Detection, monitoring and referral of chronic kidney disease

1. Detection, monitoring and referral ofchronic kidney disease Canadian Society of Nephrology Implementation Committee 2007

2. Key messages • Who to test for chronic kidney disease • What tests to order • What to do with the results

3. Identify patients in your practice at high risk for Chronic Kidney Disease • Patients with hypertension • Patients with diabetes mellitus • Patients with atherosclerotic coronary, • cerebral or peripheral vascular disease • - Patients with heart failure • Patients with unexplained anemia • Patients with a family history of end stage renal disease • First nations peoples eGFR 30-60 eGFR >60 eGFR <30 • Consider reversible factors: • Medication - Volume depletion • Intercurrent illness - Obstruction • Repeat tests in 2 - 4 weeks Individualized follow up and treatment CKD is diagnosed in this group only if other renal abnormalities are present (i.e. proteinuria, hematuria, anatomical) eGFR <30 eGFR 30-60 Nephrology referral recommended Follow eGFR at 3 months then serially Assess for persistent significant proteinuria Implement risk reduction Stable eGFR 30-60 and no significant proteinuria eGFR < 30 or progressive decline in eGFR or persistent significant proteinuria or inability to attain treatment targets

4. What is Chronic Kidney Disease • The presence of Kidney Damage or an eGFR < 60 ml/min/1.73m2and • Present for ≥ 3 months and • Not treated with dialysis or transplant The diagnosis of CKD is only present in patients with eGFR ≥60ml/min if other abnormalities (i.e. proteinuria, hematuria, anatomical) are also present.

5. Who should be tested for CKD? CSN endorses a case finding approach to testing for CKD, which should be focused on high-risk groups. CSN does not endorse mass population screening for CKD with either serum creatinine based tests or with urine dipstick testing.

6. Who should be tested for CKD? • Patients with diabetes mellitus • Patients with hypertension • Patients with heart failure • Patients with atherosclerotic coronary, cerebrovascular or peripheral vascular disease • Patients with unexplained anemia • Patients with a family history of ESRD • First nations peoples

7. Clinical case • Joe is a 68 year old welder • Past Medical History: appendectomy age 15, hypertension x 4 years, elevated cholesterol x 1 year, Type 2 DM x 1 year • Smoker- 1 pack a day since age 21 • Etoh- a case of beer on the weekend • Allergy- none known • Family History- father MI age 50, mother HTN age 48 • Medications- hydrochlorothiazide 25 mg po od, amlodipine 5mg po od, metformin 1000 mg po bid • Weight 75 kg • BP 149/84 mmHg

8. Joe should be screened for CKD because he has several risk factors. • Can you name them?

9. Which test would you choose to assess Joe’s renal function? • Serum creatinine • 24 hour urine collection • Nuclear medicine scan • eGFR

10. Na 138 mmol/L K 4.5 mmol/L Cl 103 mmol/L HCO3 23 mmol/L Glucose (R) 6.4 mmol/L Urea 10.1 mmol/L Creatinine 123 µmol/L CBC normal HgB A1C 5.6% Ca ++ 2.46 mmol/L PO4= 1.10 mmol/L Albumin 38 g/L TC 7.60 mmol/L TG 2.06 mmol/L LDL(C) 5.43 mmol/L HDL(C) 1.23 mmol/L Joe’s labs

11. Joe’s serum creatinine is in the normal range, doesn’t that mean his kidney function is also normal?

12. Assessing Joe’s renal function using eGFR 54 ml/min / 1.73m2 (Stage 3 CKD) Clearly, Joe’s renal function is not normal despite a normal serum creatinine http://www.kidney.org/professionals/kdoqi/gfr_calculator.cfm

13. Why use eGFR? It gives the health care practitioner a different sense as to a patient’s level of renal function that they may not have appreciated by using simple serum creatinine measurements.

