Transcript GFR talk - ACB South Western and Wessex Region

East Kent Hospitals
NHS Trust
Kidney Function Testing - 1
Dr Edmund Lamb
Ucr x V
Pcr x T
ACB National
Training Course,
September 2007
East Kent Hospitals
NHS Trust
Overview
Part one
• Classification of CKD
• GFR
• Creatinine and eGFR
Part two
• Cystatin C
• Proteinuria/albuminuria
East Kent Hospitals
NHS Trust
What won’t be covered
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Urea
Urinary pH
Urinary osmolality
Fractional bicarbonate
excretion
Ammonium chloride loading
test
Water deprivation test
‘Stone screens’
…etc
East Kent Hospitals
NHS Trust
Why do we care about GFR?
• GFR best overall index of kidney function
• Total kidney GFR = sum individual nephron GFR
• Decreasing GFR seen in all forms of progressive
kidney disease
• Easily understood that kidney acts as a ‘filter’
• Continuous scale, ‘Know your number!’
• Stages of CKD defined in terms of GFR
• Renal NSF recommends eGFR on all serum
creatinine requests
East Kent Hospitals
NHS Trust
Filtration takes place at the
glomerulus
17 mm Hg
100 uL/day/nephron
200 L/day = 140 mL/min
200 L UF/day
East Kent Hospitals
NHS Trust
CKD classification
(NKF-K/DOQI 2002, KDIGO 2005)
Stage
GFR
Management
Prevalencea
1
>90
3.3%
2, mild
60-89
3, moderate
30-59
4, severe
5, failure
15-29
<15
Slow progression,
CVD risk reduction
Estimate progression,
manage hypertension
Manage complications
(anaemia, LVH, 2o hyperPTH,
hyperlipidaemia)
Prepare for RRT
RRT , if appropriate
3.0%
4.3%
0.2%
0.2%
11.0%
a NHANES
III, Coresh et al, AJKD 2003;41:1-12
East Kent Hospitals
NHS Trust
Renal NSF. Part Two: Chronic Kidney Disease,
Acute Renal Failure and End of Life Care
Quality requirements
1.
Early detection of CKD
eGFR
Protein:creatinine ratios
NICE guidance on diabetes (type 1 & 2)
NICE guidance on hypertension
2.
Minimising progression/managing complications
Integrate with CHD/Diabetes NSFs
NICE guidance on anaemia (jn progress)
3.
Identify ARF
4.
Palliative care
East Kent Hospitals
NHS Trust
Renal NSF. Part Two: Chronic Kidney Disease,
Acute Renal Failure and End of Life Care
“Local health organisations can work with pathology services
and networks to develop protocols for measuring kidney
function by serum creatinine concentration together with a
formula-based estimation of GFR, calculated and reported
automatically by all clinical biochemistry laboratories”
Quality requirements
1.
Early detection of CKD
eGFR
Protein:creatinine ratios
NICE guidance on diabetes (type 1 & 2)
NICE guidance on hypertension
2.
Minimising progression/managing complications
Integrate with CHD/Diabetes NSFs
NICE guidance on anaemia (jn progress)
3.
Identify ARF
4.
Palliative care
East Kent Hospitals
NHS Trust
Why detect CKD early?
