prof. el nahas.what is new in ckd
TRANSCRIPT
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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
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Sheffield Kidney Institute
Audience Participation
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Sheffield Kidney Institute
THINK FOR YOURSELF!!!!!
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Sheffield Kidney Institute
THINK CRITICALLY!!!!!
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Sheffield Kidney Institute
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Sheffield Kidney Institute
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Sheffield Kidney Institute
Theme
5Ws
• Why
• What
• Who
• What
• What
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Sheffield Kidney Institute
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?
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Sheffield Kidney Institute
Show ME the Evidence!!!
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Sheffield Kidney Institute
CHALLENGE
DOGMAS!!!
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Sheffield Kidney Institute
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Sheffield Kidney Institute
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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Sheffield Kidney Institute
CKD: Classification
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Sheffield Kidney Institute
CRF: Old Classification
Mild CRF: sCr: 150-300 umol/l
Moderate CRF: sCr: 300-600umol/l
Severe CRF: sCr: >600umol/l
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Sheffield Kidney Institute
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
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Sheffield Kidney Institute
Audience Participation
CKD Classification: What did it add?
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Sheffield Kidney Institute
THINK CRITICALLY!!!!!
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Sheffield Kidney Institute
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 Cr
4 Severe renal insufficiency 29-15
5 Kidney Failure/ERF/ESRD <15
?
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Sheffield Kidney Institute
NICE 2008
CKD Classification
Stage Description GFR
1 Kidney damage/normal GFR >90ml/min
2 Mild renal insufficiency 89-60
3 Moderate renal insufficiency
A 59-45
B 44-30
4 Severe renal insufficiency 29-15
5 Kidney Failure/ERF/ESRD <15
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Sheffield Kidney Institute
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
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Sheffield Kidney Institute
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Sheffield Kidney Institute
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Sheffield Kidney Institute
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Sheffield Kidney Institute
Levey et al. KI, 2011
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Sheffield Kidney Institute
Audience Participation
CKD Classification
How to Improve it?
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Sheffield Kidney Institute
Lesson 1
CKD Classification: Evolving
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Sheffield Kidney Institute
CKD: Definition
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Sheffield Kidney Institute
• 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
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Sheffield Kidney Institute
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
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Sheffield Kidney Institute
QUIZ
The prevalence of microalbuminuria in the community is:
a. 5%
b. 10%
c. 20%
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Sheffield Kidney Institute
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Sheffield Kidney Institute
MicroAlbuminuria
• Age
• Hypertension, CVD
• Obesity
• Metabolic syndrome
• Smoking
• Infections: Scabies, H Pylori, Hepatitis C, HIV, etc…
• Inflammatory diseases: IBD, Psoriasis, periodontitis,
• Any “Itis”…!!!!
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Sheffield Kidney Institute
Lesson 2
Albuminuria is a non-specific and reversible sign
of ill health
The Urine ESR!
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Sheffield Kidney Institute
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Sheffield Kidney Institute
ACR
ACR = Albumin : Creatinine Ratio
<2.5mg/mmol or 25mg/g
<25-30mg/L
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Sheffield Kidney Institute
ACR
Albumin
Creatinine
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Sheffield Kidney Institute
Lesson 3
ACR: Don’t Forget uCreatinine
Raised ACR may be a sign of ageing and wasting;
low urine creatinine excretion!
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Sheffield Kidney Institute
Audience Participation
Albuminuria Evaluation
How to Improve it?
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Sheffield Kidney Institute
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Sheffield Kidney Institute
Indexing ACR to Body Mass and Size
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Sheffield Kidney Institute
US Population CKD Prevalence
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
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Sheffield Kidney Institute
• 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
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Sheffield Kidney Institute
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
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Sheffield Kidney Institute
MDRD & GC
Poggio et al, 2005
?
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Sheffield Kidney Institute
eGFR & Kidney Function
Verhave et al, 2005
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Sheffield Kidney Institute
sCr 120ummol/l
eGFR = 65
True GFR = ?
sCr 60 umol/l
eGFR = 130
True GFR = ?
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Sheffield Kidney Institute
sCr 120ummol/l
eGFR = 65
True GFR = 100
sCr 60 umol/l
eGFR = 130
True GFR = 100
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Sheffield Kidney Institute
eGFR
Is eGFR useful and reliable in the general population?
