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Diuretics and In Acute Kidney Injury PowerPoint Presentation

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Description : Check out this medical PowerPoint presentation titled "Diuretics and in Acute Kidney Injury” by Asad J. Chaudhary MD.

This medical PowerPoint presentation is about the use of diuretics in acute kidney injury (AKI). Diuretics are medications that increase the production of urine, which can help in the management of several medical conditions, including hypertension, heart failure, and edema. However, the use of diuretics in acute kidney injury (AKI) is controversial and requires careful consideration..

AKI is a sudden decline in kidney function that can be caused by a variety of factors, including decreased blood flow to the kidneys, direct damage to the kidneys, or obstruction of urine flow. In AKI, the kidneys are unable to properly filter waste products from the blood, leading to an accumulation of toxins in the body..

The use of diuretics in AKI has been debated for decades, with some studies suggesting that diuretics can help to improve urine output and reduce the need for dialysis. However, other studies have shown that diuretics can worsen kidney function by decreasing blood flow to the kidneys and increasing the risk of electrolyte imbalances, particularly in patients with pre-existing kidney disease..

In general, the use of diuretics in AKI should be based on careful evaluation of the patients individual clinical situation. Diuretics may be considered in certain cases, such as in patients with fluid overload or heart failure, but only if they are used with caution and close monitoring of kidney function, electrolyte levels, and blood pressure..

In conclusion, the use of diuretics in AKI is a complex issue that requires careful consideration of the risks and benefits in each individual case. Healthcare providers should always weigh the potential benefits of diuretics against the risks and be mindful of the potential adverse effects when prescribing them to patients with AKI.

Tags : Diuretics and in Acute Kidney Injury, hypertension, heart failure, edema, Nephrology, Nephrology PowerPoint presentation

Published on : Jun 07, 2023 | Views : 770 | Downloads : 0

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Slide 1-

Diuretics and in Acute Kidney Injury Asad J. Chaudhary M.D. Clinical Nephrology Fellow University of Tennessee Health Science Center.
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Objectives Definition of AKI Epidemiology Causes Diuretics --- Definition --- Classification --- Pharmacology Why Diuretics --- Fluid dilemma --- Renoprotection --- oliguria vs. non oliguria --- Mortality benefit --- Fluid management Prevailing evidence vs. practice parameters
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Definition Acute Kidney Injury (ARF) Clinical syndrome denoted by decline in GFR (glomerular filtration rate) With reduced excretion of nitrogenous waste (urea and creatinine) Other uremic toxins
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Measurement of Renal function Serum Cr used to estimate GFR: Problems: SCr does not accurately reflect the GFR in non steady state Creatinine is removed by dialysis studies and clinical trials have used different cut-off values
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Critical Care August 2004 Vol 8 No 4 Bellomo et al.
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Critical Care August 2004 Vol 8 No 4 Bellomo et al.
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ARF to AKI Acute Renal failure (older term) ARF: rapid decline in GFR (hrs-week) AKIN recommended AKI AKI: spectrum of ARF including minor changes in GFR may be associated with adverse clinical outcomes Failure: reserved for severe impairment of renal function that renal replacement therapy is indicated/considered JASN 18; 1987-1994, 2007
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AKIN: Diagnostic Criteria An abrupt (within 48 h) reduction in kidney function currently defined by any of the following: Absolute increase in serum creatinine of either 0.3 mg/dl A percentage increase in SCr of 50% or more A reduction in UOP (documented oliguria)
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Etiology of AKI AKI
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Classification of AKI: Non Oliguria: Urine output > 400 ml/24hr Oliguria: Urine output < 400 ml/24 hr Anuria: Urine output < 50 ml/24 hr Other terms Azotemia: Accumulation of nitrogenous waste Uremia: Symptomatic AKI (eg MS changes, loss of appetite, tremors)
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Oliguria is a well-recognized and poor prognostic indicator in patients with AKI. The development of oliguria complicates clinical management, particularly for fluid balance. Use of diuretics therefore reflects attempt to convert oliguric state to non-oliguric state. Bagshaw SM, Bellomo R, Kellum JA. Oliguria, volume over- load, and loop diuretics. Crit Care Med. 2008;36 Suppl:S172-8. Uchino S. Outcome prediction for patients with acute kidneyinjury. Nephron Clin Pract. 2008;109:c217-23.
