prof. el nahas.what is new in ckd

Sheffield Kidney Institute

What’s New in CKD?Professor Meguid El Nahas

Global Kidney Academy, UK

ERA-EDTA CME Course

Marsa Alam Egypt

February 2012


Audience Participation


THINK FOR YOURSELF!!!!!


THINK CRITICALLY!!!!!


Theme

5Ws

• Why

• What

• Who

• What

• What


5Ws• Why (are we applying this intervention) ?

• What (is the Evidence) ?

• Who (is benefiting Risk:Benefit ratio) ?

• What is the Risk : Benefit?

• What is the Cost : Benefit?


Show ME the Evidence!!!


CHALLENGE

DOGMAS!!!


CKD: What’s NEW?

•New CKD KDIGO Proposed Classification

•New CKD Definition

•New uACR

•New eGFR Formula

•CKD Screening: Who & Why?

•Prevention & Treatment: Who & How?

•How to assess CKD Progression?


CKD: Classification


CRF: Old Classification

Mild CRF: sCr: 150-300 umol/l

Moderate CRF: sCr: 300-600umol/l

Severe CRF: sCr: >600umol/l


K/DOQI 2002

CKD Classification

Stage Description GFR

1 Kidney damage/normal GFR* >90ml/min

2 Mild renal insufficiency* 89-60

3 Moderate renal insufficiency 59-30

4 Severe renal insufficiency 29-15

5 Kidney Failure/ERF/ESRD <15



CKD Classification: What did it add?


K/DOQI 2002

CKD Classification




3 Moderate renal insufficiency 59-30 Cr



?


NICE 2008

CKD Classification


1 Kidney damage/normal GFR >90ml/min

2 Mild renal insufficiency 89-60

3 Moderate renal insufficiency

A 59-45

B 44-30




Classification (cont’d)

– Stage 3 CKD should be split into two subcategories

•3A: GFR 45–59 ml/min/1.73 m2

•3B: GFR 30–44 ml/min/1.73 m2

+p


Levey et al. KI, 2011



CKD Classification

How to Improve it?


Lesson 1

CKD Classification: Evolving


CKD: Definition


• A 75 year old man presents with:

• eGFR = 79 ml/min

• Microalbuminuria: ACR = 10mg/mmol (NR < 2.5)

• BP: 172/82 mmHg

Is this Man suffering from CKD?

CASE DISCUSSION


US Population CKD Prevalence

Stage % number

1 GFR:>90 3.3?! 5.9 millions??

2 89-60 3?! 5.3 millions??

3 59-30 4.3 7.6

4 29-15 0.25 400,000

5 <15 0.2 345,000

Total 11 19.2millions

MA

eGFR


QUIZ

The prevalence of microalbuminuria in the community is:

a. 5%

b. 10%

c. 20%


MicroAlbuminuria

• Age

• Hypertension, CVD

• Obesity

• Metabolic syndrome

• Smoking

• Infections: Scabies, H Pylori, Hepatitis C, HIV, etc…

• Inflammatory diseases: IBD, Psoriasis, periodontitis,

• Any “Itis”…!!!!


Lesson 2

Albuminuria is a non-specific and reversible sign

of ill health

The Urine ESR!


ACR

ACR = Albumin : Creatinine Ratio

<2.5mg/mmol or 25mg/g

<25-30mg/L


ACR

Albumin

Creatinine


Lesson 3

ACR: Don’t Forget uCreatinine

Raised ACR may be a sign of ageing and wasting;

low urine creatinine excretion!



Albuminuria Evaluation

How to Improve it?


Indexing ACR to Body Mass and Size



Stage % number

1 GFR:>90 3.3 5.9 millions

2 89-60 3 5.3

3 59-30 4.3 7.6

4 29-15 0.25 400,000

5 <15 0.2 345,000

Total 11% 19.2millions

MA

eGFR & MDRD

sCr


• A 75 year old man presents with:

• eGFR = 59 ml/min

• Microalbuminuria: ACR = < 2.5mg/mmol

• BP: 172/82 mmHg

Is this Man suffering from CKD?

CASE DISCUSSION


eGFR

MDRD 4 variables formula:

eGFRml/min/1.73m2 =

175 x{[sCr / 88.4] -1.154}x age (years)-.203 x 0.742 if F x1.21 B


MDRD & GC

Poggio et al, 2005

?


eGFR & Kidney Function

Verhave et al, 2005


sCr 120ummol/l

eGFR = 65

True GFR = ?

sCr 60 umol/l

eGFR = 130

True GFR = ?


sCr 120ummol/l

eGFR = 65

True GFR = 100

sCr 60 umol/l

eGFR = 130

True GFR = 100


eGFR

Is eGFR useful and reliable in the general population?


eGFR

Is eGFR useful and reliable in the general population?

