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| Journal of the New Zealand Medical Association,
05-March-2010, Vol 123 No 1310
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Implication of using
estimated glomerular filtration rate (GFR) in a multi ethnic population of
diabetes patients in general practice
Chronic kidney disease (CKD) among diabetes patients is
increasing in incidence globally.1 CKD is
classified into five stages based on severity as below (Table
1)2 using glomerular filtration rate
(eGFR).
Table 1. The five stages of chronic kidney
disease
It is estimated that 16% of New Zealanders have some form of
kidney damage. Diabetes has been the primary cause of 36 to 45% of cases of end
stage kidney disease (CKD stage 5) in New Zealand patients between 1999 and
2004,3 with significant ethnic differences in
incidence.4 Surveys in primary care patients
with diabetes have identified
24%5–31%6
with evidence of CKD (eGFR <60
ml/min/1.73m2). CKD remains the second most
likely cause of death and morbidity after cardiovascular disease in diabetes,
and CKD is a major independent risk factor for cardiovascular
disease.7
Evidence suggests that progression to kidney failure in
patients with diabetes can be delayed or prevented by controlling blood sugar
levels and blood pressure and by treating
proteinuria.8–10 The key is detecting
chronic kidney disease in its earliest, most treatable stages. Primary care
physicians have been encouraged to test for macro and micro albuminuria and to
estimate the albumin-creatinine ratio (ACR). It has also been suggested that
estimating the glomerular filtration rate is a more sensitive method of
identifying early renal failure.5
The eGFR, calculated by using the MDRD equation (named after
the US Modification of Diet in Renal Disease
Study11), detects chronic kidney disease more
accurately than does the serum creatinine level alone. The eGFR rate also is
used for disease staging.
Using the MDRD equation, laboratories are now able to
routinely report eGFR derived from the serum creatinine concentration, age and
gender. It does not require body surface-area measurements. In their position
statement, the Australasian Creatinine Consensus Working Group, recommended that
an eGFR based on the abbreviated MDRD formula be reported with every request for
serum creatinine in patients over the age of 18
years.12
Over 69% of New Zealand laboratories report eGFR results
with most requests for serum creatinine in patients aged >18
years.13 New Zealand Guidelines
Group14 recommends calculation eGFR using
CG15 method which uses age, serum creatinine,
gender, body weight and height or using the MDRD
formula.11 There is concern over the validity
of either method in Māori.
The MDRD calculation makes an adjustment for ethnicity in
the case of black Americans, but no such adjustment factor has been developed
for other non-European ethnicities including
Māori.16 Consequently, we wanted to
investigate the prevalence of CKD in a population of New Zealand patients with
diabetes and measure the agreement between the MDRD and CG formulae in
identifying CKD among both Europeans and Māori in New Zealand.
Key indicators of quality treatment in patients identified
with early CKD include good glycaemic control, management of blood pressure to
agreed targets, the use of ACE inhibitors to reduce progression of renal disease
and use of statins to reduce the risk of cardiovascular
disease.14,17 We have reviewed the management
of diabetes in patients with evidence of CKD by comparing blood pressure
control, glycaemic control, the use of ACE and the use of statins among patients
with or without evidence of renal disease.
MethodA cross-sectional survey was conducted on all patients
registered with 10 practices within the Rotorua General Practice Group in
Rotorua New Zealand. The survey identified all patients registered with the
practices on 1 July 2007. Patients with diabetes were identified by searching
electronic patient records for diagnostic code for diabetes, “Get
Checked” diabetes annual review (DAR), prescription of insulin or oral
hypoglycaemic, laboratory records of HbA1c greater than 6.5%.
Records were reviewed, for patients who were identified
from prescriptions or laboratory records but did not have a diabetes code, to
confirm the diagnosis of diabetes. Information on metabolic control, blood
pressure, body measurements and treatments (Statin or ACE prescription) were
extracted either from the DAR database or from patient records where it was not
otherwise available. We excluded newly diagnosed patients as they may not have
had time to be fully assessed or optimum treatment to be instituted. Both MDRD
and CG formulas were used to calculate eGFR.
  Estimates of eGFR could only be made in patients where
age, gender, ethnicity, weight and serum creatinine were all available. Those
with missing data in any of these categories have been excluded from this
analysis. Microalbuminuria [ACR 2.5–29.9 mg/mmol creatinine (men),
3.5–29.9 (women)] and proteinuria (ACR ≥30) were defined as per
local guidelines.14 Ethnic and gender specific
prevalence of clinically significant CKD (eGFR <60
ml/min/1.73m2)
has been calculated.
Chi-squared test was used to test differences in
proportions and ANOVA was used to test differences in means. Agreement between
the two formulas in identifying patients with eGFR <60
ml/min/1.73m2 was tested using McNemar’s
Chi-squared test. Kappa statistics for agreement has also been reported.
Logistic regression model was used to identify predictors of clinically
significant CKD. All statistical analyses were performed using SAS, 9.1 (SAS
Institute, Cary, NC, USA).