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Epidemiology AKI  1 million hospitalized patients in the United States. The incidence of AKI  is reported to occur in up to 5% to 7% of all hospitalized patients. Up to two thirds of critically ill patients. 5% to 6% of patients with AKI require renal replacement therapy Mortality rate in this population that requires renal replacement therapy is ap- proximately 50% to 70%. AKI also significantly increases length of hospital stay AKI survivors are still at high risk for long-term adverse outcomes such as chronic kidney disease, end-stage renal disease, and premature death, even if the serum creatinine level returns to normal. Despite recent advances, the incidence of AKI has increased more than four-fold since 1998 Approximate incidence is 500 per 10,000 population. Annual health cost due to AKI is more than 10 billion per year. Waikar SS, Curhan GC, Wald R, McCarthy EP, Chertow GM. Declining mortality in patients with acute renal failure, 1988 to 2002. J Am Soc Nephrol. 2006;17:1143-50.Xue JL, Daniels F, Star RA, Kimmel PL, Eggers PW, MolitorisBA, et al. Incidence and mortality of acute renal failure in Medicare beneficiaries, 1992 to 2001. J Am Soc Nephrol. 2006; 17:1135-42.Palevsky PM. Epidemiology of acute renal failure: the tip of the iceberg. Clin J Am Soc Nephrol. 2006;1:6-7.
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Epidemiology
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Epidemiology
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Epidemiology
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Epidemiology
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Epidemiology
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High Risk for AKI
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Diuretics Definition Classes Practice vs. evidence
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Definition: These are the group of medications which act by diminishing sodium reabsorption at different sites in the nephron, thereby increasing urinary sodium and water losses
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Classification Loop diuretics – TAL of Henle Thiazide-type diuretics-- distal tubule and connecting segment (and perhaps the early cortical collecting tubule) Potassium-sparing diuretics--aldosterone-sensitive principal cells in the cortical collecting tubule Acetazolamide and mannitol act at least in part in the proximal tubule Vassopressin receptor Antagonists
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Loop Diuretics Fuoresemide, Bumetanide, Torsemide, ethacrynic acid. Furosemide is one of the most frequently prescribed drugs in the United States. The principle MOA involves blockade of the Na-K-2Cl transporter on the luminal side of the TAL of Henle. Expression of this transporter leads to sodium retention (accounting for high sodium reabsorption of up to 40% of filtered load that normally occurs in this nephron segment) and increases in medullary tonicity leading to increased water reabsorption. The expression of the Na-K-2Cl transporter is regulated via cyclic adenosine monophosphate pathways with vasopressin amplifying its expression and prostanoid prostaglandin E2 reducing its expression.
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Pharmacokinetics Weak organic acid Highly protein bound. Secreted in urinary space, not filtered! Conditions e.g Metabolic acidosis, medications which are protein bound can interfere with their delivery Elimination half-life is 1 hour for bumetanide, 1.5 to 2 hours for furosemide, and 3 to 4 hours for torsemide. The average bioavailability of oral furosemide is 50%; however, it is highly variable, ranging from 10% to 100%.. In comparison, absorption of oral bumetanide and oral torsemide ranges from 80% to 100%, and hence their oral dose is equivalent to the intravenous dose The elimination half-life of furosemide is prolonged (from 1.5-2 to 2.8 h) in patients with renal insufficiency because both urinary excretion and renal metabolism are reduced. In comparison, bumetanide and torsemide are metabolized predominantly in the liver and hence their half-lives are not prolonged in patients with renal insufficiency.
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. Diuretics: Still the mainstay of treatment. Wang, David; Gottlieb, Stephen Critical Care Medicine. 36(1) Suppl:S89-S94, January 2008. DOI: 10.1097/01.CCM.0000296272.68078.6B Pharmacokinetic data for select diuretics
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Pharmacodynamics Diuretic response of Loop Diuretics correlates more with their urinary rather than plasma concentration. The relationship between the natriuretic response (measured by fractional excretion of sodium) and the amount of diuretic reaching the site of action is sigmoid shaped. This relationship is important clinically in establishing a threshold below which there will be no diuretic action and also a ceiling dose above which no additional diuretic action will take place. Thus, once a maximally effective dose of a loop diuretic agent is administered, the only way to increase response is to administer another class of diuretics which act downstream.
