Hypertension and chronic kidney disease in older people

1. Hypertension and chronic kidney disease in older people Dr Rick Fielding Consultant Renal Medicine Brighton & Sussex University Hospitals

2. How big is the CKD problem? • Why is CKD important in the elderly? • What can be done about it?

3. RRT incident rates in the countries of the UK

4. Stages of CKD

5. Prevalence of CKD CKD NHANES AusDiab NEOERICA I 3.3 0.9 2 3.0 2.0 3 4.3 10.9 4.2 4 0.2 0.3 0.17 5 0.1 0.003 0.04 • 15% of >65yr olds have CKD III-V • 60% of >75yr olds have CKD III-V • ~8.8% of UK population have CKD 3-5 (3.5 million)

6. Prevalence of Chronic Kidney Disease (CKD) Stages by Age Group in NHANES 1988-1994 and 1999-2004

7. The aging kidney • Heterogeneous • Loss of renal mass • Glomerular and interstitial fibrosis • Reduced sodium handling • Acid-base balance • Water homeostasis Macías-Núñez, J. F. and Cameron, J. S. Renal Function and Disease in the Elderly. 1987

8. What is normal in an elderly population? • GFR decline of 0.8-1.4 ml/min/1.73m2/yr ? • How do you measure GFR? • MDRD • Poorly validated in elderly • Poor concordance • Cystatin-C • ?better detection of changes in GFR • Accuracy uncertain • No reference standard

9. O’Hare 2007 JASN 18: 2758–2765

10. What happens to the elderly with CKD? • No CKD • 0.07% risk of progression to ESKD over 3yr • Mortality 10% • CKD 3 • 1.1% risk of progression to ESKD over 3yr • Mortality 24.3% • CKD 4 • 17.6% risk of progression to ESKD over 3yr • Mortality 45.7% Keith et al Arch Intern Med 2004;164:659

11. Effects of CKD on mortality and cardiovascular disease in the elderly - mean 75yr Shilpak at al Ann Int Med 2006;145:237

12. Baseline eGFR threshold below which risk for ESRDexceeded risk for death for each age group O’Hare 2007 JASN 18: 2758–2765

13. What are the challenges in CKD? • Identify patients at risk of progressive CKD • Reduce cardiovascular death

14. Oxidative stress Low birth weight Dyslipidaemia Hypertension Diabetes Smoking Obesity Age Inflammation African American Increased homocysteine Poverty Proteinuria Primary kidney disease Progressive CKD Vascular compliance Vitamin D deficiency Endothelial dysfunction

15. Progression of non-diabetic CKD • Progression relates to haemodynamic + metabolic factors • Intra-glomerular hypertension • glomerular hypertrophy • albuminuria >1000 mg/day • Reduce glomerular pressure and proteinuria

17. RAS blockade and proteinuria in non-diabetic CKD • Benefit of ACEi if… • Proteinuria >1000mg/d • Even if normotensive • Combined with • low Na+ diet • Diuretics • ? 500-1000mg/d • ? if >70yr

18. Other drugs and proteinuria in non-diabetic CKD • ARBs • Antiproteinuric effect equivalent to ACEi at 5-12 months • SMART trial • 269 patients • >1g/d proteinuria on 16mg candesartan • 33% reduction in proteinuria at 128mg candesartan • Non-dihydropyridine calcium channel antagonists • Effective if >300mg/d irrespective of BP • Lesser proteinuric effect with • β-blockers • Diuretics • α-blockers

19. Combination therapy in proteinuria • ACEi + ARBs • Data in diabetic nephropathy • Limited data in non-diabetic proteinuria • No data to show improved renal outcome • ACEi +/- ARB + spironolactone • Further reduction in proteinuria • Not on maximum dose of ACEi • Risk of hyperkalaemia

20. Pragmatic approach to proteinuria in CKD • ACEI • or ARB • + loop diuretic • Think about • ACE + ARB • ACE + spironolactone • Non-dihydropyridine calcium channel blockers

22. Reducing BP and progression of CKD – MDRD trial Close circles = usual BP130/80 Open circles = low BP125/75 Klahr et al NEJM 1994;330:877

