillin induced hypersensitivity) Low grade fever (>70% of cases) Rash (>30% of cases) Arthralgia (>15% of cases) Acute Renal Failure Oliguria Malaise Nausea or Vomiting Labs: General Urinalysis Eosinophiluria Proteinuria Fractional Excretion of Sodium >1% Renal Function tests with renal insufficiency Serum Creatinine increased Blood Urea Nitrogen increased Miscellaneous Hyperchloremic Metabolic Acidosis
Slide 25-

Definitions: Acute Glomerulonephritis Glomerulonephritis, also known as glomerular nephritis, abbreviated GN, is a renal disease (usually of both kidneys) characterized by inflammation of the glomeruli, or small blood vessels in the kidneys. It may present with isolated hematuria and/or proteinuria (blood or protein in the urine); or as a nephrotic syndrome, a nephritic syndrome, acute renal failure, or chronic renal failure. Primary causes are intrinsic to the kidney. Secondary causes are associated with certain infections (bacterial, viral or parasitic pathogens), drugs, systemic disorders (SLE, vasculitis), or diabetes.
Slide 26-

Definitions: Acute Tubular Necrosis Acute tubular necrosis (ATN) is a medical condition involving the death of tubular cells that form the tubule that transports urine to the ureters while reabsorbing 99% of the water (and highly concentrating the salts and metabolic byproducts). Tubular cells continually replace themselves and if the cause of ATN is removed then recovery is likely. ATN presents with acute kidney injury (AKI) and is one of the most common causes of AKI. The presence of "muddy brown casts" of epithelial cells found in the urine during urinalysis is pathognomonic for ATN.
Slide 27-

Definitions: Crystal nephropathy Several medications that are insoluble in human urine are known to precipitate within the renal tubules. Intratubular precipitation of either exogenously administered medications or endogenous crystals (induced by certain drugs) can promote chronic and acute kidney injury, termed crystal nephropathy. Clinical settings that enhance the risk of drug or endogenous crystal precipitation within the kidney tubules include: - true or effective intravascular volume depletion - underlying kidney disease - and certain metabolic disturbances that promote changes in urinary pH favoring crystal precipitation.
Slide 28-

Definitions: Rhabdomyolysis Rhabdomyolysis is a condition in which damaged skeletal muscle tissue , breaks down rapidly. Breakdown products of damaged muscle cells are released into the bloodstream; some of these, such as the protein myoglobin, are harmful to the kidneys and may lead to kidney failure. The severity of the symptoms, which may include muscle pains, vomiting and confusion, depends on the extent of muscle damage and whether kidney failure develops. The muscle damage may be caused by physical factors (e.g. crush injury, strenuous exercise), medications, drug abuse, and infections. Some people have a hereditary muscle condition that increases the risk of rhabdomyolysis. The diagnosis is usually made with blood tests and urinalysis. The mainstay of treatment is generous quantities of intravenous fluids, but may include dialysis or hemofiltration in more severe cases. Rhabdomyolysis and its complications are significant problems for those injured in disasters such as earthquakes and bombings. Relief efforts in areas struck by earthquakes often include medical teams with the skills and equipment to treat survivors with rhabdomyolysis. The disease was first described in the 20th century, and important discoveries as to its mechanism were made during the Blitz of London in 1941. Horses may also suffer from rhabdomyolysis from a variety of causes.
Slide 29-

Definitions: Nephrotic Syndrome Nephrotic syndrome is a nonspecific kidney disorder characterised by a number of diseases: proteinuria, hypoalbuminemia and edema. It is characterized by an increase in permeability of the capillary walls of the glomerulus leading to the presence of: - high levels of protein passing from the blood into the urine (proteinuria at least 3.5 grams per day per 1.73m2 body surface area); - low levels of protein in the blood (hypoproteinemia or hypoalbuminemia), - Ascites and edema - High cholesterol (hyperlipidaemia or hyperlipemia) - Predisposition for coagulation. Kidneys affected by nephrotic syndrome have small pores in the podocytes, large enough to permit proteinuria (and subsequently hypoalbuminemia,<25g/L, because some of the protein albumin has gone from the blood to the urine) but not large enough to allow cells through (hence no haematuria). By contrast, in nephritic syndrome red blood cells pass through the pores, causing haematuria.
Slide 30-

Diagnosis: Proteinuria: >3.5g/d Hypoalbuminemia: SAlb <30g/L Edema; Hyperlipidemia. Pro ++++ Nephrotic Syndrom Edema
Slide 31-

Definitions: minimal-change nephropathy Minimal Change Disease (also known as Nil Lesions or Nil Disease (lipoid nephrosis)) is a disease of the kidney that causes nephrotic syndrome and usually affects children (peak incidence at 2–3 years of age). People with one or more autoimmune disorders are at increased risk of developing minimal change disease. Having minimal change disease also increases the chances of developing other autoimmune disorders. Most cases of MCD are idiopathic, however there have been causes of secondary MCD identified, including medications, immunizations, neoplasm, and infection. Case reports and literature reviews have shown an association between MCD and malignancies, particularly hematologic malignancies, such as Hodgkin’s disease, non-Hodgkin lymphomas, or leukemias. Colorectal cancer-associated MCD is uncommon and has been reported in only a few cases to date.
Slide 32-

CLASSIFICATIONS Anuric: < 50ml/day urine output Oliguric: 50-400ml/day urine output Non-oliguric: >400ml/day urine output
Slide 33-

Urine Analysis
Slide 34-

Kidney Function Tests
Slide 35-

نارسایی کلیوی Pre Renal: ↑ BUN/ ↑ Cr >20 Post Renal: ↑ BUN/ ↑ Cr 10 – 20 Renal: ↑ BUN/ ↑ Cr < 10
Slide 36-

Kidney Function Tests
Slide 37-

ppt slide no 37 content not found
Slide 38-

ESTIMATION OF RENAL FUNCTION Cockcroft and Gault Equation: Estimates renal function when creatinine levels are at steady-state not usually the case in acute renal failure CLCr(ml/min) = (140-Age)×(Wt.) 72(Scr) = × 0.85 (female)
Slide 39-

Serum Creatinine Creatinine 1.0 mg/dL Normal GFR Creatinine 2.0 mg/dL 50% reduction in GFR Creatinine 4.0 mg/dL 70–85% reduction in GFR Creatinine 8.0 mg/dL 90–95% reduction in GFR
Slide 40-

Estimate Creatinine Clearance: (ml/min) Cockcroft and Gault equation: CrCl: (140 - age) x IBW / (Scr x 72) (x 0.85 for females) Note: if the ABW (actual body weight) is less than the IBW use the actual body weight for calculating the CRCL. If the patient is >65yo and creatinine<1, use 1 to calculate the creatinine clearance.
Slide 41-

Estimate Ideal body weight in (kg) Males: IBW = 50 kg + 2.3 kg for each inch over 5 feet. Females: IBW = 45.5 kg + 2.3 kg for each inch over 5 feet. Adjusted body weight (ABW): ABW = IBW + 0.4(Total body weight - IBW)
Slide 42-

ppt slide no 42 content not found
Slide 43-

داروها بیشتر باعث بروز نارسایی حاد کلیوی می شوند یا نارسایی مزمن کلیوی؟ Definitions Type Onset Severity
Slide 44-

آیا احتمال دارد بیمار دچار نارسایی کلیوی حاصل از داروها شود بدون اینکه برون ده اداری او تغییر کند؟
Slide 45-

آیا عوارض کلیوی NSAIDs در کودکان بیشتر است؟
Slide 46-

آیا مرگ و میر حاصل از نارسایی حاد کلیوی ایجاد شده توسط داروها بیشتر از سایر علل آن می باشد؟
Slide 47-

کدامیک از عوارض کلیوی حاصل از داروها وابسته به دوز دارو نیست؟ Acute interstitial nephritis Acute Tubular Necrosis Obstructive
Slide 48-

Aminoglycosides Is once daily dosing less nephrotoxic compared to traditional dosing?
Slide 49-

آیا فرمولاسیون دارو می تواند در بروز عارضه کلیوی نقش داشته باشد؟
Slide 50-

Amphotericin B Are Liposomal formulations affect nephrotoxicity
Slide 51-

تشخیص زودهنگام نارسایی کلیوی حاصل از دارو در کدام بیماران رایج تر/ محتمل تر است؟ بستری سر پایی
Slide 52-

در تمامی بیماران مصرف کننده ACEI افزایش کراتینین رخ می دهد؟ درست نادرست
Slide 53-

در تمامی بیماران مصرف کننده ACEI افزایش کراتینین رخ می دهد؟ درست نادرست
Slide 54-

آیا با افزایش کراتینین در بیماران مصرف کننده ACEI دارو باید قطع گردد؟ بلی خیر بستگی دارد
Slide 55-

عوارض کلیوی با کدامیک از داروهای زیر بیشتر رخ می دهد؟ - NSAIDs - Cyclosporine - Amphotericin-B - Radiocontrast Media - Vasopressors
Slide 56-

ppt slide no 56 content not found
Slide 57-

برای جلوگیری از تشکیل کریستال و رسوب داروها در توبول ها بهتر است pH ادرار اسیدی باشد یا بازی؟ اسیدی بازی بستگی دارد
Slide 58-

کدام گزینه در مورد مکانیسم ایجاد عارضه کلیوی دارویی نادرست است؟ A. Tubular cell toxicity — ACE inhibitors B. Altered intraglomerular hemodynamics — ARBs C. Crystal nephropathy — Antivirals D. Rhabdomyolysis — Statins
Slide 59-

در کدامیک از موارد زیر دارو باید قطع گردد؟ Relative Serum Creatinine increase 50% over baseline Absolute Serum Creatinine increase Serum Creatinine baseline <2 mg/dl: Creatinine increase 0.5 mg/dl over baseline Serum Creatinine baseline >2 mg/dl: Creatinine increase 1.0 mg/dl over baseline
Slide 60-

60
Slide 61-

Drug-Induced Acute Renal Dysfunction Pseudo Renal Failure Acute Renal Failure - Prerenal NSAIDs, CyA/Tacrolimus, ACEI/ARB, Diuretics - Intrinsic – ATN vs AIN ATN – Aminoglycosides, Amphotericin B, Radiocontrast Media - Obstructive Methotrexate, Acyclovir, Indinavir, Rhabdomyolysis (Statins)
Slide 62-

DRUG-INDUCED RENAL FAILURE
Slide 63-

ETIOLOGY: pre-renal Decreased cardiac output: CHF,MI,PE, Beta-blockers Peripheral vasodilation: bacterial sepsis, vasodilators (nitrates, hydralazine,etc.) Hypovolemia: blood loss,Severe dehydration, diarrhea, burns, third-spacing, diuresis(diuretics) Vascular Obstruction: NSAIDS, ACE-I, Vasopressors, renal artery occlusion
Slide 64-

درد مسکن های غیر اوپیوئیدی داروهای ضد التهاب غیر استروئیدی(NSAIDs) استامینوفن مسکن های اوپیوئیدی اوپیوئیدهای قوی اوپیوئید های ضعیف
Slide 65-

History 1 The first reference to aspirin was by a 5th century BC Greek physician who rote of a bitter powder that came from the bark of the willow tree, and it eased pains and reduced fever. The medicinal part of the plant is the inner bark of the tree. The active extract of the bark is called salicin after the Latin name for the white willow tree. It was isolated in crystalline form in 1828 by Henri Leroux, a French pharmacist. Raffaele Piria, an Italian chemist was able to convert it to salicylic acid. Salicylic acid was isolated from the herb called meadowsweet by German researchers in 1839. While it was somewhat effective, it also caused digestive problems when consumed in high doses. A French chemist, Charles Frederic Gerhardt, first prepared acetylsalicylic acid in 1853 (named aspirin in 1899). This preparation of aspirin was one of many reactions Gerhardt conducted for his paper on anhydrides and he did nothing further with it. Six years later in 1859, von Gilm created the substance again. In 1897, a chemist at Friedrich Bayer and Co. began investigating acetylsalicylic acid as a less-irritating replacement for the commonly used salicylate medicines. By 1899 Bayer was marketing it world wide. obtained acetylsalicylic acid and claimed to discover aspirin. Regardless of that, aspirin was finally manufactured and put on the market to help those in pain or with fever.
Slide 66-

History 2 Sodium salicylate, discovered in 1763, was the first NSAID. Gastrointestinal toxicity (particularly dyspepsia) associated with the use of acetylsalicylic acid (ASA) led to the introduction of phenylbutazone, an indoleacetic acid derivative, in the early 1950s; this was the first non-salicylate NSAID developed for use in patients with inflammatory conditions. Phenylbutazone is a weak prostaglandin synthetase inhibitor that also induces uricosuria. It was shown to be a useful agent in patients with ankylosing spondylitis and gout. Concerns related to bone marrow toxicity, particularly in women over the age of 60, have essentially eliminated the use of this drug. Indomethacin was developed in the 1960s as a substitute for phenylbutazone. The following years witnessed the development of more and more NSAIDs in an effort to enhance patient compliance (by decreasing the absolute number of pills and frequency with which they are taken each day), reduce toxicity, and increase the antiinflammatory effect.
Slide 67-

History 3 Salicylates were discovered in the mid-19th century There were two periods of NSAID drug discovery post-World War 2, the period up to the 1970's which was the pre-prostaglandin period and thereafter up to the latter part of the last century in which their effects on prostaglandin production formed part of the screening in the drug-discovery process. Those drugs developed up to the 1980-late 90's were largely discovered empirically following screening for anti-inflammatory, analgesic and antipyretic activities in laboratory animal models. Some were successfully developed that showed low incidence of gastro-intestinal (GI) side effects (the principal adverse reaction seen with NSAIDs) than seen with their predecessors (e.g. aspirin, indomethacin, phenylbutazone); the GI reactions being detected and screened out in animal assays.
Slide 68-

History 3 In the 1990's an important discovery was made from elegant molecular and cellular biological studies that there are two cyclo-oxygenase (COX) enzyme systems controlling the production of prostanoids [prostaglandins (PGs) and thromboxane (TxA2)]; COX-1 that produces PGs and TxA2 that regulate gastrointestinal, renal, vascular and other physiological functions, and COX-2 that regulates production of PGs involved in inflammation, pain and fever. The stage was set in the 1990's for the discovery and development of drugs to selectively control COX-2 and spare the COX-1 that is central to physiological processes whose inhibition was considered a major factor in development of adverse reactions, including those in the GI tract. At the turn of this century, there was enormous commercial development following the introduction of two new highly selective COX-2 inhibitors, known as coxibs (celecoxib and rofecoxib) which were claimed to have low GI side effects.
Slide 69-

