Acute Poststreptococcal Glomerulonephritis

1. Acute PoststreptococcalGlomerulonephritis MR 7/27/09 J. Chen

2. Outline • Background • Pathophysiology • Histologic Findings • Clinical • History • Physical • Lab • Differential Diagnosis • Treatment • Follow Up

3. Background • Glomerulonephritis-various renal diseases in which inflammation of the glomerulus, manifested by proliferation of cellular elements, is secondary to an immunologic mechanism • Most associated with postinfectious state • 4-12yr with peak 5-6years • Male:Female 1.7-2:1 • Prognosis is good

5. Winter and Spring-respiratory infection • Latency period 10 days for pharyngitis • Summer and Fall-associated with pyoderma • Latent period difficult to determine

6. Pathophysiology • Not fully understood • Immune Complexes localize on glomerular capillary wall and activate the complement system (Zymogen and GAPDH) • Activation of complement cascade generates C5a and platelet derived inflammatory mediators • Various cytokines initiate an inflammatory response manifested by cellular proliferation and edema of glomerular tuft

7. Membrane attack complex (C4bC2a) (C4 + C2) Recruitment of PMNs C3b C3 C3a Opsonization, phagocytosis C3 convertase Alternative pathway Anaphylaxis, Chemotaxis Microbial surfaces (polysaccharides) Complement Abnormalities Ab-Ag complexes C3 convertase Classical pathway

8. Measurable reduction in volume of glomerular filtrate • Decreased capacity to excrete salt and water leading to expansion of extracellular fluid volume • Responsible for edema and in part for hypertension, anemia, circulatory congestion, encephalopathy

9. Histologic Findings • Light Microscopy-Glomerular tufts enlarged and swollen

10. Immunofluorescent microscopy

11. Electron Microscopy of renal tissue • Electron-dense deposits (humps) in the subepithelial space

12. Clinical Presentation • History: latent period 7-21 days btw streptococcal infection and glomerulonephritis characteristics • Edema most frequent manifesting symptom • 85% • Abrupt onset • Periorbital area, may be generalized • Gross hematuria 30-50% • Smoky, cola, rust, tea colored • +/- oliguria • Various degree of malaise, lethargy, anorexia, fever, abdominal pain, headache

13. History Continued • Hypertensive encephalopathy-HA, vomitting, depressed sensorium, confusion, visual disturbances, aphasia, memory loss, convulsions, coma • Possible dyspnea, orthopnea, cough • Pallor

14. Physical • Edema • Systolic and Diastolic HTN to varying degree (Inc ECF, cytokines with pressor effects) • Pallor • Pulmonary rales • Bradycardia/tachycardia • Depressed sensorium

15. Lab Studies • Urine-output reduced, concentrated, acidic • Hematuria • Proteinuria • Glucosuria • RBC Casts-60-85% • Hyaline and/or cellular casts

16. Lab Studies Cont • Renal: • Elevation of BUN/Cr usually modest • Electrolytes usually normal (hyperK and met acid with significant renal impairment)

17. Labs • Streptococcal infection: • Culture from Pharynx and skin may be positive • Strep ab titers more meaningful • Measured at 2-3 wk intervals-Rise more significant

18. Labs • Hemolytic Complement • C3 decreased in 90% • C4 normal • C5 decreased • Complement levels return to normal 6-8 weeks after onset

19. Labs • Mild Anemia-parallels the degree of ECF expansion • WBC-Nl • Plts-Nl

20. Imaging • Renal US-nl to slightly enlarged kidneys • CXR-Central venous congestion • Occasionally enlarged cardiac shadow

21. Differential Diagnosis • Normal complement • HUS • IgA Nephropathy • HSP • Alport’s / TBMD • Nephrotic Syndrome Hypocomplementemia • PIGN • Bacteria (GAS, S. viridans, pneumococcus, S. aureus, S. epi, atypical mycobacterium, meningococcus, Brucella, Leptospirosis, Propionibacterium) • Viruses (VZV, EBV, CMV, rubeola) • Parasites (Toxo, Trich, Riskettsia) • Membranoproliferative GN • SLE • Cryoglobulinemia • Bacterial Endocarditis • Shunt nephritis

22. Hematuria Myoglobin Hemaglobin Bile Urate Crystals Beets Blackberry Food dye Drugs Exercise PIGN IGAN Benign Familial Glomerulonephritis MPGN HSP SLE Alport Pyelonephritis Hypercalciuria Nephrolithiasis Trauma Sickle Cell NSAIDS Renal V. Thrombosis Cystitis MeatalStenosis Urethritis Bladder tumor Menstrual contamination Diaper rash

23. Proteinuria • Nephrotic Syndromes • Acquired Glomerular Disease • MPGN • SLE • IGAN • SBE • DM • HTN • HUS • Genetic Disorders • Nail-patella syndrome • Alport syndrome • Fabry Disease • Glycogen storage disease • CF • Hurler • Gaucher Disease • Wilson Disease • SC • Leukemia • Lymphoma • Infectious • PSGN • HIV nephropathy • HEP B and C • Malaria • Syphilis • Pyelonephritis • Drugs/toxins

24. Management • Treatment mainly supportive • Hospitalization indicated if:significant HTN, Oliguria, Generalized Edema, High Cr or K • Antibiotics do not influence course of disease-however, administered to ensure eradication of disease

25. Fluid Restriction • Salt Restriction • Loop Diuretics • Antihypertensives • Limited activity • Dialysis if necessary

26. Follow Up • Prognosis usually excellent • 0.5% mortality due to pulmonary edema or pneumonia • <1% progress to CKD stage 5 • Follow-up • Must ensure that HTN controlled, Edema resolved, hematuria/ proteinuria resolved, Cr normalized • Gross hematuria resolves within 2 weeks • Complement low for 6-8 weeks • Proteinuria remains upto 6 months • Hematuria remains upto 2 years