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Pharmacodynamics Natriuretic effect depends on filtered sodium. Other concomitant factors such as heart failure, liver failure, volume depletion, and nonsteroidal anti-inflammatory agents significantly alter the pharmacodynamic properties of loop diuretics. Under these condition increasing doses do not produce added natriuresis, in fact frequent modest doses or continuous infusion are better. Loop diuretic tolerance from flooding of the distal nephron sites by the solute not reabsorbed from the loop of Henle  hypertrophy of collecting and connecting duct segments an increase in the reabsorption of sodium at distal sites and a reduction in total diuresis. Bolus therapy vs. Continous
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Pharmacodynamics TRANSLATIONAL PHYSIOLOGYLoop diuretics: from the Na-K-2Cl transporter to clinical use
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Pharmacodynamics
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Why Diuretics…. Fluid dilemma in acquired AKI. Reno – protection Ongoing trial Atrial Natriuretic peptide Final word
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Dilemmas of fluid management in acquired AKI
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Dilemmas of fluid management in acquired AKI
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Dilemmas of fluid management in acquired AKI
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Dilemmas of fluid management in acquired AKI Patients were randomly assigned to a strategy involving either conservative or liberal use of fluids with concealed allocation in permuted blocks of eight Eligible patients were intubated and received positive-pressure ventilation, had a ratio of the partial pressure of arterial oxygen (PaO2) to the fraction of inspired oxygen (FiO2) of less than 300 Exclusion criteria were the presence of chronic conditions that could independently influence survival, impair weaning, or compromise compliance with the protocol; advanced cancer. Fluid and Catheter treatment trial (FaCtt)
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Why Diuretics…. Fluid dilemma in acquired AKI. Reno - protection Ongoing trial Atrial Natriuretic peptide Final word
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Unload the stressed kidney ? 1.Acute renal failure = “acute renal success” 2.↓ in GFR (mediated by TGF) = ↓ reabsorptive work --- 1.Preserve renal O2 supply/demand + medullary oxygenation --- 2.Mitigate ischemic/hypoxic injury 3.If protective - why do we apply strategies to ↑ GFR? Acute renal success. The unexpected logic of oliguria in acute renal failure Thurau K, Boylan JW. Am J Med. 1976 Sep;61(3):308-15
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Acute renal failure is NOT an “acute renal success”—a clinical study on the renal oxygen supply/demand relationship in acute kidney injuryRedfors, Bengt MD, PhD; Bragadottir, Gudrun MD; Sellgren, Johan MD, PhD; Swärd, Kristina MD, PhD; Ricksten, Sven-Erik MD, PhD Historical fact: The renal oxygen supply/demand relationship, are lacking and current views on renal oxygenation in the clinical situation of acute kidney injury are presumptive and largely based on experimental studies. Design: Prospectiv, two- group comparative study Setting: Cardiothoracic intensive care unit. Patients: Post cardiac surgery patients with (n= 12) and without (n= 37) AKI Measurement: 1. Renal blood flow (Renal vein thermodilution technique, Infusion clearance of PAHA) 2. Renal oxygen consumption. 3. GFR 4. Renal Oxygenation
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© 2010 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins. Published by Lippincott Williams & Wilkins, Inc. Acute renal failure is NOT an "acute renal success"-a clinical study on the renal oxygen supply/demand relationship in acute kidney injury. Redfors, Bengt; MD, PhD; Bragadottir, Gudrun; Sellgren, Johan; MD, PhD; Sward, Kristina; MD, PhD; Ricksten, Sven-Erik; MD, PhD Critical Care Medicine. 38(8):1695-1701, August 2010. DOI: 10.1097/CCM.0b013e3181e61911
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© 2010 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins. Published by Lippincott Williams & Wilkins, Inc. Acute renal failure is NOT an "acute renal success"-a clinical study on the renal oxygen supply/demand relationship in acute kidney injury. Redfors, Bengt; MD, PhD; Bragadottir, Gudrun; Sellgren, Johan; MD, PhD; Sward, Kristina; MD, PhD; Ricksten, Sven-Erik; MD, PhD Critical Care Medicine. 38(8):1695-1701, August 2010. Renal variables obtained from the thermodilution and the infusion clearance techniques
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© 2010 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins. Published by Lippincott Williams & Wilkins, Inc. Acute renal failure is NOT an "acute renal success"-a clinical study on the renal oxygen supply/demand relationship in acute kidney injury. Redfors, Bengt; MD, PhD; Bragadottir, Gudrun; Sellgren, Johan; MD, PhD; Sward, Kristina; MD, PhD; Ricksten, Sven-Erik; MD, PhD Critical Care Medicine. 38(8):1695-1701, August 2010. DOI: 10.1097/CCM.0b013e3181e61911 Figure 1. Shows the individual data on the relationship between renal oxygen consumption and glomerular filtration rate for the control group and patients with acute kidney injury (AKI). Note that the slope of the regression line was significantly (p = .04) higher in the AKI group compared with control.
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© 2010 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins. Published by Lippincott Williams & Wilkins, Inc. Acute renal failure is NOT an "acute renal success"-a clinical study on the renal oxygen supply/demand relationship in acute kidney injury. Redfors, Bengt; MD, PhD; Bragadottir, Gudrun; Sellgren, Johan; MD, PhD; Sward, Kristina; MD, PhD; Ricksten, Sven-Erik; MD, PhD Critical Care Medicine. 38(8):1695-1701, August 2010. DOI: 10.1097/CCM.0b013e3181e61911 Shows the individual data on the relationship between renal oxygen consumption (RVO2) and renal sodium resorption for the control group (RVO2 = 2.43 + 0.82 x sodium resorption) and patients with acute kidney injury (AKI) (RVO2 = 3.27 + 1.94 x sodium resorption). Note that the slope of the regression line was significantly (p = .004) higher in the AKI group compared with control, whereas the intercepts of the regression lines did not differ significantly.
