Prof. el nahas.what is new in ckd.

What’s New in CKD?
Professor Meguid El Nahas
Global Kidney Academy, UK

ERA-EDTA CME Course
Marsa Alam Egypt
February 2012
Sheffield Kidney Institute

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

1
2
Kidney damage/normal GFR*
Mild renal insufficiency*
>90ml/min
89-60
?
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


CASE DISCUSSION

• 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?

US Population CKD Prevalence

Stage % number
1 GFR:>90 3.3?! 5.9 millions??
MA
2 89-60 3?! 5.3 millions??
3 59-30 4.3 eGFR 7.6
4 29-15 0.25 400,000
5 <15 0.2 345,000
Total 11 19.2millions

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
MA
2 89-60 3 5.3
3 59-30 4.3 eGFR & MDRD 7.6
4 29-15 0.25 400,000
5 <15 0.2 sCr 345,000
Total 11% 19.2millions


CASE DISCUSSION

• 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?

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 sCr 60 umol/l
eGFR = 65 eGFR = 130
True GFR = ? True GFR = ?

sCr 120ummol/l sCr 60 umol/l
eGFR = 65 eGFR = 130
True GFR = 100 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


Indexing eGFR to Body Mass and Size

JASN 2011

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
40%
35%
30% >30%
25%
Prevalence <2%
20%
(%)
15%
10%
5%
0%
20-39 40-59 60-69 70+
Age Group (years)


NEOERICA UK

>30%

Stevens et al, 2007

Lesson 6

CKD in communities is a disease of older age


70% have CVD

De Lusignan et al, 2011

Estimated GFR with Age

160

140
eGFR (mL/min/1.73m2)

120

100
95th Percentile
80 50th Percentile
5th Percentile
60

40

20

0
18- 25- 30- 35- 40- 45- 50- 55- 60- 65- 70- 75- 80- 85+
24 29 34 39 44 49 54 59 64 69 74 79 84

Age (years)

Nijmegen Biomedical Study, 2008

Lesson 7

Fall in GFR:
Consequence of Ageing
(Is it a Disease…?!)


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 CKD 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
ESRD
Total 11 19.2millions

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


Hallan and Orth, 2010

Detection and Prevention Programs

Detection: C-K-D

Prevention: CVD

Age impacts on outcomes in CKD
210,000 subjects, eGFR<60mls/minute/1.73m², outcomes at 3.5 years

O’Hare A et al. 2007

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 Population Primary Model Predictors Added Original AUC Change in AUC with
Year outcome Biomarkers biomarkers
Wang42 Framingham Fatal and nonfatal Age, sex,DM, smoking ACR, +0.01
2006 Offspring Study MI, coronary status, BP categories, 0.76
insufficiency, CHF, TC, HDL, BMI, BNP
stroke creatinine

Hallan10 Population- Cardiovascular Age, sex, DM, eGFR and Age<70 +0.002
2007 based death (ICD-10 smoking status, SBP, 0.76
Norwegian codes I10-I15, I20- BP medication, TC, ACR
study I25, I44-I49, I50, HDL, prevalent CVD categorie
I60-I69, I70-I77)

Weiner44 Pooled from 2 CHD death, Age, sex, DM, eGFR<60 +0.002
2007 population- nonfatal MI smoking status, BP 0.78
based US categories, TC, HDL
studies, one
study with adults
>65 years age

Zethelius45 Community- Cardiovascular Age, DM, smoking Cystatin +0.01 (cystatin C)
2008 based cohort of death (ICD-10 status, SBP, BP 0.69
elderly Swedish codes I00-I99) medication, TC, HDL, C,
men (subsample cholesterol troponin,
without CVD) medication, BMI
CRP, NT-
proBNP
Shlipak46 Adults with pre- CHD death, Age, sex, race, DM, ACR, +0.04 (all 3
2008 existing CHD nonfatal MI, stroke smoking status, HTN, 0.73
BMI, creatinine, CRP, NT- biomarkers)
aspirin use, LVEF<50, proBNP
prior MI, prior stroke
Ito Population- CVD death, Age, sex, DM, Creatinin
201047 based multi- resuscitated smoking status, SBP, 0.72 -0.01 (creatinine)
ethnic US study cardiac arrest, BP medication, TC, e or +0.02 (cystatin C)
Sheffield Kidney clinical
Institute
without nonfatal MI, stroke, HDL, cholesterol cystatin C
CVD angina, PAD, CHF medication, BMI
Chang and Kramer, 2011

CVD Risk Prediction Scores
• Age
• Hypertension
• Diabetes mellitus
•
•
Smoking
Dyslipidemia
76%
• Past history of CVD
• Family Hx of CVD
• +
•
•
Albuminuria?
eGFR?
76.2%
Chang and Kramer, 2011

Lesson 10

CKD screening of the general population to
prevent CVD is doubtful


CKD: Management


K/DOQI 2002
CKD Classification
Prevent
4 Severe renal insufficiency 29-15 sCr


Refer and Treat!

To Prevent C-K-D
• Prevent
• Detect
• Treat

NCD: DM, HT, CVD

Primary Prevention
National Programmes

C-K-D

K/DOQI 2002
CKD Classification
Prevent
4 Severe renal insufficiency 29-15 sCr

Refer and Treat!

CKD Management

Early Referral
Blood Pressure Control
?Reduce Proteinuria
Treat Complications


Prof. el nahas.what is new in ckd.

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