Race differences in prevalence of chronic kidney disease among young adults using creatinine-based glomerular filtration rate-estimating equations

Article (PDF Available)inNephrology Dialysis Transplantation 25(12):3934-9 · December 2010with36 Reads
DOI: 10.1093/ndt/gfq299 · Source: PubMed
Abstract
Despite a higher incidence of end-stage renal disease (stage 5), blacks have been shown to have the same or lower prevalence of chronic kidney disease (CKD stages 3 and 4). Current creatinine-based glomerular filtration rate (GFR)-estimating equations may misclassify young, healthy blacks. Among 3501 young adults (mean age 45), we compared the prevalence of CKD in blacks and whites using the Modification of Diet in Renal Disease (MDRD) and the CKD Epidemiology Collaboration (CKD-EPI) equations. In addition, we used measured creatinine excretion rates to determine the actual excretion ratio for CARDIA (race coefficient 12%) and applied this to the CKD-EPI equation. We also studied the prevalence of CKD risk factors among black and white participants near the CKD threshold cut-off (eGFR CKD-EPI 60-80 mL/min/1.73 m(2)) to estimate the relative likelihood of misclassification in blacks and whites. Using the MDRD equation, prevalence of CKD stages 4 and 5 was higher for blacks compared with whites (0.6% vs. 0.1%, P-value 0.05). In contrast, prevalence of eGFR <60 mL/min/1.73 m(2) was significantly higher for whites (3.6%) compared with blacks (1.9%), due to higher prevalence of stage 3 among whites. Prevalence of CKD was similar for blacks and whites using CKD-EPI equation (1.2%), but was higher among blacks when using the CARDIA-derived race coefficient (1.6% vs.1.2%, P-value = 0.03). Among persons with eGFR by CKD-EPI of 60-80 mL/min/1.73 m(2), blacks had higher levels of albuminuria, uric acid, systolic blood pressure and higher diabetes prevalence. CKD classification among young blacks is very sensitive to the race coefficients. Despite whites having higher rates of CKD stage 3, blacks with eGFRs just above the CKD threshold had higher rates of CKD risk factors. Current equations used to define CKD may systematically miss a high-risk group of blacks at a time in the disease course when interventions are crucial.

Figures

obesity and metabolic syndrome; however, this replicated
genetic association suggests that it makes important con-
tributions to nephropathy susceptibility in Asian- and
European-derived indiv iduals with T2DM. Novel treat-
ments to prevent diabetic kidney disease could result from
this observation.
Acknowledgments. This study was supported by the Seed Funding
Programme for Basic Research of the University of Hong Kong (S.C.W.T.)
and NIH grants R01 DK053591 (D.W.B.) and RO1 DK070941 (B.I.F.).
The authors are grateful to Wendy W.S. Tsui, Desmond Y.H. Yap, Maggie
K.M. Ma, all Sai Ying Pun GOPC doctors and nurses for helping with
patient recruitment, to Anita Tsang for specimen sorting, to Sandra Luen
for coordination and to all the study participants.
Conflict of interest statement. None declared.
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Received for publication: 26.3.10; Accepted in revised form: 10.5.10
Nephrol Dial Transplant (2010) 25: 39343939
doi: 10.1093/ndt/gfq299
Advance Access publication 2 June 2010
Race differences in prevalence of chronic kidney disease among
young adults using creatinine-based glomerular filtration
rate-estimating equations
Carmen A. Peralta
1,2
, Feng Lin
3
, Michael G. Shlipak
1,2,3
, David Siscovick
4
, Cora Lewis
5
,
David R. Jacobs Jr
6
and Kirsten Bibbins-Domingo
3,7,8
1
Department of Medicine, University of California San Francisco, San Francisco, CA, USA,
2
San Francisco Veterans Affairs Medical
Center, San Francisco, CA, USA,
3
Department of Epidemiology and Biostatistics, University of California, San Francisco, CA, USA,
4
Department of Medicine and Epidemiology, University of Washington, Seattle, WA, USA,
5
Division of Preventive Medicine,
University of Alabama, Birmingham, AL, USA,
6
University of Minnesota, Division of Epidemiology, School of Public Health,
Minneapolis, MN, USA,
7
Division of General Internal Medicine, San Francisco General Hospital, San Francisco, CA, USA and
8
UCSF Center for Vulnerable Populations at San Francisco General Hospital, CA, USA
Correspondence and offprint requests to: Car men A. Peralta; E-mail: Carmenalicia.peralta@ucsf.edu
Abstract
Background. Despit e a higher incidence of end-st age re-
nal disease (stage 5), blacks have been shown to have the
same or lower prevalence of chronic kidney disease (CKD
stages 3 and 4). Current creatinine-based glomerular filtra-
tion rate (GFR)-estimating equations may misclassify
young, healthy blacks.