History 4 While found to have fulfilled these aims in part, an alarming turn of events took place in the late 2004 period when rofecoxib was withdrawn worldwide because of serious cardiovascular events and other coxibs were subsequently suspected to have this adverse reaction, although to a varying degree. Major efforts are currently underway to discover why cardiovascular reactions took place with coxibs, identify safer coxibs, as well as elucidate the roles of COX-2 and COX-1 in cardiovascular diseases and stroke in the hope that there may be some basis for developing newer agents (e.g. nitric oxide-donating NSAIDs) to control these conditions. Moreover, new anti-inflammatory drugs are being discovered and developed based on their effects on signal transduction and as anti-cytokine agents and these drugs are now being heralded as the new therapies to control those diseases where cytokines and other nonprostaglandin components of chronic inflammatory and neurodegenerative diseases are manifest.
Slide 70-

ppt slide no 70 content not found
Slide 71-

ليست داروهای موجود
Slide 72-

ppt slide no 72 content not found
Slide 73-

ppt slide no 73 content not found
Slide 74-

Endothelium, brain, spinal cord Kidney (Macula densa), ovaries, uterus N.B.: COX-2 also in + GCS Classical NSAID’s
Slide 75-

Mechanism of action Prostaglandins act (among other things) as messenger molecules in the process of inflammation. This mechanism of action was elucidated by John Vane (1927–2004), who received a Nobel Prize for his work (see Mechanism of action of aspirin). Acetaminophen is not considered an NSAID because it has little anti-inflammatory activity. It treats pain mainly by blocking COX-2 mostly in the central nervous system, but not much in the rest of the body. The COX-3 pathway was believed to fill some of this gap but recent findings make it appear unlikely that it plays any significant role in humans and alternative explanation models are proposed. NSAIDs are also used in the acute pain caused by gout because they inhibit urate crystal phagocytosis besides inhibition of prostaglandin synthase.
Slide 76-

Mechanism of action Antipyretic activity NSAIDS have antipyretic activity and can be used to treat fever. Fever is caused by elevated levels of prostaglandin E2, which alters the firing rate of neurons within the hypothalamus that control thermoregulation. Antipyretics work by inhibiting the enzyme COX, which causes the general inhibition of prostanoid biosynthesis (PGE2) within the hypothalamus. PGE2 signals to the hypothalamus to increase the body's thermal set point. Ibuprofen has been shown more effective as an antipyretic than acetaminophen (paracetamol). Arachidonic acid is the precursor substrate for cyclooxygenase leading to the production of prostaglandins F, D & E.
Slide 77-

Pharmacokinetics: - Most NSAIDs are absorbed completely - Have negligible first-pass hepatic metabolism - Tightly bound to serum proteins - Have small volumes of distribution - Half-lives of the NSAIDs vary but in general can be divided into : "short-acting" (less than six hours, including ibuprofen, diclofenac, ketoprofen and indomethacin) and "long-acting" (more than six hours, including naproxen, celecoxib, meloxicam, nabumetone and piroxicam). Patients with hypoalbuminemia (due, for example, to cirrhosis or active rheumatoid arthritis) may have a higher free serum concentration of the drug.
Slide 78-

Drug interactions NSAIDs reduce renal blood flow and thereby decrease the efficacy of diuretics,
Slide 79-

Drug interactions NSAIDs reduce renal blood flow and thereby decrease the efficacy of diuretics, and inhibit the elimination of lithium and methotrexate. NSAIDs cause hypocoagulability, which may be serious when combined with other drugs that also decrease blood clotting, such as warfarin. NSAIDs may aggravate hypertension (high blood pressure) and thereby antagonize the effect of antihypertensives, such as ACE Inhibitors. NSAIDs may interfere and reduce efficiency of SSRI antidepressants
Slide 80-

Indications NSAIDs are usually indicated for the treatment of acute or chronic conditions where pain and inflammation are present. Research continues into their potential for prevention of colorectal cancer, and treatment of other conditions, such as cancer and cardiovascular disease. NSAIDs are generally indicated for the symptomatic relief of the following conditions: Rheumatoid arthritis Osteoarthritis Inflammatory arthropathies (e.g. ankylosing spondylitis, psoriatic arthritis, Reiter's syndrome) Acute gout Dysmenorrhoea (menstrual pain) Metastatic bone pain Headache and migraine Postoperative pain Mild-to-moderate pain due to inflammation and tissue injury Muscle stiffness and pain due to Parkinson's disease Pyrexia (fever) Ileus Renal colic Ductus arteriosus is not closed within 24 hours of birth Aspirin, the only NSAID able to irreversibly inhibit COX-1, is also indicated for inhibition of platelet aggregation. This is useful in the management of arterial thrombosis and prevention of adverse cardiovascular events. Aspirin inhibits platelet aggregation by inhibiting the action of thromboxane A2.
Slide 81-

NSAIDs - Common Adverse Effects Platelet Dysfunction Gastritis and peptic ulceration with bleeding (inhibition of PG + other effects) Acute Renal Failure in susceptible Sodium+ water retention and edema Analgesic nephropathy Prolongation of gestation and inhibition of labor. Hypersenstivity (not immunologic but due to PG inhibition) GIT bleeding and perforation
Slide 82-

عوارض جانبیNSAIDs عوارض کلیوی شیوع 10-1% احتیاط مصرف NSAIDs در بیماران با نارسایی کلیوی و مصرف کنندگان داروهای مسدودكننده گیرنده آنژیوتانسین (لوزارتان، والزارتان) و مهار کننده های ACE (کاپتوپریل، انالاپریل) توجه به سطح کراتينین در بیماران مسن و بیماران دچار نارسایی کلیوي
Slide 83-

NSAIDs/COXibs 5% بیماران مصرف کننده NSAIDs در سال دچار نارسایی حاد کلیوی می شوند. که باعث بستری در بیمارستان یا افزایش طول مدت بستری می شود.
Slide 84-

NSAIDs/COXibs Use with caution in CKD (grade 3 or greater) Inhibit renal vasodilatory prostaglandins E2 & I2 􀂄 Produced by COX-2 Reversible reduction in GFR 􀂄 Higher risk if intravascular volume depletion 􀂄 Management: D/C drug, use alternate analgesia Hypertension 􀂄 Edema, sodium and water retention 􀂄 Mean increase SBP 5 mm Hg Hyperkalemia Risk 􀂄 blunting of PG-mediated renin release
Slide 85-

چه مدت پس از قطع مصرف NSAIDs مشکلات کلیوی حاصل از آنها بهبود می بابد؟ یک هفته دو هفته یک ماه سه ماه یک سال برگشت پذیر نمی باشد
Slide 86-

کدام NSAIDs مشکلات کلیوی کمتری ایجاد می کنند؟
Slide 87-

کدام NSAIDs مشکلات کلیوی کمتری ایجاد می کنند؟ Sulindac Naproxen
Slide 88-

Analgesic nephropathy Analgesic nephropathy involves damage to one or both kidneys caused by overexposure to mixtures of medications, especially over-the-counter pain remedies (analgesics). - Injuries: renal papillary necrosis and chronic interstitial nephritis. - Result: decreased blood flow to the kidney, rapid consumption of antioxidants, and subsequent oxidative damage to the kidney. This kidney damage may lead to progressive chronic renal failure, abnormal urinalysis results, high blood pressure, and anemia.
Slide 89-

Analgesic nephropathy Causes, incidence, and risk factors - Analgesic nephropathy involves damage within the internal structures of the kidney. It is caused by long-term use of analgesics, especially over-the-counter (OTC) medications that contain phenacetin or acetaminophen and nonsteroidal anti-inflammatory drugs (NSAIDs) such as aspirin or ibuprofen. - About 6 or more pills per day for 3 years increases the risk some for this problem. This frequently occurs as a result of self-medicating, often for some type of chronic pain. - Analgesic nephropathy occurs in about 4 out of 100,000 people, mostly women over 30. The rate has decreased significantly since phenacetin is no longer widely available in OTC preparations.
Slide 90-

Analgesic nephropathy Risk factors include: - Use of OTC analgesics containing more than one active ingredient - Chronic headaches, painful menstrual periods, backache, or musculoskeletal pain - History of dependent behaviors including smoking, alcoholism, and excessive use of tranquilizers
Slide 91-

Analgesic nephropathy Symptoms There may be no symptoms. Symptoms of chronic kidney disease are often present over time and may include: Weakness, Fatigue Increased urinary frequency or urgency Blood in the urine Flank pain or back pain Decreased urine output Decreased alertness : Drowsiness , Confusion, delirium , Lethargy Decreased sensation, numbness (especially in the legs) Nausea, vomiting Easy bruising or bleeding Swelling, generalized
Slide 92-

Analgesic nephropathy Signs and tests A physical examination may show signs of interstitial nephritis or kidney failure. Blood pressure may be high abnormal heart or lung sounds There may be signs of premature skin aging Lab tests may show blood and pus in the urine, with or without signs of infection There may be mild or no loss of protein in the urine. Tests that may be done include: - CBC - sedimentation in the urine - Intravenous pyelogram(IVP) - Toxicology screen - Urinalysis
Slide 93-

Analgesic nephropathy Treatment The primary goals of treatment are to prevent further damage and to treat any existing kidney failure. Stop taking all suspect painkillers, particularly OTC medications. Signs of kidney failure should be treated as appropriate. This may include diet changes, fluid restriction, dialysis or kidney transplant, or other treatments. Counseling, behavioral modification, or similar interventions may help you develop alternative methods of controlling chronic pain. Expectations (prognosis) The damage to the kidney may be acute and temporary, or chronic and long term.
Slide 94-

Analgesic nephropathy Complications Acute renal failure Chronic renal failure Interstitial nephritis Renal papillary necrosis (tissue death) Urinary tract infections, chronic or recurrent Hypertension Transitional cell carcinoma of the kidney or ureter
Slide 95-

Drug-Induced Acute Renal Dysfunction Acute Renal Failure - Prerenal NSAIDs, CyA/Tacrolimus, ACEI/ARB, Diuretics
Slide 96-

Cyclosporine, Tacrolimus Can cause: - pre-renal (hemodynamically mediated) - chronic interstitial nephritis Pre-renal – dose-related 􀂄 preglomerular arteriolar vasoconstriction or direct proximal tubule damage 􀂄 ↑ SCr ~ 30% 􀂄 More common in first 6 mos of therapy 􀂄 Hypertension, ↑ K, ↓ Mg may occur 􀂄 Reversible with lowering dose (caution rejection) 􀂄 Monitor blood levels 􀂄 Renal biopsy to distinguish acute CyA nephrotoxcity from allograft rejection
Slide 97-

تست تشخیصی عارضه کلیوی حاصل از سیکلوسپورین از رد پیوند چیست؟ BUN/Cr Angiography Biopsy
Slide 98-

Drug-Induced Acute Renal Dysfunction Acute Renal Failure - Prerenal NSAIDs, CyA/Tacrolimus, ACEI/ARB, Diuretics
Slide 99-

Side Effects
Slide 100-

Putting Guidelines into Practice — ACE INHIBITORS — ACE Inhibitors – In Whom and When? Indications: Potentially all patients with heart failure First-line treatment (along with beta-blockers) in NYHA class I–IV heart failure Contra-indications: History of angioneurotic oedema Cautions/seek specialist advice: Significant renal dysfunction (creatinine >2.5 mg/dL or 221 µmol/L) or hyperkalaemia (K+ >5.0 mmol/L) Symptomatic or severe asymptomatic hypotension (SBP <90 mmHg) Drug interactions to look out for: K+ supplements/ K+ sparing diuretics (including spironolactone) NSAIDs* *avoid unless essential AT1-receptor blockers
Slide 101-

Drug induced renal structural functional alteration Psuedo renal failure Hemodynamically mediated renal failure Renal vascular alterations Glomerular alteration Acute tubular necrosis Tubulointerstitial disease Obstructive nephropathy Nephrolithiasis Increase in BUN and Cr without a decrease in GFR Increase in BUN and Cr=norm Corticosteroid,TC(these increase protein catabolism Increase in Cr,BUN=norm TMP,Pyrimethamine,Cimetidine Reduction glumerular capillary hydrostatic pressure Inhibition of prostaglandin-dependant renal blood flow Nonspecific renal vasocons Increase vascular permeability Increase in colloid oncotic pressure
Slide 102-

ppt slide no 102 content not found
Slide 103-

Afferent Arteriolar vasoconstrictors Vasodilatory Prostaglandin Inhibitors - NSAIDs - COX-2 Inhibitors Direct Afferent Arteriolar Vasoconstrictors - Cyclosporine - Amphotericin-B - Radiocontrast Media - Vasopressors
Slide 104-

Efferent Arteriolar vasodilators Renin-Angiotensin-Aldosterone - ACEIs - ARBs Direct Efferent Arteriolar Vasodilators - CCBs dihydropyridine: Diltiazem, Verapamil
Slide 105-

ppt slide no 105 content not found
Slide 106-

Acute Renal Failure:PRE-RENAL ACEI/ARB NSAIDs Diuretics Immunosuppressives (CyA, Tacrolimus)
Slide 107-

Acute Renal Failure:PRE-RENAL ACEI/ARB At the start of the treatment a decrease of urine volume and increase of creatinine by 30% indicates Damage is reversible Rehydration of patient is advisable Initiate treatment with short acting (captopril) and titrate later with long acting
Slide 108-

ACE Inhibitors & ARBs Uremia, hyper K, dialysis dependence Cr > 3.5  consult nephrology! Avoid in bilat renal artery stenosis - ARB causes less renal failure than ACE Inhibitor Strategy: BP, K, Cr “diuretic holiday” x days before start start captopril 1st, then long-acting Ramipril: CrCl < 40, give 25% of normal dose Losartan: avoid if GFR < 30
Slide 109-

Risk Factors for ARF with ACEI/ARB Decreased intravascular volume (dehydration, diuretic overuse, poor fluid intake, CHF, vomiting, diarrhea) Use of afferent vasoconstrictor agents (NSAIDs, cyclosporine, tacrolimus) Sepsis Renal-artery stenosis Polycystic kidney disease
Slide 110-