14. Measuring renal function:what’s eGFR?

15. GFR • Glomerular filtration rate (GFR): is the volume of fluid filtered from the renal glomerular capillaries into the Bowman’s space per unit time. • Normal for a 20 year old is ~ 120ml/min

16. Methods to assess GFR • Serum urea • Serum creatinine • Serum cystatin C • Timed urine collections • Creatinine clearance • Inulin clearance • Calculated GFR calculations • based on serum creatinine • many formulas including Cockcroft Gault and MDRD • Nuclear medicine methods

17. The perfect marker • Endogenous • Freely filtered • Not secreted or reabsorbed • Inexpensive to measure doesn’t exist !

18. Problems with creatinine Stevens L et al, NEJM 2006; 354:2473-2483

19. Problems with timed collections • Cumbersome • Prone to error • No longer recommended in most situations

20. Problems with other methods • Cystatin • Inulin • Nuclear medicine (iothalamate, EDTA etc) • Complex • Time-consuming • Expensive • Not practical for serial monitoring

21. Creatinine based approximations 1) Cockcroft-Gault equation CrCl (ml/min)= (140-age) x actual weight (kg) x 1.2 (if male) SCreat (µmol/L) 2) MDRD (Modification of Diet in Renal Disease) 6 variable or abbreviated version GFR(ml/min/1.73m2)=170 (PCr)-0.999 x (Age)-0.176 x (0.762 if female) x (1.21 if African American) x (serum urea)-0.170 x (Albumin)+0.318 Weight probably not available for lab to calculate Lab has patient age and gender – can do abbreviated version

22. eGFR equation provisos • eGFR calculations may be less reliable in: • individuals with near normal GFR (>60 ml/min/1.73m2) • individuals with markedly abnormal body composition • extreme obesity • cachexia • paralysis • amputations • Controversies exist as to the applicability of these formulae to various ethnic groups and the very elderly

23. Estimate of Glomerular Filtration Rate (eGFR) • It is not recommended that clinicians rely on serum creatinine measurements alone when assessing kidney function. • CSN calls for the reporting of kidney function as an estimate of glomerular function rate (eGFR) using equations and standardized creatinine measurements • If neither eGFR reporting, nor calculators are available to a physician, tables based on serum creatinine and other variables are available to provide approximations of eGFR.

24. Developed by the BC Medical Services Commission, Guidelines and Protocols group

25. Developed by the BC Medical Services Commission, Guidelines and Protocols group

26. Is it just about GFR? Should also assess urine protein losses • 24 hour urines are no longer recommended • For same reasons as with GFR • Urine dipsticks are affected by hydration status Quantify protein excretion with random urine for: • Urine albumin to creatinine ratio or • Urine protein to creatinine ratio

27. What do those values mean? Microalbuminuria (ie in diabetics) Alarm values to refer

28. Who should be tested for CKD? • Patients with diabetes mellitus • Patients with hypertension • Patients with heart failure • Patients with atherosclerotic coronary, cerebrovascular or peripheral vascular disease • Patients with unexplained anemia • Patients with a family history of ESRD • First nations peoples

29. What tests to order? • Assess kidney function with • eGFR • As reported by lab • As calculated using equations (and PDA!) • As estimated by tables • Quantification of protein with random urine samples • Urine albumin to creatinine or • Urine protein to creatinine

30. What to do with the results Now that I know Joe’s GFR is not normal what should I do?

31. What to do with the results • Is one eGFR measurement enough? • Consider reversible factors • Assess risk of progressive renal disease • who needs referral to Nephrology

32. Natural history of elevated creatinine levels Marcotte and Godwin, Canadian Family Physician 2006;52:1264-1265,e1-5 1434 patients in a family medicine practice • 57 patients had an elevated initial serum Cr levels (>130umol/L) and subsequent Cr levels within 4-5 years of follow-up

33. Is one eGFR measurement enough? • Decisions about investigation, treatment or referral should not be made based on a single isolated test of kidney function • In a primary care setting, many patients will show improvement or normalization of kidney function upon repeat testing. • The diagnosis of CKD is based on serial measurements of kidney function and it is not possible to diagnose CKD on the basis of a single serum creatinine concentration transformed through equations.