Methods. Among 3501 young adults (mean age 45), we
compared the prevalence of CKD in blacks and whites using
the Modification of Diet in Renal Disease (MDRD) and the
CKD Epidemiology Collaboration (CKD-EPI) equations.
In addition, we used measured creatinine excretion rates
to determine the actual excretion ratio for CARDIA (race
coefficient 12%) and applied this to the CKD-EPI equation.
3934 C.A. Peralta et al.
© The Author 2010. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.
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We also studied the prevalence of CKD risk factors among
black and white participants near the CKD threshold cut-off
(eGFR CKD-EPI 6080 mL/min/1.73 m
2
)
to e stima te the
relative likelihood of mis classification in blacks and whites.
Results. Using the MDRD equation, prevalence of CKD
stages 4 and 5 was higher for blacks compared with whites
(0.6% vs. 0.1%, P-value 0.05). In contrast, prevalence of
eGFR <60 mL/min/1.73 m
2
was significa ntly higher for
whites (3.6%) compa red with blacks (1.9%), due to higher
prevalence of stage 3 among whites. Prevalence of CKD
was similar for blacks and whites using CKD-EPI equa-
tion (1.2%), but was higher among blacks when using
the CARDIA-derived race coefficient (1.6% vs.1.2%,
P-value = 0.03). Among persons with eGFR by CKD-
EPI of 6080 mL/min/1.73 m
2
, blacks had higher levels
of albuminuria, uric acid, systolic blood pressure and
higher diabetes prevalence.
Conclusions. CKD classification among young blacks is
very sensitive to the race coefficients. Despite whites having
higher rates of CKD stage 3, blacks with eGFRs just above
the CKD threshold had higher rates of CKD risk factors.
Cur rent equations used to define CKD may systematically
miss a high-risk group of blacks at a time in the disease
course when interventions are crucial.
Keywords: chronic kidney disease; glomerular filtration rate; race
Introduction
Black Americans have a 24-fold incidence of end-stage
renal disease (ESRD) compared with whites [1,2]. Par-
adoxically, national studies have found that chronic kidney
disease (CKD) prevalence is lower for blacks compared
with whites, except at advanced stages [3]. These observa-
tions have led to the hypothesis th at blacks may progress
faster from CKD to ESRD compared with whites [4].
An additional explanation for these observations may be
that prevalence studies are limited by the lack of accurate
tools for estimation of glom erular filtration rate (GFR) in
non-white populations without known CKD (eGFR
60 mL/min/1.73 m
2
). This inaccuracy could lead to spu-
rious or biased estimates of CKD prevalence. The current
standard is to estimate GFR by usi ng the creatinine-
based Modification of Diet in Renal Disease (MDRD)
equation [5,6], which includes a cor rection factor for
race (a 21% higher eGFR for the same creatinine value
for blacks compared with whites) [5]. This equation was
developed in a cohort with advanced CKD, so the race
correction factor may not apply to a younger population
of blacks without CKD. In addition, the MDRD equa-
tion is known to be less accurate among subjects with
normal or mildly redu ced kidney function when tested
against gold standar d direct G FR measurement methods
[710]. Recently, a new equation was developed by the
CKD Epidemiology Co llaboration (CKD-EPI) group that
may be more accurate at higher GFR levels. The develop-
ment datasets for CKD-EPI included a larger proportion of
younger participants, and the race correction factor is lower
(16%). However, this equation has not yet been validated in
young blacks without CKD [11].