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Conclusion: Acute renal failure is not renal success. Renal oxygen consumption in and around time of AKI is significantly higher. The amount of oxygen consumed to absorb certain mmol of Na is significantly higher in AKI as compared to control. Acute renal failure is NOT an "acute renal success"-a clinical study on the renal oxygen supply/demand relationship in acute kidney injury.Redfors, Bengt; MD, PhD; Bragadottir, Gudrun; Sellgren, Johan; MD, PhD; Sward, Kristina; MD, PhD; Ricksten, Sven-Erik; MD, PhDCritical Care Medicine. 38(8):1695-1701, August 2010.
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How can Diuretics be put to use in a condition which predisposes kidneys at risk of oxygen demand and supply mismatch !!!
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Differential effect of human atrial natriuretic peptide and furosemide on GFR and renal oxygen consumptionKristina Swärd1, Felix Valsson1, Johan Sellgren1 and Sven-Erik RickstenDepartment of Cardiothoracic Anesthesia and Intensive Care, Sahlgrenska University Hospital, 41345 Gothenburg, Sweden Sward et al ICM 2005 Conclusions h-ANP improves glomerular filtration rate but does not have energy-conserving tubular effects. furosemide decreases tubular sodium reabsorption and renal oxygen consumption and thus has the potential to improve the oxygen supply/demand relationship in clinical ischemic acute renal failure Design and setting :Prospective two-agent interventional study in a university hospital cardiothoracic ICU Patients. Nineteen uncomplicated, mechanically ventilated post cardiac surgery patients with normal renal function. Interventions h-ANP (25 and 50 ng/kg per minute, n=10) or furosemide (0.5 mg/kg per hour, n=9
Slide 44-

Can Diuretics prevent AKI….
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Experimental Evidence of Loop Diuretics The bulk of the kidney’s metabolic activity is devoted to sodium reabsorption. The medullary thick ascending limb lives on thin balance. (partial pressure 15mm Hg) prone to ischemic injury Experimental evidence has shown that loop diuretics: Increase oxygenation of renal tissue. Prevent renal adenosine 5’ triphosphate depletion. Increases in glomerular filtration rate. Improvement in renal blood flow. Prevention of tubular obstruction by increasing tubular flow by flushing tubular debris. Low-dose furosemide can reduce ischemia/reperfusion injury by improving renal hemodynamics and attenuating ischemia-related changes in angiogenic gene transcription. Low-dose furosemide infusion also has been shown to attenuate ischemia/reperfusion-induced apoptosis.
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Effects of Saline, Mannitol, and Furosemide on Acute Decreases in Renal Function Induced by Radiocontrast AgentsRichard Solomon, Craig Werner, Denise Mann, John D'Elia, and Patricio SilvaN Engl J Med 1994; 331:1416-142November 24, 1994 Prospective study; 78 patients with CRI (mean [±SD] SCr = 2.1 ±0.6 mg per deciliter who underwent cardiac angiography. Randomly assigned to receive 0.45 percent saline alone for 12 hours before and 12 hours after angiography,saline plus mannitol, or saline plus furosemide. The mannitol and furosemide were given just before angiography. Serum creatinine was measured before and for 48 hours after An acute radiocontrast-induced decrease in renal function was defined as an increase in the base-line SCr concentration of at least 0.5 mg per deciliter (44 μmol per liter) within 48 hours after the injection of radiocontrast agents.
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Effects of Saline, Mannitol, and Furosemide on Acute Decreases in Renal Function Induced by Radiocontrast AgentsRichard Solomon, Craig Werner, Denise Mann, John D'Elia, and Patricio SilvaN Engl J Med 1994; 331:1416-142November 24, 1994 Absolute Changes in Serum Creatinine Concentration after the Administration of Radiocontrast Agents and the Incidence of Acute Renal Dysfunction, According to Treatment Group
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Effects of Saline, Mannitol, and Furosemide on Acute Decreases in Renal Function Induced by Radiocontrast AgentsRichard Solomon, Craig Werner, Denise Mann, John D'Elia, and Patricio SilvaN Engl J Med 1994; 331:1416-142November 24, 1994 CONCLUSION: In patients with chronic renal insufficiency who are undergoing cardiac angiography, hydration with 0.45 percent saline provides better protection against acute decreases in renal function induced by radiocontrast agents than does hydration with 0.45 percent saline plus mannitol or furosemide.
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Forced euvolemic diuresis with mannitol and furosemide for prevention of contrast-induced nephropathy in patients with CKD undergoing coronary angiography: a randomized controlled trial.Majumdar SR, Kjellstrand CM, Tymchak WJ, Hervas-Malo M, Taylor DA, Teo KK.Department of Medicine, University of Alberta, Edmonton, Alberta, Canada. Am J Kidney Dis. 2009 Oct;54(4):602-9. Epub 2009 Jun 17 BACKGROUND: Contrast-induced nephropathy is common in patients with coronary angiography. Mechanistically, forced euvolemic diuresis with mannitol and furosemide ought to prevent contrast-induced nephropathy. Objective: (1) undertake a randomized trial testing this hypothesis, and (2) conduct a meta-analysis of our findings with 2 earlier studies. STUDY DESIGN:(1) Randomized allocation-concealed controlled trial with blinded ascertainment of outcomes, and (2) random-effects meta-analysis of 3 trials.