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Sheffield Kidney Institute
eGFR
Is eGFR useful and reliable in the general population?
NO!!!
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Sheffield Kidney Institute
Lesson 4
Calculated GFR in the general population
= Inaccurate
Cannot accurately distinguish CKD1 and 2!
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Sheffield Kidney Institute
Audience Participation
eGFR
How to Improve it?
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Sheffield Kidney Institute
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Sheffield Kidney Institute
eGFR Improvement
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Sheffield Kidney Institute
JASN 2011
Indexing eGFR to Body Mass and Size
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Sheffield Kidney Institute
Lesson 5
Calculated eGFR is NOT measured GFR
All the problems of serum Creatinine as a
marker of GFR!!!!
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Sheffield Kidney Institute
Serum Creatinine
•1. Intake
• 2. Metabolism
• 3. Glomerular Filtration
• 4. Tubular Secretion
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Sheffield Kidney Institute
CKD:Screening
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Sheffield Kidney Institute
CKD Screening
Who does it pick up?
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Sheffield Kidney Institute
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%
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Sheffield Kidney Institute
NEOERICA UK
Stevens et al, 2007
>30%
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Sheffield Kidney Institute
Lesson 6
CKD in communities is a disease of older age
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Sheffield Kidney Institute
De Lusignan et al, 2011
70% have CVD
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Sheffield Kidney Institute
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
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Sheffield Kidney Institute
Fall in GFR:
Consequence of Ageing
(Is it a Disease…?!)
Lesson 7
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Sheffield Kidney Institute
Lesson 8
CKD in the West
A Disease of Older People
+ CVD
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Sheffield Kidney Institute
El Nahas, KI 2010
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Sheffield Kidney Institute
CKD Screening: Why?
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Sheffield Kidney Institute
Detection and Prevention Programs
Detection: CKD
Prevention: ESRD?
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Sheffield Kidney Institute
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
CKD
ESRD
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Sheffield Kidney Institute
CKD to ESRD
200-100: 1
Nature is doing a great job of prevention of
ESRD!!!!!
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Sheffield Kidney Institute
ESRD Cost
0.1% Cost 1% of Healthcare Budgets
US= 30billion/year!
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Sheffield Kidney Institute
Manns et al, AKDN, 2010
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Sheffield Kidney Institute
Lesson 9
CKD screening of the general population to
prevent ESRD is NOT cost-Effective
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Sheffield Kidney Institute
Screening and Referral of
CKD3 + Proteinuria
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Sheffield Kidney InstituteHallan and Orth, 2010
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Sheffield Kidney Institute
Detection and Prevention Programs
Detection: C-K-D
Prevention: CVD
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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
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Sheffield Kidney Institute
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Sheffield Kidney Institute
KDIGO 2010
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Sheffield Kidney Institute
Low eGFR and Risk of Mortality
Tonelli et al, 2011
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Sheffield Kidney Institute
KDIGO 2010
Lancet 2010
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Sheffield Kidney Institute
THINK CRITICALLY!!!!!
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Sheffield Kidney Institute
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
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Sheffield Kidney Institute
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%
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Sheffield Kidney Institute
Lesson 10
CKD screening of the general population to
prevent CVD is doubtful
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Sheffield Kidney Institute
CKD: Management
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Sheffield Kidney Institute
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 sCr
5 Kidney Failure/ERF/ESRD <15
Refer and Treat!
Prevent
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Sheffield Kidney Institute
To Prevent C-K-D
• Prevent
• Detect
• Treat
NCD: DM, HT, CVD
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Sheffield Kidney Institute
Primary Prevention
National Programmes
C-K-D
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Sheffield Kidney Institute
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 sCr
5 Kidney Failure/ERF/ESRD <15
Refer and Treat!
Prevent
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Sheffield Kidney Institute
CKD Management
Early Referral
Blood Pressure Control
?Reduce Proteinuria
Treat Complications
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Sheffield Kidney Institute
THINK CRITICALLY!!!!!
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Sheffield Kidney Institute
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Sheffield Kidney Institute
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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Sheffield Kidney Institute
Audience Participation