Primary Glomerular Diseases Part 1

• Primary Glomerular Diseases are discussed in part 1.

Objectives

• Gain familiarity with common clinical disorders related to nephritic syndrome.
• Describe the etiology, injury mechanisms, clinical course, and prognosis in acute post-infectious glomerulonephritis.
• Characterize the pathology in acute post-infectious glomerulonephritis using light microscopy, immunofluorescence, and electron microscopy.
• Describe the etiology, injury mechanisms, clinical course, and prognosis of rapidly progressive glomerulonephritis.
• Describe the pathology of rapidly progressive glomerulonephritis via light microscopy, immunofluorescence, and electron microscopy.
• The Nephrotic Syndrome is to be defined.

Glomerular Diseases and Syndromes

• Primary Glomerulopathies include acute diffuse proliferative glomerulonephritis (post streptococcal and non-post streptococcal), rapidly progressive (crescentic) glomerulonephritis, membranous glomerulopathy, minimal change disease, focal segmental glomerulosclerosis, membranoproliferative glomerulonephritis, IgA nephropathy, and chronic glomerulonephritis.

Glomerular Syndromes

• Acute nephritic syndrome presents as hematuria, azotemia, variable proteinuria, oliguria, edema, and hypertension.
• Rapidly progressive glomerulonephritis involves acute nephritis, proteinuria, and acute renal failure resulting in 50% or greater loss of renal function within three months.
• Nephrotic syndrome presents as more than 3.5 grams of proteinuria, hypoalbuminemia, hyperlipidemia, and lipiduria.
• Chronic renal failure involves azotemia progressing to uremia over years.
• Asymptomatic hematuria or proteinuria is characterized by glomerular hematuria and subnephrotic proteinuria.
• Acute nephritic syndrome is a primary characteristic in patients with acute post-infectious glomerulonephritis.
• It is also a significant component of rapidly progressive (crescentic) glomerulonephritis.

Acute Post-Infectious Glomerulonephritis

• The etiology may involve infectious agents that cause deposition of immune complexes in the glomerulus.
• Post-streptococcal glomerulonephritis primarily affects children aged 6 to 10 years.
• This condition usually appears 1-4 weeks after a pharynx or skin AB-hemolytic streptococci infection.
• Clinical features manifest as nephritic syndrome, including microscopic or macroscopic hematuria, edema, hypertension, and oliguria.
• Patients typically exhibit elevated serum anti-streptolysin O(ASO) titers and low serum C3 levels.
• The acute clinical episode is typically self-limited; depressed complement levels return to normal within six weeks.
• Most children recover, but a small percentage rapidly progress to renal failure.
• Approximately 40% of adults develop chronic renal failure.
• Light microscopy reveals diffuse mesangial and endocapillary proliferation with infiltration of neutrophils and mononuclear inflammatory cells.
• Immunofluorescence microscopy reveals granular deposits of C3 and IgG along the capillary loops and in the mesangium.
• Electron microscopy shows subepithelial "hump-like" and mesangial deposits.
• Capillary loop deposits become less frequent after a few weeks, while mesangial deposits persist for a longer period.

Rapidly Progressive Glomerulonephritis

• Clinical features may be mediated by anti-glomerular basement membrane antibody (type I), immune-complexes (type II), or exhibit Pauci-immune/ANCA association (type III).
• Patients with nephritis, secondary to anti-glomerular basement membrane disease, may also experience pulmonary hemorrhage (Goodpasture's disease).
• In Anti-GBM glomerulonephritis, etiology involves the development of autoantibodies against the non-collagenous C-terminal domain of alpha 3 (IV) collagen.
• The immune response is secondary to a conformational change in the alpha 3 (IV) collagen, although the triggers for this change are not completely known.
• RPGN is defined clinically as glomerulonephritis that results in the loss of 50% or more of renal function within three months.
• Characteristically, crescents are present in at least 30-50% of glomeruli.
• Clinical Features:
  • If untreated, the aggressive course leads to chronic renal failure within weeks or months.
  • Prognosis depends on the number of crescents present in the biopsy; a more diffuse crescentic process indicates a worse prognosis.
  • Cases associated with infection tend to have slightly less unfavorable prognoses.
• Light microscopy reveals a disruption of the glomerular capillary loops with extravasation of blood and cells into Bowman's space, forming a cellular crescent.
• ImmunoFluorescence Microscopy:
  • Shows bright linear staining of GBM for IgG in anti-glomerular basement membrane-mediated disease.
  • Negative in ANCA-Associated nephritis.
  • Other immune complexes may appear in immune-complex-mediated disease.
• Immunosuppressive therapies produce beneficial effects if initiated early in the disease.
• Plasmapheresis has beneficial effects in anti-GBM antibody disease cases.