Putting Guidelines into Practice — ACE INHIBITORS — ACE Inhibitors – How to Use Start with a low dose Double dose at not less than two weekly intervals Aim for target dose or, failing that, the highest tolerated dose Remember some ACE inhibitor is better than no ACE inhibitor Monitor blood chemistry (urea, creatinine, K+) and blood pressure When to stop up-titration/down-titration – see PROBLEM SOLVING
Slide 111-

Putting Guidelines into Practice — ACE INHIBITORS — ACE Inhibitors – Problem Solving (continued) Worsening renal function: Some increase in urea (blood urea nitrogen), creatinine and K+ is to be expected after initiation; if the increase is small and asymptomatic no action is necessary An increase in creatinine of up to 50% above baseline, or 3 mg/dL (266 µmol/L), whichever is the smaller, is acceptable An increase in K+  6.0 mmol/L is acceptable If urea, creatinine or K+ rise excessively, consider stopping concomitant nephrotoxic drugs (e.g. NSAIDs), other K+ supplements/ K+ retaining agents (triamterene, amiloride) and, if no signs of congestion, reducing the dose of diuretic If greater rises in creatinine or K+ than those outlined above persist, despite adjustment of concomitant medications, halve the dose of ACE inhibitor and recheck blood chemistry; if there is still an unsatisfactory response, specialist advice should be sought
Slide 112-

Putting Guidelines into Practice — ACE INHIBITORS — ACE Inhibitors – Problem Solving (continued) Worsening renal function (cont.): If K+ rises to >6.0 mmol/L, or creatinine increases by >100% or to above 4 mg/dL (354 µmol/L), the dose of ACE inhibitor should be stopped and specialist advice sought Blood chemistry should be monitored serially until K+ and creatinine have plateaued NOTE: it is very rarely necessary to stop an ACE inhibitor and clinical deterioration is likely if treatment is withdrawn; ideally, specialist advice should be sought before treatment discontinuation
Slide 113-

ACE-Inhibitors “A limited increase in serum creatinine of as much as 35% above baseline with ACE inhibitors or ARBs is acceptable and not a reason to withhold treatment unless hyperkalemia develops.” “an increase in SCr level, if it occurs, will happen within the first 2 weeks of therapy initiation.” JNC-7
Slide 114-

با توجه به مطالب ارائه شده، ACEIs نفروتوکسیک هستند یا نفروپروتکتیو؟
Slide 115-

با توجه به مطالب ارائه شده، ACEIs نفروتوکسیک هستند یا نفروپروتکتیو؟ در دیابتی ها که پروتئین دفع می کنند با کاهش فشار گلومرولی نقش نفروپروتکتیو دارند.
Slide 116-

ACEIs - Additional Considerations Compelling indications: DM, HF, post-MI, high risk CAD, chronic kidney disease, recurrent stroke prevention (6 of 7) May have unfavorable effects on: hyperkalemia Contraindicated in pregnancy
Slide 117-

Receptors Angiotensin Receptor Blocker: Mechanism of Action AT II Receptor Blocker Antiproliferative Action Vasodilation Proliferative Action Vasoconstriction ATII ATI Angiotensinogen Other Pathways Renin AT I Receptor Blocker Angiotensin I Angiotensin II ACE
Slide 118-

Angiotensin II Receptor Antagonists Candesartan (Atacand) Eprosartan (Tevetan) Irbesartan (Avapro) Losartan (Cozaar) Olmesartan (Benicar) Telmisartan (Micardis) Valsartan (Diovan)
Slide 119-

Angiotensin II Receptor Antagonists
Slide 120-

Renin Angiotensin Aldosterone
Slide 121-

Drug-Induced Acute Renal Dysfunction Acute Renal Failure - Prerenal NSAIDs, CyA/Tacrolimus, ACEI/ARB, Diuretics
Slide 122-

Drug-Induced Acute Renal Dysfunction Acute Renal Failure - Prerenal NSAIDs, CyA/Tacrolimus, ACEI/ARB, Diuretics - Intrinsic – ATN vs AIN ATN : Aminoglycosides, Amphotericin B, Radiocontrast Media AIN : B-Lactams, Sulfa, Rifampin, Ciprofloxacin, Cimetidine, NSAIDs, PPIs, Allopurinol, Phenytoin, Diuretics
Slide 123-

Acute interstitial nephritis Causes Medications (AIN occurs >2 weeks after drug started) Penicillins and Cephalosporins Hypersensitivity (fever, rash, arthralgia) Sulfonamides Vasculitis reaction NSAIDs Nephrotic Syndrome type reaction Rifampin , Diuretics (Thiazides and Lasix), Allopurinol , Cimetidine , Ciprofloxacin Dilantin Other medications have caused AIN to a lesser extent Miscellaneous conditions Glomerulonephritis , Necrotizing Vasculitis, Systemic Lupus Erythematosus Acute kidney transplant rejection
Slide 124-

Acute interstitial nephritis Causes Infection Diphtheria , Group A beta hemolytic Streptococcus (classic) Legionella , Yersinia , Staphylococcus or Streptococcus infection Mycobacterium , Toxoplasmosis , Mycoplasma , Leptospira Rickettsia , Syphilis , Herpes viruses (e.g. CMV, EBV, HSV) Human Immunodeficiency Virus (HIV),Hantavirus Hepatitis C , Mumps Medications (AIN occurs >2 weeks after drug started) Penicillins and Cephalosporins Hypersensitivity (fever, rash, arthralgia) Sulfonamides Vasculitis reaction NSAIDs Nephrotic Syndrome type reaction Rifampin , Diuretics (Thiazides and Lasix), Allopurinol , Cimetidine , Ciprofloxacin Dilantin Other medications have caused AIN to a lesser extent Miscellaneous conditions Glomerulonephritis , Necrotizing Vasculitis, Systemic Lupus Erythematosus Acute kidney transplant rejection Symptoms and Signs Classic triad (Methicillin induced hypersensitivity) Low grade fever (>70% of cases) Rash (>30% of cases) Arthralgia (>15% of cases) Acute Renal Failure Oliguria Malaise Nausea or Vomiting Labs: General Urinalysis Eosinophiluria Proteinuria Fractional Excretion of Sodium >1% Renal Function tests with renal insufficiency Serum Creatinine increased Blood Urea Nitrogen increased Miscellaneous Hyperchloremic Metabolic Acidosis
Slide 125-

ppt slide no 125 content not found
Slide 126-

ppt slide no 126 content not found
Slide 127-

Dose of Aminoglycosides G,T: 3-5mg/kg/d A: 15-25mg/kg/d S: 1g/d P: 0.5-1g QID N: 1g q4-6h 127
Slide 128-

AminoglycosidesSerum concentration - Sampling G & T Peak: 5-8 mcg/ml Trough: less 2 mcg/ml A Peak: 20-30 mcg/ml Trough: less 10 mcg/ml V Peak: 15-30 mcg/ml Trough: less 5-20 mcg/ml Infusion time: G & A 30 min, V 60 min(less 1250 mg) , 90 min(more 1250 mg) 128
Slide 129-

ppt slide no 129 content not found
Slide 130-

Antibiotics Aminoglycosides Trough >2mg/L, repeated course in months  nonoliguric ATN Recommendations: hi OD dose (5-7mg/kg/24h x 2-3wks) is less nephrotoxic and equally effective Follow levels, correct K CrCl > 60, 1-2.5mg/kg Q8H CrCl 40-60, Q12H CrCl 20-40, Q24H CrCl <20, loading dose then monitor levels
Slide 131-

سمیت کلیوی Neomycin< Gentamicin,Tobramycin > Netilmicin,Streptomycin
Slide 132-

Risk factor for Aminoglycoside Nephrotoxicity Related to AMG dosing Large total cummulative dose Prolong therapy High peak or trough conc. Recet previous AMG therapy Related to Predisposing condition in the patient Preexisting renal insufficiency Increased age Poor nutrition Shock Gramnegative bactermia Liver disease Hypoalbuminemis Obstructive jaundice K+ or Mg++ deficiency Related to synergistic nephrotoxicity AMG combination with Cyclosporin Amphotericin B Vancomycin Diuretics Irreversible Damage!
Slide 133-

Aminoglycoside Nephrotoxicity Prevention Switching to alternative antibiotics Avoid volume depletion, concomitant therapy with other nephrotoxic drugs Limit total dose Decreasing the frequency of AMG dosing to at least daily (as direct by renal clearance) Management Monitor Scr, concentration, renal fn and electrolytes Discontinue AMG if changes are seen.
Slide 134-

Aminoglycoside Drug interactions with other nephrotoxic medications: Cephalothin and other Cephalosporins Cyclosporin A Cisplatin NSAIDs ACE Inhibitors Loop Diuretics Amino acids
Slide 135-

Drug-Induced Acute Renal Dysfunction Acute Renal Failure - Prerenal NSAIDs, CyA/Tacrolimus, ACEI/ARB, Diuretics - Intrinsic – ATN vs AIN ATN : Aminoglycosides, Amphotericin B, Radiocontrast Media AIN : B-Lactams, Sulfa, Rifampin, Ciprofloxacin, Cimetidine, NSAIDs, PPIs, Allopurinol, Phenytoin, Diuretics
Slide 136-

Amphotericin B nephrotoxicity Dose dependant ↓ RBF & GFR ↑ SCr,concentrate urine and K,Na,Mg wasting Risk factors: Higher average daily doses ,diuretic use, Volume depletion Prevention: Limiting the dose Volume repletion Amphotericin+IV saline Liposomal amphotericin with lipids CCBs Discontinuation
Slide 137-

ppt slide no 137 content not found
Slide 138-

ppt slide no 138 content not found
Slide 139-

ppt slide no 139 content not found
Slide 140-

Drug-induced nephrotoxicity caused by amphotericin B lipid complex and liposomal amphotericin B: a review and meta-analysis. Lipid preparations of amphotericin B, commonly used to treat fungal infections, have been demonstrated to have reduced nephrotoxicity compared to conventional amphotericin B. However, to our knowledge, a comprehensive comparison of nephrotoxicity induced by different lipid preparations of amphotericin B has not been performed. We conducted a meta-analysis to evaluate nephrotoxicity associated with amphotericin B lipid complex (ABLC) and liposomal amphotericin B (L-AmB). We searched the PubMed MEDLINE database and abstracts presented at key scientific meetings, and identified 11 studies reported between 1995 and 2008 that compared nephrotoxicity resulting from the use of these agents. Eight of the 11 studies were included in the meta-analysis. The Cochran-Mantel-Haenszel test was used to determine odds ratio (OR) and relative risk (RR), and the Breslow-Day test was used to analyze homogeneity of ORs across different studies. Analysis of all 8 studies (n = 1160) included in the meta-analysis showed an increased probability of nephrotoxicity in patients treated with ABLC versus L-AmB (OR, 1.75; RR, 1.55), but there was a significant lack of homogeneity across these studies (p < 0.001). After excluding the study by Wingard et al, the probability of experiencing nephrotoxicity was more similar between the 2 AmB lipid preparations (OR, 1.31; RR, 1.24; n = 916), particularly when the analysis included only the salvage patient population reported by Hachem et al (OR, 1.12; RR, 1.09; n = 839); the 7 remaining studies were more homogenous by Breslow-Day test (p = 0.054). Our results suggest that nephrotoxicity is generally similar for ABLC and L-AmB in patients receiving antifungal therapy and prophylaxis.
Slide 141-

ppt slide no 141 content not found
Slide 142-

کدام دسته دارویی بیشترین میزان نارسایی کلیوی را در بیماران بستری در بیمارستان ایجاد می کنند؟
Slide 143-

کدام دسته دارویی بیشترین میزان نارسایی کلیوی را در بیماران بستری در بیمارستان ایجاد می کنند؟ Contrast media
Slide 144-

Drug-Induced Acute Renal Dysfunction Acute Renal Failure - Prerenal NSAIDs, CyA/Tacrolimus, ACEI/ARB, Diuretics - Intrinsic – ATN vs AIN ATN : Aminoglycosides, Amphotericin B, Radiocontrast Media AIN : B-Lactams, Sulfa, Rifampin, Ciprofloxacin, Cimetidine, NSAIDs, PPIs, Allopurinol, Phenytoin, Diuretics
Slide 145-

ppt slide no 145 content not found
Slide 146-

IV Contrast Vasospasm & ARF Risk factors: DM, myeloma, CRF, dehydration, diuretics, CHF Prophylaxis: Hold NSAIDs & diuretics, 24h pre & post contrast IV NS pre & post contrast 2 x 600mg PO Acetylcysteine Low dose, low-osmolar contrast Avoid multiple procedures in 48h Monitor renal fxn for 48h
Slide 147-

ppt slide no 147 content not found
Slide 148-

ppt slide no 148 content not found
Slide 149-

Sodium bicarbonate-based hydration prevents contrast-induced nephropathy: a meta-analysis. Abstract BACKGROUND: Contrast-induced nephropathy is the leading cause of in-hospital acute renal failure. This side effect of contrast agents leads to increased morbidity, mortality, and health costs. Ensuring adequate hydration prior to contrast exposure is highly effective at preventing this complication, although the optimal hydration strategy to prevent contrast-induced nephropathy still remains an unresolved issue. Former meta-analyses and several recent studies have shown conflicting results regarding the protective effect of sodium bicarbonate. The objective of this study was to assess the effectiveness of normal saline versus sodium bicarbonate for prevention of contrast-induced nephropathy. METHODS: The study searched MEDLINE, EMBASE, Cochrane databases, International Pharmaceutical Abstracts database, ISI Web of Science (until 15 December 2008), and conference proceedings for randomized controlled trials that compared normal saline with sodium bicarbonate-based hydration regimen regarding contrast-induced nephropathy. Random-effects models were used to calculate summary odds ratios. RESULTS: A total of 17 trials including 2,633 subjects were pooled. Pre-procedural hydration with sodium bicarbonate was associated with a significant decrease in the rate of contrast-induced nephropathy (odds ratios 0.52; 95% confidence interval 0.34-0.80, P = 0.003). Number needed to treat to prevent one case of contrast-induced nephropathy was 16 (95% confidence interval 10-34). No significant differences in the rates of post-procedure hemodialysis (P = 0.20) or death (P = 0.53) was observed. CONCLUSION: Sodium bicarbonate-based hydration was found to be superior to normal saline in prevention of contrast-induced nephropathy in this updated meta-analysis.
Slide 150-