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Forced euvolemic diuresis with mannitol and furosemide for prevention of contrast-induced nephropathy in patients with CKD undergoing coronary angiography: a randomized controlled trial.Majumdar SR, Kjellstrand CM, Tymchak WJ, Hervas-Malo M, Taylor DA, Teo KK.Department of Medicine, University of Alberta, Edmonton, Alberta, Canada. Am J Kidney Dis. 2009 Oct;54(4):602-9. Epub 2009 Jun 17
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Forced euvolemic diuresis with mannitol and furosemide for prevention of contrast-induced nephropathy in patients with CKD undergoing coronary angiography: a randomized controlled trial.Majumdar SR, Kjellstrand CM, Tymchak WJ, Hervas-Malo M, Taylor DA, Teo KK.Department of Medicine, University of Alberta, Edmonton, Alberta, Canada. Am J Kidney Dis. 2009 Oct;54(4):602-9. Epub 2009 Jun 17
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Forced euvolemic diuresis with mannitol and furosemide for prevention of contrast-induced nephropathy in patients with CKD undergoing coronary angiography: a randomized controlled trial.Majumdar SR, Kjellstrand CM, Tymchak WJ, Hervas-Malo M, Taylor DA, Teo KK.Department of Medicine, University of Alberta, Edmonton, Alberta, Canada. Am J Kidney Dis. 2009 Oct;54(4):602-9. Epub 2009 Jun 17
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Forced euvolemic diuresis with mannitol and furosemide for prevention of contrast-induced nephropathy in patients with CKD undergoing coronary angiography: a randomized controlled trial.Majumdar SR, Kjellstrand CM, Tymchak WJ, Hervas-Malo M, Taylor DA, Teo KK.Department of Medicine, University of Alberta, Edmonton, Alberta, Canada. Am J Kidney Dis. 2009 Oct;54(4):602-9. Epub 2009 Jun 17 Conclusion Forced euvolemic diuresis led to a significantly increased risk of contrast-induced nephropathy. This strategy should be abandoned, and our results suggest that oral furosemide therapy perhaps should be held before angiography.
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Loop diuretics in the management of acute renal failure: a prospective, double-blind, placebo-controlled, randomized studyShilliday IR, Quinn KJ, Allison ME.Nephrol Dial Transplant. 1997 Dec;12(12):2592-6. Method: Total number of patients = 92 All received IV dopamine 2 ug/kg body weight/ min throughout. 20 % mannitol 100ml q6h first 3 days Than in a double blind manner either furosemide, torsemide or placebo 3mg/kg body weight I.V q6h for 21 days or until renal recovery or Death.
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Loop diuretics in the management of acute renal failure: a prospective, double-blind, placebo-controlled, randomized studyShilliday IR, Quinn KJ, Allison ME.Nephrol Dial Transplant. 1997 Dec;12(12):2592-6.
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Loop diuretics in the management of acute renal failure: a prospective, double-blind, placebo-controlled, randomized studyShilliday IR, Quinn KJ, Allison ME.Nephrol Dial Transplant. 1997 Dec;12(12):2592-6. In conclusion loop diuretics have no benefecial effect on duration of renal dysfunction, need for dialysis, or, in mortality in ARF.
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Diuretics, Mortality, and Nonrecovery of Renal Function in Acute Renal FailureRavindra L. Mehta, MD; Maria T. Pascual, RN, MPH; Sharon Soroko, MS M. Chertow, MD, MPH; for the PICARD Study Group Secondary retrospective analysis from the Project to Improve Care in Acute Renal Disease (PICARD) database Population: 552 (64%) critically ill patients with AKI (defined as BUN>40 mg/dL, sCr>2 mg/dL or sustained rise >1 mg/dL above baseline. Intervention/Exposure: Diuretic use at any time in 7 days following nephrology consultation. Outcome: Death, non-recovery Mehta et al JAMA 2002
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Diuretics, Mortality, and Nonrecovery of Renal Function in Acute Renal FailureRavindra L. Mehta, MD; Maria T. Pascual, RN, MPH; Sharon Soroko, MS M. Chertow, MD, MPH; for the PICARD Study Group
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Table 1. Baseline Patient Characteristics on First Day of Nephrology Consultation*. Mehta, R. L. et al. JAMA 2002;288:2547-2553
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Figure 2. Time to Death or Dialysis From Day of Consultation in Intensive Care Unit Groups are stratified by day 1 status. Mehta, R. L. et al. JAMA 2002;288:2547-2553
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Figure 1. Time Trends in Mean Serum Creatinine Levels, Mean Blood Urea Nitrogen Levels, and Median Urine Output Among the 416 Patients Who Survived for at Least 7 Days After Nephrology Consultation in the Intensive Care Unit (ICU) Groups are stratified by day 1 status: no diuretics vs diuretic therapy with response. Mehta, R. L. et al. JAMA 2002;288:2547-2553
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Table 2. Effect of Diuretics on Mortality and Nonrecovery of Renal Function Compared With No Diuretic Use*. Mehta, R. L. et al. JAMA 2002;288:2547-2553 Conclusion: The use of diuretics in critically ill patients with acute renal failure was associated with an increased risk of death and nonrecovery of renal function.
