Snapshot A 14-year-old boy presents with hematuria, problems with vision, and deafness. Approximately 2 weeks prior to symptom development, he recovered from a viral upper respiratory tract infection. Family history is significant for deafness and early initiation of lisinopril in his father. His temperature is 99°F (37.2°C), blood pressure is 140/90 mmHg, pulse is 75/min, and respirations are 18/min. Physical examination is signifcant for anterior lenticonus and sensorineural hearing loss. Urinalysis demonstrates dysmorphic red blood cells and red blood cell casts. (Alport syndrome) 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 Immunofluorescence diffuse granular pattern on glomerular capillary walls and mesangium deposition of IgG, IgM, and C3 Electron microscopy electron-dense, glomerular subepithelial immune-complex deposits ("humps") Streptococcus titers and serologies are positive ↓ 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 immunofluorescence crescent-shaped deposition of fibrin, C3b, glomerular parietal cells, monocytes, and macrophages Granulomatosis with polyangiitis PR3-ANCA/c-ANCA positive Microscopic polyangiitis MPO-ANCA/p-ANCA Corticosteroids and cyclophosphamide IgA nephropathy (Berger's disease) IgA immune-complex deposition in glomerular mesangial cells that results in its proliferation patients present with hematuria and upper respiratory tract or gastrointestinal infection Light microscopy mesangial proliferation Immunofluorescence 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 dominant disorder characterized by renal involvement ocular involvement sensorineural hearing loss Electron microscopy glomerular basement membrane lamellation "basket weave" appearance 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 Light microscopy mesangial proliferation and thickening of the capillary wall Immunofluorescence "tram-track" appearance ↓ serum C3 and C4 levels Treat underlying disease in secondary causes e.g., control of hepatitis C virus infection Diffuse proliferative glomerulonephritis (DPGN) > 50% of glomeruli (thus diffuse) demonstrates an inflammatory process on histology Common in patients with systemic inflammatory diseases (e.g., systemic lupus erythematosus) can be secondary to membranoproliferative glomerulonephritis Light microscopy capillary "wire-looping" Electron microscopy immune complex deposition affecting the subendothelial region maybe intramembranous Immunofluorescence granular appearance Can lead to death in patients with systemic lupus erythematosus Aggressively treat with steroids