CKD: An Inflated Bubble?!

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