2. Glomerular Diseases Dr. Atapour

3. Differential diagnosis and evaluation of glomerular disease

4. CLINICAL PATTERNS OF GLOMERULAR DISEASE Nephrotic Nephritic

5. Nephrotic pattern The nephrotic proteinuria that is usually above 3.5 g/day Lipiduria Edema Hyperlipidemia Some patients also have microscopic hematuria Red cell casts

6. Asymptomatic proteinuria Full-blown nephrotic syndrome

7. The bland sediment Absence of immune complex deposition in most of these disorders: – Minimal change disease – Focal segmental glomerulosclerosis – Diabetic nephropathy – Amyloidosis.

8. Lack of inflammation The serum creatinine concentration

9. Acute kidney injury in the nephrotic syndrome Concurrent acute tubular necrosis Usually in minimal change disease

10. Nephritic pattern Presence of red cells White blood cells Red cell – Dysmorphic appearance – Acanthocytes Mixed cellular casts Variable degrees of proteinuria

11. dysmorphic RBCs muddy brown casts tubular cell casts oval fat body

12. RBC cast Hyaline cast

13. Pathologic classification Light microscopy Focal Diffuse – This terminology is most often used in lupus nephritis – ANCA-positive vasculitis.

14. Limitations of this classification Same pathology and multiple causes Nonspecific nature of the histologic patterns

15. MPGN Can be a systemic immune complex disease – To infective endocarditis – Systemic lupus erythematosus – Hepatitis C virus complement

16. Membranous nephropathy Systemic lupus erythematosus Chronic hepatitis B virus infection Underlying malignancy Drugs

17. Focal segmental glomerulosclerosis Primary condition Secondary change induced by intraglomerular hypertension or healing of previous glomerular injury.

19. Nephrotic syndrome without a nephritic sediment Mild hematuria No red cell casts

20. Depend on age What do you think?

21. Less than 15 years : – Minimal change disease – Focal segmental glomerulosclerosis – Mesangial proliferative glomerulonephritis

22. 15 to 40 years : – Minimal change disease – Membranous nephropathy – Focal segmental glomerulosclerosis – Diabetic nephropathy – Preeclampsia – Postinfectious glomerulonephritis

23. Greater than 40 years: – Focal segmental glomerulosclerosis – Membranous nephropathy – Diabetic nephropathy – Minimal change disease – IgA nephropathy – Primary amyloidosis – Benign nephrosclerosis – Postinfectious glomerulonephritis

24. Mild glomerulonephritis Mild glomerulonephritis is defined as a nephritic sediment and: – Normal or near normal estimated GFR – Do not have the nephrotic syndrome

25. Less than 15 years – Mild postinfectious glomerulonephritis – IgA nephropathy – Thin basement membrane disease – Hereditary nephritis – Henoch-Schönlein purpura – Mesangial proliferative glomerulonephritis

26. 15 to 40 years IgA nephropathy Thin basement membrane disease Lupus nephritis, hereditary nephritis Mesangial proliferative glomerulonephritis

27. Greater than 40 years – IgA nephropathy

28. Moderate to severe glomerulonephritis Moderate to severe glomerulonephritis is defined as a nephritic sediment – Reduced estimated GFR – Nephrotic syndrome ±

29. Less than 15 years – Postinfectious glomerulonephritis – Membranoproliferative glomerulonephritis

30. 15 to 40 years – Postinfectious glomerulonephritis – lupus nephritis – RPGN (crescentic glomerulonephritis) – IgA nephropathy – Fibrillary glomerulonephritis – Membranoproliferative glomerulonephritis

31. Greater than 40 years : – Rapidly progressive glomerulonephritis – Vasculitis – IgA nephropathy – Fibrillary glomerulonephritis – Postinfectious glomerulonephritis

32. Effect of race

33. In black patients : – Focal segmental glomerulosclerosis (57 percent) – Membranous nephropathy (24 percent) – Minimal change disease (14 percent) – Membranoproliferative glomerulonephritis, IgA nephropathy, and immunotactoid nephropathy were each present in 1 to 2 percent.

34. In white patients: – Membranous nephropathy (36 percent), – Focal segmental glomerulosclerosis (23 percent) – Minimal change disease (20 percent) – IgA nephropathy (8 percent) – Membranoproliferative glomerulonephritis (6%) – Immunotactoid glomerulopathy (6 percent).

35. Positive family history Thin basement membrane nephropathy Hereditary nephritis (Alport syndrome) Focal segmental glomerulosclerosis are examples:

36. LABORATORY TESTING IN PATIENTS WITH SUSPECTED GLOMERULAR DISEASE serum creatinine serum albumin complete blood count Estimation of protein excretion in patients with proteinuria serologic testing for disorders that cause glomerular disease measurement of serum complement levels

37. membranous nephropathy The value of hepatitis B virus Hepatitis C virus (HCV) infection Congenital and secondary syphilis HIV infection (FSGS)

38. Chronic bacterial – Endocarditis – Shunt nephritis – Abscesses Fungal Parasitic infections can cause

39. SUMMARY AND RECOMMENDATIONS There are many causes of glomerular disease, the characteristics of the urine sediment, The degree of proteinuria Patient’s age often

40. Two different urinary patterns are seen: – Nephrotic – Nephritic.

41. The nephrotic pattern = proteinuria > 3.5 g/day Lipiduria

42. The nephritic Red cells White blood cells Red cell or mixed cellular casts Acanthocytes Some patients have the concurrent presence of two glomerular diseases,

43. Approaching a patient Urinalysis Estimated glomerular filtration rate Patient age help to identify Race Family history Renal biopsy

44. Standard laboratory testing Serum creatinine Serum albumin Protein excretion in patients with proteinuria Serologic testing for disorders that cause glomerular disease

45. Serologic tests – Lupus – Amyloidosis – Hepatitis B (HBV) – Hepatitis C (HCV) – HIV infection – ANA – Anti-dsDNA – C3 – C4

46. Primary amyloidosis and light chain deposition disease – Serum and urine immunofixation – Serum free light chain ratio analysis

47. Glomerulonephritis Nephritic urine RBCs, RBC casts Low – mod proteinuria Nephrotic urine No casts, few RBCs Heavy proteinuria Diabetes Amyloid Membranous Nephropathy FSGS Minimal Change Disease Sometimes MPGN C3, C4 LowNormal Postinfectious Lupus nephritis MPGN (often Hep C) progress fast progress slow ANCA (+)ANCA (-) Vasculitis Wegener’s MPA Churg-Strauss IgA nepropathy Anti-GBM/Goodpasture’s