Innovator and generic cisplatin formulations: comparison of renal toxicity. To compare the incidence and degree of renal toxicity associated with innovator and generic cisplatin formulations, increase in the serum creatinine (CRN) levels (mg/dL) and incidence of grade 2-3 CRN elevation during the first and all cycles of chemotherapy were retrospectively evaluated in patients treated with innovator (group 1, n = 296) and generic (group 2, n = 321) cisplatin formulations. There were no differences in the sex, age, performance status or number of chemotherapy cycles between groups 1 and 2. The median increases in CRN levels during the first cycle were 0.20 mg/dL regardless of the sex or group. There was no difference in the incidence of grade 2-3 CRN elevation between groups 1 and 2 among female or male patients. The median increases in CRN levels during all cycles were 0.2 (0-1.0) and 0.3 (0-1.8) in the female patients of groups 1 and 2, respectively (P = 0.68), and 0.3 (0-2.1) and 0.5 (0-3.6) in the male patients of groups 1 and 2, respectively (P < 0.001). Grade 2-3 CRN elevation was observed in 18.1% and 24.7% of the female patients in groups 1 and 2, respectively (P = 0.33), and 9.4% and 20.9% of the male patients in groups 1 and 2, respectively (P < 0.001). Renal toxicity was slightly more severe in patients treated with the generic cisplatin formulation than in those treated with the innovator formulation, especially among the male patients.
Slide 151-

Case: A 46-year-old morbidly obese man was admitted to the medical intensive care unit with respiratory failure. He required pressure-control ventilation and high levels of sedation with continuous-infusion lorazepam. He developed Stenotrophomonas maltophilia pneumonia; treatment included scheduled intravenous trimethoprim-sulfamethoxazole. On day 17 of his hospital course, 3 days after starting the trimethoprim-sulfamethoxazole, the patient developed acute renal failure consistent with acute tubular necrosis. therefore, all drugs were discontinued, and laboratory data were collected. A marked osmol gap, metabolic acidosis, and renal toxicity were attributed .
Slide 152-

Propylene glycol is a viscous, colorless liquid solvent used for many drugs with poor aqueous solubility. For many years, propylene glycol has been thought of as safe; however, a review of the literature reveals cases of propylene glycol- associated hyperosmolality, anion gap metabolic acidosis, hemolysis, hyperosmolality, osmol gap, central nervous system depression, arrhythmias, and, although less commonly, renal dysfunction. Several case reports link high doses of intravenous lorazepam with propylene glycol- related toxicities. Other commonly prescribed drugs, including intravenous nitroglycerin, digoxin, phenobarbital, phenytoin, diazepam, trimethoprim-sulfamethoxazole and etomidate, contain large amounts of propylene glycol and have also been associated with toxicity. Laboratory signs of propylene glycol toxicity include hyperosmolality, hyperlactatemia, and osmol gap.
Slide 153-

Serum Osmolality 2(Na) + BUN/2.8 + Glucose/18 Anion Gap Na - (CL + HC03)
Slide 154-

Osmolar Gap Calculated Osmoles = 2(sodium) + urea + glucose= 290-300 osmolar gap = calculated - measured osmoles = 0-10 Theoretically, unaccounted osmols may signify a toxic alcohol ingestion.(i.e.. ETOH) ( Mannitol, Alcohols, Dye, DMSO, Glycerol, Acetone, Sorbital ) Not sensitive enough to rule out a toxic alcohol ingestion.
Slide 155-

Anion Gap AG= (sodium) - (bicarbonate + chloride)=12-16 High Anion Gap Metabolic Acidosis Methanol Uremia Diabetic Ketoacidosis Paraldehyde INH, iron Lactate Ethylene glycol Salicylates Cyanide Alcoholic Ketoacidosis Toluene
Slide 156-

The ABG A normal pH and anion gap rules out many ingestions e.g. ASA, cyanide, toxic alcohol If a patient ingested ETOH and a toxic alcohol, he may not become acidotic until his ETOH is cleared. Consider serial ABG’s or toxic alcohol levels
Slide 157-

Drug-induce renal structural-functional changes Proximal convoluted tubule (s1/s2 segment) Aminoglycoside Cephaloridine Cadmium Cl K dichromate Renal vessel NSAIDs ACE Inhibitor Cyclosporin A Pappillae Phenacetin Interstitium Cephalosporin Cadmium NSAIDs Glomeruli Interferon-α Gold Penicillamine Proximal straigt tubule (s3 segment) Cisplatin Mercuric Cl Dichlorovinyl-L-cysteine
Slide 158-

Chronic Interstitial fibrosis Lithium,5-aminosalicylic acid, mesalazine, ifosfamide Cidofovir, acyclovir, indinavir Cyclosporin, tacrolimus Usually progressive, irreversible with interstitail fibrosis, no systemic symptoms
Slide 159-

عارضه کلیوی کدام یک از استاتین ها بیشتر است؟- آتورواستاتین و سیم واستاتین- روزوواستاتین و پراواستاتین
Slide 160-

ppt slide no 160 content not found
Slide 161-

ECSTASY
Slide 162-

TREATMENT Hypotension Control: Normal Saline Infusion: 10-20 ml/kg Vasopressor amines( Dopamine, norepinepherine) Cardiac Dysrhythmeia Amidaron, Lidocaine, Atropine Rhabdomyolysios Treatment: Normal Saline Infusion, Diuretic (Mannitol, Furosemide)
Slide 163-

ppt slide no 163 content not found
Slide 164-

ppt slide no 164 content not found
Slide 165-

ppt slide no 165 content not found
Slide 166-

ETIOLOGY: post renal Bladder obstruction infection tumor BPH anticholinergics (diphenydramine, meclizine, benztropine) ganglionic blockers (trimethaphan)
Slide 167-

Classification of nephrotoxic drugs by their therapeutic use:
Slide 168-

.
Slide 169-

ppt slide no 169 content not found
Slide 170-

ppt slide no 170 content not found
Slide 171-

ppt slide no 171 content not found
Slide 172-

ppt slide no 172 content not found
Slide 173-

ppt slide no 173 content not found
Slide 174-

ppt slide no 174 content not found
Slide 175-

ppt slide no 175 content not found
Slide 176-

ppt slide no 176 content not found
Slide 177-

ppt slide no 177 content not found
Slide 178-

178
Slide 179-

Overview of mechanisms for renal susceptibility to drug toxicity: Kidney appear more sensitive than other organ to drug toxicity: Immunologic mechanisms: 1-glomerulonephritides 2-allergic interstitial nephritis(with or without nephrotic syndrome) Nonimmunologic mechanism:
Slide 180-

Overview of mechanisms for renal susceptibility to drug toxicity: High blood flow and specialized homodynamic: Introduction:0.4%,20-25% HTN due to PG,Vasoactive peptide,RAS Sympathetic nerve system Drugs:Beta blockers: RBF Radiographic contrast media:shunt RBF Mannitol: GBF due to glomerular feedback ACEIs:dilate glomerular efferent arterioles reduction in GFR
Slide 181-

Overview of mechanisms for renal susceptibility to drug toxicity: Tubular epithelia cell absorptive & secretary function: Introduction Drugs: Probenecid AG Cyclosporin Toxic drug may cause cell injury by some mechanisms(impairment of mitocondrial function and decrease ATP synthesis,increase oxidative stress,…)
Slide 182-

Overview of mechanisms for renal susceptibility to drug toxicity: Drug metabolism to toxic species: Cytochrome p-450 (in proximal tubular epithelial cells) IN CONTRAST PG and endoperoxide synthetase (renal papilla and medulla) EXP :Acetaminophen (ATN,Analgesic nephropathy)
Slide 183-

Overview of mechanisms for renal susceptibility to drug toxicity: High energy requirement by renal tubular cells: Introduction Amphotericin B
Slide 184-

Overview of mechanisms for renal susceptibility to drug toxicity: Concentration of solute in the tubular lumen: Systemic volume depletion increases the percent of water reabsorption in proximal tubule decreases tubular flow increases the concentration of solute and toxins in lumen increases binding of drugs to tubular cell Aminoglycoside:nephrotoxicity by systemic volume depletion
Slide 185-

Overview of mechanisms for renal susceptibility to drug toxicity: Uric acidification:(Urine PH up to 4.5),(Chemotherapy leads to acute uric acid nephropathy) Increase function of individual nephrons in adoptions to chronic renal insufficiency 1-chronic renal insufficiency: injury to some glomerular and tubular unit increases filtering remaining nephrons increases the susceptibility of this nephrons Radiographic contrast media
Slide 186-

Principles for prevention of drug nephropathy Avoid the use of nephrotoxic agents in high risk When exposure can not be avoided ,specific techniques be used to decrease nephrotoxicity Hydration ,Oral PG,CCB
Slide 187-

Reduction glumerular capillary hydrostatic pressure ACEIs RAS deteriorate the glumerular filtration rate Patient at risk for ACEIs Diagnosis of decrease glumerular filtration rate Pathogenesis of ACEI nephropathy
Slide 188-

Inhibition of prostaglandin dependent renal blood flow NSAIDs PGE2 and prostacyclin Patient at greatest risk for NSAIDs Prevention of NSAIDs induced acute renal failure and NSAIDs nephropathy NSAIDs with ACEIs and cyclosporine Caution and monitoring
Slide 189-

Nonspecific renal vasoconstriction: Triamterene Mannitol Cyclosporin Propranolol Decrease in Clcr +HCTZ +Indomethacin Mechanism of cause renal failure Decrease RBF Mechanism=Unknown Nadolol increase RBF Mechanism Risk factor Therapy Prophylaxis Acute oligoanuric renal failure Risk factors
Slide 190-

Increase in vascular permeability: OKT3 Cr Mechanism Increase in colloid oncotic pressure & blood viscosity: Dextran-40(IV) alter blood rheology Exogenous erythropoietin increase in blood viscosity
Slide 191-

Renal vascular alteration Systemic polyarteritis nodosa Pathogenesis Drugs:Methamphetamine,Penicillin,Sulfonamides Thrombotic microangiopathy has been described with OCPs,cyclosporine,mitomycin C,cisplatin,quinine Nephrotoxicity following long term chemotherapy with mitomycin alone or with some drugs(+5FU,…) Microangiopathic hemolytic anemia & thrombocytopenia Renal failure
Slide 192-

Glomerular alterations:Nephrotic syndrome and glomerulonephritis Mechanism Nephrotic syndrome definition Minimal change nephrotic syndrome(drug induced,therapy) Focal segmental glomerulosclerosis Membrane nephropathy(most common,immune mediated dx,drugs) Membranoproliferative glomerulonephritis Glomerular amyloidosis(drugs,pathogenesis)
Slide 193-

Acute tubular necrosis One of the most responsible for drug induced renal insufficiency Drugs:AG,Radiographic contrast media,Cisplatin,Amphotericin Sub clinical manifestation Mechanism of renal failure in acute tubular necrosis
Slide 194-

Aminoglycoside nephrotoxicity Decrease glomerular filtration(5-20%) Initial manifestation Pathogenesis The toxicity of AG in directly proportional to the number of their cationic charges Neomycin(most) Netilmicin,Streptomycin(least) Gentamicin,Tobramycin(intermediate) Prevention and therapy Risk factors
Slide 195-

Radiographic contrast media nephrotoxicity IV common cause of administration hospital-acquired acute renal failure Toxicity ranges Manifestation Major risk factors for contrast nephropathy Pathogenesis Prevention and therapy: New drugs Re hydration CCBs,IV Theophylline,Mannitol,Dopamine
Slide 196-

Cisplatin nephrotoxicity Cause renal tubular damage Risk factors Manifestation Mechanism Prevention and treatment: Decrease doses Hypertonic saline Probenecid,Glutathione Mg monitoring,MgCl2
Slide 197-

Pentamidine Nephrotoxicity 60-90% azotemia Manifestations:Hyperkalemia,metabolic acidosis,Hypomagnesemia Toxicity more frequent in AIDs Mechanism :Unknown Prevention
Slide 198-

Tubulointerstitial disease Acute allergy interstitial nephritis Chronic interstitial nephritis Papillary necrosis: Is common(3-14%ARF) Methicilin,NSAIDs,Cytokine therapy,INF-A,IL-2,LAK Treatment Li,Cyclosporin Mild renal insufficiency with long term therapy of Li(10%) Prevention:Avoidance of dehydration and renal monitoring Cyclosporine also cause interstitial fibrosis and chronic irreversible insufficiency Prevention:lessen the dose Chronic excessive consumption of combination analgesics containing Phenacetin Phenacetin & Acetaminophen + NSAIDs,Dapsone Prevention:Reduce doses,Inh of comb therapy,Hydration
Slide 199-

Obstructive nephropathy: Renal tubular obstruction: Caused by intratubular precipitation of tissue degeneration Products & drugs Diagnosis:Urine uric acid to Cr ratio>1 Prevention and therapy:Hydration,urinary alkalization to PH=7,Allopurinol ARF induced by drugs after muscle necrosis and Nontraumatic rhabdomyolysis(alcohol,heroin,phencyclidine, Lovastatin,cyclosporine,erythromycin,gemfibrozil,niacin) External urinary tract obstruction: Drug therapy may leads to urinary tract obstruction Elder males with prostate hypertrophy and antich,TCAs, Disopyramide,Antiarrhythmia,Cyclophosphamide Use of MESNA
Slide 200-

Nephrolithiasis: Renal calculus formation Sulfdiazine:6% Triamterene-H :1/1500 Massive ingestion of magnesium-Trisilicate Magnesium phosphate stones Laxative abuse Ammonium urate stones
Slide 201-

Patient outcome: Drug induced renal disease is an important clinical problem For management several guidelines can help : Know the potential nephrotoxicity of diagnostic & therapeutic pharmacologic agents used Compare the potential risks and expected benefits Consider alternative diagnostic and therapeutic approaches Use the lowest dose and shortest course of therapy Monitor Modify therapy if toxicity occurs
Slide 202-