The use of creatinine-based GFR-estimating equations
with differing race cor rection coefficients could directly
impact the classification of CKD, which is critical for un-
derstanding racial/ethnic differences in CKD prevalence.
Moreover, classification of CKD is important for accurate-
ly capturing those at high risk of adverse events in clinical
practice, where GFR is now routinely reported [12]. We
designed t hese analyses to: (i) study the prevalence of
CKD in a young, healthy, bi-racial cohort using the MDRD
and the newly developed CKD-EPI equations; and (ii)
evaluate the impact of the race correction coefficients on
CKD classification by race.
Materials and methods
Participants
Study de sign details of Coronary Artery Risk Development in Young
Adults (CARDIA) have been previously published [13]. Briefly, a cohort
of healthy young adults from the community, age 1830 at the time of
enrolment, balanced by race (black and white) and sex was recruited by
telephone or door-to-door between 1985 and 1986 from four participating
sites: Birmin gham, AL; Chicago, IL; Minneapolis, MN; and Oakland,
CA. In order to be enrolled in CARDIA, participants had to be free of
any chronic disease. Follow-up examinations occurred at Year 2, 5, 7,
10, 15 and 20. We restricted the present analysis to the 3549 participants
who completed the Year 20 examination. We excluded those with no serum
creatinine measure at Year 20, for a total sample size of 3501. All study
protocols were approved by the appropriate institutional review boards.
Kidney function measures
Serum creatinine was measured by nephelometry an d calibrated to Na-
tional Institute of Standards and Technology (NIST) standards as recom-
mended by th e National Kidney Disease Education Program (NKDEP)
Laboratory Working Group [14]. We estimated GFR for blacks and whites
separately using both the MDRD equation [5] and the newly developed
CKD-EPI equation using Year 20 serum creatinine values [11].
Variables of interest
Sociodemographic factors were assessed by questionnaire at all study vis-
its. Race was determined by participant self-report at baseline. We used so-
cioeconomic data from Year 20 rather than baseline as a more accurate
reflection of a persons socioeconomic status at the time of kidney function
assessment. As a marker of socioeconomic status, we used income (cate-
gorized as <$25 000, $25 000<$50 000 and $50 000) and level of highest
educational attainment (categorized as less than high school, high school
graduate, some college, completed college and more than college). Systolic
and diastolic blood pressure were defined as average of the second and third
of three measurements taken at 1-min intervals after a 5-min rest. A diag-
nosis of hypertension was recorded if the participant ever had a systolic
blood pressure 140 mmHg or diastolic blood pres sure 90 mmHg, or
use of anti-hypertensive medications. Height and weight were used to cal-
culate body mass index [weight (kilog ram) divided by height squared
(square metre)]. Diabetes was defined by fasting glucose 126 mg/dL or
use of diabetes medications. History of cardiovascular disease (CVD) was
defined by an adjudicated CVD CARDIA end point [myocardial infarction,
congestive heart failure (CHF) or stroke] before the Year 20 examination.
LDL cholesterol (LDL-c) was derived using the Friedewald formula from
fasting samples. Serum uric acid was calibrated to NIST standards and ex-
pressed in milligram per decilitre. Urin ary albumin and creatinine from
Year 20 were reported as albumin-to-creatinine ratio in milligram per gram.
Statistical analyses
We first estimated GFR by each of the equations, MDRD and CKD-EPI
for all participants, and classified them by CKD stage, according to Na-
tional Kidney Foundation criteria [6]. Using each equation separately, we
Race coefficient and CKD 3935
estimated the prevalence of stage 3 (eGFR 3059 mL/min/1.73 m
2
) and
stages 4 and 5 (eGFR <30 mL/min/1.73 m
2
) for blacks and whites sepa-
rately. We also estimated the overall prevalence of CKD, defined as eGFR
<60 mL/min/1.73 m
2
at Year 20, overall and by race. We then estimated
the prevalence rate ratio of CKD for blacks compared with whites, using
each equation.