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Secondary analysis of the Beginning and Ending Support Therapy (BEST) for the Kidney database 1. Population: 1,731 critically ill patients with AKI (defined by: need for RRT; BUN>86 mg/ dL, K>6.5 mmol/L; oliguria <200mL/12hr; anuria) 2. Intervention/Exposure: Diuretic use after study enrolment 3. Outcome: In-hospital death Diuretics and mortality in acute renal failure . Uchino, Shigehiko; Doig, Gordon; Bellomo, Rinaldo; Morimatsu, Hiroshi; Morgera, Stanislao; Schetz, Miet; Tan, Ian; Bouman, Catherine; Macedo, Ettiene; Gibney, Noel; Tolwani, Ashita; Ronco, Claudio; Kellum, John Beginning and Ending Support Therapy for the Kidney (B.E.S.T. Kidney) Investigator
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Diuretics and mortality in acute renal failure .Uchino, Shigehiko; Doig, Gordon; Bellomo, Rinaldo; Morimatsu, Hiroshi; Morgera, Stanislao; Schetz, Miet; Tan, Ian; Bouman, Catherine; Macedo, Ettiene; Gibney, Noel; Tolwani, Ashita; Ronco, Claudio; Kellum, JohnBeginning and Ending Support Therapy for the Kidney (B.E.S.T. Kidney) Investigator
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© 2004 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins. Published by Lippincott Williams & Wilkins, Inc. Diuretics and mortality in acute renal failure *. Uchino, Shigehiko; Doig, Gordon; Bellomo, Rinaldo; Morimatsu, Hiroshi; Morgera, Stanislao; Schetz, Miet; Tan, Ian; Bouman, Catherine; Macedo, Ettiene; Gibney, Noel; Tolwani, Ashita; Ronco, Claudio; Kellum, John Critical Care Medicine. 32(8):1669-1677, August 2004. DOI: 10.1097/01.CCM.0000132892.51063.2F
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© 2004 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins. Published by Lippincott Williams & Wilkins, Inc. . Diuretics and mortality in acute renal failure *. Uchino, Shigehiko; Doig, Gordon; Bellomo, Rinaldo; Morimatsu, Hiroshi; Morgera, Stanislao; Schetz, Miet; Tan, Ian; Bouman, Catherine; Macedo, Ettiene; Gibney, Noel; Tolwani, Ashita; Ronco, Claudio; Kellum, John Critical Care Medicine. 32(8):1669-1677, August 2004. DOI: 10.1097/01.CCM.0000132892.51063.2F Table 2. Diagnostic group at intensive care unit admission for patients with acute renal failure
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© 2004 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins. Published by Lippincott Williams & Wilkins, Inc. . Diuretics and mortality in acute renal failure *. Uchino, Shigehiko; Doig, Gordon; Bellomo, Rinaldo; Morimatsu, Hiroshi; Morgera, Stanislao; Schetz, Miet; Tan, Ian; Bouman, Catherine; Macedo, Ettiene; Gibney, Noel; Tolwani, Ashita; Ronco, Claudio; Kellum, John Critical Care Medicine. 32(8):1669-1677, August 2004. DOI: 10.1097/01.CCM.0000132892.51063.2F Table 3. Physiologic and laboratory variables for patients with acute renal failure
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Diuretics and mortality in acute renal failure .Uchino, Shigehiko; Doig, Gordon; Bellomo, Rinaldo; Morimatsu, Hiroshi; Morgera, Stanislao; Schetz, Miet; Tan, Ian; Bouman, Catherine; Macedo, Ettiene; Gibney, Noel; Tolwani, Ashita; Ronco, Claudio; Kellum, JohnBeginning and Ending Support Therapy for the Kidney (B.E.S.T. Kidney) Investigator
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PICARD/ BEST Studies Caveats to these studies: 1. Observational → Confounding 2. Selection/information bias 3. Severe/advanced AKI at inclusion (sCr>3.5) 4. No data on specifics of fluid resuscitation 5. No data on fluid overload/ accumulation 6. No data on timing of diuretic use
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The efficacy of loop diuretics in acute renal failure: Assessment using Bayesian evidence synthesis techniquesSampath, Sriram MD (Gen Med); Moran, John L. FRACP, FJFICM, MD; Graham, Petra L. PhD; Rockliff, Sue BA, Grad Dip Lib; Bersten, Andrew D. MD, FANZCA, FJFICM; Abrams, Keith R. PhD Data Source: Randomized controlled trials or nonrandomized studies, 1966 to January 2007. Study Selection: Studies with assessable predefined end points, exclusive of those pertaining to acute renal failure prophylaxis or chronic renal failure. Data Extraction: Data extraction was performed jointly by the first two authors; independent study assessment was via standard checklist, unblinded. Data Synthesis: The primary outcome was mortality; secondary outcomes were time to renal function normalization and total number of dialyses
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© 2007 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins. Published by Lippincott Williams & Wilkins, Inc. The efficacy of loop diuretics in acute renal failure: Assessment using Bayesian evidence synthesis techniques. Sampath, Sriram; Moran, John; FRACP, FJFICM; Graham, Petra; Rockliff, Sue; BA, Grad; Bersten, Andrew; MD, FANZCA; Abrams, Keith Critical Care Medicine. 35(11):2516-2524, November 2007. DOI: 10.1097/01.CCM.0000284503.88148.6F Figure 4. Forest plot showing effect of randomized and nonrandomized studies on dialysis rate, as incidence rate ratio. Small solid squares, study estimates; vertically capped horizontal lines, 95% credible intervals (CI); vertical lines within vertically capped diamond-shaped boxes, subgroup and overall point estimates and 95% CI; vertical straight line, the null effect.
