Glomerular Diseases & Syndromes PDF Presentation

Primary Glomerular Diseases Part 1 Axel Baez Torres, M.D.  Objectives Know the most common clinical disorders associated with the nephritic syndrome Describe the etiology, mechanisms of injury, clinical course and prognosis of acute post-infectious glomerulonephri...

Primary Glomerular Diseases Part 1 Axel Baez Torres, M.D.  Objectives Know the most common clinical disorders associated with the nephritic syndrome Describe the etiology, mechanisms of injury, clinical course and prognosis of acute post-infectious glomerulonephritis Describe the pathology of acute post-infectious glomerulonephritis in terms of light microscopy, immunofluorescence and electron microscopy  Objectives Describe the etiology, mechanisms of injury, clinical course and prognosis of rapidly progressive glomerulonephritis Describe the pathology of rapidly progressive glomerulonephritis in terms of light microscopy, immunofluorescence and electron microscopy Define the Nephrotic Syndrom  Glomerular Diseases Primary Glomerulopathies – Acute diffuse proliferative glomerulonephritis Post streptococcal Non-post streptococcal – Rapidly progressive (crescentic) glomerulonephritis – Membranous glomerulopathy – Minimal change disease – Focal segmental glomerulosclerosis – Membranoproliferative glomerulonephritis – IgA nephropathy – Chronic glomerulonephritis  Glomerular Syndromes Acute nephritic Syndrome – Hematuria, azotemia, variable proteinuria, oliguria, edema, and hypertension Rapidly progressive glomerulonephritis – Acute nephritis, proteinuria, and acute renal failure accounting for 50% or greater loss of renal function within three months Nephrotic syndrome – >3.5 gm proteinuria, hypoalbuminemia, hyperlipidemia, lipiduria  Glomerular Syndromes Chronic renal failure – Azotemia → uremia progressing for years Asymptomatic hematuria or proteinuria – Glomerular hematuria; subnephrotic proteinuria  Acute Nephritic Syndrome Among the primary glomerulonephritides, the acute nephritic syndrome is characteristically present in patients with acute post-infectious glomerulonephritis and is an important component of rapidly progressive (crescentic) glomerulo- nephritis  Acute Post-Infectious Glomerulonephritis Etiology: – May be caused by a number of infectious agents with deposition of immune complexes in the glomerulus – Post-streptococcal glomerulonephritis is primarily a disease of children 6 to 10 years of age – Usually appears 1 to 4 weeks after infection of pharynx or skin (impetigo) with certain strains of group AB-hemolytic streptococci  Acute Post-Infectious Glomerulonephritis Clinical Features – Manifested by the nephritic syndrome with common initial manifestations including hematuria (microscopic or macroscopic),edema, hypertension and oliguria – Patients typically have elevated serum anti-streptolysin O(ASO) titers and low serum C3 levels  Acute Post-Infectious Glomerulonephritis Clinical Features – The acute clinical episode is usually self-limited and complement levels, which are usually depressed acutely, return to normal within 6 weeks – Most cases in children recover, but a minority may rapidly progress to renal failure – About 40% of adults go on to develop chronic renal failure  Acute Post-Infectious Glomerulonephritis Light Microscopy – The glomeruli shows diffuse mesangial proliferation and endocapillary proliferation with infiltration of neutrophils and mononuclear inflammatory cells  Acute Post-Infectious Glomerulonephritis Immunofluorescence Microscopy – Granular deposits of C3 and IgC along the capillary loops and in the masangium  Acute Post-Infectious Glomerulonephritis Electron Microscopy – Large subepithelial “hump-like” deposits as well as mesangial deposits – The capillary loop deposits become less frequent after a few weeks, but the mesangial deposits persists for a larger period  Rapidly Progressive Glomerulonephritis Clinical Features May Be: – Mediated by anti-golerular basement membrane antibody (type I) – Immune-complex mediated (type II) – Pauci-immune / ANCA – Associated (type III) – Patients with nephritis secondary to anti- glomerular basement membrane disease may also have pulmonary hemorrhage (Goodpasture’s disease)  Rapidly Progressive Glomerulonephritis Anti-GBM glomerulonephritis – Etiology: Development of autoantibody against the non-collagenous C- terminal domain of alpha 3 (IV) collagen Immune response is secondary to a conformational change in the alpha 3 (IV) collagen. The events that trigger this conformational change are unknown  Rapidly Progressive Glomerulonephritis Clinically, RPGN is defined as glomerulonephritis causing 50% or greater loss of renal function within three months. Characteristically, crescents are present in at least 30-50% of glomeruli.  Rapidly Progressive Glomerulonephritis Clinical Features – The course is aggressive, without treatment progression to chronic renal failure occurs within a few weeks or months.  Rapidly Progressive Glomerulonephritis Clinical Features – The prognosis depends on the number of crescents present in the biopsy; a more diffuse crescentic process predicts a worse prognosis. – Cases associated with infection had a slightly less unfavorable prognosis.  Rapidly Progressive Glomerulonephritis Light Microscopy – Disruption of the glomerular capillary loops with extravasation of blood and cells into Bowman’s space, forming a cellular crescent.  Rapidly Progressive Glomerulonephritis ImmunoFluorescence Microscopy – Bright linear staining of GBM for IgC in anti-glomerular basement membrane mediated disease. – Negative in ANCA-Associated nephritis – Other immune complexes present in immune-complex mediated disease  Rapidly Progressive Glomerulonephritis Treatment – Immunosuppressive therapies have had a beneficial effect if started early in the disease – Plasmapheresis has been found to have a beneficial effect in cases of anti-GBM antibody disease