ResultsThe total population in the 10 practices was 48,545 (34,051
aged 18 or above). Of the 1819 (3.74%) diabetes patients identified, 1353 (74%)
had a DAR in the last 2 years. 342 (19%) patients did not attend a DAR. 124
(6.8%) were newly diagnosed (36 Māori, 74 NZ European, 14 Others). 1796
were aged 18 or above. Glomerular filtration rate could be estimated using both
MDRD and CG equations for 942 adult patients aged 18+, who had serum creatinine,
body weight and height data available from DAR records. Among them, 772 (82%)
were recorded as having Type 2 diabetes and 65 (7%) as having Type 1 diabetes.
105 (11%) did not have type of diabetes recorded. Clinical and demographic
characteristics of these patients are summarised in Table 2.
Table 2. Demographic and clinical
characteristics of diabetes patients by ethnicity and gender
* Serum creatinine and ACR are reported as median
(interquartile range). Other data are mean±SD or n
(%).
Compared with Europeans, Māori patients were on average
5.9 years younger (p<0.0001), had higher BMI (+3.1
kg/m2, p<0.0001), significantly higher rates
of microalbuminuria /proteinuria (51% versus 28% among Europeans, p<0.0001)
and higher HbA1c levels (42% with
HbA1c >8% versus 30% among Europeans,
p<0.0002). The extent of Statin and ACE therapy among Māori patients was
similar to that in Europeans, but their prevalence of smoking was substantially
higher (26% versus 12% among Europeans, p<0.0001).
Overall prevalence of CKD among diabetes patients as
identified through eGFR<60 ml/min/1.73m2 was
19.5% using MDRD and 23.5% using CG. Prevalence of CKD, among European (18.8%
using MDRD, 25.9% using CG) and Māori (20.4% using MDRD, 19.1% using CG)
diabetes patients, in various subgroups of clinical characteristics is outlined
in Tables 3 and 4 respectively. The prevalence of eGFR <30
ml/min/1.73m2 among European and Māori was
2% and 3% respectively using MDRD, 3% and 3% respectively using CG.
There are significant differences in the agreement between
MDRD and CG equations in identifying patients with eGFR <60
ml/min/1.73m2 for Māori females, European
females and European males (Table 5). While CG equation identifies more European
of both genders, more Māori females are identified by MDRD.
Table 3. Prevalence of renal disease
(eGFR<60 ml/min/1.73m2) among European
diabetes patients, eGFR estimated using MDRD and Cockroft-Gault (CG)
equations
Data are number of people [n
(%)] with eGFR<60 ml/min/1.73m2 in each
subgroup; * The BMI cut-off points as in the
2002/03 New Zealand Health Survey were used to classify overweight and obesity
(25 and 30 respectively in European, 26 and 32 respectively in Maori);
† Systolic BP ≥ 130 mmHg or
Diastolic BP ≥ 80 mmHg
Table 4. Prevalence of renal disease
(eGFR<60 ml/min/1.73m2) among Māori
diabetes patients, eGFR estimated using MDRD and Cockroft-Gault (CG)
equations
Data are number of people [n
(%)] with eGFR<60 ml/min/1.73m2 in each
subgroup; * The BMI cut-off points as in the
2002/03 New Zealand Health Survey were used to classify overweight and obesity
(25 and 30 respectively in European, 26 and 32 respectively in Maori)’
† Systolic BP ≥ 130 mmHg or
Diastolic BP ≥ 80 mmHg.
Table 5. Agreement between MDRD and CG
equations in identifying patients with eGFR<60
ml/min/1.73m2
Statin and ACE prescriptions among CKD patients were higher
in the presence of microalbuminuria / proteinuria (71% vs. 57%, p=0.02 and 79%
vs. 61%, p=0.001 respectively). CKD patients with normal ACR levels had better
control of HbA1c (80% with
HbA1c<8% vs. 66%, p=0.01) and blood pressure
(34% with BP<130/80 vs. 20%, p=0.01) compared with CKD patients with
microalbuminuria / proteinuria. (Table 6).
Table 6. Differences in management of diabetes
patients with evidence of CKD compared with diabetes patients with normal renal
function
After adjustment for age, gender and BMI, Māori
diabetes patients were significantly more likely to have clinically significant
CKD compared with Europeans [odds ratio 1.8 (1.2, 2.8) using MDRD equation].
Similar results were yielded using CG equation.
DiscussionMāori and Pacific people with Type 2 diabetes have
significantly higher rates of End Stage Renal Failure (ESRF), proteinuria and
microalbuminuria than Europeans.19 They are
have higher rates of risk factors; obesity, smoking and poorer metabolic
control.4 Differences in rates of proteinuria
and microalbuminuria and degree of glomerular hyperfiltration are seen within 5
years of diagnosis.20
The increased risk of diabetic nephropathy among Māori
and Pacific people is thought to be related to a family history of nephropathy
rather than family history of diabetes.21
We investigated the prevalence and associations of CKD in
this general practice based study of diabetes patients aged 18 and above, with
high Māori representation. Overall prevalence of clinically significant CKD
(eGFR<60 ml/min/1.73m2) using eGFR was
similar to that found in general practice populations in
Australia.6 (24.3% using CG), but lower than
that in the UK5 (31.3% using MDRD). The
prevalence of proteinuria and microalbuminuria were similar to previous studies.