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The efficacy of loop diuretics in acute renal failure: Assessment using Bayesian evidence synthesis techniques. Sampath, Sriram; Moran, John; FRACP, FJFICM; Graham, Petra; Rockliff, Sue; BA, Grad; Bersten, Andrew; MD, FANZCA; Abrams, Keith Critical Care Medicine. 35(11):2516-2524, November 2007. DOI: 10.1097/01.CCM.0000284503.88148.6F Table 1. Characteristics of studies included for meta-analysis
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The efficacy of loop diuretics in acute renal failure: Assessment using Bayesian evidence synthesis techniques. Sampath, Sriram; Moran, John; FRACP, FJFICM; Graham, Petra; Rockliff, Sue; BA, Grad; Bersten, Andrew; MD, FANZCA; Abrams, Keith Critical Care Medicine. 35(11):2516-2524, November 2007. DOI: 10.1097/01.CCM.0000284503.88148.6F
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The efficacy of loop diuretics in acute renal failure: Assessment using Bayesian evidence synthesis techniques. Sampath, Sriram; Moran, John; FRACP, FJFICM; Graham, Petra; Rockliff, Sue; BA, Grad; Bersten, Andrew; MD, FANZCA; Abrams, Keith Critical Care Medicine. 35(11):2516-2524, November 2007. DOI: 10.1097/01.CCM.0000284503.88148.6F Figure 1. Forest plot showing effect of randomized and nonrandomized studies on mortality treatment effect as risk ratio. Small solid squares, study estimates; vertically capped horizontal lines, 95% credible intervals (CI); vertical lines within vertically capped diamond-shaped boxes, subgroup and overall point estimates and 95% CI; vertical straight line, the null effect.
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The efficacy of loop diuretics in acute renal failure: Assessment using Bayesian evidence synthesis techniques. Sampath, Sriram; Moran, John; FRACP, FJFICM; Graham, Petra; Rockliff, Sue; BA, Grad; Bersten, Andrew; MD, FANZCA; Abrams, Keith Critical Care Medicine. 35(11):2516-2524, November 2007. DOI: 10.1097/01.CCM.0000284503.88148.6F Figure 2. Forest plot showing effect of randomized and nonrandomized studies on time taken to normalize creatinine/urea, as mean difference (days). Small solid squares, study estimates; vertically capped horizontal lines, 95% credible intervals (CI); vertical lines within vertically capped diamond-shaped boxes, subgroup and overall point estimates and 95% CI; vertical straight line, the null effect.