In a second analysis, we estimated the overall prevalence of CKD and
each CKD stage at Year 20 using the CKD-EPI equation with a CARDIA-
derived race coefficient of 1.12 (i.e. 12% increase in eGFR for blacks for
same value of creatinine). This coefficient was derived using three sepa-
rate 24-h urine collections from a subsample of 443 black and 392 white
CARDIA participants. Creatinine excretion rates for each individual were
expressed in milligram/24 h. Mean creatinine excretion by race was esti-
mated. The ratio of creatinine excretion was estimated at 12% milligram/
24 h higher for blacks [15]. We then estimated the prevalence rate ratio of
CKD for blacks compared with whites, using the CKD-EPI equation with
CARDIA-derived race coefficient.
We hypothesized that the magnitude of the race coefficient (i.e. 1.21
vs. 1.16 in MDRD vs. CKD-EPI) would strongly influence the prevalence
of stage 3 CKD among blacks and would change the estimates of racial
differences. We further hypothesized that the current estimating equations
may systematically misclassify blacks as being free of CKD. If this were
true, the misclassification would occur in those with eGFR 6080 mL/
min/1.73 m
2
, and blacks would have more advanced CKD than whites
when captured by the equations. Therefore, we compared characteristics
of black vs. whites with CKD by gender using chi-square or t-test where
appropriate. Furthermore, we examined the characteristics of those with
eGFR 6080 mL/min/1.73 m
2
reasoning that blacks in this group near the
CKD threshold would have greater evidence of kidney disease and kidney
disease risk factors than whites in this range. We compared the prevalence
of the major CKD risk factors among blacks and white subjects with
eGFR 6080 mL/min/1.73 m
2
(systolic blood pressure, diabetes, lipids
and BMI) in addition to possible markers of CKD presence including al-
buminuria and serum uric acid levels using chi-square, Fishers exact or
Wilcoxon tests where appropriate. We presented the mean values of the
albumin-to-creatinine ratio and log-transformed the ratio for comparisons
to achieve normality.
All analyses were performed using STATA version 9 (StataCorp, TX,
USA). Statistical significance was determined at P < 0.05.
Results
Participant characteristics
Of the 3501 CARDIA participants included in these anal-
yses, 47% self-identified as black. Mean age of the cohort
at Year 20 visit was 45 years, 11% had diabetes and 21%
had hypertension. Mean eGFR by MDRD was 90 ±
22 mL/min/1.73 m
2
, and mean eGFR CKD-EPI was 97 ±
18 mL/min/1.73 m
2
. Mean albumin-to-creatinine ratio was
13 ± 60 mg/g.
Compared with white, blacks had higher levels of al-
buminuria, body ma ss index and systolic blood pres-
sure, and were more likely to be hypertensive and diabetic
(Table 1).
Prevalence of CKD in blacks and whites by
creatinine-based eGFR-estimating equations
The overall prevalence of eGFR <30 mL/min/1.73 m
2
(CKD stages 4 and 5) in CARDIA was 0.3%, and this es-
timate did not vary significantly when using the CKD-EPI
or MDRD equation. Blacks had a higher prevalence of
eGFR <30 mL/min/1.73 m
2
compared with whites using
either equation (0.6% vs. 0.1%, P-value 0.05 for MDRD;
and 0.6% vs. 0.05%, P-value 0.05 with CKD-EPI).
In contrast, when we considered the combined CKD
stages 35, the overall prevalence of eGFR <60 mL/min/
1.73 m
2
using the MDRD equation was higher for whites
compared with blacks. Blacks had an overall CKD prev-
alence of 1.9%, compared with 3.7% for whites (P-value =
0.001), with a prevalence rate ratio of 0.53 for blacks com-
Table 1. Characteristics of 3501 CARDIA participants at Year 20 examination by race
Characteristic
Black (n = 1651) White (n = 1898) P-value
Mean (SD) or n (%)
Age 45 ± 4 46 ± 3 <0.001
Female 991 (61%) 989 (53%) <0.001
Income <0.001
<$25 000 392 (24%) 148 (8%)
$25 000$49 999 411 (25%) 263 (14%)
$50 000+ 788 (48%) 1447 (77%)
Education <0.001
Less than high school graduate 108 (7%) 40 (2%)
High school graduate 449 (28%) 242 (13%)
Some college 569 (35%) 376 (20%)
College 322 (20%) 581 (31%)
More than college 167 (10%) 628 (34%)
Body mass index (kg/m
2
) 31 ± 8 28 ± 7 <0.001
LDL cholesterol (mg/dL) 110 ± 34 110 ± 31 0.89
Systolic blood pressure (mmHg) 121 ± 16 113 ± 13 <0.001
Fasting glucose (mg/dL) 100 ± 31 96 ± 22 0.0001
Serum creatinine (mg/dL) 0.94 ± 0.55 0.87 ± 0.24 <0.001
MDRD estimated GFR 97 ± 24 84 ± 19 <0.001
CKD-EPI estimated GFR 102 ± 20 93 ± 14 <0.001
Albumin/creatinine ratio (mg/g) 16.5 ± 63.6 10.5 ± 56.2 0.003
Hx of cardiovascular events
a
19 (1%) 13 (1%) 0.14
Diabetes 231 (14%) 161 (9%) <0.001
Hypertension 486 (30%) 234 (12%) <0.001
Smoker 651 (40%) 763 (41%) 0.69
a
History of cardiovascular events includes heart failure, myocardial infarction or stroke during study period.