East Kent Hospitals
Increased risk in CKD
NHS Trust
Age-standardised
Age-standardisedrate
rateofofhospitalizations
cardiovascular
events
death
(per
(per
100
100
person-y)
person-y)
from
any
cause (per 100 person-y)
36.60
144.61
14.14
160
40
16
140
35
14
11.36
120
30
12
86.75
21.80
100
25
10
80
20
8
60
15
6
45.26
11.29
4.79
40
10
4
20
5
2
13.54
2.11
0.76
17.22
3.65
1.08
0
≥60
45–59
30–44
15–29
<15
Estimated
GFR (mL/min/1.73
(ml/min/1.73 m
m22))
Estimated GFR
No. of events
366,757
73,108
25,803
106,543
34,690
11,569
49,177
18,580
7802
20,581
8809
4408
11,593
3824
1842
Go et al NEJM 2004; 351: 1296-1305
East Kent Hospitals
Why detect CKD early? – (1)
complications
NHS Trust
• Better manage CVD risk: increased awareness leading to improved RAAS blockade in hypertensives with
proteinuria
earlier treatment of anaemia
less development of LVH
• Better manage other complications metabolic bone disease
acidosis
nutritional advice
diabetic control
• Avoidance of nephrotoxic drugs
• Suggestion that 45 mL/min/1.73 m2 better threshold (3A/3B)
East Kent Hospitals
NHS Trust
Why detect CKD early? – (2) RRT
• Late referral (i.e. < 3 months before RRT required) of
patients with CKD requiring RRT is common (approx 1/3)
• Late referral commoner in older, female, socially deprived,
sicker patients
• Late referral associated with poor prognosis (even after
adjusting for above) – 3 x risk of death in first months of
dialysis
• Due to dialysis preparation (better access), pre-emptive
transplantation, avoiding uraemic complications (e.g.
hyperkalaemia, pulmonary oedema)
East Kent Hospitals
NHS Trust
East Kent Hospitals
NHS Trust
A questionable test
BY Margaret McCartney, Published: March 3rd 2007
You take your car to the garage. The windscreen wiper isn’t working
properly. Nor is the rear light. It’s minor stuff so you expect a quick turnaround
and an affordable bill. You are told, however, that there is a problem with the
exhaust. It is failing and there is nothing much you can do about it. The mechanic
can offer no odds about how likely the exhaust is to fail but he does offer you
some expensive equipment that may or may not help. You’ll need to let your
insurance company know either way and you’ll need to come to terms with a
large chunk of uncertainty either way about the car’s future driving potential…..
This is not a perfect analogy but it is an approximation of the kinds of
dilemmas being caused by the “eGFR" test. You may or may not have heard of
eGFR, or know that it stands for ESTIMATED GLOMERULAR FILTRATION
RATE. But if you’re on blood pressure medication and have had a blood test
recently, you are likely to have had it measured.
The eGFR……..
East Kent Hospitals
NHS Trust
What are the risks of eGFR reporting?
• Misclassification of CKD due to
imprecision/inaccuracy
• Use of MDRD formula in inappropriate
patient/ethnic group
• Identifying non-disease (e.g. in older people)
• Directing health-care resources to the wrong people
• Clinician didn’t want to know eGFR!
East Kent Hospitals
NHS Trust
How do we assess
GFR?
East Kent Hospitals
NHS Trust
Clearance
Traditionally, GFR assessed using concept of ‘clearance’
Clearance = USV/PST
When substance S has: stable concentration in plasma,
physiologically inert, freely filtered, not secreted,
synthesised, reabsorbed nor metabolised by kidney
then clearance = GFR
East Kent Hospitals
NHS Trust
Gold standard - Inulin
• Fructose polymer (Mr 5,000 Da)
• Gold standard is a constant infusion, urinary clearance
method
• Requires urine collection and infusion
• (Single bolus methods can be used)
• Time-consuming & inconvenient for patient
• Exogenous compound
• Extra-renal clearance 0.083 mL/min/kg
• Expensive and difficult to measure
East Kent Hospitals
NHS Trust
Single bolus technique
Distribution
phase
Log
conc.
