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
Stage
GFR
Description
1
90+
Normal kidney function but urine or other abnormalities
may point to kidney disease
2
60-89
Mildly reduced kidney function, but urine or other
abnormalities may point to kidney disease
3
30-59
Moderately reduced kidney function
4
15-29
Severely reduced kidney function
5
14 or
less
Very severe, or endstage kidney failure (sometimes
called established renal failure)
Prevalence of CKD
CKD
I
2
3
4
5
NHANES
3.3
3.0
4.3
0.2
0.1
AusDiab
0.9
2.0
10.9
0.3
0.003
NEOERICA
4.2
0.17
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)
Prevalence of Chronic Kidney Disease (CKD) Stages by
Age Group in NHANES 1988-1994 and 1999-2004
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 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
Rate of change in eGFR by age and eGFR at baseline
% with annual eGFR reduction
>3ml/min/1.73m
60
50
40
CKD 3a
CKD 3b
30
CKD 4
CKD 5
20
10
0
18-44
45-55
55-64
65-74
75-84
85-100
Age group
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
8
Normal kidney function
CKD 1-2
7
CKD 3-5
Events/100 yrs
6
5
4
3
2
1
0
All cause
death
CV death
Non-CV
death
Heart failure
MI
Stroke
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
Obesity
Dyslipidaemia
Proteinuria
Low birth
weight
Age
Oxidative
stress
Hypertension
Primary
kidney disease
Diabetes
Progressive CKD
Inflammation
Smoking
Vascular compliance
African
American
Poverty
Increased
homocysteine
Vitamin D
deficiency
Endothelial
dysfunction
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
– ? 500-1000mg/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 <60 + ACR >30 = 13%
• Absolute indication?
– Proteinuria >1g (uPCR >100)
“Recommendations”
• Target BP…….
– Proteinuria low: ACR<70 or PCR<100
• Target BP <140/90 (NICE suggests 130139/90)
– Proteinuria high: ACR>70 or PCR>100
• Target BP <130/80 (NICE suggests 120129/80)
• 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”
Figure 7.3b: Kaplan-Meier 10-year survival of incident patients 1997-2006
cohort (from day 0), w ith censoring at transplantation
100
90
Percentage survival
80
70
60
50
40
30
20
10
18-34
35-44
45-54
55-64
65-74
75+
0
0.0 0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0 5.5 6.0 6.5 7.0 7.5 8.0 8.5 9.0 9.5 10.0
Period (years)
UK Renal Registry 11th Annual Report
Unadjusted survival of all incident patients by
age band – 2005 cohort
100
95
90
Percentage survival
85
80
75
70
65
60
55
50
45
40
18- 35- 45- 55- 65- 75- 85+
34 44 54 64 74 84
90 day
18- 35- 45- 55- 65- 75- 85+
34 44 54 64 74 84
Age bands
1yr after day 90
18- 35- 45- 55- 65- 75- 85+
34 44 54 64 74 84
0-1yr
Figure 3.5: Incident rates by age and gender
in 2007
Males
All UK
Females
600
500
400
300
200
100
Age band
85+
80-84
75-79
70-74
65-69
60-64
55-59
50-54
45-49
40-44
35-39
30-34
25-29
0
20-24
Rate per million population
700
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
Tamura et al NEJM 2009: 361, 1539–1547
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?