3936 C.A. Peralta et al.
pared with whites. The observed contrast in the race diffe-
rences was due to a higher prevalence of CKD stage 3
among whites compared with blacks (Figure 1).
With the CKD-EPI equation, the overall prevalence of
eGFR <60 mL/min/1.73 m
2
was reduced across the entire
CARDIA cohort, and this was due to a lower prevalence of
CKD stage 3. This effect was more pronounced among
whites. In contrast to the findings with the MDRD equa-
tion, the overall prevalence of eGFR <60 mL/min/1.73 m
2
did n ot differ significantly by race using CKD-EPI
equation (prevalence 1.2% for whites vs. 1.3% for blacks,
P-value = 0.76) (Figure 1).
In analyses using the CKD-EPI equation with the
CARDIA-derived race coeff icient (12%), the overall
prevalence of CKD was 1.4% (n = 4 8). Similar to the
results above, blacks had a higher prevalence of CKD stage
4 and 5. However, when including stage 3 in our estimates,
the overall prevalence of CKD was higher for blacks com-
pared with whites. The prevalence of CKD was 1.6% for
blacks, compared with 1.2% for whites, for a prevalence
rate ratio of 1.33 (P-value = 0.03) (Figure 1).
The prevalence of CKD varied within each ethnic group
using different equations, but the magnitude of this differ-
ence was higher for whites. The overall prevalence of CKD
varied by 50% (1.9% by MD RD compared with 1.3% by
CKD-EPI) among blacks and over 3-fold among whites
(3.7% by MDRD compared with 1.2% by CKD-EPI).
Characteristics of participants with CKD (CKD-EPI
eGFR <60 mL/min/1.73 m
2
)
Among those with CKD, black men had much lower eGFR
and higher prevalence of albuminuria. Mean CKD-EPI
eGFR for black men was 26 ± 22 mL/min/1.73 m
2
, com-
pared with 49 ± 19 mL/min/1.73 m
2
among white men (P-
value 0.0 4). Mean albumin-to-creatinine ratio was 147 ±
131 mg/g among black men and 11 ± 12 mg/g for white
men (P-value 0.02).
Fig. 1. Prevalence of CKD (GFR <60 mL/min/1.73 m
2
) by race and gender using MDRD, CKD-EPI equation and CKD-EPI equation with CARDIA-
derived coefficient.
Table 2. Characteristics of CARDIA participants with eGFR 6080 mL/min/1.73 m
2
by CKD-EPI
Characteristic
Black men White men
P-value
Black women White women
P-value(n = 86) (n = 161) (n = 104) (n = 223)
Albumin/creatinine ratio (mg/g)
b
38 ± 200 13 ± 55 0.004
a
21 ± 60 7 ± 11 0.006
a
Serum uric acid (mg/dL) 7.34 ± 1.53 6.88 ± 1.29 0.02 5.86 ± 1.61 4.98 ± 0.99 <0.001
Systolic blood pressure (mmHg) 124 ± 16 117 ± 13 0.001 123 ± 20 108 ± 11 <0.001
Hypertension % (n) 35 (30) 19 (31) 0.006 38 (40) 4 (10) <0.001
Fasting glucose (mg/dL) 104 ± 25 101 ± 25 0.41 105 ± 50 91 ± 8 0.005
Diabetes % (n) 7 (6) 5 (8) 0.52 17 (18) 6 (14) 0.001
Body mass index 31 ± 6 28 ± 4 <0.001 32 ± 7 26 ± 6 <0.001
LDL cholesterol (mg/dL) 113 ± 32 115 ± 30 0.69 112 ± 35 104 ± 30 0.03
a
Represents mean albumin/creatinine ratio, and P-value is for log-transformed comparisons.
