evaluation and management of chronic kidney disease dr. d.adu ghana college cpd august 2011
TRANSCRIPT
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EVALUATION AND MANAGEMENT OF CHRONIC KIDNEY DISEASE
Dr. D.Adu
Ghana College CPD August 2011
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LEARNING OBJECTIVES
• To describe the methods for assessing chronic kidney disease
• To understand the KDOQI classification for staging of CKD
• To understand the epidemiologic burden of CKD• To evaluate the efficacy of medical interventions
needed to slow progression of chronic kidney disease
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WHAT IS CHRONIC KIDNEY DISEASE
• The persistent and usually progressive reduction of kidney function as measured by the glomerular filtration rate
• Retention of urea and creatinine
• Proteinuria and/or haematuria
• Hypertension
• Late stage anaemia and bone disease
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CHRONIC RENAL FAILURE IN AFRICA
0 20 40 60 80 100
MATEKOLE
AKINSOLA
ABBOUD
SEEDAT (B)
SEEDAT (I)
USRDS
HYPERT GN PYELON DIABETES OTHER
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Key Investigations
• Urine Dipstick test for blood and protein• Urine microscopy for rbc, wbc and casts• Urine albumin/creatinine ratio or protein/creatinine
ratio• Creatinine and eGFR• Ultrasound kidneys
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Serum creatinine an inaccurate measure of GFR
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GFR
• Serum creatinine only rises when kidney function is half normal!
• MDRD (Modification of diet in renal disease study) GFR validated (normal 90-120ml/min)
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GFR
• http://www.renal.org/eGFRcalc/GFR.pl
Calculate GFR using the MDRD formula: GFR = 186 X (Creatinine x 0.0113)-1.154 X age-0.203 Women = Multiply x 0.742 Black = Multiply x 1.21
Calculation available online
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UA
LB/C
R
UALB. G/24HR0 1 2 3 4 5 6 7 8 9 10
0
100
200
300
400
500
600
700
800
900
1000
ACR vrs 24 hr Urine Albumin
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K/DOQI Stages of CKD Stage Description GFR mL/min/1.73m2
1 Kidney damage with normal or ↑GFR
>90
2 Kidney damage with mild ↓GFR
60-89
3 Moderate ↓GFR 30-59
4 Severe ↓GFR 15-29
5 Kidney failure <15 or dialysis
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CKD PREVALENCE WORLDWIDE
Country Study CKD Prevalence
95% CI
USA Coresh et al. 2007
13.1% 12.0%-14.1%
Australia White et al. 2010
13.4% 11.1-16.1
Norway Hallan et al. 2006
10.2% (se 0.5)
UK Stevens et al. 2007
8.5% (ckd 3-5)
Nigeria Afolabi et al. 2009
10.4% (ckd 3-5)
DRC Sumaili et al. 2008
12.4% 11-15.1
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Does CKD Matter?
• Few patients with CKD 1-3 progress to renal failure
• But patients with CKD have a high mortality from cardiovascular disease
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Crude incidence rate of end-stage renal disease by category of estimated glomerular filtration rate and category of albuminuria
van der Velde M et al. Kidney Int. 79(12):1341-52
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Age-Standardized Rates of Death from Any Cause (Panel A), Cardiovascular Events (Panel B), and Hospitalization (Panel C), According to the Estimated GFR among 1,120,295 Ambulatory Adults.
Go AS et al. N Engl J Med 2004;351:1296-1305.
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Does CKD Matter?
• CKD associated with increased risk of cardiovascular disease
• Proteinuria and albuminuria associated with increased risk of cardiovascular disease
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DRIVERS FOR CKD IN GHANA
• ≈ 30% of the Ghanaian population older than 40 years have hypertension
• 6.3% of adult Ghanaians have diabetes mellitus
• Glomerulonephritis• Genetic factors: APOL-1 and MYH9
polymorphisms• Herbal nephrotoxins
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9.5
16.2
0
2
4
6
810
12
14
16
18
%
2006
2009
KIDNEY DISEASE AS A PROPORTION OFMEDICAL ADMISSIONS AT KORLE BU
HOSPITAL
10% OF DEATHS ON MEDICAL WARDS DUE TO CKD
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UK Renal Registry 11th Annual Report 2008
Figure 3.5: Incident rates by age and gender in 2007
0
100
200
300
400
500
600
700
20-2
4
25-2
9
30-3
4
35-3
9
40-4
4
45-4
9
50-5
4
55-5
9
60-6
4
65-6
9
70-7
4
75-7
9
80-8
4
85+
Age bandR
ate
per
mill
ion
popu
latio
n
MalesAll UKFemales
CKD ADMISIONS BY AGE KORLE BU
0
20
40
60
80
100
120
11-20
21-30
31-40
41-50
51-60
61-70
71-80
81-90
91-100
AGE
Nu
mb
er o
f su
bje
cts
MALE
FEMALE
TOTAL
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CKD GHANA HOSPITAL QUESTIONS
• Why is the proportion of CKD amongst medical admissions in Ghana increasing
• Why are the peak ages for CKD 20-50 in Ghana as compared with 65-85 in the UK?
