GLOMERULAR DISEASES

1. GLOMERULAR DISEASES Antonio V. Cayco, MD Section of Nephrology

2. OBJECTIVES Introduction Approach to Glomerular Diseases • Syndrome Diagnosis • Clinical Diagnosis • Histologic Diagnosis • Clinicopathologic Correlation General Principles of Management

3. CAUSES OF ESRD IN THE PHILIPPINES: Renal Registry Data, PSN, 2003

4. Afferent arteriole Parietal EC Capillary loop Endothelium Macula densa Mesangium JG cells Urinary space Visceral EC Efferent arteriole

5. Mesangium Normal Glomerulus

6. Normal glomerulus

7. PATHOLOGY Definition of Terms • Glomerulopathy vs. Glomerulonephritis • Primary vs. Secondary • Diffuse vs. Focal • Global vs. Segmental • Fibrosis vs. Sclerosis • Membranous vs. Proliferative • Endocapillary vs. Extracapillary

8. Fibrosis – increase in the deposition of collagen fibers Sclerosis – increase in the amount of homo-genous nonfibrillar extracellular material Sclerosis

9. Segmental – lesion involves < 50% of the glomerulus Sclerosis Global – lesion involves > 50% of the glomerulus Sclerosis

10. Diffuse Global Glomerulosclerosis Focal – lesion seen in less than 50% of glomeruli Diffuse – lesion seen in more than 50% of glomeruli

11. Mesangial cells Normal glomerulus Mesangial cells Proliferation – increase in the glomerular cell number Mesangial proliferativeGN

12. Endocapillary proliferation Extracapillary proliferation

13. Normal glomerulus Membranous – expansion and thickening of the glomerular basement membrane (GBM) by immune deposits

14. Primary Mechanisms of Glomerular Injury

15. Primary Mechanisms of Glomerular Injury

16. Immunologic Glomerular Injury Humoral Antibody-Mediated Injury • Autoantibodies against intrinsic antigens (example: Goodpasture’s syndrome) • Autoantibodies against extrinsic “trapped antigens (example: Postinfectious GN) • Trapping of circulating immune complexes (example: Cryoglobulinemic GN) Cellular Mediated Injury

18. GN Loss of nephrons Glomerular hyperfiltration Glomerular HTN Non-selective prtoteinuria Glomerular sclerosis Tubulointerstitial inflammation Ischemia Tubulointerstitial atrophy/fibrosis Two Final Common Pathways in Glomerular Injury

19. OBJECTIVES Introduction Approach to Glomerular Diseases • Syndrome Diagnosis • Clinical Diagnosis • Histologic Diagnosis • Clinicopathologic Correlation General Principles of Management

20. Approach to Glomerular Diseases • Syndrome Diagnosis • Clinical Diagnosis • Histologic Diagnosis • Clinicopathologic Correlation

21. Syndrome Diagnosis History Physical Examination Ancillary Laboratory Tests • Chemistry • Serology • Urinalysis

22. Syndromes inGlomerular Diseases

23. Syndromes inGlomerular Diseases

28. Approach to Glomerular Diseases • Syndrome Diagnosis • Clinical Diagnosis • Histologic Diagnosis • Clinicopathologic Correlation

30. C-ANCA: Cytoplasmic Antineutrophil Cytoplasmic Antibodies • C-ANCA • Antibodies against • Proteinase 3 • Associated with • Wegener’s ggranulomatosis

31. P-ANCA: Perinuclear Antineutrophil Cytoplasmic Antibody • P-ANCA • Antibodies against • myeloperoxidase • Associated with a • variety of vasculitides • Non-specific for • Wegener’s granulomatosis

32. Clinical Diagnosis

33. Clinical Diagnosis

34. Approach to Glomerular Diseases • Syndrome Diagnosis • Clinical Diagnosis • Histologic Diagnosis • Clinicopathologic Correlation

35. Indications for a Kidney Biopsy • Unexplained ARF • Unexplained RPRF • Adult nephrotic syndrome w/out systemic disease • Proteinuria < 2 g/d w/ deterioration of renal function • Proteinuria > 2 g/d • DM w/ acute onset of proteinuria and renal failure • DM with proteinuria but w/out retinopathy • Selected cases of Lupus nephritis

36. Crescent

37. Membrane thickening Mesangial expansion Cellular proliferation MPGN

38. Deposits Splitting MPGN

40. Normal glomerulus

41. Fusion of foot processes Minimal Change Disease

42. Sclerosis FSGS

43. Foot process fusion FSGS

44. Membranous Nephropathy

45. Deposits Membranous GN

46. Mesangial proliferation

47. Mesangial IgA Deposits

48. IgA Nephritis

49. Approach to Glomerular Diseases • Syndrome Diagnosis • Clinical Diagnosis • Histologic Diagnosis • Clinicopathologic Correlation

50. Clinicopathologic Correlation * SLE, Postinfectious GN, IE, Cryoglobulinemia ** Wegener’s granulomatosis, Microscopic PAN