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

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

RRT incident rates in the countries of the UK

Stages of CKD StageGFRDescription 190+Normal kidney function but urine or other abnormalities may point to kidney disease Mildly reduced kidney function, but urine or other abnormalities may point to kidney disease Moderately reduced kidney function Severely reduced kidney function 514 or less Very severe, or endstage kidney failure (sometimes called established renal failure)

Prevalence of CKD CKDNHANESAusDiabNEOERICA I % 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)

Prevalence of Chronic Kidney Disease (CKD) Stages by Age Group in NHANES and

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

What is normal in an elderly population? GFR decline of ml/min/1.73m 2 /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

O’Hare 2007 JASN 18: 2758–2765

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

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

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

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

Progressive CKD Oxidative stress Endothelial dysfunction Inflammation Vascular compliance Vitamin D deficiency DyslipidaemiaAgeHypertensionDiabetes African American Smoking Increased homocysteine Primary kidney disease Proteinuria Low birth weight Poverty Obesity

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

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

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

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

Pragmatic approach to proteinuria in CKD 1.ACEI 2.or ARB 3.+ loop diuretic 4.Think about –ACE + ARB –ACE + spironolactone –Non-dihydropyridine calcium channel blockers

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

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

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 30 = 13% Absolute indication? –Proteinuria >1g (uPCR >100)

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

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 -

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?

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

What happens to elderly patients with progressive CKD?

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

UK Renal Registry 11th Annual Report

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

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%

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

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%

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

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

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

Functional status before dialysis was maintained in only 13% of survivors

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?