b
Corrected for age and sex.
t-test for continuous variables, Wilcoxon test for median, chi-square test or Fisher exact test for categorical variables.
Race coefficient and CKD 3937
Similar patterns of a more severe disease were also seen
in black women. Among women with eGFR <60 mL/min/
1.73 m
2
, mean eGFR for black women was 38 ± 19 mL/
min/1.73 m
2
, compared with 52 ± 10 mL/min/1.73 m
2
for
white women (P-value 0.003). Mean albumin-to-creatinine
ratio was similarly higher among black compared wi th
white women, thoug h not statistically significant (167 ±
535 mg/g for black women and 113 ± 195 mg/g for white
women, P-value 0.73).
Characteristics of particip ants with CKD-EPI eGFR
6080 mL/min/1.73 m
2
Because we found that the prevalence of CKD stage 3 was
surprisingly l ower among young blacks compared with
young whites and that this was due to the race coefficient
in estimating equations, we hypothesized that some blacks
may be misclassified as being free of CKD. Because this
misclassification would most likely occur among those
with eGFR 6080 mL/min/1.73 m
2
, we compared the char-
acteristics of black and white CARDIA participants with
eGFR by CKD-EPI 6080 mL/min/1.73 m
2
. Among
men with eGFR by CKD-EPI of 6080 mL/min/1.73 m
2
,
black men had a 2.5-fold higher prevalence of album inuria
and higher serum uric acid levels compared with white
men. In addition, blacks had 80% higher prevalence of hy-
pertension and higher BMI. Among women with eGFR
6080 mL/min/1.73 m
2
, black women had a 4-fold higher
prevalence of albuminuria, 10-fold prevalence of hyperten-
sion, and substantially higher BMI, fasting glucose and
LDL levels compared with white women (Table 2).
Discussion
We found that racial differences in prevalence estimates
of CKD are very sensitive to the equation use d to est i-
mate GFR in a young, bi-racial cohort. When using the
MDRD equation, whites had higher overall preva lence
of CKD compared with blacks, due to a higher preva-
lence of stage 3 CKD among whites. I n contrast, when
using the CKD-EPI equation, not only was the overall
prevalence of CKD reduced but we observed no race dif-
ferences in CKD e stimates. Moreover, when using the
CARDIA-derived coefficient for the CKD-EPI equation,
blacks had higher prevalence of CKD. Interestingly, de-
spite having a higher prevalence of CK D stage 3 com -
pared wit h blacks based on the validated e quations,
whites had a strikingly lower prevalence of risk factors
for CKD. Rather than attributing this constellation of
findings to an epidemiological paradox, we believe that
an alternative explanation is that the current race coeffi-
cient for blacks may lead to a systemat ic misclassification
of CKD among young blacks.
Our study shows that applying different race coefficients
(1.21 in MDRD vs. 1.16 in CKD-EPI) in a young, healthy
population signif icantly changes the association between
race and CKD. This is of substantial importance epidemi-
ologically as we attempt to understand why reports show
that blacks have a lower preva lence of CKD [3] but higher
ESRD incidence compared with white s [1]. Blacks have
been shown to progress faster from CKD to ESRD [4],
but this faster progression may not fully account for the
higher ESRD incidence rates.
Our findings also show that blacks who are classified as
having CKD (eGFR <60 m L/min/1.73 m
2
) have much
lower eGFR and a worse CKD risk factor profile compared
with whites in CARDIA. The creatinine threshold required
to reach an eGFR of 60 mL/min/1.73 m
2
is substantially
higher for blacks (1.7 mg/dL for a black man age 45 com-
pared with 1.4 mg/dL for a white man age 45). In young
adults, it is unclear whether these creatinine differences are
solely a correction for muscle mass or rather represent dif-
ferent severities of kidney disease.