Drug-Induced Interstitial Nephritis Abstract:Drug-induced interstitial nephritis (DIN) is characterized by a sudden impairment of renal function and is mainly a result of an immune-mediated reaction after intake of a drug. Many different drugs, such as antibiotics, anticonvulsants, diuretics, proton pump inhibitors, non-steroidal anti-inflammatory drugs and many others, are known to cause DIN. The clinical manifestations are characterized by arthralgias, macular or maculopapular exanthema and fever, together with mild proteinuria, sterile pyuria, and eosinophilia. In many cases the only sign is an asymptomatic increase in serum creatinine. Histopathological analysis shows inflammatory infiltrates in the interstitium, the composition of which differs as a function of different forms of T-cell activation and cytokine production. Consequently, the infiltrate shows mostly T cells, and, dependent on the T-cell function, either a monocyte-rich granulomatous reaction, an eosinophilic or neutrophilic inflammation. Often, plasma cells are present, while glomeruli and vessels are spared. The diagnosis of DIN is confirmed with certainty only by biopsy. The lymphocyte transformation test can demonstrate sensitization to a certain drug, but it is often negative - perhaps because the relevant antigen is a metabolite produced in the endothelial cells of the tubuli. The mainstay of treatment is drug discontinuation; the role of steroids is controversial.
Slide 203-

Acute Glomerulonephritis Acute glomerulonephritis refers to a specific set of renal diseases in which an immunologic mechanism triggers inflammation and proliferation of glomerular tissue that can result in damage to the basement membrane, mesangium, or capillary endothelium. Hippocrates originally described the manifestation of back pain and hematuria, which lead to oliguria or anuria. With the development of the microscope, Langhans was later able to describe these pathophysiologic glomerular changes.
Slide 204-

Drug-Induced Acute Interstitial Nephritis Acute interstitial nephritis (AIN) is a form of inflammatory renal disease affecting predominantly the tubules and the interstitium. Drugs, particularly β-lactam antibiotics and non-steroidal anti-inflammatory drugs, are currently the most common causes. The pathogenesis of drug-induced AIN is complex but there is good clinical evidence for an immune-mediated reaction. Clinical findings may be variable depending on the drug involved and the individual response. Most patients recover from the acute renal failure; however, in older patients or in patients with pre-existing renal insufficiency the recovery of renal function may be incomplete.
Slide 205-

Medications (Inhibit tubular secretion of Creatinine) Aminoglycosides Cephalosporins Cefoxitin Cephalothin Hydantoin Diuretics Methyldopa Cimetidine Trimethoprim
Slide 206-

Aminoglycoside Risk Factors for Nephrotoxicity? Advanced age Prior renal insufficiency Dehydration Hypokalemia Hypomagnesemia Liver disease Sepsis
Slide 207-

Uric acid is the end-product of purine metabolism and is primarily removed by the kidney. The process of excretion involves filtration, secretion, and reabsorption. Many drugs have been found to alter these processes and induce a state of hyperuricemia. Diuretic-induced hyperuricemia is probably the single most common form of hyperuricemia seen in clinical practice. In most cases, the uric acid level returns to normal after the removal of the offending drug provided there has not been any drug-induced renal injury. Alcohol Amiloride Bumetanide Chorthalidone Cisplatin Cyclophosphamide Cyclosporine Ethacrynic acid Ethambutol Furosemide Hydrochlorothiazide Indapamide Isotretinoin Ketoconazole Levodopa Metolazone Pentamidine (renal damage) Phencyclidine Pyrazinamide Salicylates Theophylline Thiazide diuretics (in addition to the ones listed above) Vincristine
Slide 208-

208
Slide 209-

The best option for a patient with severe pulmonary edema, who remains anuric after trials of 10 and 20 mg/h IV furosemide is: A) Increase the dose of furosemide to 40 mg/h B) Change the furosemide to bolus dosing; start with 200 mg IV C) Add metolazone 5 mg daily D) Discontinue furosemide and begin metolazone 10 mg twice daily E) Change to bumetanide 2 mg/h
Slide 210-

The best option for a patient with severe pulmonary edema, who remains anuric after trials of 10 and 20 mg/h IV furosemide is: A) Increase the dose of furosemide to 40 mg/h B) Change the furosemide to bolus dosing; start with 200 mg IV C) Add metolazone 5 mg daily D) Discontinue furosemide and begin metolazone 10 mg twice daily E) Change to bumetanide 2 mg/h
Slide 211-

Which of the following therapies might worsen fluid or electrolyte disturbances typically present in the patient with ARF? A) Metronidazole 500 mg orally every 6 hours for diarrhea caused by Clostridium difficile B) Monobasic and dibasic sodium phosphate (Fleet Phospho-Soda) 45 mL daily as needed for bowel movement C) Diltiazem 10 mg/h for rate control because of atrial fibrillation D) Sodium polystyrene sulfonate (Kayexalate) 30 g orally once E) All of the above
Slide 212-

Which of the following therapies might worsen fluid or electrolyte disturbances typically present in the patient with ARF? A) Metronidazole 500 mg orally every 6 hours for diarrhea caused by Clostridium difficile B) Monobasic and dibasic sodium phosphate (Fleet Phospho-Soda) 45 mL daily as needed for bowel movement C) Diltiazem 10 mg/h for rate control because of atrial fibrillation D) Sodium polystyrene sulfonate (Kayexalate) 30 g orally once E) All of the above
Slide 213-

Prerenal ARF can be exacerbated by the continuation of all of the following medications, except? A) Lisinopril B) Metolazone C) Indomethacin D) Prednisone E) Valsartan
Slide 214-

Prerenal ARF can be exacerbated by the continuation of all of the following medications, except? A) Lisinopril B) Metolazone C) Indomethacin D) Prednisone E) Valsartan
Slide 215-

All of the following should be assessed daily in a patient with ARF, except? A) Liver aminotransferases B) Serum creatinine C) Weight D) Medication dosages E) Urine output
Slide 216-

All of the following should be assessed daily in a patient with ARF, except? A) Liver aminotransferases B) Serum creatinine C) Weight D) Medication dosages E) Urine output
Slide 217-

Which of the following is not an important consideration when selecting a dosage of a renally eliminated antibiotic in a patient with ARF? A) Cardiac output B) Fluid status C) Renal replacement therapy D) Estimated GFR E) Hemoglobin
Slide 218-

Which of the following is not an important consideration when selecting a dosage of a renally eliminated antibiotic in a patient with ARF? A) Cardiac output B) Fluid status C) Renal replacement therapy D) Estimated GFR E) Hemoglobin
Slide 219-

A 58-year-old male with unknown past medical history has prerenal acute renal failure from acute blood loss because of a limb amputation in an industrial accident, and aggressive fluid resuscitation is initiated. Which of the following set of monitoring parameters are most appropriate for during the next 8 hours? A) Urine output, rales, and blood pressure B) Heart rate, blood pressure, and BUN C) Bowel sounds, blood pressure, funduscopic findings D) Blood pressure, serum potassium, and serum sodium E) Blood pressure, weight, and blood glucose
Slide 220-

A 58-year-old male with unknown past medical history has prerenal acute renal failure from acute blood loss because of a limb amputation in an industrial accident, and aggressive fluid resuscitation is initiated. Which of the following set of monitoring parameters are most appropriate for during the next 8 hours? A) Urine output, rales, and blood pressure B) Heart rate, blood pressure, and BUN C) Bowel sounds, blood pressure, funduscopic findings D) Blood pressure, serum potassium, and serum sodium E) Blood pressure, weight, and blood glucose
Slide 221-

The use of serum creatinine as a marker of glomerular filtration rate (GFR) in the setting of ARF is limited by: A) The test is not readily available in most laboratories B) Its lack of responsiveness to abrupt changes in GFR C) Its accuracy increases in the setting of volume overload D) The glomerulus increases its filtration of creatinine during ARF E) Numerous medications cross-react with the assay, rendering the results unreliable
Slide 222-

The use of serum creatinine as a marker of glomerular filtration rate (GFR) in the setting of ARF is limited by: A) The test is not readily available in most laboratories B) Its lack of responsiveness to abrupt changes in GFR C) Its accuracy increases in the setting of volume overload D) The glomerulus increases its filtration of creatinine during ARF E) Numerous medications cross-react with the assay, rendering the results unreliable
Slide 223-

Which if the following is true regarding the treatment of established ARF? A) Dopamine 2 mcg/kg/min is effective to reverse intrinsic ARF B) The liberal use of loop diuretics hasten GFR recovery C) Mannitol is useful to employ in the anuric patient D) The mainstays of therapy are primarily supportive in nature E) Thyroxine is helpful to increase GFR in the elderly patient with subclinical hypothyroidism
Slide 224-

For the patient with ARF, goals include: A) Avoid exposure to additional nephrotoxins B) Minimize extrarenal complications C) Expedite recovery of renal function D) Restore previous degree of renal function E) All of the above
Slide 225-

In a patient with ARF and gram-negative sepsis receiving gentamicin therapy, which of the following should be considered in developing a treatment regimen? A) Gentamicin removal can be faster in ARF compared to CKD B) Administration of the gentamicin immediately post the intermittent hemodialysis session C) Careful assessment of the patient’s actual volume of distribution of gentamicin D) Determining the viability of other antimicrobial alternatives E) All of the above
Slide 226-

In a patient with ARF and gram-negative sepsis receiving gentamicin therapy, which of the following should be considered in developing a treatment regimen? A) Gentamicin removal can be faster in ARF compared to CKD B) Administration of the gentamicin immediately post the intermittent hemodialysis session C) Careful assessment of the patient’s actual volume of distribution of gentamicin D) Determining the viability of other antimicrobial alternatives E) All of the above
Slide 227-

Which of the following is false regarding ARF in the hospitalized patient? A) Occurs in approximately 7% of hospitalized patients B) Is associated with increased mortality C) Can lead to long-term kidney damage and life-long hemodialysis D) Should be aggressively treated with high-dose diuretics
Slide 228-

Which of the following is false regarding ARF in the hospitalized patient? A) Occurs in approximately 7% of hospitalized patients B) Is associated with increased mortality C) Can lead to long-term kidney damage and life-long hemodialysis D) Should be aggressively treated with high-dose diuretics
Slide 229-

Causes of diuretic resistance include the following except: A) Inappropriate diuretic dose or regimen B) NSAID-associated decrease in sodium resorption C) Presence of heart failure D) Vasodilator-associated reduction in renal blood flow 19
Slide 230-

Causes of diuretic resistance include the following except: A) Inappropriate diuretic dose or regimen B) NSAID-associated decrease in sodium reasorption C) Presence of heart failure D) Vasodilator-associated reduction in renal blood flow 19
Slide 231-

A 76-year-old, 60-kg patient with a history of heart failure is admitted for severe nausea and fever of several days’ duration, as well as acute onset of chest pain. There is a single serum creatinine value of 2.4 mg/dL, and tests for several drugs eliminated primarily by the kidney are ordered. It is 2:00 in the afternoon. Choose the best consideration for those agents eliminated primarily by the kidney.
Slide 232-

A) The creatinine clearance can be calculated to estimate a GFR, and then an adjusted dosing regimen should implemented for the duration of this admission. B) Send out the initially ordered doses immediately and do not check if any were administered in the emergency room. C) Assess if any drugs were recently administered, and only recommend one day of new therapies if not already started; request a second serum creatinine value to assess if the patient’s renal function is stable; check to see if the patient is producing any urine as a additional assessment of renal function. D) Assess if any drugs were recently administered, and send out one dose.
Slide 233-

A) The creatinine clearance can be calculated to estimate a GFR, and then an adjusted dosing regimen should implemented for the duration of this admission. B) Send out the initially ordered doses immediately and do not check if any were administered in the emergency room. C) Assess if any drugs were recently administered, and only recommend one day of new therapies if not already started; request a second serum creatinine value to assess if the patient’s renal function is stable; check to see if the patient is producing any urine as a additional assessment of renal function. D) Assess if any drugs were recently administered, and send out one dose.
Slide 234-

In continuous renal replacement therapy (CRRT), the following is true: A) Goal of therapy in CRRT is a ultrafiltration rate of 25 mL/h/kg B) Thrombosis is a concern where anticoagulation can be necessary C) Requires specialized staff and equipment D) Is frequently used in unstable patients where IHD can increase the risk of a hypotensive episode E) All the above
Slide 235-

The most common manifestation of drug-induced kidney disease is: A) Proteinuria B) Pyuria C) Hematuria D) A decline in the glomerular filtration rate (GFR) E) A reduction in tubular secretion
Slide 236-

The most common manifestation of drug-induced kidney disease is: A) Proteinuria B) Pyuria C) Hematuria D) A decline in the glomerular filtration rate (GFR) E) A reduction in tubular secretion
Slide 237-

Regarding drug-induced kidney disease, all of the following are applicable except: A) Temporal relationship with potentially toxic agent B) The offending agent is rarely identified C) Significant source of morbidity in the hospital setting D) Abrupt and sustained reduction in GFR E) The most common presentation in the hospital setting is acute tubular necrosis
Slide 238-

Which of the following drugs would be the most likely culprit in a patient with newly diagnosed renal intratubular obstruction? A) Ibuprofen B) Losartan C) Amphotericin B D) Ciprofloxacin E) Acyclovir
Slide 239-

Which of the following drugs would be the most likely culprit in a patient with newly diagnosed renal intratubular obstruction? A) Ibuprofen B) Losartan C) Amphotericin B D) Ciprofloxacin E) Acyclovir
Slide 240-

Hemodynamically mediated renal failure induced by angiotensin-converting enzyme inhibitors (ACEI) involves all of the following except: A) Enhanced efferent arteriolar constriction B) Patients with renal artery stenosis at increased risk C) Decrease in glomerular capillary hydrostatic pressure D) Reduced glomerular ultrafiltration E) None of the above
Slide 241-

Hemodynamically mediated renal failure induced by angiotensin-converting enzyme inhibitors (ACEI) involves all of the following except: A) Enhanced efferent arteriolar constriction B) Patients with renal artery stenosis at increased risk C) Decrease in glomerular capillary hydrostatic pressure D) Reduced glomerular ultrafiltration E) None of the above
Slide 242-

Which of the following drugs has been associated with chronic interstitial nephritis? A) Cyclosporine B) Ifosfamide C) Lithium D) Streptozotocin E) All of the above
Slide 243-

Which of the following drugs has been associated with chronic interstitial nephritis? A) Cyclosporine B) Ifosfamide C) Lithium D) Streptozotocin E) All of the above
Slide 244-

Which of the following drugs has been associated with collapsing glomerulosclerosis? A) Propylthiouracil B) Aminoglycosides C) Pamidronate D) Radiographic contrast media E) Hydralazine
Slide 245-

The following renal structural-functional alteration is associated with exposure to radiographic contrast media: A) Allergic interstitial nephritis B) Intratubular obstruction C) Glomerulosclerosis D) Acute tubular necrosis E) Papillary necrosis
Slide 246-