k
Co
Time after injection
GFR = k x Co
East Kent Hospitals
NHS Trust
Other exogenous markers
• 51Cr-ethylenediaminetetraacetic acid (EDTA)
• 99mTc-diethylenetriaminepentaacetic acid (DTPA)
• 125I-iothalamate
• Iohexol (Niculescu-Duvaz et al, Kidney Int 2006)
• All have relative advantages and disadvantages
• All give reasonable agreement with gold standard
• 51Cr-EDTA preferred ‘silver standard’ method in UK
Iohexol - outpatient
procedure
East Kent Hospitals
NHS Trust
Non-radioisotopic
HPLC or capillary
electrophoresis
R2=0.96
(Niculescu-Duvaz et al, Kidney
Int 2006)
East Kent Hospitals
NHS Trust
Endogenous markers
No need for injection
Single blood sample (+/- urine) required
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Creatinine clearance
Serum creatinine
Calculated clearances (estimated GFR, eGFR)
Cystatin C
East Kent Hospitals
NHS Trust
Creatinine clearance
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First used in 1937 (Popper and Mandel)
Problems of timed collection
Tubular secretion (exceeds GFR by 10-100%)
Day-to-day CV 25%
“Health resources are wasted by the routine
measurement of creatinine clearance; it should be
abandoned” - Payne 1986
East Kent Hospitals
NHS Trust
Serum creatinine (Mr 113 Da)
• Creatine stored in muscle cells, where it is precursor of
phosphocreatine; a high energy storage compound
• ~2%/day spontaneously breaks down to creatinine
• Clearance predominantly renal
• Therefore, blood conc. reflects renal function
• Most widely used test of renal function
• In east Kent, 450,000 tests/y/600,000 popn.
• Equates to 45 million creatinine assays/y in UK
East Kent Hospitals
NHS Trust
GFR=k/serum
creatinine
GFR
1/Serum
creatinine
Serum
creatinine
Serum creatinine is inversely
related to GFR
GFR
East Kent Hospitals
NHS Trust
Why isn’t serum
creatinine good
enough?
East Kent Hospitals
NHS Trust
Serum creatinine - problems
Non-renal influences:
• gender, ethnicity and age
• nutrition/diet
• drugs (e.g. cimetidine)
• muscle mass
Clinical utility
• Poor sensitivity for CKD
• Not useful in ARF
• Muscle wasting disorders
Analytical problems:
• Non-specificity (protein, ketones, ascorbic acid) (pseudo-chromogens)
• Spectral interferences (icterus/lipaemia/haemolysis)
• No international standardization
East Kent Hospitals
NHS Trust
SCr 110 umol/L
SCr 110 umol/L
GFR 40 mL/min
GFR 120 mL/min
East Kent Hospitals
NHS Trust
Serum creatinine - sensitivity for kidney disease
Plasma
creatinine
(umol/L)
Stage of
kidney disease
5
4
3
2
Glomerular Filtration Rate (ml/min)
Reference
Range
East Kent Hospitals
NHS Trust
Estimated GFR
Equations based on serum creatinine but taking into account
non-renal influences improve its relationship with GFR
“GFR should be estimated from prediction equations that
take into account serum creatinine and some or all of age,
gender, race and body size…….In adults, either
Cockcroft & Gault or MDRD equations are useful”
NKF-KDOQI 2002
East Kent Hospitals
NHS Trust
Serum creatinine - problems
Non-renal influences:
• gender, ethnicity and age
• nutrition/diet
• drugs (e.g. cimetidine)
• muscle mass
Clinical utility
• Poor sensitivity for CKD
• Not useful in ARF
• Muscle wasting disorders
Analytical problems:
• Non-specificity (protein, ketones, ascorbic acid) (pseudo-chromogens)
• Spectral interferences (icterus/lipaemia/haemolysis)
• No international standardization
East Kent Hospitals
NHS Trust
Why eGFR?
