DOM Morning Report: Nephrotic Syndrome

1. DOM Morning Report:Nephrotic Syndrome Week of December 1, 2008

2. Objectives To know the main characteristics To understand the clinical sequelae To be able to differentiate and treat the underlying disorders

3. Definition Proteinuria Hypoalbuminemia Edema Hyperlipidemia Lipiduria

4. Proteinuria Typically asx until > 2g/24hrs Severe or nephrotic range > 3g/24hrs

5. Hypoalbuminemia Decreased plasma oncotic pressure Transudation of fluid into interstitium

6. Edema Perceived ? in effective arterial volume Salt and water retention Activation of RAAS Distal tubular mechanisms Usually prompts patient presentation

7. Hypercholesterolemia Increased hepatic synthesis Hypoalbuminemia Decreased oncotic pressure Cholesteryl ester transfer protein Converts cholesterol to LDL Significantly increased Severe (300-400mg/dL)

8. Sequelae Proteinuria Coagulation abnormalities ? ? VTE risk Urinary loss of fibrinolytic factors Urinary loss of antithrombin III Increased platelet aggregation Increased serum fibrinogen levels

9. Sequelae Hypothyroidism Urinary losses of thyroid-binding globulin Urinary losses of thyroxine Hypocalcemia Hypoalbuminemia Urinary losses of vitamin D binding protein Low levels of 25-hydroxyvitamin D Low levels of 1,25-dihydroxyvitamin D

10. Sequelae Anemia Urinary losses of transferrin Urinary losses of erythropoietin Hypercholesterolemia Accelerated atherosclerosis Exacerbation of CKD

11. Disorders Minimal change disease Focal segmental glomerulosclerosis Membranous nephropathy Membranoproliferative GN

12. Epidemiology Age is major factor Throughout adulthood Minimal change disease ? FSGS and membranous nephropathy ? FSGS most common in black patients Membranous nephropathy most common in white patients

13. Treatment BP control Goal = 125/75 mmHg ACEI or ARB is standard of care Decreases proteinuria Ameliorates nephrotic syndrome

14. Treatment Hypercholesterolemia TLC only marginally effective Statins ? LDL goal of 100-129mg/dL Fibrates for hypertriglyceridemia

15. Minimal Change Disease Clinical Presentation Proteinuria develops suddenly Relapsing and remitting disease 1/3 have only one episode First relapse typically within six months ~ 10% become corticosteroid dependent

16. Minimal Change Disease Acute renal failure Occurs in adult patients Baseline atherosclerosis Rapid development of proteinuria or edema Resolves with control of proteinuria

17. Minimal Change Disease Treatment Prednisone 60mg daily or QOD x 4 weeks Then 40mg/m2 QOD x 4 weeks Resistance = lack of full response

18. Focal Segmental Glomerulosclerosis Clinical presentation Indolent Wide range of proteinuria

19. Focal Segmental Glomerulosclerosis Treatment 16 weeks of daily or QOD prednisone Cyclosporine Remission in 70% of steroid-resistant patients Relapse in 40% after discontinuation Mycophenolate mofetil

20. Membranous Nephropathy Clinical Presentation 1/3 have spontaneous remission 1/3 have persistent proteinuria 1/3 have rapidly progressive course

21. Membranous Nephropathy Treatment Corticosteroid therapy alone ineffective Combination for persistent nephrosis Pulse corticosteroids Cytotoxic therapy Cyclosporine appropriate alternative monotherapy Process returns when discontinued

22. Membranoproliferative Glomerulonephritis Clinical presentation Frequent glomerular hematuria Activated alternative complement pathway Low or depressed C3 Normal C4

23. Membranoproliferative Glomerulonephritis Treatment Varies based on signs and symptoms Usually improves with associated disease

24. Secondary Causes Diabetic nephropathy Amyloidosis Multiple myeloma HIV-associated nephropathy

25. Diabetic Nephropathy Clinical presentation Longstanding DM Proteinuria Microalbuminuria ? macroalbuminuria HTN Decline in glomerular filtration rate

26. Diabetic Nephropathy Epidemiology Less prevalent in white patients than� Native Americans Mexican Americans African Americans Predictors Family h/o kidney disease Family h/o HTN

27. Diabetic Nephropathy Treatment Glycemic control Blocking RAAS and ? blood pressure Goal = 125/75 ACEI or ARB Slows rate of GFR decline Equal renoprotective effect

28. Diabetic Nephropathy TLC Protein restriction Treatment of hypercholesterolemia Smoking cessation Renal transplant for ESRD

29. Amyloidosis Clinical presentation Occurs in 30% of pts with AL disease Massive edema Hypotension Mean survival ~ 16 months

30. Amyloidosis Treatment Prednisone Melphalan Cyclophosphamide With or without colchicine

31. Multiple Myeloma Clinical presentation Kidney disorders (men > women) LCDD (?) Secondary amyloidosis (?) First signs Proteinuria Renal insufficiency ESRD occurs in up to 50%

32. Multiple Myeloma Treatment Resolution of underlying disorder Systemic chemotherapy Stem cell transplantation Decrease risk for intratubular casts Fix hypercalcemia Alkalinize urine to pH > 6

33. HIV-Associated Nephropathy Clinical presentation Primarily effects black patients Heavy proteinuria Renal insufficiency Rapid progression to ESRD

34. HIV-Associated Nephropathy Treatment HAART ACEI Immunosuppression

35. Objectives Revisited Characteristics Proteinuria Hypoalbuminemia Edema Hypercholesterolemia Lipiduria

36. Objectives Revisited Clinical sequelae Coagulation abnormalities ? ? VTE risk Hypothyroidism Hypocalcemia Anemia Accelerated atherosclerosis Exacerbation of chronic kidney disease

37. Objectives Revisited Underlying disorders Minimal change disease Rapid onset, relapsing/remitting Steroids FSGS Variable presentation, most common in blacks Steroids ? cyclosporine

38. Objectives Revisited Membranous nephropathy 1/3, 1/3, 1/3 Steroids ? combination therapy Membranoproliferative GN Glomerular hematuria, low C3 Manage associated disease

39. Objectives Revisited Diabetic nephropathy Long standing DM, HTN Glycemic control, RAAS blockade, TLC Aymloidosis Multisystem disease TBD

40. Objectives Revisited Multiple myeloma LCDD, renal insufficiency Chemo, stem cell transplant HIV-associated nephropathy Black, HIV+, renal insufficiency HAART