The following renal structural-functional alteration is associated with exposure to radiographic contrast media: A) Allergic interstitial nephritis B) Intratubular obstruction C) Glomerulosclerosis D) Acute tubular necrosis E) Papillary necrosis
Slide 247-

All of the following strategies can be used to prevent radiographic contrast media nephrotoxicity except: A) Amifostine B) Acetylcysteine C) Low osmolality agents D) Hydration E) Reduced doses of contrast
Slide 248-

The preferred agent for preventing cisplatin-induced nephrotoxicity is: A) Fenoldopam B) Amifostine C) Dopamine D) Acetylcysteine E) Mesna
Slide 249-

All of the following drugs are linked to the development of antineutrophil cytoplasmic antibody (ANCA)-positive vasculitis except: A) Hydralazine B) Allopurinol C) Warfarin D) Propylthiouracil E) Penicillamine
Slide 250-

Each of the following statements regarding aminoglycoside-induced acute tubular necrosis is true except: A) Risk factors include prolonged therapy and increased age B) It manifests as a gradual increase in serum creatinine 4 to 6 weeks after exposure to the drug C) Patients typically present with nonoliguria, maintaining urine volumes greater than 500 mL/day D) Toxicity of various aminoglycosides is related to cationic charge of the drug E) “Once-daily” dosing is one method to maintain antimicrobial efficacy while reducing nephrotoxicity 12
Slide 251-

Each of the following statements regarding aminoglycoside-induced acute tubular necrosis is true except: A) Risk factors include prolonged therapy and increased age B) It manifests as a gradual increase in serum creatinine 4 to 6 weeks after exposure to the drug C) Patients typically present with nonoliguria, maintaining urine volumes greater than 500 mL/day D) Toxicity of various aminoglycosides is related to cationic charge of the drug E) “Once-daily” dosing is one method to maintain antimicrobial efficacy while reducing nephrotoxicity
Slide 252-

The preferred treatment for a patient with drug-induced minimal change glomerular injury accompanied by interstitial nephritis is: A) Amifostine B) Cyclophosphamide C) Pamidronate D) Prednisone E) Hydration
Slide 253-

The signs and symptoms of penicillin-induced allergic interstitial nephritis include all of the following except: A) Rash, eosinophilia, pyuria B) Fever, eosinophilia, reduced intraglomerular pressure C) Fever, rash, eosinophilia D) Elevated serum creatinine, rash, eosinophilia E) Hematuria, proteinuria, oliguria
Slide 254-

The signs and symptoms of penicillin-induced allergic interstitial nephritis include all of the following except: A) Rash, eosinophilia, pyuria B) Fever, eosinophilia, reduced intraglomerular pressure C) Fever, rash, eosinophilia D) Elevated serum creatinine, rash, eosinophilia E) Hematuria, proteinuria, oliguria
Slide 255-

A 60-year-old woman with a 5-year history of NSAID use is prescribed enalapril and develops acute renal failure. What is the most likely cause of her renal failure? A) Acute allergic interstitial nephritis B) Chronic interstitial nephritis C) Minimal change glomerular injury D) Focal segmental glomerulosclerosis E) Hemodynamically-mediated renal failure
Slide 256-

A 60-year-old woman with a 5-year history of NSAID use is prescribed enalapril and develops acute renal failure. What is the most likely cause of her renal failure? A) Acute allergic interstitial nephritis B) Chronic interstitial nephritis C) Minimal change glomerular injury D) Focal segmental glomerulosclerosis E) Hemodynamically-mediated renal failure
Slide 257-

Potential causes of pseudo-renal failure include all of the following except: A) Competitive inhibition of creatinine tubular secretion by cimetidine B) Drug induced increase in protein catabolism C) Direct interference with the enzymatic measurement of creatinine D) Increased synthesis and release of creatinine into serum E) Competitive inhibition of creatinine tubular secretion by trimethoprim
Slide 258-

Potential causes of pseudo-renal failure include all of the following except: A) Competitive inhibition of creatinine tubular secretion by cimetidine B) Drug induced increase in protein catabolism C) Direct interference with the enzymatic measurement of creatinine D) Increased synthesis and release of creatinine into serum E) Competitive inhibition of creatinine tubular secretion by trimethoprim
Slide 259-

Glomerulonephritis
Slide 260-

In a patient with nephrotic syndrome, which of the following is not expected to be present? A) Proteinuria B) Edema C) Hyperlipidemia D) Hypercoagulable state E) Hematuria
Slide 261-

Which of the following is not expected to reduce proteinuria when used for patients with glomerulonephritis? A) Angiotensin-converting enzyme (ACE) inhibitors B) Angiotensin II receptor blockers C) Nondihydropyridine calcium channel blockers (e.g., diltiazem) D) Dihydropyridine calcium channel blockers (e.g., nifedipine, amlodipine) E) All of the above are expected to reduce proteinuria
Slide 262-

Treatment of which of the following is expected to reduce the progression of renal failure in patients with glomerulonephritis? A) Edema B) Proteinuria C) Hyperlipidemia D) Coagulopathy E) Hematuria
Slide 263-

ACE inhibitors are often used in patients with glomerulonephritis because of their ability to reduce: A) Proteinuria B) Blood pressure C) Immunologically induced glomerular damage D) Both A and B E) All A, B, and C
Slide 264-

Intravascular thrombosis is a common and serious complication of nephrotic syndrome associated with which of the following glomerular disease? A) Minimal-change nephropathy B) Focal segmental glomerulonephritis C) Membranous nephropathy D) Immunoglobulin A nephropathy E) Membranoproliferative glomerulonephritis
Slide 265-

Which of the following glomerulonephritis is more commonly seen in pediatric patients? A) Minimal-change nephropathy B) Focal segmental glomerulonephritis C) Immunoglobulin A nephropathy D) Membranous nephropathy E) Membranoproliferative glomerulonephritis
Slide 266-

Which of the following agent is known to be most effective in inducing remission in patients with recently diagnosed minimal-change nephropathy? A) Steroid B) Cyclosporine C) Azathioprine D) Cyclophosphamide E) Levamisole
Slide 267-

Which of the following is not correct regarding the use of cyclosporine for the treatment of minimal-change nephropathy? A) Cyclosporine may reduce lymphokine production by activated T lymphocytes B) Cyclosporine may improve the permselectivity of GBM C) Cyclosporine is often effective in preventing relapse D) Cyclosporine is often effective in inducing remission during relapse E) Cyclosporine is useful for patients who are steroid dependent
Slide 268-

Compared with minimal-change nephropathy, patients with focal segmental glomerulonephritis are: A) More likely to be adults B) Less responsive to steroid treatment C) More likely to develop progressive renal failure D) Only A and B above are correct E) All A, B, and C above are correct
Slide 269-

In patients with mild focal segmental glomerulonephritis, which of the following is (are) commonly used? A) ACE inhibitors B) Angiotensin II receptor blockers C) Immunosuppressive agents D) Both A and/or B can be used E) All A, B, and C are necessary to induce remission
Slide 270-

Fish oil may be beneficial in certain patients with which of the following types of glomerulonephritis? A) Minimal-change nephropathy B) Focal segmental glomerulonephritis C) Immunoglobulin A nephropathy D) Membranous nephropathy E) Membranoproliferative glomerulonephritis
Slide 271-

Which of the following is correct with respect to treatment for membranous nephropathy? A) Spontaneous remission is common, and steroid treatment alone is commonly used to reduce proteinuria and progression of disease B) Spontaneous remission is common, and steroid treatment alone is not effective in reducing proteinuria and progression of disease C) Spontaneous remission is unlikely, and steroid treatment is needed to reduce proteinuria and progression of disease D) Spontaneous remission is unlikely, and steroid treatment alone is not effective in reducing proteinuria and progression of disease E) Steroid and cytotoxic agents are commonly needed to induce remission
Slide 272-

A patient with IgA nephropathy who has normal renal function, isolated micro-hematuria, and proteinuria less than 1 g/day should be: A) Observed closely without specific treatment B) Given fish oil C) Given steroid treatment D) Given cytotoxic agents E) Given cyclosporine
Slide 273-

Which of the following is not normally considered when selecting the optimal treatment for patients with lupus nephritis? A) Type of underlying lesion B) Disease activity according to pathologic findings C) Severity of symptoms D) Duration of symptoms E) All of the above are commonly considered
Slide 274-

Which of the following is frequently used for chronic maintenance treatment of lupus nephritis? A) Steroid B) Cytotoxic agent C) Cyclosporine D) Mycophenolate mofetil E) Fish oil
Slide 275-

Monoclonal antibodies has been evaluated for the treatment of which of the following glomerular disease? A) Minimal-change nephropathy B) Focal segmental glomerulonephritis C) IgA nephropathy D) Lupus nephritis E) Poststreptococcal glomerulonephritis
Slide 276-

The presence of crescents in glomeruli of patients with rapidly progressive glomerulonephritis (RPGN) indicates: A) Severe disease requiring early aggressive therapy B) Type I RPGN C) Type II RPGN D) Type III RPGN E) The need for close observation but no specific treatment
Slide 277-

Which of the following is (are) known to cause glomerulonephritis? A) Group A streptococci B) Hepatitis C virus C) HIV D) Parasites E) All of the above
Slide 278-

Antibiotic treatment after poststreptococcal glomerulonephritis may: A) Prevent subsequent poststreptococcal glomerulonephritis B) Reduce severity of disease C) Prevent the spread of infection to family members D) Both B and C E) Both A and C
Slide 279-

279
Slide 280-

تنظیم دوز داروها در نارسایی کلیوی Drug Therapy Individualization with Renal Insufficiency
Slide 281-

Which of the following is the predominant mechanism by which the bioavailability of some drugs is increased in patients with severe stage 5 chronic kidney disease? A) Decreased renal clearance B) Decreased first-pass metabolism C) Increased volume of distribution D) Increased plasma protein binding
Slide 282-

Which of the following drugs will most likely have an increased fraction unbound in patients with end-stage renal disease (ESRD)? A) Clonidine B) Disopyramide C) Phenytoin D) Propafenone
Slide 283-

Unbound drug concentrations for drugs that are highly protein bound should not be used to monitor therapy and make dose modifications in patients with chronic kidney disease. A) True B) False
Slide 284-

The metabolism of many drugs is altered in patients with renal insufficiency. Select which of the following statements is true regarding this phenomenon: A) The onset of the effect on metabolism is rapid, thus there is no difference between patients with acute and chronic kidney disease B) The observed reductions in nonrenal clearance in CKD patients are not proportional to the reductions in glomerular filtration rate (GFR) C) The effect on metabolism is greater in patients with ARF than in patients with ESRD D) Data suggest a differential effect on the individual CYP450 enzymes with the activity of some enzymes being reduced, although the activity of other enzymes is not affected E) The degree of increase in drug metabolism is highly variable
Slide 285-

Which of the following statements regarding renal drug excretion is true? A) The P-glycoprotein transport system in the kidney is also involved in the tubular secretion of anionic drugs B) The decrease in renal drug clearance for drugs that are primarily secreted will be proportional to the reduction in glomerular filtration rate C) The renal clearance (CLr) of a drug that undergoes secretion (CLr >300 mL/min) is likely to be reduced more in a patient with glomerulonephritis than in one with tubulointerstitial renal disease D) A patient with acute tubular necrosis will have lower ß-lactam renal clearance than a patient with chronic glomerulonephritis (assuming comparable CLcr)
Slide 286-

An HIV-infected patient who has a creatinine clearance (CLcr) of 34 mL/min is to receive tenofovir for the treatment of human immunodeficiency virus (HIV) infection (in combination with other antiretroviral agents). After intravenous administration of tenofovir, approximately 75% of the dose is recovered in the urine as unchanged drug. Based on this information, calculate the most appropriate dosing interval for this patient with impaired renal function. Assume the normal dosing interval (TN) is every 24 hours. A) 12 hours B) 24 hours C) 36 hours D) 48 hours E) 72 hours
Slide 287-

A 72-year-old, 65-kg man is to receive ciprofloxacin. The usual dose of ciprofloxacin is 500 mg twice daily for patients with normal renal function. Calculate a new dose to be given every 12 hours. The patient’s measured CLcr is 48 mL/min, and the relationship between ciprofloxacin oral clearance (CL/F) and renal function is CL/F (mL/min) = 2.83 (CLcr) + 363. A) 125 mg every12 hours B) 250 mg every 12 hours C) 375 mg every 12 hours D) 500 mg every 12 hours
Slide 288-

A.C. is to receive amoxicillin for a suspected urinary tract infection. His measured CLcr is 45 mL/min, and the clearance and fraction of drug eliminated renally unchanged of amoxicillin in a patient with normal renal function (CLcr = 120 mL/min) are 221 mL/min and 86%, respectively. What do you project his clearance of amoxicillin will be? A) 150 mL/min B) 119 mL/min C) 102 mL/min D) 83 mL/min E) 19 mL/min
Slide 289-

Which of the following statements concerning the relative efficiency of drug removal by dialysis is false? A) Peritoneal dialysis is less effective than hemodialysis at removing drug substances B) High-flux hemodialysis drug clearances are greater in ARF patients than in CVVHD C) The clearance (mL/min) values of all drugs with continuous renal replacement therapies are smaller than the values reported with conventional hemodialysis D) CVVH clearance of a given drug always will be less than CVVHDF clearance E) Conventional hemodialysis produces greater removal of most drugs when compared with high-flux hemodialysis
Slide 290-

Which of the following drugs is least likely to be removed by conventional hemodialysis (i.e., hemodialysis using a cellulose membrane)? A) Foscarnet (MW = 94; Vd = 0.7 1/kg; Fraction bound = 0.17) B) Cefazolin (MW = 454; Vd = 0.2 1/kg; Fraction bound = 0.50) C) Ceftriaxone (MW = 450; Vd = 0.2 1/kg; Fraction bound = 0.90) D) Inulin (MW = 5,200; Vd = 0.05 1/kg; Fraction bound = 0.00)
Slide 291-

Which of the following is the optimal approach to determine the effect of hemodialysis on the pharmacokinetics of a new drug? A) Determine the half-life of the drug during dialysis and compare with the value observed in those with normal renal function B) Calculate the recovery clearance, CL = amount in dialysate/AUC0-t in serum during dialysis C) Collect the dialysate and calculate the ratio of the concentration of the drug in dialysate to concentration of drug in blood D) Measure the blood clearance, CLblood = Qb[(CLarterial –CLvenous)/CLarterial] E) Determine the total-body clearance of the drug when administered on a nondialysis day relative to the total-body clearance observed when the drug is given during dialysis
Slide 292-

