DOM Morning Report: Glomerulonephritis

1. DOM Morning Report:Glomerulonephritis Week of December 8, 2008

2. Objectives To be able to list the characteristics of the nephritic syndrome To know the definition of rapidly progressive glomerulonephritis To understand the clinical presentation of diseases that cause glomerulonephritis

3. The Nephritic Syndrome Characteristics Hypertension Edema Oliguria Azotemia Hematuria Nephrotic syndrome Proteinuria Hypoalbuminemia Edema Hyperlipidemia Lipiduria

4. The Nephritic Syndrome Influx of leukocytes Neutrophils Mononuclear phagocytes Lesions Proliferative/necrotizing ? Bowman�s capsule Crescenteric (> 50%) ? Scarring of glomerulus (glomerulosclerosis) Scarring/fibrosis of tubulointerstitial compartment (occurs within days to weeks of onset)

5. Rapidly Progressive GN Increase in creatinine over days to weeks = 50% loss of kidney function

6. Diseases IgA Nephropathy (Berger�s Disease) Poststreptococcal Glomerulonephritis Lupus Nephritis Anti-GBM Antibody Disease Systemic Vasculitis

7. Natural History Many progress Glomerular scarring Decline in kidney function Third leading cause of ESRD in US Chronic Glomerular scarring Interstitial fibrosis Arteriosclerosis

8. IgA Nephropathy Clinical presentation 30-40% present w/ macroscopic hematuria Pharyngitis or gastroenteritis Episodic with resolution Infrequent disease recurrence Excellent long term prognosis 40% have persistent hematuria/proteinuria HTN Progressive renal failure Remission uncommon

9. IgA Nephropathy Long-term prognosis 1/3 achieve clinical remission with resolution of� Hematuria Proteinuria 1/3 develop more benign disease Urinary protein excretion < 1g/24hrs 1/3 have progressive decline in renal function

10. IgA Nephropathy Positive prognostic indicators Normal renal function Normal BP Urinary protein excretion < 1g/24hrs Treatment Good prognostic indicators ACEI and/or ARB Progressive disease Pulse corticosteroids

11. Poststreptococcal GN Begins suddenly Edema Hematuria Renal insufficiency 2-3 weeks after streptococcal� Pharyngitis Cellulitis

12. Poststreptococcal GN Serologic findings Low C3 and low normal C4 Antistreptococcal antibodies ? antistreptolysin O titers in ~ 70% of affected pts ? anti-DNAse B antibodies in ~ 90% of affected pts Rapid resolution Diuresis begins within one week Kidney function back to baseline in 3-4 weeks

13. Low Complements Membranoproliferative GN Post-infectious GN Subacute bacterial endocarditis Cryoglobulinemia Lupus nephritis

14. Lupus Nephritis Clinical presentation Mirrors pattern of histology Class I or II Hematuria Proteinuria Class III or IV Hematuria Proteinuria Erythrocyte casts Renal insufficiency

15. Lupus Nephritis Prognostic factors Presence of renal insufficiency at time of biopsy Severity of renal histology Presence of crescents Presence of interstitial fibrosis indicating scarring Black race

16. Lupus Nephritis Treatment Determined by disease severity NIH study with IV cyclophosphamide Monthly x 6 then every 3 months for up to 2 years Provides long-term improvement in renal function Substantial side effects Major infection Mutagenesis Premature ovarian failure

17. Lupus Nephritis Mycophenolate mofetil Equivalent as induction therapy in diffuse disease Recurrence more common

18. Anti-GBM Antibody Disease Young men ? kidney and lung Older women ? only kidney Most commonly rapidly progressive GN Prognostic factors Serum creatinine level at time of diagnosis Promptness of therapy

19. Anti-GBM Antibody Disease Treatment Pulmonary hemorrhage Emergent plasmapheresis to remove offending Ab Induction of remission Corticosteroids Cyclophosphamide ~ 30% have ANCA vasculitis Tend to relapse

20. Systemic Vasculitis Clinical presentation Associated with type of vessel involved Large and middle sized vessels Ischemic disease of supported tissues Small vessels ANCA-associated Present with hematuria and proteinuria Symptoms Myalgias Migratory polyarthropathy Weight loss

21. Systemic Vasculitis Frequently present as rapidly progressive GN Treatment ANCA-associated small vessel vasculitis Methylprednisolone taper over 16 weeks IV or oral cyclophosphamide for 3-6 months Plasmapheresis Pulmonary hemorrhage Dialysis patients at onset

22. Systemic Vasculitis Based on likelihood of relapse (PR3 ANCA and upper/lower respiratory tract dz) High Azathioprine Mycophenolate mofetil Low Discontinuation of therapy Very close follow-up

23. Objectives Revisited Characteristics Hypertension Edema Oliguria Azotemia Hematuria Nephrotic syndrome Proteinuria Hypoalbuminemia Edema Hyperlipidemia Lipiduria

24. Objectives Revisited Rapidly progressive glomerulonephritis Increase in creatinine over days to weeks = 50% loss of kidney function Clinical presentation IgA nephropathy Macrohematuria during pharyngitis/gastroenteritis Streptococcal glomerulonephritis Rapid onset 2-3 weeks after pharyngitis/cellulitis

25. Objectives Revisited Lupus nephritis Proteinuria Anti-GBM antibody disease Rapidly progressive GN +/- lung involvement Systemic vasculitis Myalgias, arthralgias, weight loss