• GFR is the best overall index of kidney function
• Gold-standard GFR techniques are not practical
for the entire CKD population
• Estimates of GFR are better/more practical than
creatinine clearance
• Estimates of GFR are more sensitive for CKD
than creatinine alone
East Kent Hospitals
NHS Trust
GFR prediction equations
Cockcroft & Gault, 1976
(140 - age) x weight/0.814 x serum creatinine (x 0.85 if female)
Original MDRD (6-v), 1999
170 x [serum creatinine x 0.011312]-0.999 x age-0.176 x (0.762 if female) x (1.180 if
black) x (serum urea x 2.801)-0.170 x (serum albumin x 0.1)+0.318
Abbreviated MDRD (4-v), 2000
186 x [serum creatinine x 0.011312]-1.154 x age-0.203 x (1.212 if black) x (0.742 if F)
ID-MS traceable MDRD (4-v), 2005
175 x [serum creatinine x 0.011312]-1.154 x age-0.203 x (1.212 if black) x (0.742 if F)
East Kent Hospitals
NHS Trust
Cockcroft & Gault (1976)
R2 0.48
R2 0.69
Coresh et al, AASK study 1998
East Kent Hospitals
NHS Trust
The MDRD Study
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Modification of Diet in Renal Disease Study
1628 patients with CKD
(1070 equation development, 558 testing)
Reference GFR – 125I-iothalamate clearance
Creatinine – kinetic Jaffe on Beckman Astra CX3
(Cleveland Clinic Foundation)
• Stepwise regression approach
East Kent Hospitals
NHS Trust
MDRD formula (6-v)
R2 0.84
Bias 19.8%
Levey et al 1999
R2 0.90
Bias -11.5%
East Kent Hospitals
NHS Trust
MDRD formula (2000)
Abbreviated MDRD (4-v)
186 x [serum creatinine (umol/L) x 0.011312]-1.154 x age0.203 x (1.212 if black) x (0.742 if F)
Published in abstract form only
No requirement for urea and albumin (or weight)
Little loss of accuracy R2 = 0.89, bias -12.1%
90% of subjects within 30% of true GFR
East Kent Hospitals
NHS Trust
ID-MS traceable MDRD formula
(2005)
186 x [serum creatinine x 0.011312]-1.154 x age-0.203 x (1.212 if
black) x (0.742 if F)
Becomes:
175 x [serum creatinine x 0.011312]-1.154 x age-0.203 x (1.212 if
black) x (0.742 if F)
Levey et al 2006
East Kent Hospitals
NHS Trust
C&G vs MDRD
Lewis et al 2001
African-Americans
Vervoort et al 2002
Type 1 diabetes
Bostom et al 2002
CKD patients
Lin et al 2003
Healthy donors
Rodrigo et al 2003
Transplant recipients
Pierrat et al 2003
Children >12 y
Van den Noortgate et al 2003 ‘Old old’
Lamb et al 2003
Older people
Rule et al 2004
Healthy donors
Poggio et al 2005
CKD patients
Poggio et al 2005
Kidney donors
Froissart et al 2005
European CKD
• Reviewed in Ann Clin Biochem September 2005
4v-MDRD offers practical advantages & is more accurate & precise
for stage 3-5 CKD
East Kent Hospitals
National/International
Recommendations
NHS Trust
• NKF – now favour 4v MDRD
• NKDEP – 4v MDRD
• ERA EBPG – any method validated against BSAcorrected GFR
• KDIGO - method validated against a goldstandard measure of GFR
• Kidney Health Australia – 4v MDRD
• UK CKD guidelines/DoH – 4v MDRD
East Kent Hospitals
DoH eGFR Guidance
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a)
b)
c)
Implement eGFR nationally on 1st April 2006
Use IDMS traceable MDRD equation
Report in all adults (not children)
Screen high risk groups (e.g. diabetes, vascular disease, heart failure,
hypertension, urinary tract obstruction, …etc.)
If eGFR exceeds 89 then report as >90
Use UKNEQAS factors to improve consistency
Communicate with users that:
GFR 60-89≠CKD unless other evidence
x1.212 for African-Caribbean’s
not valid in ARF, pregnancy, oedema, muscle wasting, amputees,
malnourished
NHS Trust
East Kent Hospitals
NHS Trust
Why April 1st 2006?
• Quality and Outcomes Framework 2006-7
ChKD 1
Register of patients with CKD 6 points
ChKD 2
% with BP recording
6 points
ChKD 3
% with BP<140/85
11 points
ChKD 4
% on ACEI/ARB
4 points
Context: >600 points in QOF, only 27 for CKD
Approx £250/point for practice of 10,000
Therefore £6,700 for CKD
QOF may = 40% of practice income
East Kent Hospitals
NHS Trust
eGFR –
jumping the gun or
just what the doctor
ordered?