T.D. is a 34-year-old, 60-kg man with a residual CLcr of 8 mL/min who has been receiving hemodialysis for 3 months. He was just started on gabapentin 300 mg orally every 8 hours by his neurologist. What dosage regimen would you recommend given that the volume of distribution is 0.7 L/kg, the fraction eliminated in the urine unchanged is 90%, and protein binding is 3%? A) 300 mg every 8 hours B) 150 mg every 8 hours C) 50 mg every 8 hours D) 300 mg every 24 hours E) 300 mg every 48 hours
Slide 293-

S.M. is a 58-year-old, 75-kg man with a residual CLcr of 9 mL/min who has been receiving hemodialysis for 9 months. His nephrologist wants to start him on gentamicin (initial dose 150 mg IV over 0.5 hours) to treat an infected foot. What do you project his serum concentration will be in 40 hours, just prior to his next dialysis session, given that the volume of distribution is 0.3 L/kg, the CLgentamicin = CLcr × 0.983, and protein binding is 3%? A) 8.3 mg/L B) 6.6 mg/L C) 4.8 mg/L D) 2.5 mg/L E) 1.8 mg/L
Slide 294-

If the serum gentamicin concentration was determined to be 3.6 mg/L, what do you project S.M.’s gentamicin serum concentration will be after 4 hours of dialysis with a high-flux dialyzer for which the reported gentamicin clearance is 116 mL/min? A) 0.7 mg/L B) 1.1 mg/L C) 1.6 mg/L D) 2.0 mg/L E) 2.5 mg/L 15
Slide 295-

The serum gentamicin concentration after the end of dialysis is determined to be 1.8 mg/L. What is the supplemental dose that should be given to achieve a target peak concentration of 8 mg/L? Calculate the dose using the simplified approach. A) 75 mg B) 90 mg C) 110 mg D) 220 mg
Slide 296-

ppt slide no 296 content not found
Slide 297-

همه سئوالات فوق
Slide 298-

Which of the following is the most common cause of intrinsic ARF? A) Tubular damage from aminoglycoside use B) Glomerular damage from severe inflammation C) Tubular damage from prolonged ischemia D) Occlusion of the renal vasculature
Slide 299-

The best option for a patient with severe pulmonary edema, who remains anuric after trials of 10 and 20 mg/h IV furosemide is: A) Increase the dose of furosemide to 40 mg/h B) Change the furosemide to bolus dosing; start with 200 mg IV C) Add metolazone 5 mg daily D) Discontinue furosemide and begin metolazone 10 mg twice daily E) Change to bumetanide 2 mg/h
Slide 300-

Which of the following therapies might worsen fluid or electrolyte disturbances typically present in the patient with ARF? A) Metronidazole 500 mg orally every 6 hours for diarrhea caused by Clostridium difficile B) Monobasic and dibasic sodium phosphate (Fleet Phospho-Soda) 45 mL daily as needed for bowel movement C) Diltiazem 10 mg/h for rate control because of atrial fibrillation D) Sodium polystyrene sulfonate (Kayexalate) 30 g orally once E) All of the above
Slide 301-

Prerenal ARF can be exacerbated by the continuation of all of the following medications, except? A) Lisinopril B) Metolazone C) Indomethacin D) Prednisone E) Valsartan
Slide 302-

All of the following should be assessed daily in a patient with ARF, except? A) Liver aminotransferases B) Serum creatinine C) Weight D) Medication dosages E) Urine output
Slide 303-

Which of the following is not an important consideration when selecting a dosage of a renally eliminated antibiotic in a patient with ARF? A) Cardiac output B) Fluid status C) Renal replacement therapy D) Estimated GFR E) Hemoglobin
Slide 304-

A 58-year-old male with unknown past medical history has prerenal acute renal failure from acute blood loss because of a limb amputation in an industrial accident, and aggressive fluid resuscitation is initiated. Which of the following set of monitoring parameters are most appropriate for during the next 8 hours? A) Urine output, rales, and blood pressure B) Heart rate, blood pressure, and BUN C) Bowel sounds, blood pressure, funduscopic findings D) Blood pressure, serum potassium, and serum sodium E) Blood pressure, weight, and blood glucose
Slide 305-

The use of serum creatinine as a marker of glomerular filtration rate (GFR) in the setting of ARF is limited by: A) The test is not readily available in most laboratories B) Its lack of responsiveness to abrupt changes in GFR C) Its accuracy increases in the setting of volume overload D) The glomerulus increases its filtration of creatinine during ARF E) Numerous medications cross-react with the assay, rendering the results unreliable
Slide 306-

Which if the following is true regarding the treatment of established ARF? A) Dopamine 2 mcg/kg/min is effective to reverse intrinsic ARF B) The liberal use of loop diuretics hasten GFR recovery C) Mannitol is useful to employ in the anuric patient D) The mainstays of therapy are primarily supportive in nature E) Thyroxine is helpful to increase GFR in the elderly patient with subclinical hypothyroidism
Slide 307-

Which if the following is true regarding the treatment of established ARF? A) Dopamine 2 mcg/kg/min is effective to reverse intrinsic ARF B) The liberal use of loop diuretics hasten GFR recovery C) Mannitol is useful to employ in the anuric patient D) The mainstays of therapy are primarily supportive in nature E) Thyroxine is helpful to increase GFR in the elderly patient with subclinical hypothyroidism
Slide 308-

For the patient with ARF, goals include: A) Avoid exposure to additional nephrotoxins B) Minimize extrarenal complications C) Expedite recovery of renal function D) Restore previous degree of renal function E) All of the above
Slide 309-

In a patient with ARF and gram-negative sepsis receiving gentamicin therapy, which of the following should be considered in developing a treatment regimen? A) Gentamicin removal can be faster in ARF compared to CKD B) Administration of the gentamicin immediately post the intermittent hemodialysis session C) Careful assessment of the patient’s actual volume of distribution of gentamicin D) Determining the viability of other antimicrobial alternatives E) All of the above 17
Slide 310-

Which of the following is false regarding ARF in the hospitalized patient? A) Occurs in approximately 7% of hospitalized patients B) Is associated with increased mortality C) Can lead to long-term kidney damage and life-long hemodialysis D) Should be aggressively treated with high-dose diuretics
Slide 311-

Causes of diuretic resistance include the following except: A) Inappropriate diuretic dose or regimen B) NSAID-associated decrease in sodium resorption C) Presence of heart failure D) Vasodilator-associated reduction in renal blood flow 19
Slide 312-

A 76-year-old, 60-kg patient with a history of heart failure is admitted for severe nausea and fever of several days’ duration, as well as acute onset of chest pain. There is a single serum creatinine value of 2.4 mg/dL, and tests for several drugs eliminated primarily by the kidney are ordered. It is 2:00 in the afternoon. Choose the best consideration for those agents eliminated primarily by the kidney.
Slide 313-

A) The creatinine clearance can be calculated to estimate a GFR, and then an adjusted dosing regimen should implemented for the duration of this admission. B) Send out the initially ordered doses immediately and do not check if any were administered in the emergency room. C) Assess if any drugs were recently administered, and only recommend one day of new therapies if not already started; request a second serum creatinine value to assess if the patient’s renal function is stable; check to see if the patient is producing any urine as a additional assessment of renal function. D) Assess if any drugs were recently administered, and send out one dose.
Slide 314-

In continuous renal replacement therapy (CRRT), the following is true: A) Goal of therapy in CRRT is a ultrafiltration rate of 25 mL/h/kg B) Thrombosis is a concern where anticoagulation can be necessary C) Requires specialized staff and equipment D) Is frequently used in unstable patients where IHD can increase the risk of a hypotensive episode E) All the above
Slide 315-

The most common manifestation of drug-induced kidney disease is: A) Proteinuria B) Pyuria C) Hematuria D) A decline in the glomerular filtration rate (GFR) E) A reduction in tubular secretion
Slide 316-

Regarding drug-induced kidney disease, all of the following are applicable except: A) Temporal relationship with potentially toxic agent B) The offending agent is rarely identified C) Significant source of morbidity in the hospital setting D) Abrupt and sustained reduction in GFR E) The most common presentation in the hospital setting is acute tubular necrosis
Slide 317-

Which of the following drugs would be the most likely culprit in a patient with newly diagnosed renal intratubular obstruction? A) Ibuprofen B) Losartan C) Amphotericin B D) Ciprofloxacin E) Acyclovir
Slide 318-

Hemodynamically mediated renal failure induced by angiotensin-converting enzyme inhibitors (ACEI) involves all of the following except: A) Enhanced efferent arteriolar constriction B) Patients with renal artery stenosis at increased risk C) Decrease in glomerular capillary hydrostatic pressure D) Reduced glomerular ultrafiltration E) None of the above 5 Which of the following drugs has been associated with chronic interstitial nephritis? A) Cyclosporine B) Ifosfamide C) Lithium D) Streptozotocin E) All of the above 6 Which of the following drugs has been associated with collapsing glomerulosclerosis? A) Propylthiouracil B) Aminoglycosides C) Pamidronate D) Radiographic contrast media E) Hydralazine 7 The following renal structural-functional alteration is associated with exposure to radiographic contrast media: A) Allergic interstitial nephritis B) Intratubular obstruction C) Glomerulosclerosis D) Acute tubular necrosis E) Papillary necrosis 8 All of the following strategies can be used to prevent radiographic contrast media nephrotoxicity except: A) Amifostine B) Acetylcysteine C) Low osmolality agents D) Hydration E) Reduced doses of contrast 9 The preferred agent for preventing cisplatin-induced nephrotoxicity is: A) Fenoldopam B) Amifostine C) Dopamine D) Acetylcysteine E) Mesna 10 All of the following drugs are linked to the development of antineutrophil cytoplasmic antibody (ANCA)-positive vasculitis except: A) Hydralazine B) Allopurinol C) Warfarin D) Propylthiouracil E) Penicillamine 11 Each of the following statements regarding aminoglycoside-induced acute tubular necrosis is true except: A) Risk factors include prolonged therapy and increased age B) It manifests as a gradual increase in serum creatinine 4 to 6 weeks after exposure to the drug C) Patients typically present with nonoliguria, maintaining urine volumes greater than 500 mL/day D) Toxicity of various aminoglycosides is related to cationic charge of the drug E) “Once-daily” dosing is one method to maintain antimicrobial efficacy while reducing nephrotoxicity 12 The preferred treatment for a patient with drug-induced minimal change glomerular injury accompanied by interstitial nephritis is: A) Amifostine B) Cyclophosphamide C) Pamidronate D) Prednisone E) Hydration 13 The signs and symptoms of penicillin-induced allergic interstitial nephritis include all of the following except: A) Rash, eosinophilia, pyuria B) Fever, eosinophilia, reduced intraglomerular pressure C) Fever, rash, eosinophilia D) Elevated serum creatinine, rash, eosinophilia E) Hematuria, proteinuria, oliguria 14 A 60-year-old woman with a 5-year history of NSAID use is prescribed enalapril and develops acute renal failure. What is the most likely cause of her renal failure? A) Acute allergic interstitial nephritis B) Chronic interstitial nephritis C) Minimal change glomerular injury D) Focal segmental glomerulosclerosis E) Hemodynamically-mediated renal failure 15 Potential causes of pseudo-renal failure include all of the following except: A) Competitive inhibition of creatinine tubular secretion by cimetidine B) Drug induced increase in protein catabolism C) Direct interference with the enzymatic measurement of creatinine D) Increased synthesis and release of creatinine into serum E) Competitive inhibition of creatinine tubular secretion by trimethoprim
Slide 319-

Which of the following drugs has been associated with chronic interstitial nephritis? A) Cyclosporine B) Ifosfamide C) Lithium D) Streptozotocin E) All of the above
Slide 320-

Which of the following drugs has been associated with collapsing glomerulosclerosis? A) Propylthiouracil B) Aminoglycosides C) Pamidronate D) Radiographic contrast media E) Hydralazine
Slide 321-

The following renal structural-functional alteration is associated with exposure to radiographic contrast media: A) Allergic interstitial nephritis B) Intratubular obstruction C) Glomerulosclerosis D) Acute tubular necrosis E) Papillary necrosis
Slide 322-

All of the following strategies can be used to prevent radiographic contrast media nephrotoxicity except: A) Amifostine B) Acetylcysteine C) Low osmolality agents D) Hydration E) Reduced doses of contrast
Slide 323-

The preferred agent for preventing cisplatin-induced nephrotoxicity is: A) Fenoldopam B) Amifostine C) Dopamine D) Acetylcysteine E) Mesna
Slide 324-

All of the following drugs are linked to the development of antineutrophil cytoplasmic antibody (ANCA)-positive vasculitis except: A) Hydralazine B) Allopurinol C) Warfarin D) Propylthiouracil E) Penicillamine
Slide 325-

Each of the following statements regarding aminoglycoside-induced acute tubular necrosis is true except: A) Risk factors include prolonged therapy and increased age B) It manifests as a gradual increase in serum creatinine 4 to 6 weeks after exposure to the drug C) Patients typically present with nonoliguria, maintaining urine volumes greater than 500 mL/day D) Toxicity of various aminoglycosides is related to cationic charge of the drug E) “Once-daily” dosing is one method to maintain antimicrobial efficacy while reducing nephrotoxicity 12
Slide 326-

The preferred treatment for a patient with drug-induced minimal change glomerular injury accompanied by interstitial nephritis is: A) Amifostine B) Cyclophosphamide C) Pamidronate D) Prednisone E) Hydration
Slide 327-

The signs and symptoms of penicillin-induced allergic interstitial nephritis include all of the following except: A) Rash, eosinophilia, pyuria B) Fever, eosinophilia, reduced intraglomerular pressure C) Fever, rash, eosinophilia D) Elevated serum creatinine, rash, eosinophilia E) Hematuria, proteinuria, oliguria
Slide 328-

A 60-year-old woman with a 5-year history of NSAID use is prescribed enalapril and develops acute renal failure. What is the most likely cause of her renal failure? A) Acute allergic interstitial nephritis B) Chronic interstitial nephritis C) Minimal change glomerular injury D) Focal segmental glomerulosclerosis E) Hemodynamically-mediated renal failure
Slide 329-

