Approach to Renal Disorders

1. Approach to Renal Disorders AIMGP Seminar Revised by Nick Hariton November 2006

2. Objectives • To identify appropriate strategies for investigation of the patient with kidney disease • To discuss interventions that may alter the course of disease • To discuss indications for referral to a nephrologist

3. Guidelines • Elevated Serum creatinine: recommendations for management and referral. CMAJ 1999: 161:413-17 • National Kidney Foundation: Kidney Disease Outcomes Quality Initiative (NKF-KDOQI), 2002 • Practice guidelines for Chronic Kidney Disease. 2003. Annals of Internal medicine. Vol. 139 Number 2.

4. Stages of Renal Failure

5. Creatinine is an estimate of GFR • Cockcroft-Gault: (140-age) x wt x 100 = GFR (cc/min) 72 x serum Cr GFR (females) = GFR (males) x 0.85 • MDRD • 24 hour urine for creatinine

6. CASES: What is Considered an ELEVATED Creatinine? 55 yo 70 kg male with Cr of 220: 75 yo 45kg female with Cr of 220: 75 yo 45kg female with Cr of 85: 75 yo 45kg female with Cr of 45: GFR =37 moderate GFR = 16 severe GFR =40 moderate GFR =76 mild

7. Workup of a decreased GFR • Approach • 1. Identify chronicity (Acute vs chronic) • 2. Identify the cause, especially reversible causes • 3. Identify Indications for Referral to a Nephrologist • 4. Initiate a cause specific management plan in a multidisciplinary team.

8. ACUTE Fever Hypovolemia Sepsis New hypertension Recent nephrotoxins No hypocalcemia No hyperphosphatemia No anemia CHRONIC previous confirmed nephropathy Already diminished CrCl Atrophic kidneys (<10cm on U/S) Normochromic normocytic anemia Hypocalcemia Hyperphosphatemia Acute vs Chronic Renal Failure

9. Abdominal Imaging • Normal size kidneys in chronic kidney disease • Diabetes • Polycystic kidney disease • Myeloma Kidney • Amyloidosis • HIV Nephropathy

10. Underlying Cause

11. Pre-Renal Disease • Medications: • NSAID • Diuretic • Renal Artery Stenosis • Decrease effective circulating volume • Congestive heart failure • Cirrhosis • Hypovolemia (losses or decreased intake) • Normal urine sediment, decreased urine [na+], increased BUN:Cr

12. Post-Renal Disease • Intraluminal obstruction: • Nephrolithiasis • Luminal obstruction • Transitional cell carcinoma • Severe BPH • Extraluminal obstruction • Retroperitoneal fibrosis • Lymphadenopathy (lymphoma) • Mass

13. Glomerular Disease • Active Sediment (RBC casts, hematuria) • IgA Nephropathy • Post-infectious GN • Autoimmune disease and vasculitis • Chronic hepatitis and HIV • Nephrotic Syndrome (bland sediment, >3g/day proteinuria) • Primary and secondary causes • DIABETES

14. Interstitial Disease • Polycystic Kidney Disease • Chronic infectious pyelonephritis • Allergic interstitial nephritis • Autoimmune interstitial nephritis • Reflux nephropathy • Myeloma Kidney

15. Vascular Disease • Large-sized Arteries • Renal artery stenosis • Medium-sized Arteries • HYPERTENSIVE NEPHROSCLEROSIS • Vasculitis • Arterioles • Microangiopathies (scleroderma, HUS/TTP, cyclosporine) • Venous thrombosis

16. History and Physical Exam • signs or symptoms of • underlying disorder: i.e. volume status, flank pain, obstruction, diabetes, hypertension, vasculitis • altered kidney function: urine output, urine discoloration, edema • renal failure: anorexia, vomiting, altered mental status, HTN • medications: NSAID, ACEI, analgesics, aminoglycosides, contrast, Chinese herbs

17. Laboratory Investigations • Required: • Estimation of GFR • Urinalysis • Albumin:Creatinine Ratio • Renal Imaging • CBC, Electrolytes, Calcium, Phosphate, Bicarb, Albumin • Potentially useful: • 24-hour Urine protein • Fasting Glucose • Serum / Urine Protein Electrophoresis • HIV and Hepatitis serology • Autoimmune serologies • MR Angiography

18. UptoDate

19. Renal Biopsy • Should be considered: • Ff noninvasive tests have failed to establish a diagnosis in a patient with: • Nephrotic syndrome (except in DM or established amyloid) • Non-nephrotic proteinuria if associated with renal dysfunction • Lupus nephritis (for dx and staging) • Acute nephritic syndrome • Unexplained acute/ subacute renal failure • To direct and evaluate effectiveness of therapy

20. Management of Renal Disease • Treatment of Reversible Causes • Preventing or Slowing Progression • Treating and Preventing the Complications • Identifying Individuals Requiring Renal Replacement Therapy

21. Slowing Progression

22. Hypertension • ACE inhibitors preferred because: • More potent antiproteinuric effect, especially in non-diabetics • Large body of evidence from RCTs (in diabetics and non-diabetics) • RRR 30% for progression to ESRD • Benefit persists in severe kidney disease