We have found a higher prevalence of clinically significant
CKD (as indicated by an eGFR<60
ml/min/1.73m2) among those with longer duration
of diabetes (10+ years).Raised HbA1c and blood
pressure was associated with microalbuminuria/proteinuria and those patients
were more likely to be prescribed statin or ACE.
Among people with clinically significant CKD, those without
microalbuminuria/proteinuria were less likely to be prescribed statin or ACE
than those with microalbuminuria / proteinuria, although they were also at high
risk of cardiovascular disease. Interestingly, this group of patients tended to
have good metabolic control, but only 34% were recorded as having blood pressure
<130/80 mmHg. Routine monitoring of eGFR along with serum creatinine would
identify this group of patients to their general practitioner as being in need
of more intensive treatment of their blood pressure as well as glycaemic
control.
Treatment with ACE inhibitors was much higher compared with
figures from the UK where only one-third of diabetes patient with CKD stages
3–5 were ACE treated.5 Only those
patients with completed data were included in the analyses, which could possibly
introduce a selection bias favouring regular attendees, raising the proportion
with ACE / Statin prescriptions.
The MDRD equations were derived from patients with varying
degrees of renal impairment employing a stepwise regression technique, where GFR
was measured from the renal clearance of [125I]
iothalamate.11 On the other hand,
Cockcroft-Gault formula was constructed from hospitalised patients to predict
creatinine clearance from the serum creatinine in the absence of urine
collection.15
It has been shown that MDRD equation consistently
underestimates GFR, whereas the CG equation
consistently overestimates GFR in people
without kidney disease.22 In contrast, a New
Zealand study with predominantly Europeans subjects found that the MDRD formula
produced a statistically significant overestimation of GFR and the CG prediction
equation gave a statistically significant underestimation of
GFR,23 but there was no significant difference
in performance in estimating GFR between the two prediction equations.
A validation study in patients with ESRD showed that the
MDRD equation is more accurate than the
Cockcroft-Gault formula in
predicting the group
mean.24 However, the predicted GFR using either
formula was related to the basal GFR and
percentage body fat. MDRD is said to be preferable to the CG method in patients
with diabetes.25 However, our results indicate
that while CG will identify more European diabetes patients at risk of CKD, it
seem to miss some Māori women with diabetes.
The National Kidney Foundation in the
US26 and the National Service Framework for
Renal Services in the UK27 have recommended
routine eGFR reporting. It has been endorsed by several other counties including
New Zealand, Australia, Canada.28,29 A recent
review has shown the increasing use of eGFR in America, Europe, Asia and
Australia, in population based studies which look at the prevalence of
CKD.30 Automatic reporting of eGFR, which
constitutes de facto screening for chronic kidney disease is of
concern,31 given that and the validity of eGFR
for this purpose has not been appropriately
tested.32,33
Given the higher rates of renal complications among
Māori, robust screening tools are needed to identify complications at an
early stage. Automatic reporting of MDRD eGFR serves as a useful screening tool
for kidney disease, although clinicians should recalculate it using the
patient's actual body surface area for patients with extreme body
size.12
The MDRD equation has a correction factor for black
ethnicity. Given the high obesity rates, a similar correction factor may be
required for Māori and other high risk ethnic minorities. Australasian
Creatinine Consensus Working Group's recommends that laboratories continue to
automatically report eGFR (MDRD) in Aboriginal and Torres Strait Islander
peoples and other ethnic groups, pending publication of ethnic specific
validation studies.28
More research is needed to develop a modified equation with
a correction factor for Māori and similar high risk ethnicities. It appears
that a generic approach will be unsuccessful in considering the validity of the
eGFR in ethnic subpopulations. Each such subpopulation may need to be validated
separately, and by gender.
Competing interests: None known.
Author information: Grace Joshy, Waikato
Clinical School, University of Auckland, Hamilton; Tesa Porter, Medical Student,
University of Otago, Christchurch;
Clem Le Lievre, Rotorua General Practice Group, Rotorua; Jane Lane, Rotorua General Practice Group, Rotorua; Mike Williams, Rotorua General Practice Group, Rotorua; Ross Lawrenson, Waikato Clinical School, University of Auckland, Hamilton Acknowledgements: This study was supported
by a grant for summer studentship from the Royal College of New Zealand General
Practitioners. We also thank Dr Margaret Fisher (Renal Physician, Waikato
Hospital) for her valuable input.
Correspondence: Grace Joshy,
Research Fellow in Diabetes Epidemiology, Waikato Clinical School,
Private Bag 3200, Waikato Hospital, Hamilton, New Zealand. Email joshyg@waikatodhb.govt.nz
References:
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