Approach to an abnormal eGFR in primary care

1. Approach to an abnormal eGFR in primary care Hugh Gallagher Consultant Nephrologist SW Thames Renal Unit

2. Changes in the way we measure kidney function • eGFR • Total protein-creatinine ratio • Chronic kidney disease (CKD), classification, clinical features and consequences • Approach to an abnormal eGFR in primary care • The management of CKD in primary care

3. Changes in the way we measure kidney function • eGFR • Total protein-creatinine ratio • Chronic kidney disease (CKD), classification, clinical features and consequences • Approach to an abnormal eGFR in primary care • The management of CKD in primary care

4. “Local health organisations can work with pathology services and networks to develop protocols for measuring kidney function by serum creatinine concentration together with a formula-based estimation of glomerular filtration rate (eGFR), calculated and reported automatically by all clinical biochemistry laboratories.” Renal NSF Part 2, Dept of Health, 2004

5. The problem with creatinine…. • Affected by muscle mass (age/sex/weight) so poor surrogate for GFR • Insensitive – can lose 50% of renal function before serum creatinine rises • Therefore poor marker of early renal disease

6. GFR = Glomerular filtration rate “Normal” = 80-120 ml/min Therefore see as “% renal function” Calculate 1) Actual – iohexol/EDTA clearance 2) Estimated – using formula

7. Formulae in use • *MDRD formula • Age • Sex • Creatinine • Ethnicity (black vs. non-black) • Cockcroft-Gault formula • Age • Sex • Creatinine • Weight

8. Cockcroft Gault & MDRD Formula

9. Age Sex Weight Serum Estimated (kg) creatinine GFR ( mol/L) (ml/min) μ 60 M 70 150

10. Age Sex Weight Serum Estimated (kg) creatinine GFR ( mol/L) (ml/min) μ 60 M 70 150 46

11. Age Sex Weight Serum Estimated (kg) creatinine GFR ( mol/L) (ml/min) μ 60 M 70 150 46 80 M 60 170

12. Age Sex Weight Serum Estimated (kg) creatinine GFR ( mol/L) (ml/min) μ 60 M 70 150 46 80 M 60 170 26

13. Age Sex Weight Serum Estimated (kg) creatinine GFR ( mol/L) (ml/min) μ 60 M 70 150 46 80 M 60 170 26 80 F 60 170

14. Age Sex Weight Serum Estimated (kg) creatinine GFR ( mol/L) (ml/min) μ 60 M 70 150 46 80 M 60 170 26 80 F 60 170 22

15. The introduction of eGFR will allow early identification of CKD and Will result in increased awareness of advanced CKD previously not recognised as such

16. The “normal” eGFR is age related

18. Urine total protein:creatinine ratio • Replaces timed 24 hour urine collections for protein • Random spot urine (preferably early morning, but not essential) • Result in mg/mmol (mg of protein per mmol of creatinine) • Multiply by 10 = total daily protein excretion in mg

19. Total protein:creatinine ratio

20. Urine total protein:creatinine ratio Urine protein = 500 mg/l Urine creatinine = 5 mmol/l Therefore TPCR = 500/5 = 100 mg/mmol Therefore daily protein excretion = 100 x 10 = 1000 mg = 1 g

21. Not to be confused with…. Urine albumin:creatinine ratio NOT for quantifying urine total protein excretion BUT simply to diagnose the earliest stage of diabetic nephropathy Raised ACR = treat with ACEI/ARB (even if normotensive) and address CV risk

22. Changes in the way we measure kidney function • eGFR • Total protein-creatinine ratio • Chronic kidney disease (CKD), classification, clinical features and consequences • Approach to an abnormal eGFR in primary care • The management of CKD in primary care

23. K-DOQI Classification of CKD Chronic kidney disease is defined as either kidney damage or GFR < 60 ml/min for > 3 months. 1 Kidney damage is defined as pathological abnormalities or markers of damage, including abnormalities in urinalysis or imaging

24. K-DOQI Classification of CKD Chronic kidney disease is defined as either kidney damage or GFR < 60 ml/min for > 3 months. 1 Kidney damage is defined as pathological abnormalities or markers of damage, including abnormalities in urinalysis or imaging

25. In real money... • GP practice 10,000 patients • Stage 3 CKD: 500 patients • Stage 4 CKD: 20 patients • Stage 5 CKD: 20 patients • Unreferred stage 4 and 5: 28 patients • Renal unit, serving 1.8 million population • Unreferred stage 4 and stage 5: 5,100 patients

26. Functional consequences of CKD • Hypertension (all stages) • Anaemia (stage 4-5, earlier in DM) • Disorders of Ca/Pi/PTH metabolism (stage 4-5) • renal osteodystrophy • vascular calcification

28. Causes of CKD in the elderly

29. Snapshot of a CKD population in primary care • GFR estimated on patients from 12 practices in Surrey, Kent and Greater Manchester • 19% of sample (5% population) stage 3-5 CKD • mean age 74 years (control 57 years) • 75% stage 3-5 (22% control) co-existing circulatory disease • 25% stage 3-5 (men) prostatic disease • 15% stage 3-5 anaemic by WHO (4% requiring treatment by European Best Practice guidelines) • 3% recorded as having a renal disease

30. Comorbidities in CKD

31. Cardiovascular diseases in CKD Damage to the heart (Uraemic cardiomyopathy) Damage to the arteries (Uraemic arteriopathy)

32. Cardiovascular Mortality Rates are Higher among Dialysis Patients 100 10 1 Dialysis: male Dialysis: female 0.1 General population: male 0.01 General population: female 0.001 Adapted from Levey AS et al. Am J Kidney Dis 1998; 32: 853-906.

