Snapshot A 26-year-old man presents with hematuria, periorbital edema, and jaundice. He has a medical history of opioid use disorder with prior hospitalizations for heroin overdose. He is on methadone but is non-adherent. His blood pressure is 155/102 mmHg. Physical examination is significant for scleral icterus, hepatomegaly, and palpable purpura. Serology shows decreased C3 and C4 levels and elevated anti-hepatitis C antibodies. Urinalysis demostrates dysmorphic red blood cells and red blood cell casts. (Membranoproliferative glomerulonephritis) Introduction Clinical definition renal disease secondary to an inflammatory process injuring the glomerulus this results in damage involving the basement membrane capillary endothelium mesangium Presentation symptoms hypertension hematuria oliguria headache physical exam edema can be peripheral and/or periorbital Diagnosis studies complete blood cell count anemia may be noted azotemia complement levels C3, C4, and CH50 should be obtained urinalysis dysmorphic red blood cells (RBCs) suggests hematuria is of glomerular origin RBC casts subnephrotic range proteinuria (< 3.5 g/day) if the nephritic syndrome is severe enough it can lead to nephrotic range proteinuria (> 3.5 g/day) renal biopsy may be necessary to arrive to a definitive diagnosis and to determine prognosis Nephritic Syndrome Type Pathophysiology Renal Biopsy Diagnostic Studies and Treatment Acute poststreptococcal glomerulonephritis Glomerulonephritis secondary to nephritogenic strains of streptococcus - type III hypersensitivity reaction Light microscopy - glomerular hypercellularity e.g., polymorphonuclear leukocytes Immunofluoresence - diffuse granular pattern on glomerular capillary and mesangium deposition of IgG, IgM, and C3 Electron microscopy - electron-dense, glomerular subepithelial immune-complex deposits ("humps") Streptococcus titers and serologies are positive e.g., ASO levels ↓ serum C3 levels Typically self-resolves Rapidly progressive glomerulonephritis Goodpasture syndrome - type II hypersensitivity - anti-GBM antibodies against α3-chain of collagen type IV - antibodies to the alveolar basement membrane result in hemoptysis and lung disease Pauci-immune processes - granulomatosis with polyangiitis - microscopic polyangiitis Light microscopy and immunofluoresence - crescent-shaped deposition of fibrin, C3b, glomerular parietal cells, monocytes, and macrophages Granulomatosis with polyangiitis - PR3-ANCA/c-ANCA Microscopic polyangiitis - MPO-ANCA/p-ANCA Corticosteroids and cyclophosphamide IgA nephropathy (Berger disease) IgA immune-complex deposition in glomerular mesangial cells that results in its proliferation - patients present with hematuria and upper respiratory tract or gastrointenstinal infection Light microscopy - mesangial proliferation Immunofluoresence - IgA immune-complex deposition in the mesangium ACE inhibitor or ARB for proteinuria and hypertension Alport syndrome Collagen type IV mutation that results in an abnormal basement membrane - more commonly an X-linked genetic disorder characterized by: renal involvement ocular involvement sensorineural hearing loss Electron microscopy - glomerular basement membrane lamellation No curative treatment Membranoproliferative glomerulonephritis (MPGN) Immune-complex and/or complement protein deposition in the mesangium and subendothelium of the capillaries - this results in proliferation of the mesangium and remodeling of the capillary wall - may be secondary to hepatitis C virus hepatitis B virus C3 nephritic factor MPGN type II Can also present as a nephrotic syndrome Light microscopy - mesangial proliferation and thickening of the capillary wall Immunofluoresence - "tram-track" appearance ↓ serum C3 and C4 levels - Treat underlying disease in secondary causes e.g., control of hepatitis C virus infection