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CKD IN HYPERTENSIVE PATIENTS IN GHANA
53.1
8.7
10.4
23.7
3.11
0
10
20
30
40
50
60
70
80
90
100
% o
f s
ub
jec
ts
CKD 5
CKD 4
CKD 3
CKD 2
CKD 1
NO CKD
Osafo C, Mate-Kole M, Affram K, Adu D. Prevalence of chronic kidney disease in hypertensive patients in Ghana. Renal Failure. 2011;33(4):388-92.
27.8% OF HYPERTENSIVE ADULTS IN GHANA HAVE CKD STAGES 3-5
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CKD IN HYPERTENSIVE PATIENTS IN GHANA
• Overall 46.9% of patients had CKD
• 27.8% of patients with hypertension had CKD 3-5 i.e. a GFR of less than 60ml/min/1.73m2
• Blood pressure control overall was poor
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CONCLUSIONS 1
• We report a high prevalence of CKD in hypertensive patients in Ghana
• The cause of the CKD is not known from our study but may be due to hypertension
• The implications of our study if confirmed are of great public health significance
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1
In diabetic and non-diabetic renal disease the following slow the progression of renal impairment
• Treatment of hypertension
• Reducing proteinuria
• Angiotensin blockade
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2
In diabetic and non-diabetic renal disease the following may reduce cardiovascular morbidity
• Stopping smoking
• Statins
• Aspirin
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REMNANT KIDNEY MODEL
right nephrectomy
2/3 ligation ofleft A. renalis
Brenner B.M.
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Hyperfiltration hypothesis (Brenner)
Reduced nephron mass
Glomerular hyperfiltration
Glomerulosclerosis
Glomerular hypertension
Progressive renal failure PROTEINURIA
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Pathologic Processes Leading to Progressive Glomerular Injury and Proteinuria
Increasedglomerularpressure
Ang II
Urinary protein
Efferent arteriolar
constriction
=angiotensin AT1 receptor
ACE INH OR ARB
Increased filtration
Afferent arteriolardilatation
Ang II
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Early Treatment Makes a Difference
Brenner, et al., 2001
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What is the evidence that blood pressure control retards progression of renal disease
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Meta Analysis: Lower Mean BP Results in Slower Rates of Decline in GFR in Diabetics and Non-Diabetics
9595 9898 101101 104104 107107 110110 113113 116116 119119
r = 0.69; P < 0.05
MAP (mmHg)
GF
R (
mL
/min
/yea
r)
130/85 140/90
UntreatedHTN
00
-2-2
-4-4
-6-6
-8-8
-10-10
-12-12
-14-14Parving HH, et al. Br Med J. 1989. Moschio G, et al. N Engl J Med. 1996.Viberti GC, et al. JAMA. 1993. Bakris GL, et al. Kidney Int. 1996.Klahr S, et al. N Eng J. Med 1994. Bakris GL. Hypertension. 1997.Hebert L, et al. Kidney Int. 1994. The GISEN Group. Lancet. 1997.Lebovitz H, et al. Kidney Int. 1994.
Bakris GL, et al. Am J Kidney Dis. 2000;36(3):646-661., www.hypertensiononline.org
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What is the evidence that blood pressure control and angiotensin blockade retards progression of
non diabetic renal disease
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REIN Study: ACE Inhibition in Proteinuric Non-Diabetic Nephropathy
Baseline SBP ∆ SBP Baseline DBP ∆ DBP
Ramipril 149.8 -5.8 mmHg 92.4 -4.2 mmHg
Placebo 148.0 -3.4 mmHg 91.3 -3.4 mmHg
00 66 1212 1818 2424 3030 3636
100
80
60
40
20
0
100
80
60
40
20
0
RamiprilRamipril
PlaceboPlacebo
P=0.02P=0.02
The GISEN Group. Lancet. 1997;349:1857–1863.
% o
f pati
ents
wit
hout
com
bin
ed e
ndp
oin
t*
*Combined endpoint = doubling of baseline serum creatinine concentration or end stage renal failure
www.hypertensiononline.org
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Copyright restrictions may apply.
Agodoa, L. Y. et al. JAMA 2001;285:2719-2728.
