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Sheffield Kidney Institute
CKD: An Inflated Bubble?!
Professor Meguid El Nahas, PhD, FRCPSheffield Kidney InstituteGlobal Kidney Academy
Sheffield Kidney Institute
CKDNephrology
Sheffield Kidney Institute
CKD in the Community
a.5%
b.10%
c.30%
Sheffield Kidney Institute
CKD in the > 60 Community
a.5%
b.10%
c.30%
Sheffield Kidney Institute
CKD in the Community
10-15%!?
Sheffield Kidney Institute
CKD in the Community (Did we Invent a Disease?)
UK CKDeGFR ReportingKDOQI
Classification
Sheffield Kidney Institute
K/DOQI 2002
CKD ClassificationStage Description GFR
1 Kidney damage/normal GFR* >90ml/min2 Mild renal insufficiency* 89-603 Moderate renal insufficiency 59-304 Severe renal insufficiency 29-155 Kidney Failure/ERF/ESRD <15
Sheffield Kidney Institute
US Population CKD Prevalence
Stage % number1 GFR:>90 3.3 5.9 millions2 89-60 3 5.33 59-30 4.3 7.64 29-15 0.25 400,0005 <15 0.2 345,000
11% 19.2M
MAeGFR
Sheffield Kidney Institute
Sheffield Kidney Institute
MicroAlbuminuria
• Age• Hypertension, CVD• Metabolic syndrome/ Obesity• Smoking• Infections: Scabies, H Pylori, Hepatitis C, HIV, etc…• Inflammatory diseases: IBD, Psoriasis, periodontitis,• Any “Itis”…!!!!
Sheffield Kidney Institute
Lesson # 1
Albuminuria is a non-specific sign of ill health
The Urine ESR/CRP!
Sheffield Kidney Institute
Is Isolated Microalbuminuria sufficientTo label an individual as suffering from CKD?
Sheffield Kidney Institute
US Population CKD Prevalence
Stage % number1 GFR:>90 3.3 5.9 millions2 89-60 3 5.33 59-30 4.3 7.64 29-15 0.25 400,0005 <15 0.2 345,000
11% 19.2M
MAeGFR
Sheffield Kidney Institute
MDRD & GC
Poggio et al, 2005
?
Sheffield Kidney Institute
eGFR & Kidney Function
Verhave et al, 2005
Sheffield Kidney Institute
Lesson # 2
MDRD eGFR1. Too inaccurate to differentiate between
CKD 1 and 22. Overestimates CKD1-3a
Sheffield Kidney Institute
US Population CKD PrevalenceNHANES III
Stage % number1 GFR:>90 3.3 5.9 millions2 89-60 3 5.33 59-30 4.3 7.64 29-15 0.25 400,0005 <15 0.2 345,000
11% 19.2M
Sheffield Kidney Institute
NEOERICA UK
Stevens et al, 2007
>30%
Sheffield Kidney InstituteDe Lusignan et al, 2011
70% have CVD
Sheffield Kidney Institute
Lesson # 3
CKD in the CommunityManifestation of Older Age
Sheffield Kidney Institute
Albuminuria & AgeingNHANESIII
19%
32.7%
Garg et al, 2002
Sheffield Kidney Institute
Sheffield Kidney Institute
ACR
Albumin
Creatinine
Sheffield Kidney Institute
Lesson # 4
Albuminuria in the CommunityManifestation of Older Age
+Comorbidities
Sheffield Kidney Institute
US Population CKD Prevalence
Stage % number1 GFR:>90 3.3 5.9 millions2 89-60 3 5.33 59-30 4.3 7.64 29-15 0.25 400,0005 <15 0.2 345,000
MAeGFR
Sheffield Kidney Institute
Estimated GFR in “Healthy” Caucasian Females
0
20
40
60
80
100
120
140
160
18-24
25-29
30-34
35-39
40-44
45-49
50-54
55-59
60-64
65-69
70-74
75-79
80-84
85+
Age (years)
eGFR
(m
L/m
in/1
.73m
2)
95th Percentile50th Percentile5th Percentile
Nijmegen Biomedical Study, 2008
Sheffield Kidney Institute
Fall in GFR:Consequence of Ageing
(Is it a Disease…?!)
