Download Free Medical Scleroderma and the Kidney PowerPoint Presentation

Scleroderma and the Kidney PowerPoint Presentation

DOWNLOAD MEDICAL POWERPOINT PRESENTATION

About This Presentation

Description : This medical presentation titled "Scleroderma and the Kidney" provides us details on scleroderma, a long-lasting disease affecting skin, connective tissue, and internal organs including kidney.

Tags : Scleroderma, Kidney, Local, Systemic Disease, Renal Failure, Renal Scleroderma Crisis, Calcinosis cutis, Raynaud Phenomenon, Esophageal dysmotility, Sclerodactyly, Telangiectasia

Published on : Apr 27, 2021 | Views : 2568 | Downloads : 1

Shareable Url :

Embed Code :

Comment

Transcript

Slide 1-

Scleroderma and the Kidney David Shure
Slide 2-

DD: Renal Failure ATN Renal Scleroderma Crisis
Slide 3-

Epidemiology Prevalence: 19-75 cases per 100,000 Susceptibility Age: peak occurrence 35-65 F:M 7-12:1 Environmental Factors: infection Occupational exposure: silica dust Usually occurs w/in 4-5 yrs of SSc onset
Slide 4-

Local vs Systemic Disease
Slide 5-

Classification dcSSC: diffuse cutaneous SSc lcSSc: limited cutaneous SSC SSc sine scleroderma – internal organ involvement Environmentally induced scleroderma Overlap syndrome: ie MCTD
Slide 6-

Calcinosis cutis Raynaud Phenomenon Esophageal dysmotility Sclerodactyly Telangiectasia
Slide 7-

Pathogenesis Complex and poorly understood Immune activation Inflammatory response Vascular damage Excessive synthesis EC matrix and collagen deposition Hypothesis: interplay between early immunological events and vascular changes leading to generation of a pop of activated fibrogenic fibroblasts believed to be effector cells in disease
Slide 8-

Vascular and Endothelial Changes Appear to precede other features of SSc Vasoconstriction ET-1: significantly elevated in SSc and assoc with pulm htn, may initiate fibrosis Superoxide anions: released from endothelium neutralize NO Defective vasculogenesis: fewer circulating endothelial ell precursors ie CD34+, CD133+ and VEGF type 2 Pts with SSc have incr in endothelial cell surface expression of adhesion molecules and elevation in circulating levels of their soluble forms. Cytokine induced upregulation of adhesion molecules ie ICAM-1, VCAM-1, ELAM-1
Slide 9-

Autoantibodies 75% pts with SSc have circulating autoantibodies Topoisomerase I (anti-scl 70) anti-topoisomerase antibodies highly specific for SSc, and correlate with greater risk for ILD and more extensive skin involvement Centromere antigens (12-44%) Anticentromere antibodies assoc with limited cutaneous involvement
Slide 10-

Fibrosis Fibrosis gradually replaces vascular inflammatory phase and ultimately disrupts architecture of affected tissue TGF-b CTGF PDGF
Slide 11-

TGF b Main Cell Source: macrophages, fibroblasts, T/B cells, platelets, endothelial cells Pathogenic relevance: Induces proliferation fibroblasts and production CTGF and endothirlin-1 Stimulates synthesis collagen, fibronectin Inhibits EC matrix degradation by reduced synthesis of MMP and induction of TIMP-1 Effect in SCL Increased levels in skin Elevated expression/ phosphorylation of smad2,3 effectors of TGF b signaling pathway
Slide 12-

Blobe G et al. N Engl J Med 2000;342:1350-1358 Mechanism of Signal Transduction Mediated by Transforming Growth Factor {beta} (TGF-{beta})
Slide 13-

CTGF Cell source: fibroblasts, endothelial cells, smooth muscle cells Pathogenic relevance: induced by TGFb, IL-4, and VEGF Induces proliferation and chemotaxis of fibroblasts and stimulates production of EC matrix Effect in SCL Elevated levels in serum Incr gene expression in skin and in fibroblasts
Slide 14-

PDGF Cell source: platelets, macrophages, endothelial cells, fibroblasts Pathogenic Relevance: Mitogen and chemoattractant for fibroblasts Induces syntehsis of collagen, fibronectin, proteoglycans, Stimulates secretion of TGF b type I, MCP-1, IL-6 Effect in SCL Elevated expression PDGN in skin Incr levels in BAL
Slide 15-

ppt slide no 15 content not found
Slide 16-

Tan F. N Engl J Med 2006;354:2709-2711 Selective Up-Regulation of PDGFR by Fibroblasts in Scleroderma
Slide 17-

SRC: Diagnosis New/abrupt onset BP >150/85 Progressive/sudden rise in creat Additional findings MAHA and thrombocytopenia Acute retinal changes of malignant HTN New onset proteinuria/ hematuria Urine sediment is bland with limited but incr protein MAHA/TMA Characteristic changes on renal bx
Slide 18-

Renal Biopsy Subintimal Fibrin Deposition – Interlobular artery Muscular Renal Artery – Onion Skin thickening with complete obliteration of vascular lumen
Slide 19-

Fibrin Deposition
Slide 20-

Prevention/Treatment Prevention: avoidance glucocorticoids If left untreated, SRC can progress to ESRD over 1-2 months and death usually within 1 yr Treatment: Mainstay prompt control HTN, return to baseline bp in 72 hrs Optimal anti-HTN is ACE-I ie captopril Captopril? Advantage = rapid onset and short DOA allowing for more frequent titration Also follow: plt count, LDH, Hb, haptoglobin, LDH for resolution of intravascular hemolysis Indefinite continuation of ACE for bp control
Slide 21-

ACE Inhibitors Retrospective & case-control studies show no efficacy in prevention of SRC Prospective cohort study- treated vs. untreated: treated w/↑ recovery of renal fxn & ↑ survival at 1 yr (76% vs 15%)
Slide 22-

Long-term Outcomes of Scleroderma Reanl Crisis Steen V, et al, Annals of Int Med, 2000 Prospective observational cohort w5-10 yr f/u 145 pts with SRC who received continuous ACE-I, and 662 pts with SCL who did not have renal crisis Results: At time of renal crisis, 75% pts had SCL sxs for <4 yrs 61 % pts with SRC had good outcomes (55 received no HD, 34 received temp HD). Only 4% of later group progressed to ESRD >1/2 of pts who began HD could dc it 3 to 18 mths later Survival of pts in good outcome group was similar to pts with diffuse SCL without renal crisis
Slide 23-

ppt slide no 23 content not found
Slide 24-

Autologous non-myeloablative hematopoietic stem cell transplantation in pts with systemic sclerosis Burt RK, et al 2007 Bone Marrow Transplantation Phase I non-myeloablative autologous HSCT 10 pts with SSc and poor prognostic features PBCS mobilized with CY and G-CSF PBSC graft re-infused after tx with non-myeloablative conditioning regimen statistically significant improvement of modified Rodnan skin score, however cardiac, pulmonary function, and creat remained unchanged F/U: 25 mths, overall and progression free survival rates are 90 and 70% Concl: Autologous HSCT with non-myeloablative conditioning regimen may lead to improved skin flexibility similar to a myeloablative TBI , but without the toxicity and risks