34. For patients with a new finding of an eGFR between 30-60ml/min/1.73m2 CSN recommends that clinicians determine the stability of the patient’s eGFR Repeat test within 2-4 weeks, and then in 3-6 months

35. Consider reversible factors • Intercurrent illness • Volume depletion • Medications • NSAIDs, aminoglycosides, IV contrast dye • Obstruction • An abdominal ultrasound may be indicated at eGFRs <60ml/min/1.73m2

36. Back to Joe • You measure Joe’s eGFR in 2 weeks and then again in 3 months and it is unchanged • You order an ultrasound and it is normal • His urinalysis is normal

37. Conclusions about Joe • Given the stability of these we can conclude that he has stable CKD. • It is important to continue to serially follow his renal function. • Serial measurement is a cornerstone of chronic kidney disease management.

38. CSN recommends that most patients with non-progressive CKD can be managed by non-nephrologists without referral. The recognition that many patients with an eGFR between 30 and 60 ml/min/1.73m2 do not have a high risk of progressive kidney disease is important.

39. CKD is common

40. Estimated prevalence of CKD in Canadians ≥ 20 years old Stage 1 CKD > 90 ml/min 792,000 Stage 2 CKD 60 – 89 ml/min 720,000 Stage 3 CKD 30 – 59ml/min 1,032,000 Stage 4 CKD 15 – 29 ml/min 48,000 Stage 5 CKD < 15 ml/min 24,000 Numbers are estimates based on an extrapolation of US data Stigant, C, et al. CMAJ 2003;168:1553-60.

41. Other common conditions also managed by primary care physicians CKD is a common general health problem

42. Estimated prevalence of CKD in Canadians ≥ 20 years old Stage 1 CKD > 90 ml/min 792,000 Stage 2 CKD 60 – 89 ml/min 720,000 Stage 3 CKD 30 – 59ml/min 1,032,000 Stage 4 CKD 15 – 29 ml/min 48,000 Stage 5 CKD < 15 ml/min 24,000 ESRD is not common Stigant, C, et al. CMAJ 2003;168:1553-60.

43. If many patients with CKD do not progress to end stage renal failure why then as a primary care physician should I even be looking for them using eGFR?

44. ESRD is not the problem Patients with CKD have high rates of cardiovascular disease and many patients die before progressing to end stage renal failure thus it is important to screen for CKD.

45. Go,A et al. NEJM 2004;351:1291-1305

46. Quick Tips on Management of CKD Implement measures to slow rate of CKD progression • Treat to target BP <130/80; most will need 3 or more meds, diuretics and salt restriction are very useful • Target urine ACR <40 or PCR <60. ACEI and/or ARB are first line therapies for albuminuria or proteinuria • Control blood sugar in diabetes, target HbA1C <7% Implement measures to modify CV risk factors • Follow guidelines as per groups at highest risk for CV disease Minimize further kidney injury • If possible, avoid nephrotoxins such as NSAIDs, aminoglycosides, IV and intra-arterial contrast etc • If contrast is necessary, consider prophylactic measures (if eGFR <60) Remember to adjust dosages of renally excreted medications

47. Joe: three years later • You have continued to follow his eGFR and notice that it is now 42 ml/min/1.73m2 • All clinical targets (BP, HBA1C, cholesterol) are stable • No intercurrent illnesses His CKD is no longer stable Refer to Nephrology

48. Who should be referred to a Nephrologist? • Patients with acute renal failure • Patients with eGFR <30ml/min/1.73m2 • Patients with progressive loss of renal function • Persistent significant proteinuria (present on 2 out of 3 samples) • on dipstick or • quantified PCR >100mg/mmol or • quantified ACR >60 mg/mmol. • Inability to achieve treatment targets or other difficulties in the management of the CKD patient

49. Violet • 78 year old female • longstanding patient of a colleague’s – followed for her hypertension and “mild” renal failure • You are on call and see her because she is c/o nausea and lethargy

50. Using an “eGFR approach”