Potential causes of pseudo-renal failure include all of the following except: A) Competitive inhibition of creatinine tubular secretion by cimetidine B) Drug induced increase in protein catabolism C) Direct interference with the enzymatic measurement of creatinine D) Increased synthesis and release of creatinine into serum E) Competitive inhibition of creatinine tubular secretion by trimethoprim
Slide 330-

Glomerulonephritis
Slide 331-

In a patient with nephrotic syndrome, which of the following is not expected to be present? A) Proteinuria B) Edema C) Hyperlipidemia D) Hypercoagulable state E) Hematuria
Slide 332-

Which of the following is not expected to reduce proteinuria when used for patients with glomerulonephritis? A) Angiotensin-converting enzyme (ACE) inhibitors B) Angiotensin II receptor blockers C) Nondihydropyridine calcium channel blockers (e.g., diltiazem) D) Dihydropyridine calcium channel blockers (e.g., nifedipine, amlodipine) E) All of the above are expected to reduce proteinuria
Slide 333-

Treatment of which of the following is expected to reduce the progression of renal failure in patients with glomerulonephritis? A) Edema B) Proteinuria C) Hyperlipidemia D) Coagulopathy E) Hematuria
Slide 334-

ACE inhibitors are often used in patients with glomerulonephritis because of their ability to reduce: A) Proteinuria B) Blood pressure C) Immunologically induced glomerular damage D) Both A and B E) All A, B, and C
Slide 335-

Intravascular thrombosis is a common and serious complication of nephrotic syndrome associated with which of the following glomerular disease? A) Minimal-change nephropathy B) Focal segmental glomerulonephritis C) Membranous nephropathy D) Immunoglobulin A nephropathy E) Membranoproliferative glomerulonephritis
Slide 336-

Which of the following glomerulonephritis is more commonly seen in pediatric patients? A) Minimal-change nephropathy B) Focal segmental glomerulonephritis C) Immunoglobulin A nephropathy D) Membranous nephropathy E) Membranoproliferative glomerulonephritis
Slide 337-

Which of the following agent is known to be most effective in inducing remission in patients with recently diagnosed minimal-change nephropathy? A) Steroid B) Cyclosporine C) Azathioprine D) Cyclophosphamide E) Levamisole
Slide 338-

Which of the following is not correct regarding the use of cyclosporine for the treatment of minimal-change nephropathy? A) Cyclosporine may reduce lymphokine production by activated T lymphocytes B) Cyclosporine may improve the permselectivity of GBM C) Cyclosporine is often effective in preventing relapse D) Cyclosporine is often effective in inducing remission during relapse E) Cyclosporine is useful for patients who are steroid dependent
Slide 339-

Compared with minimal-change nephropathy, patients with focal segmental glomerulonephritis are: A) More likely to be adults B) Less responsive to steroid treatment C) More likely to develop progressive renal failure D) Only A and B above are correct E) All A, B, and C above are correct
Slide 340-

In patients with mild focal segmental glomerulonephritis, which of the following is (are) commonly used? A) ACE inhibitors B) Angiotensin II receptor blockers C) Immunosuppressive agents D) Both A and/or B can be used E) All A, B, and C are necessary to induce remission
Slide 341-

Fish oil may be beneficial in certain patients with which of the following types of glomerulonephritis? A) Minimal-change nephropathy B) Focal segmental glomerulonephritis C) Immunoglobulin A nephropathy D) Membranous nephropathy E) Membranoproliferative glomerulonephritis
Slide 342-

Which of the following is correct with respect to treatment for membranous nephropathy? A) Spontaneous remission is common, and steroid treatment alone is commonly used to reduce proteinuria and progression of disease B) Spontaneous remission is common, and steroid treatment alone is not effective in reducing proteinuria and progression of disease C) Spontaneous remission is unlikely, and steroid treatment is needed to reduce proteinuria and progression of disease D) Spontaneous remission is unlikely, and steroid treatment alone is not effective in reducing proteinuria and progression of disease E) Steroid and cytotoxic agents are commonly needed to induce remission
Slide 343-

A patient with IgA nephropathy who has normal renal function, isolated micro-hematuria, and proteinuria less than 1 g/day should be: A) Observed closely without specific treatment B) Given fish oil C) Given steroid treatment D) Given cytotoxic agents E) Given cyclosporine
Slide 344-

Which of the following is not normally considered when selecting the optimal treatment for patients with lupus nephritis? A) Type of underlying lesion B) Disease activity according to pathologic findings C) Severity of symptoms D) Duration of symptoms E) All of the above are commonly considered
Slide 345-

Which of the following is frequently used for chronic maintenance treatment of lupus nephritis? A) Steroid B) Cytotoxic agent C) Cyclosporine D) Mycophenolate mofetil E) Fish oil
Slide 346-

Monoclonal antibodies has been evaluated for the treatment of which of the following glomerular disease? A) Minimal-change nephropathy B) Focal segmental glomerulonephritis C) IgA nephropathy D) Lupus nephritis E) Poststreptococcal glomerulonephritis
Slide 347-

The presence of crescents in glomeruli of patients with rapidly progressive glomerulonephritis (RPGN) indicates: A) Severe disease requiring early aggressive therapy B) Type I RPGN C) Type II RPGN D) Type III RPGN E) The need for close observation but no specific treatment
Slide 348-

Which of the following is (are) known to cause glomerulonephritis? A) Group A streptococci B) Hepatitis C virus C) HIV D) Parasites E) All of the above
Slide 349-

Antibiotic treatment after poststreptococcal glomerulonephritis may: A) Prevent subsequent poststreptococcal glomerulonephritis B) Reduce severity of disease C) Prevent the spread of infection to family members D) Both B and C E) Both A and C
Slide 350-

تنظیم دوز داروها در نارسایی کلیوی Drug Therapy Individualization with Renal Insufficiency
Slide 351-

Which of the following is the predominant mechanism by which the bioavailability of some drugs is increased in patients with severe stage 5 chronic kidney disease? A) Decreased renal clearance B) Decreased first-pass metabolism C) Increased volume of distribution D) Increased plasma protein binding
Slide 352-

Which of the following drugs will most likely have an increased fraction unbound in patients with end-stage renal disease (ESRD)? A) Clonidine B) Disopyramide C) Phenytoin D) Propafenone
Slide 353-

Unbound drug concentrations for drugs that are highly protein bound should not be used to monitor therapy and make dose modifications in patients with chronic kidney disease. A) True B) False
Slide 354-

The metabolism of many drugs is altered in patients with renal insufficiency. Select which of the following statements is true regarding this phenomenon: A) The onset of the effect on metabolism is rapid, thus there is no difference between patients with acute and chronic kidney disease B) The observed reductions in nonrenal clearance in CKD patients are not proportional to the reductions in glomerular filtration rate (GFR) C) The effect on metabolism is greater in patients with ARF than in patients with ESRD D) Data suggest a differential effect on the individual CYP450 enzymes with the activity of some enzymes being reduced, although the activity of other enzymes is not affected E) The degree of increase in drug metabolism is highly variable
Slide 355-

Which of the following statements regarding renal drug excretion is true? A) The P-glycoprotein transport system in the kidney is also involved in the tubular secretion of anionic drugs B) The decrease in renal drug clearance for drugs that are primarily secreted will be proportional to the reduction in glomerular filtration rate C) The renal clearance (CLr) of a drug that undergoes secretion (CLr >300 mL/min) is likely to be reduced more in a patient with glomerulonephritis than in one with tubulointerstitial renal disease D) A patient with acute tubular necrosis will have lower ß-lactam renal clearance than a patient with chronic glomerulonephritis (assuming comparable CLcr)
Slide 356-

An HIV-infected patient who has a creatinine clearance (CLcr) of 34 mL/min is to receive tenofovir for the treatment of human immunodeficiency virus (HIV) infection (in combination with other antiretroviral agents). After intravenous administration of tenofovir, approximately 75% of the dose is recovered in the urine as unchanged drug. Based on this information, calculate the most appropriate dosing interval for this patient with impaired renal function. Assume the normal dosing interval (TN) is every 24 hours. A) 12 hours B) 24 hours C) 36 hours D) 48 hours E) 72 hours
Slide 357-

A 72-year-old, 65-kg man is to receive ciprofloxacin. The usual dose of ciprofloxacin is 500 mg twice daily for patients with normal renal function. Calculate a new dose to be given every 12 hours. The patient’s measured CLcr is 48 mL/min, and the relationship between ciprofloxacin oral clearance (CL/F) and renal function is CL/F (mL/min) = 2.83 (CLcr) + 363. A) 125 mg every12 hours B) 250 mg every 12 hours C) 375 mg every 12 hours D) 500 mg every 12 hours
Slide 358-

A.C. is to receive amoxicillin for a suspected urinary tract infection. His measured CLcr is 45 mL/min, and the clearance and fraction of drug eliminated renally unchanged of amoxicillin in a patient with normal renal function (CLcr = 120 mL/min) are 221 mL/min and 86%, respectively. What do you project his clearance of amoxicillin will be? A) 150 mL/min B) 119 mL/min C) 102 mL/min D) 83 mL/min E) 19 mL/min
Slide 359-

Which of the following statements concerning the relative efficiency of drug removal by dialysis is false? A) Peritoneal dialysis is less effective than hemodialysis at removing drug substances B) High-flux hemodialysis drug clearances are greater in ARF patients than in CVVHD C) The clearance (mL/min) values of all drugs with continuous renal replacement therapies are smaller than the values reported with conventional hemodialysis D) CVVH clearance of a given drug always will be less than CVVHDF clearance E) Conventional hemodialysis produces greater removal of most drugs when compared with high-flux hemodialysis
Slide 360-

Which of the following drugs is least likely to be removed by conventional hemodialysis (i.e., hemodialysis using a cellulose membrane)? A) Foscarnet (MW = 94; Vd = 0.7 1/kg; Fraction bound = 0.17) B) Cefazolin (MW = 454; Vd = 0.2 1/kg; Fraction bound = 0.50) C) Ceftriaxone (MW = 450; Vd = 0.2 1/kg; Fraction bound = 0.90) D) Inulin (MW = 5,200; Vd = 0.05 1/kg; Fraction bound = 0.00)
Slide 361-

Which of the following is the optimal approach to determine the effect of hemodialysis on the pharmacokinetics of a new drug? A) Determine the half-life of the drug during dialysis and compare with the value observed in those with normal renal function B) Calculate the recovery clearance, CL = amount in dialysate/AUC0-t in serum during dialysis C) Collect the dialysate and calculate the ratio of the concentration of the drug in dialysate to concentration of drug in blood D) Measure the blood clearance, CLblood = Qb[(CLarterial –CLvenous)/CLarterial] E) Determine the total-body clearance of the drug when administered on a nondialysis day relative to the total-body clearance observed when the drug is given during dialysis
Slide 362-

T.D. is a 34-year-old, 60-kg man with a residual CLcr of 8 mL/min who has been receiving hemodialysis for 3 months. He was just started on gabapentin 300 mg orally every 8 hours by his neurologist. What dosage regimen would you recommend given that the volume of distribution is 0.7 L/kg, the fraction eliminated in the urine unchanged is 90%, and protein binding is 3%? A) 300 mg every 8 hours B) 150 mg every 8 hours C) 50 mg every 8 hours D) 300 mg every 24 hours E) 300 mg every 48 hours
Slide 363-

S.M. is a 58-year-old, 75-kg man with a residual CLcr of 9 mL/min who has been receiving hemodialysis for 9 months. His nephrologist wants to start him on gentamicin (initial dose 150 mg IV over 0.5 hours) to treat an infected foot. What do you project his serum concentration will be in 40 hours, just prior to his next dialysis session, given that the volume of distribution is 0.3 L/kg, the CLgentamicin = CLcr × 0.983, and protein binding is 3%? A) 8.3 mg/L B) 6.6 mg/L C) 4.8 mg/L D) 2.5 mg/L E) 1.8 mg/L
Slide 364-

If the serum gentamicin concentration was determined to be 3.6 mg/L, what do you project S.M.’s gentamicin serum concentration will be after 4 hours of dialysis with a high-flux dialyzer for which the reported gentamicin clearance is 116 mL/min? A) 0.7 mg/L B) 1.1 mg/L C) 1.6 mg/L D) 2.0 mg/L E) 2.5 mg/L 15
Slide 365-

The serum gentamicin concentration after the end of dialysis is determined to be 1.8 mg/L. What is the supplemental dose that should be given to achieve a target peak concentration of 8 mg/L? Calculate the dose using the simplified approach. A) 75 mg B) 90 mg C) 110 mg D) 220 mg
Slide 366-

ppt slide no 366 content not found
Slide 367-

Prevention Identify at risk patients pre-existing CRF, diabetes, jaundice, myeloma, elderly Optimise renal perfusion IV fluids, inotropes, central line Maintain adequate diuresis Mannitol, frusemide, NOT dopamine Avoid nephrotoxic agents ACE inhibitors, NSAIDS, radiological contrast, aminoglycosides
Slide 368-

Interventions to Prevent Contrast Nephrotoxicity Which is best proven prevention strategy? NS 1-2 mL/kg/hr starting 12 hours pre and continued 12 hours post-procedure Sodium Bicarbonate 150mEq/L D5W infused at 3mL/kg/h x 1 hours pre, then 1mL/kg/h x 6 hours post-procedure N-acetylcysteine 600mg PO BID x 4 doses on day prior to and on day after admin of contrast
Slide 369-

Which of the following is an example of a preventive measure to avoid nephrotoxicity? Using alternatives to nephrotoxic drugs Adequate hydration Avoiding use of contrast dye in patients taking aminoglycosides Recognizing a 50% rise from baseline creatinine is considered acute renal failure All of the above are correct
Slide 370-

Drug-Induced Acute Renal Dysfunction Acute Renal Failure - Prerenal NSAIDs, CyA/Tacrolimus, ACEI/ARB, Diuretics - Intrinsic – ATN vs AIN ATN : Aminoglycosides, Amphotericin B, Radiocontrast Media AIN : B-Lactams, Sulfa, Rifampin, Ciprofloxacin, Cimetidine, NSAIDs, PPIs, Allopurinol, Phenytoin, Diuretics - Obstructive Methotrexate, Acyclovir, Indinavir, Rhabdomyolysis (Statins)
Slide 371-

CLASSIFICATIONS Anuric: < 50ml/day urine output Oliguric: 50-400ml/day urine output Non-oliguric: >400ml/day urine output
Slide 372-

372