Issues and questions
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•
East Kent Hospitals
NHS Trust
Accuracy
Precision and level of GFR
Sample type – fasting/random
Does it work on older people?
What about South Asians and Chinese?
What about type 2 diabetes?
What about monitoring rate of decline?
Drug dosage – absolute or relative clearance?
Should we correct for BSA? Du Bois or Haycock formula?
Is 1.73 m2 still appropriate? Does it matter (e.g. 1.0 m2 for
LVMI)?
• Outcomes – BSA corrected versus uncorrected GFR
• Etc…
East Kent Hospitals
NHS Trust
Issues and questions
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•
•
Accuracy/standardization
Precision and level of GFR
Sample type – fasting/random
Does it work on older people?
What about South Asians and
Chinese?
• What about type 2 diabetes?
East Kent Hospitals
NHS Trust
Serum creatinine - measurement
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Jaffe methods
Enzymatic methods
HPLC
ID-MS – reference method
Review of the sedimentation
process which is caused in normal
urine by picric acid and a new
reaction of creatinine
By M. Jaffe (Submitted to the
editor on 26th June 1886)
East Kent Hospitals
NHS Trust
3% use enzymatic assay + 13% dry-slide enzymatic
East Kent Hospitals
NHS Trust
UKNEQAS survey: accuracy against ID-MS
% Method Bias from MS Target
60
All methods
55
OCD (J&J) slides [1JJ]
50
Abbott reagents [11AB]
45
Bayer reagents [11TE]
40
Beckman reagents [11BK]
35
Olympus reagents [11OL]
Roche Integra reagents [11RO]
30
Roche Modular reagents [11BO]
25
In-house reagents [14OO]
20
Olympus reagents [14OL]
15
Synermed reagents [14SR]
10
ILab reagents [6IL]
5
0
-5
-10
-15
0
100
200
300
400
500
600
Mass Spec Creatinine (umol/L)
700
800
900
East Kent Hospitals
NHS Trust
Accuracy – possible solutions
• Align all assays to MDRD lab (Beckman Astra
CX3)
• International standardization
• Harmonise equations for assays (UKNEQAS
approach)
East Kent Hospitals
NHS Trust
International standardization
“Serum creatinine assays should be
calibrated using an international standard”
NKF-KDOQI 2002
East Kent Hospitals
NHS Trust
International standardization
Reference measurement system for creatinine, Panteghini et al 2006
East Kent Hospitals
NHS Trust
Harmonisation approaches
SRM 967
NKDEP/IFCC
Assay specific
adjustments
Standardization
Creatinine
result
Specificity
Enzymatic,
IDMS assays
MDRD
equation
eGFR
East Kent Hospitals
NHS Trust
UKNEQAS ‘adjustment’ factors
• Allow alignment of
all major assays for
use in ID-MS
traceable MDRD
formula
Method
Intercept Slope
Abbott
13.21
0.940
Bayer
17.78
0.927
• E.g. for Abbott:
175 x [((serum
creatinine –
13.21)/0.940) x
0.011312]-1.154 x age0.203 x (1.212 if
black) x (0.742 if F)
Beckman
5.92
0.994
Olympus
16.14
0.955
Roche (I)
2.03
0.988
Enzymatic -0.26
1.011
May 2006
40 y old white female,
true creatinine 81 umol/L,
‘true’ eGFR 67 mL/min/1.73 m2
East Kent Hospitals
NHS Trust
as reported by
labs
CV 8.5%,
eGFR 63.1
what could be
achieved with
slope adjustors
CV 6.0%,
eGFR 64.6
East Kent Hospitals
NHS Trust
Issues and questions
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•
•
Accuracy/Standardization
Precision and level of GFR
Sample type – fasting/random
Does it work on older people?
What does it mean in older people?
What about South Asians and Chinese?
What about type 2 diabetes?