33. The Kaiser Permanante experience Derangements in renal function are independently associated with a graded increase in (cardiovascular) risk. This effect is seen even with relatively minor impairments in function. Go, A. S. et al. N Engl J Med 2004;351:1296-1305

34. John, RI et al. AJKD 43:825-835; 2004

35. ESRD is the tip of an iceberg DIALYSIS DEPENDENT 0.04% PROGRESSIVE STAGE 4 CKD 0.05% STABLE STAGE 4 CKD 0.15% STAGE 3 CKD 4%

36. 3 Key Messages • Most patients with CKD are elderly • The majority have stable disease and die of CV causes well before they reach ESRD • Their management is therefore that of their CV risk

37. Changes in the way we measure kidney function • eGFR • Total protein-creatinine ratio • Chronic kidney disease (CKD), classification, clinical features and consequences • Approach to an abnormal eGFR in primary care • The management of CKD in primary care

38. Questions to ask with a newly detected abnormal eGFR (< 60 ml/min) • Is this acute renal failure? • Historical records • Repeat within 1/52 • Is it in the context of intercurrent illness? • Repeat after illness treated • Is there suspicion of obstruction? • Renal tract US (not otherwise) • Are there abnormalities on urinalysis? • Dipstick urine, send simultaneous MSU/TPCR • Should the patient be referred?

39. Urinanalysis and the patient with a newly detected abnormal eGFR (< 60 ml/min) • Nephrology referral is indicated in the presence of persistent microscopic haematuria (if age > 45 then urological malignancy should be excluded first) • Nephrology referral is also indicated (in the presence or absence of microscopic haematuria) if total protein-creatinine ratio > 100 mg/mmol (1 g proteinuria) • Nephrology referral is not required (in the absence of microscopic haematuria) for lower levels of proteinuria, although these patients should be labelled as Stage 3 CKD and entered into appropriate care pathway

40. Should the patient with newly detected eGFR < 60 ml/min be referred? • Not in the majority of cases • ARF • Obstruction (urology) • Abnormalities on urinalysis • For those patients with previously abnormal creatinine/eGFR, treat as CKD

41. What about referral indication in patients with eGFR > 60 ml/min? • Proteinuria > 1g/day (TPCR > 100 mg/mmol) • Proteinuria > TPCR 45 mg/mmol plus microscopic haematuria • Multisystem disease with evidence of kidney damage • Accelerated hypertension with evidence of kidney damage • Suspicion of renal artery stenosis • New diagnosis of APKD

42. Changes in the way we measure kidney function • eGFR • Total protein-creatinine ratio • Chronic kidney disease (CKD), classification, clinical features and consequences • Approach to an abnormal eGFR in primary care • The management of CKD in primary care

43. General management of CKD • Blood pressure • Home meter • 140/90 threshold • 130/80 target (125/75 if TPCR > 100 mg/mmol) • ACEI/ARB if MA/proteinuria/heart failure • Refer if >150/90 despite 3 complementary drugs • Lipid management • JBS guidelines • Other • Aspirin if 10 year CV risk > 20% • Influenza/pneumococcal vaccination • Smoking/weight • Medication review

44. Frequency of monitoring

45. Specific management of Stage 3 CKD • Renal US only if: • Refractory hypertension • Lower tract symptoms • 50% dose reduction metformin if eGFR < 45 ml/min • Refer if: • Progressive (fall in eGFR > 10 % over 1 year) • Functional haematological/biochemical consequences: • Hb < 11 • K > 6 • Ca < 2.1, Pi > 1.5, PTH > 7 pmol/l • Poorly controlled hypertension

46. Specific management of Stage 4 CKD • Discuss with nephrology • Renal US • Stop metformin • Refer if: • Diabetic • Progressive (fall in eGFR > 15 % over 1 year) • eGFR < 20 ml/min • Functional haematological/biochemical consequences: • Hb < 11 • K > 6 • Ca < 2.1, Pi > 1.5, PTH > 11 pmol/l • Poorly controlled hypertension

47. Specific management of Stage 5 CKD • Refer

48. Take home messages • eGFR as a “% kidney function” • 0.5-1%/year lost from 40+ • Most CKD patients are stable and management is that of CV risk • CKD patients that should be referred are those: • With progressive disease • With advanced disease (Stage 5 +/- Stage 4) • With functional consequences of disease

49. The nephrologist’s view

50. The GP’s view