23. Other trials • African American Study of Kidney Disease (AASK) • Ramipril more effective than amlodipine or metoprolol in African Americans • No difference in GFR decline between 128/78 and 141/85 • 22% reduction in composite with ACEi (GFR decline, ESKD and death) • Meta-analysis • Risk of progression correlates with: • Proteinuria >500mg/d • Systolic >120 Wright et al JAMA 2002;288;2421

24. ACEi in elderly with CKD? • All CKD trials excluded >70yr olds • More side effects with ACEi • Hypotension • Hyperkalaemia • Elderly less likely to have proteinuria • NHANES • >70 yrs + eGFR <60 + ACR >30 = 13% • Absolute indication? • Proteinuria >1g (uPCR >100)

25. “Recommendations” • Target BP……. • Proteinuria low: ACR<70 or PCR<100 • Target BP <140/90 (NICE suggests 130-139/90) • Proteinuria high: ACR>70 or PCR>100 • Target BP <130/80 (NICE suggests 120-129/80) • ACEi 

26. BP targets and age in CKD • Do the CKD guidelines need to be modified for the elderly? • Benefits from blood pressure reduction do not seem to have age limits • Consider average BP at different ages -

27. Any other strategies to reduce progression or CV risk? • Lipid lowering therapy? • SHARP • 9500 pts with CKD • Simvastatin vs simva+ezetimibe vs placebo • Composite of major vascular event (MI or stroke) • Reporting Nov 2010 • Correct anaemia with EPO?

28. Functional ability in the elderly with CKD • 3x more likely to be frail than if normal renal function (10% vs 4%) • Associated with increased hospitalisation • Institutionalisation • Death • Increased falls • 30%/yr of >75yr olds with ESKD • Cognitive decline • 70% of >55yr olds with ESKD • Nutrition • Poor cardiovascular fitness

29. What happens to elderly patients with progressive CKD?

30. “The aim of dialysis is not only to prolong life but also to restore quality by permitting a sufficiently independent existence with minimal support”

31. UK Renal Registry 11th Annual Report

32. Unadjusted survival of all incident patients by age band – 2005 cohort

34. Patients with multiple co-morbidities may not benefit from dialysis • Can we predict those who are likely to do poorly? • Renal association and The Gold Standards Framework • “ if patient should have at least 1 core and 1 disease specific indicator then that a patient may benefit from a palliative care approach” • Core indicators are likely to be • Recent, significant functional decline (loss of ADLs) • Dependency in 3 or more ADLs • Multiple co-morbidities • Weight loss • Serum albumin less than 25 • Karnofsky score less than or equal to 50%

35. Conservative management of CKD 5 • Outlined in the NSF “Patients with progressive renal failure in whom dialysis is deemed inappropriate or who choose not to start RRT should continue to receive the benefit of the resources available to the renal service to provide a robust support package.” • Supportive care should be offered as alternative to dialysis • Does NOT mean no treatment • Continued support from multidisciplinary team • Symptom treatment • Treatment of anaemia with erythropoietin

36. What’s the evidence? • Study done at The Lister • Cohort of low clearance pts 19% (63) recommended for palliative therapy, pts more functionally impaired but co-morbidity score not an independent factor • 10 opted for dialysis • median survival on dialysis 8.3 m,vs 6.3 m (NS) • death in hospital: dialysis 65% vs palliative 27%

37. Dialysis vs conservative care Murtagh et al NDT 2007;22:1955–1962

38. Ischaemic heart disease P = 0.27 No ischaemic heart disease P <0.0001

39. Dialysis in nursing home residents • “treatment may improve functioning and/or alleviate symptoms, even if it does not extend life” • 3,702 nursing home residents with ESRD (mean age 73.4y • MDS-ADL score Tamura et al NEJM 2009: 361, 1539–1547

40. Functional status before dialysis was maintained in only 13% of survivors Tamura et al NEJM 2009: 361, 1539–1547

41. To summarise…. • Majority of CKD in elderly • Non-proteinuric • Non-progressive • CKD guidelines are not one-size-fits-all • The main challenge is reducing cardiovascular death • Which patients will benefit from dialysis?