Scatter increases as GFR
approaches physiological levels
East Kent Hospitals
NHS Trust
Froissart et al 2005
East Kent Hospitals
NHS Trust
Equation Performance
M. Mafham (Unpublished) 2005
University of Oxford,
Clinical Trials Support Unit
East Kent Hospitals
NHS Trust
MDRD and level of GFR
CKD
‘healthy’
Rule et al 2004
-6.2%
-29%
Poggio et al 2005
-0.5 mL/min/1.73 m2 - 9.0 mL/min/1.73 m2
Froissart et al 2005
1.3 mL/min/1.73 m2
-3.3 mL/min/1.73 m2
•NKDEP/KHA – don’t report if >60 mL/min/1.73 m2
•Scottish Renal Registry – don’t report if >60 mL/min/1.73 m2
•UK CKD – don’t report if >90 mL/min/1.73 m2
East Kent Hospitals
NHS Trust
Issues and questions
•
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•
•
•
•
Accuracy/Standardization
Precision and level of GFR
Sample type – fasting/random
Does it work on older people?
What does it mean in older people?
What about South Asians and Chinese?
What about type 2 diabetes?
East Kent Hospitals
NHS Trust
Creatinine and diet
• Physiologically, protein intake increases GFR
• Cooking meat converts creatine to creatinine
• Readily absorbed and causes increased serum
creatinine (effect persists for hours)
• Reported in BMJ and Lancet letters late
1970’s/early 1980’s
• Effect on eGFR largely ignored – no
recommendation re: sample type
East Kent Hospitals
Effect on serum creatinine
n=32
NHS Trust
Median serum creatinine (Jaffe, umol/L)
Preprandial
1 to 2 h pp
3 to 4 h pp
Meat
80.5
101.0*
99.0*
Non meat
89.5
88.5
86.5
*p<0.001, enzymatic and ID-MS methods showed same trend
Cystatin C was unaffected by meat intake
Preiss et al 2007
East Kent Hospitals
NHS Trust
Effect on eGFR
Median eGFR (Jaffe, mL/min/1.73 m2)
Preprandial
1-2 h pp
3-4 h pp
Meat
84.0
59.5*
64.0*
Non meat
76.5
77.5**
80.0**
*p<0.001, **p<0.01
Preiss et al 2007
East Kent Hospitals
NHS Trust
Issues and questions
•
•
•
•
•
•
Accuracy/standardization
Precision and level of GFR
Sample type – fasting/random
Does it work on older people?
What about South Asians and Chinese?
What about type 2 diabetes?
East Kent Hospitals
NHS Trust
MDRD in older people (1)
Whilst approx. 10% of population overall have
CKD, in over 70 y age group >25% have GFR
<60 mL/min/1.73 m2
A. Is this an artificial problem induced by the
MDRD equation?
B. Does it reflect normal ageing?
East Kent Hospitals
NHS Trust
MDRD in older people (2)
• 46 older people, mean age 80, range 69-92 years
• Mean 51Cr EDTA 55 (range 24-100) mL/min/1.73
m2
• Creatinine results recalibrated to give Beckman
Astra CX3 equivalent data
• eGFR calculated with 4v-MDRD
• Mean bias vs. EDTA -2.0 (95% CI -18 to 14)
mL/min/1.73 m2 (not significant)
Lamb et al 2007
East Kent Hospitals
NHS Trust
Issues and questions
•
•
•
•
•
•
Accuracy/standardization
Precision and level of GFR
Sample type – fasting/random
Does it work on older people?
What about South Asians and Chinese?
What about type 2 diabetes?