23. Management of Complications • Coronary artery disease • Anemia • Calcium and phosphate homeostasis • Renal osteodystrophy • Platelet dysfunction • Fluid overload • Acidosis and hyperkalemia • Decreased drug clearance

24. Referral to Nephrologist • Late referral (< 12 months pre dialysis) is common • Survey of Ontario Family MDs: • 84% would not refer with creat 120-150 (>50% loss of GFR) • 28% would not refer with creat 150-300 • almost all would refer with creat>300 • Consequences of referral shortly before dialysis: • more complications • longer hospitalization to initiate dialysis • more difficulty with initiation of dialysis • worse survival! • Better outcomes with early multidisciplinary care CMAJ 1999: 161:413-17

25. Canadian Guidelines • Renal replacement therapy is NOT rationed (i.e. everyone should be considered) • Reversible causes should be sought at diagnosis • At least 1 year is required to prepare for dialysis • Refer, at the latest, at Cr clearance of 30 ml/min, or Cr of 300 • But…there are probably not enough nephrologists/ clinics to meet this demand • Adequate communication with the Nephrologist will allow proper stratification of patients CMAJ 1999: 161:413-17

26. For AIMGP Clinic • It is reasonable to follow stable renal failure patients, and work up and manage appropriately • Refer to nephrology when: • Cr >300 or Cr clearance <30 ml/min • Renal biopsy indicated • Indicators of aggressive disease are present: • Rapid decline in creatinine • homeostatic derangement i.e. acidosis, volume overload, high K • high protein excretion • Difficult to control BP • low HDL • black race

27. In Summary

28. Appoach To Proteinuria • Normal Protein Elimination: • < 150mg / day protein • < 30mg / day albumin • Classification of Proteinuria • Transient • Orthostatic • Persistant

29. Glomerular barrier tubule • Normally, the larger proteins are excluded at • the glomerular barrier • Smaller proteins can pass, but are mostly • reabsorbed

30. Mechanisms of Proteinuria • Glomerular Dysfunction • Leakage of large proteins through glomerular membrane and podocytes • Transient (epinephrine and AII mediated) • Fever • Exercise • Congestive Heart Failure • Persistant • Glomerular Disease

31. Leaky Glomerular barrier tubule • Large proteins are able to pass by the abnormal glomerular barrier

32. Mechanisms of Proteinuria • Tubular Dysfunction • Inability of renal tubules to reabsorb small filtered proteins • Specific transporter dysfunction • Eg Fanconi’s syndrome • Generalized tubular dysfunction • Progressive chronic renal failure • Interstitial Disease

33. tubule Malfunctioning tubules unable to reabsorb the smaller proteins filtered at the glomerulus

34. Mechanisms of Proteinuria • Increased filtered protein load • Overwhelms ability of kidney to reabsorb protein • Increased GFR (mild proteinuria) • Pregnancy, fever • Increased filtered protein • Myeloma, MGUS

35. Glomerular barrier tubule • Filtered load of proteins exceeds the tubular • reabsorption rate (similar to glucosuria in • hyperglycemia)

36. Diagnostic Approach • Step 1 • Clinical Assessment (History and Physical) and examination of urinary sediment • History: urinary symptoms, infections, rash, risk factors for HIV and hepatitis • Pmhx: Cancer, CHF, HTN, CTD, DM • FHx: Alports, Fabry’s • Drugs: NSAIDS, Gold, Heroin • Physical exam: vitals, JVP, peripheral edema, ascites, rash, joint swellings

37. Diagnostic Approach • Rule out transient proteinuria with repeat urinalysis: • Fever, exercise, UTI • In young patients (age < 30) perform a split urine collection (upright and supine) to exclude orthostatic proteinuria • If the above investigations are negative - STOP

38. Diagnostic Approach • Persistant proteinuria not due to a known underlying cause (eg CHF or diabetes) requires further investigation for glomerular and interstitial disease: • 24h urine for protein or urine albumin:creatinine ratio • Serum creatinine and estimation of GFR • CBC, electrolyes, Fasting blood sugar • Serum and urine protein electrophoresis • Serology: Hep B, Hep C, HIV, ASOT, VDRL • ANA, Rheum factor, C3/C4, ANCA • Renal Imaging (eg ultrasound) • Malignancy screen

39. Renal Biopsy • Indications for renal biopsy: • Diagnosis unclear and • Persistant proteinuria with > 3g / day • Increasing proteinuria • Declining GFR • Prognosis and management • Eg staging SLE nephritis

42. Summary • Asymptomatic proteinuria is a common problem • Initial investigations are targeted to rule out transient, self-limited conditions and benign orthostatic proteinuria • Persistent proteinuria, particularly nephrotic range or associated with declining GFR, requires further investigation

43. Conclusions • When evaluating a patient with a renal disorder: • Identify and treat reversible causes of renal failure • Initiate management to slow the decline in renal function • Manage coexisting conditions • Have clear indications for when to refer to nephrology subspecialists • Organize an approach to asymptomatic proteinuria