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The efficacy of loop diuretics in acute renal failure: Assessment using Bayesian evidence synthesis techniques Conclusion: The use of loop diuretics was found to significantly decrease the oliguric period by a mean of 7.7 days
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Why Diuretics…. Fluid dilemma in acquired AKI. Reno – protection Ongoing trial Atrial Natriuretic peptide Final word
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The Effect of Loop Diuretics on Severity and Outcome of Acute Kidney InjuryClinicalTrials.gov Identifier: NCT01275729 Sponsor: University of Chicago Inclusion Criteria: 18 yrs or older increase in serum creatinine of 0.3 mg/dl within 48 hours or an increase of greater than or equal to 150% from baselinie or sustained oliguria (UOP < 0.5 cc/kg/hr for 6 hours with the last 48hours) written informed consentpatients with an indwelling bladder catheter Exclusion Criteria: Voluntary refusal Patients with advanced chronic kideny disease - as defined by a baseline GFR < 30 ml/min (MDRD) history of renal transplant Pregnant patients Allergy / Sensitivity to Loop diuretics (furosemide) Pre-renal AKI defined by a FENa of < 1% and no urinary casts under-resuscitated per the treating clinical teamactive bleed Post renal AKI evidence of hydro-ureter clincal scenario wherein obstruction is considered a likely possibility Estimated Enrollment: 150 Study Start Date: December 2010 Estimated Study Completion Date: December 2015 Estimated Primary Completion Date: December 2012 (Final data collection date for primary outcome measure) Study Type: Interventional Study Design: Non randomized Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Diagnostic Condition: AKI Intervention: Furosemide(1mg/kg (naïve), 1.5mg/kg (non- naïve)
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Why Diuretics…. Fluid dilemma in acquired AKI. Reno – protectionOngoing trial Atrial Natriuretic peptide Final word
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Atrial Natriuretic Peptide
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Natriuretic peptide (NP) family ANP : -atrial natriuretic peptide (28 a.a.) -ANP : dimmeric form of human ANP N-terminal proANP (98 a.a.) BNP : brain natriuretic peptide (32 a.a.) N-terminal proBNP (76 a.a.) CNP : C-type natriuretic peptide (22 and 53 a.a.)
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Fig. Schematic representation of the ANP and BNP precursors with sequence numbering defining low-molecular-mass forms, N-terminal forms and high-molecular-mass precursors
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Amino Acid Sequences of the Three Human Natriuretic Peptides
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-atrial natriuretic peptide(ANP) Prohormone (Pro-ANP) in cardiac tissue is cleaved into two fragments : N-terminal fragment (ANP 1-98) C-terminal 28a.a. peptide (ANP 99-126) mRNA has been found in many tissues but is most abundant in the atria of the heart Urodilatin (ANP 95-126)
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Action of Atrial Natriuretic Peptide at Target Cells
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Physiology ANP and BNP concentrations increase in response to volume expansion and pressure overload of the heart natriuretic-peptide family counterbalance the effects of the renin-angiotensin-aldosterone system
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Physiology ANP and BNP have been shown to be physiological antagonists of the effects of (1) angiotensin II on vascular tone (2) aldosterone secretion (3) renal-tubule sodium reabsorption (4) vascular-cell growth
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Identification of LV hypertrophy in hypertension Recognition of obstructive hypertrophic cardiomyopathy Detection of LV diastolic dysfunction Screening for mild heart failure Evaluation of LV systolic dysfunction Assessment of severity of congestive heart failure Monitoring of therapy in congestive heart failure Estimation of infarct size after myocardial infarction Prognostic outcome after myocardial infarction Prediction of mortality in the elderly Conditions investigated for possible uses of plasma natriuretic peptides
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Therapeutic potential ANP and BNP infusion Decrease right-atrial and pulmonary-capillary pressure renin and aldosterone concentration Increase urinary sodium and water excretion
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Atrial Natriuretic factor in Oliguric Acute Renal Failure 222 patients with oliguric acute renal failure were enrolled into a multicenter, randomized, double-blind, placebo-controlled trial. Designed to assess prospectively the safety and efficacy of ANP compared with placebo. Subjects were randomized to treatment with a 24-hour infusion of ANP (anaritide, 0.2 microgram/kg/min; synthetic form of human ANP) or placebo. Dialysis and mortality status were followed up for 60 days. The primary efficacy end point was dialysis-free survival through day 21.
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Atrial Natriuretic factor in Oliguric Acute Renal Failure
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Atrial Natriuretic factor in Oliguric Acute Renal Failure
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Atrial Natriuretic factor in Oliguric Acute Renal Failure Cause of ATN in Anaritide and placebo group
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Atrial Natriuretic factor in Oliguric Acute Renal Failure Dialysis free survival through day 21
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Atrial Natriuretic factor in Oliguric Acute Renal Failure Conclusion: Dialysis-free survival rates were 21% in the ANP group and 15% in the placebo group (P = 0.22). By day 14 of the study, 64% and 77% of the ANP and placebo groups had undergone dialysis, respectively (P = 0.054),. Although a trend was present, there was no statistically significant beneficial effect of ANP in dialysis-free survival or reduction in dialysis in these subjects with oliguric acute renal failure.
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Why Diuretics…. Fluid dilemma in acquired AKI. Reno – protection Ongoing trial Atrial Natriuretic peptide Final word
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Diuretics in the management of acute kidney injury: a multinational survey.Bagshaw SM, Delaney A, Jones D, Ronco, C Bellomo RDivision of Critical Care Medicine, University of Alberta Hospital, University of Alberta, Edmonton, Alta., Canada, Contrib Nephrol. 2007;156:236-49 BACKGROUND: To determine the practice patterns of diuretic use by clinicians. METHODS:Multinational, multicenter survey of intensive care and nephrology clinicians that utilized an 18-question self-reported questionnaire.
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Thank you Acknowledgement Dr. Showkat