East Kent Hospitals
Chinese
NHS Trust
• 684 participants (mean GFR 55+35)
• 99mTc-DTPA reference GFR
• Creatinine calibrated to Beckman Astra CX3
• MDRD underestimates true GFR at normal function and
overestimates GFR at low levels
• 58% within 30% of true GFR
• 175 x [serum creat. x 0.011312]-1.234 x age-0.179 x (0.79 if F)
• Approx. 80% within 30% of true GFR
Zuo et al 2005
Ma et al 2006
East Kent Hospitals
NHS Trust
Other Asian studies
• Pakistani individuals but reference method was
creatinine clearance. Jafar et al. 2005
• Japanese-Americans but reference method was creatinine
clearance, Gerchman et al. Diabetes Res Clin Pract. 2006
East Kent Hospitals
NHS Trust
Issues and questions
•
•
•
•
•
•
Accuracy/standardization
Precision and level of GFR
Sample type – fasting/random
Does it work on older people?
What about South Asians and Chinese?
What about type 2 diabetes?
East Kent Hospitals
Type 2 diabetes
NHS Trust
• MDRD better than C&G for identifying stage 3 and 4
CKD
Rigalleau et al 2005
• Neither MDRD nor C&G accurate in stage 1 or 2 CKD:
underestimate GFR and rate of change in GFR
Rossing et al 2006
• MDRD and C&G underestimate GFR in stage 1 CKD
but can be used to monitor patients in stage 2-3 CKD
Fontsere et al 2006
East Kent Hospitals
NHS Trust
How robust is eGFR?
• Better than creatinine clearance
• As robust as the underlying serum
creatinine measurement….
• But highlights age and gender related
influences
• eGFR is improving recognition of CKD
• But, there are problems…
East Kent Hospitals
NHS Trust
Remaining issues
Need to:
• be more prescriptive about sample (fasting, delay)
• improve methodology (? enzymatic assays,
international standardization – NIST SRM 967)
• better define CKD and identify progressors
• better understand natural history of CKD
(especially wrt older people)
East Kent Hospitals
NHS Trust
Where do we go from here?
• Debate has been started in laboratory and nephrology
community
• Attention re-focused on creatinine measurement
• Manufacturer’s likely to move towards ID-MS alignment
with an international creatinine standard
• Validation of MDRD equation being expanded and
limitations better understood
• Many areas remain controversial
• Better markers of GFR still needed
East Kent Hospitals
NHS Trust
Serum urea
• Poor indicator of GFR
• Affected by extra-renal factors (high-protein diet,
increased protein catabolism, GI haemorrhage,
liver disease, dehydration)
• Main use is in conjunction with creatinine (ratio)
• Many laboratories have abandoned ‘U & E’s’
Hierarchy of GFR tests
Inaccurate
• Urea
East Kent Hospitals
NHS Trust
Relatively
practical
• 24 hr CCr
• Creatinine
• Cystatin C
• eGFR
• 3 hr CCr with Cimetidine
•
99mTc-DTPA
•
125I-iothalamate
• Iohexol
•
51Chromium-EDTA
• Inulin
Accurate
Impractical for
widespread use
East Kent Hospitals
NHS Trust
End
East Kent Hospitals
NHS Trust
56 y white male, pool 123
Distribution 8, May 2006
CV 5.6%, eGFR 58
Distribution 16, Feb 2007
CV 4.9%, eGFR 59
East Kent Hospitals
NHS Trust
Has the eGFR UK NEQAS been a
success?
• Appears to have been early and widespread
participation and uptake of factors in laboratories
• Between lab. CVs for eGFR respectable
• UK NEQAS have undertaken to provide support
(factors) for new methods and on-going periodic
adjustment/checks of existing factors
• Ultimate aim is to improve creatinine
measurement
East Kent Hospitals
NHS Trust
CKD prevalence: calibration &
population estimates
Stage GFR
Prevalencea Prevalenceb Prevalencec
1
2
3
4
5
3.3%
3.0%
4.3%
0.2%
0.2%
>90
60-89
30-59
15-29
<15
a NHANES
5.43%
0.22%
0.05%
9.19%
0.35%
0.05%
III, Coresh et al, AJKD 2003;41:1-12
b NEOERICA, n=162,000, crude data, Stevens et al Kidney Int 2007
c NEOERICA, n=162,000, after calibration, Stevens et al Kidney Int 2007