Cumulative Incidence of Renal Events and Death with ACE Inhibition in African-Americans
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What is the evidence that blood pressure control and angiotensin blockade retards progression of
diabetic renal disease
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ACE Inhibitors Slow Progression of CKD in Type 1 Diabetes
Lewis et al, NEJM 1993;329:1456-62
p=0.007n=202 vs 207
Years follow-up
0
30
20
10
0 0.5 1.0 2.0 2.51.5 3.0 3.5
% w
ith d
oubl
ing
crea
tinin
e
40
50
Captopril
Placebo
4.0
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0
10
20
30
40
50
Brenner BM, et al. N Engl J Med. 2001;345(12):861-869.©2001 Massachusetts Medical Society. All rights reserved.
†In combination with open-label diuretic, calcium channel blocker, beta-blocker, alpha-blocker, and/or centrally acting agent *doubling of serum creatinine, end stage renal disease, death
RENAAL Patients Reaching the Primary Composite Endpoint*
Cu
mu
lati
ve %
of
pati
en
ts w
ith
even
t
Months240 12 36 48
554
583
Placebo
Losartan
Risk reduction=16%
P=0.02
762
751
689
692
295
329
36
52
Placebo† (n)
Losartan† (n)
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Angiotensin Blockade Provides Greater Renoprotection
Than Other Blood Pressure drugs in Patients with Diabetic and Non-Diabetic Nephropathy
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Who benefits from Angiotensin Treatment and Good Blood Pressure Control? Does Proteinuria Matter?
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Copyright ©2007 American Society of Nephrology
Kent, D. M. et al. J Am Soc Nephrol 2007;18:1959-1965
Risk-stratified outcome rates (doubling of baseline serum creatinine or kidney failure) in patients (with non-diabetic kidney disease) treated with ACE-inhibitors) with and without urinary protein excretion >=500 mg/d.
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ANGIOTENSIN BLOCKADE CONCLUSIONS
• Benefits of angiotensin blockade only seen in patients with significant proteinuria (>0.5 G/day)
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Cumulative Incidence of the Composite Primary Outcome, According to Baseline Proteinuria Status (AASK Study)
Appel LJ et al. N Engl J Med 2010;363:918-929.
x
No proteinuria good prognosis and no
protection from good BP control
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BLOOD PRESSURE CONTROL AND CKD
• Good blood pressure control slows progression of CKD in patients with proteinuria and has no effect in patients without proteinuria
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Target Blood Pressure
• 125/75 if 24 hour urine protein >1G or ACR >100
• 130/80 if 24 hour urine protein<1G or ACR<100
• If aged > 65 aim for 140/80
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What to do with ACEi or ARB induced reduction in GFR
• Check chemistry 2 weeks after starting these drugs and 4 weeks after each change in dose
• If GFR drop >20% discontinue drug and refer ? Renal artery stenosis /ischaemia
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Should we Stop ACEI or ARB in Advanced CKD
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Changes in eGFR after stopping ACEi/ARB in patients with advanced CKD.
Ahmed A K et al. Nephrol. Dial. Transplant. 2010;25:3977-3982
© The Author 2009. Published by Oxford University Press [on behalf of ERA-EDTA]. All rights reserved. For Permissions, please e-mail: [email protected]
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Should we Stop ACEI or ARB in Advanced CKD
YES
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What is the Size of the Problem
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Estimated CKD in Ghana using International Prevalence
Stage Description GFR Prevalence (%)
Number in Ghana
1 Kidney damage with normal GFR
>90 3.3 792,000
2 Mild decrease in GFR
60-90 3.0 72,000
3 Moderate decrease in GFR
30-60 4.3 103,2000
4 Severe decrease in GFR
15-30 0.2 48,000
5 Kidney failure <15 0.1 24,000
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Known CKD <1% of population
Unrecognised CKD
10% of population
• Public education of CKD• Strategies required for prevention of progression• Screen for BP, glucose and proteinuria at Health Centres• Treat with ACEI
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EDUCATION OF THE PUBLIC
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Conclusion 1
• CKD is common in medical admissions in Ghana
• CKD occurs at a younger age (20-50) in Ghana than in the UK
• CKD more common in men than in women
• CKD common in hypertensive patients in Ghana
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Conclusion 2
In diabetic and non-diabetic renal disease
• Treatment of hypertension slows the progression of renal impairment
• Reducing proteinuria slows the progression of renal impairment
• Angiotensin blockade slows the progression of renal impairment
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Statement:
• Any intervention that reduces the incidence or
progression of diabetic/hypertensive renal disease will
have a HUGE IMPACT
• on life expectancy
• quality of life
• costs to society and healthcare payers