NO!!!


Lesson 4

Calculated GFR in the general population

= Inaccurate

Cannot accurately distinguish CKD1 and 2!



eGFR

How to Improve it?


eGFR Improvement


JASN 2011

Indexing eGFR to Body Mass and Size


Lesson 5

Calculated eGFR is NOT measured GFR

All the problems of serum Creatinine as a

marker of GFR!!!!


Serum Creatinine

•1. Intake

• 2. Metabolism

• 3. Glomerular Filtration

• 4. Tubular Secretion


CKD:Screening


CKD Screening

Who does it pick up?


Prevalence of CKD

NHANESIII

0%

5%

10%

15%

20%

25%

30%

35%

40%

Prevalence

(%)

20-39 40-59 60-69 70+

Age Group (years)

<2%

>30%


NEOERICA UK

Stevens et al, 2007

>30%


Lesson 6

CKD in communities is a disease of older age


De Lusignan et al, 2011

70% have CVD


Estimated GFR with Age

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)

eG

FR (

mL/m

in/1

.73m

2)

95th Percentile

50th Percentile

5th Percentile

Nijmegen Biomedical Study, 2008


Fall in GFR:

Consequence of Ageing

(Is it a Disease…?!)

Lesson 7


Lesson 8

CKD in the West

A Disease of Older People

+ CVD


El Nahas, KI 2010


CKD Screening: Why?


Detection and Prevention Programs

Detection: CKD

Prevention: ESRD?



Stage % number

1 GFR:>90 3.3 5.9 millions

2 89-60 3 5.3 millions

3 59-30 4.3 7.6

4 29-15 0.25 400,000

5 <15 0.2 345,000

Total 11 19.2millions

CKD

ESRD


CKD to ESRD

200-100: 1

Nature is doing a great job of prevention of

ESRD!!!!!


ESRD Cost

0.1% Cost 1% of Healthcare Budgets

US= 30billion/year!


Manns et al, AKDN, 2010


Lesson 9

CKD screening of the general population to

prevent ESRD is NOT cost-Effective


Screening and Referral of

CKD3 + Proteinuria

Sheffield Kidney InstituteHallan and Orth, 2010


Detection and Prevention Programs

Detection: C-K-D

Prevention: CVD


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


KDIGO 2010


Low eGFR and Risk of Mortality

Tonelli et al, 2011


KDIGO 2010

Lancet 2010


Description of Studies examining Chronic Kidney Disease Measures to Improve CVD Risk Prediction

Author

Year

Population Primary

outcome

Model Predictors Added

Biomarkers

Original AUC Change in AUC with

biomarkers

Wang42

2006

Framingham

Offspring Study

Fatal and nonfatal

MI, coronary

insufficiency, CHF,

stroke

Age, sex,DM, smoking

status, BP categories,

TC, HDL, BMI,

creatinine

ACR,

BNP0.76 +0.01

Hallan10

2007

Population-

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

2007

Pooled 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

2008

Community-

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

2008

Adults 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


CVD Risk Prediction Scores

• Age

• Hypertension

• Diabetes mellitus

• Smoking

• Dyslipidemia

• Past history of CVD

• Family Hx of CVD

• +

• Albuminuria?

• eGFR?

Chang and Kramer, 2011

76%

76.2%


Lesson 10

CKD screening of the general population to

prevent CVD is doubtful


CKD: Management


K/DOQI 2002

CKD Classification





4 Severe renal insufficiency 29-15 sCr


Refer and Treat!

Prevent


To Prevent C-K-D

• Prevent

• Detect

• Treat

NCD: DM, HT, CVD


Primary Prevention

National Programmes

C-K-D


K/DOQI 2002

CKD Classification





4 Severe renal insufficiency 29-15 sCr


Refer and Treat!

Prevent


CKD Management

Early Referral

Blood Pressure Control

?Reduce Proteinuria

Treat Complications


CKD: What’s NEW?

•New CKD KDIGO Proposed Classification

•New CKD Definition

•New uACR

•New eGFR Formula

•CKD Screening: Who & Why?

•Prevention & Treatment: Who & How?

•How to assess CKD Progression?

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