Lesson # 5
Sheffield Kidney Institute
Sheffield Kidney Institute
ATS & MA
Vascular Stiffness & MA
Sheffield Kidney Institute Minamino and Komuro, 2008
Albumin
Sheffield Kidney Institute
Steno Hypothesis
Deckert et al. 1989
Sheffield Kidney Institute
CKD
Albuminuria
Sheffield Kidney Institute
Lesson # 6
Albuminuria:Consequence of Ageing
Consequence of Vascular Damage
Sheffield Kidney Institute
Ageing & Atherosclerosis
Chonchol et al, 2008
Sheffield Kidney Institute Wesson LG. Physiology of the human kidney.Grune& Straton 1969: 96
ERPF (mL/min/1.73mERPF (mL/min/1.73m²²))
Ageing
ATS
ERPF
Sheffield Kidney Institute
Estimated GFR in “Healthy” Caucasian Females
0
20
40
60
80
100
120
140
160
18-24
25-29
30-34
35-39
40-44
45-49
50-54
55-59
60-64
65-69
70-74
75-79
80-84
85+
Age (years)
eGFR
(m
L/m
in/1
.73m
2)
95th Percentile50th Percentile5th Percentile
Nijmegen Biomedical Study, 2008
Sheffield Kidney Institute
Baltimore Longitudinal
Study on Aging
446 men; >5 years observational period
Subjects with edema and proteinuria
Subjects with hypertension
Subjects without co-morbidity
Creatinine clearance (mCreatinine clearance (mll/min/min)
Sheffield Kidney Institute
Risk of developing CKD with Ageing
Kshirsagar et al, 2008
Sheffield Kidney Institute
Ageing & Atherosclerosis
Sheffield Kidney Institute
ATS & GS
subjects with severe subjects with severe atherosclerosis (n = 57)atherosclerosis (n = 57)
subjects with mild subjects with mild atherosclerosis (n = 57)atherosclerosis (n = 57)
Kasiske BL. 1987
Sheffield Kidney Institute
Lesson # 7
Fall in GFR:Consequence of Ageing
&Vascular Damage/ATS
Sheffield Kidney InstituteCVD
Lipids Smoking
CKD
Arthritis Drugs
DMHT
Lifecourse Exposure
InfectionsPoverty
Sheffield Kidney Institute El Nahas, KI 2010
Cardio-Kidney-Damage (C-K-D)
Sheffield Kidney Institute
Ageing
Albuminuria
GFR
So What?!
Sheffield Kidney Institute KDIGO 2010
Sheffield Kidney Institute KDIGO 2010
Sheffield Kidney Institute
KDIGO 2010
Lancet 2010
Sheffield Kidney Institute
Detection and Prevention Programs
Detection: CKD
Prevention: ESRD
Sheffield Kidney Institute
Sheffield Kidney Institute
US Population CKD Prevalence
Stage % number1 GFR:>90 3.3 5.9 millions2 89-60 3 5.3 millions3 59-30 4.3 7.64 29-15 0.25 400,0005 <15 0.2 345,000
Total 11 19.2millions
CKD
ESRD
Sheffield Kidney Institute
CKD to ESRD
200-100: 1
Nature is doing a great job of prevention of ESRD!!!!!
Sheffield Kidney Institute
Lesson # 8
Only 1:100 CKD patients reach ESRD!!!!
The majority die before they reach ESRD
Sheffield Kidney Institute
Lesson # 9
Screening for CKD to Prevent ESRD Is NOT Cost-Effective!!!
Sheffield Kidney Institute
Age impacts on outcomes in CKD
O’Hare A et al. 2007
210,000 subjects, eGFR<60mls/minute/1.73m², outcomes at 3.5 years
Sheffield Kidney Institute
Detection and Prevention Programs
Detection: C-K-D
Prevention: CVD
Sheffield Kidney Institute
KDIGO 2010
Lancet 2010
Sheffield Kidney Institute
CVD Risk Prediction Scores• Age• Hypertension• Diabetes mellitus• Smoking• Dyslipidemia• Past history of CVD• Family Hx of CVD• +• Albuminuria?• eGFR?
Sheffield Kidney Institute
Description of Studies examining Chronic Kidney Disease Measures to Improve CVD Risk PredictionAuthor Year
Population Primary outcome
Model Predictors Added Biomarkers
Original AUC Change in AUC with biomarkers
Wang42
2006Framingham Offspring Study
Fatal and nonfatal MI, coronary insufficiency, CHF, stroke
Age, sex,DM, smoking status, BP categories, TC, HDL, BMI, creatinine
ACR, BNP
0.76 +0.01
Hallan10
2007Population- based Norwegian study
Cardiovascular death (ICD-10 codes I10-I15, I20- I25, I44-I49, I50, I60-I69, I70-I77)
Age, sex, DM, smoking status, SBP, BP medication, TC, HDL, prevalent CVD
eGFR and ACR categorie
0.76 Age<70 +0.002
Weiner44
2007Pooled from 2 population- based US studies, one study with adults >65 years age
CHD death, nonfatal MI
Age, sex, DM, smoking status, BP categories, TC, HDL
eGFR<60 0.78 +0.002
Zethelius45
2008Community- based cohort of elderly Swedish men (subsample without CVD)
Cardiovascular death (ICD-10 codes I00-I99)
Age, DM, smoking status, SBP, BP medication, TC, HDL, cholesterol medication, BMI
Cystatin C, troponin, CRP, NT- proBNP
0.69 +0.01 (cystatin C)
Shlipak46
2008Adults with pre- existing CHD
CHD death, nonfatal MI, stroke
Age, sex, race, DM, smoking status, HTN, BMI, creatinine, aspirin use, LVEF<50, prior MI, prior stroke
ACR, CRP, NT- proBNP
0.73 +0.04 (all 3 biomarkers)
Ito 201047
Population- based multi- ethnic US study without clinical CVD
CVD death, resuscitated cardiac arrest, nonfatal MI, stroke, angina, PAD, CHF
Age, sex, DM, smoking status, SBP, BP medication, TC, HDL, cholesterol medication, BMI
Creatinin e or cystatin C
0.72 -0.01 (creatinine) +0.02 (cystatin C)
Chang and Kramer, 2011
Sheffield Kidney Institute
Lesson # 10
Adding Albuminuria and/or eGFR toCVD Prediction Scores has little value
Sheffield Kidney Institute
C-K-D
CKDCVD
Sheffield Kidney Institute
CKDNephrology
Sheffield Kidney Institute
Nephrologist