Most interestingly, despite a much lower prevalence of
risk factors for CKD, whites had a higher prevalence of
CKD stage 3. If the current classification is accurate, then
we would expect whites near the CKD cut-off to have higher
severity of risk factors for CKD. However, we found that
among those with eGFR 6 080 mL/min/ 1.73 m
2
,blacks
had much higher prevalence of CKD-associated abnorma-
lities and risk factors, particularly albuminuria, a critical
marker of kidney damage. Although our study cannot deter-
mine the exact coefficient appropriate for young blacks, it is
likely that the current most clinically available 21% higher
eGFR for the same serum creatinine (i.e. MDRD equation)
may misclassify young blacks as having no CKD. In ad-
dition, since the prevalence of CKD varied even further
among whites than blacks using MDRD vs. CKD-EPI equa-
tions, it is possible that whites may be mislabel led as having
CKD. These equa tions have not b een validated in young
adults with no established CKD. Importantly, the prevalence
of st ages 4 and 5 d id not vary a mong blacks using either
MDRD or CKD-EPI equation, where equations were deve-
loped and thus are thought to be most accurate [5,11]. These
findings are of major importance because the current use of
race coefficients in estimating equations may systematically
misclassify young blacks as low CKD risk, and only capture
them at advanced stages of disease, or mislabel whites as
having CKD. Unfortunately, until a population-based study
measures GFR in healthy, young adults, we cannot discern
the extent of misclassification in whites and blacks.
Our study is the first to explore the impact of the current
creatinine-based equations on CKD prevalence estimates
by race and gender. We used a large, well-characterized
young cohort with calibrated serum creatinine measures.
We used both the accepted standard and the newly im-
proved estimating equations for these analyses in addition
to a CARDIA- derived coefficient. However, our study is
limited by its cross-sectional nature, so it cannot assess
theprogressionofCKD.Wemayalsobelimitedbythe
overall low prevalence of CKD in this cohort. In addition,
we did not have gold standard GFR measures to establish
true CKD status. Unfortunately, no community-based
study of blacks without CKD has measured GFR to date.
Although we show that blacks near the CKD threshold
have higher albuminuria and higher serum uric acid levels,
we do not have information on other important metabolic
parameters associated with CKD.
In summary, we found that CK D classification among
blacks is very sensitive to the race coefficie nts of the cur-
rent GFR-estimating equations, particularly at stage 3. Al-
3938 C.A. Peralta et al.
though whites had a higher prevalence of CKD stage 3
compared with blacks, th eir CKD risk factor profile was
strikingly better than that of blacks. Our findings suggest
that the current equations may underestimate CKD in
blacks, particularly at stage 3, where interventions are most
crucial. Future studies to develop GFR-estimating equa-
tions should include young, healthy, non-white populations
and should consider alternative filtration markers that may
be less biased by race.
Acknowledgements. C.A.P. is funded by grant 1K23DK082793-01 from
NIDDK.
Conflict of interest statement. None declared.
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Received for publication: 21.1.10; Accepted in revised form: 7.5.10
Nephrol Dial Transplant (2010) 25: 39393948
doi: 10.1093/ndt/gfq322
Advance Access publication 10 June 2010
Long-term outcomesmycophenolate mofetil treatment for lupus
nephritis with addition of tacrolimus for resistant cases
Josefina Cortés-Hernández
1
, María Teresa Torres-Salido
1
, Alfonso Segarra Medrano
2
,
Miquel Vilardell Tarrés
1
and Josep Ordi-Ros
1
1
Systemic Autoimmune Diseases Research Unit. Internal Medicine Department and
2
Renal Department, Vall dHebron Hospital,
Passeig Vall dHebron 119-129, 08035 Barcelona, Spain
Correspondence and offprint requests to: Josefina Cortés-Hernández; E-mail: jocortes@ir.vhebron.net
Abstract
Background. Although mycophenolate mofetil (MMF) is
being increasingly used to manage lupus nephritis (LN),
long-term experience is limited. Despite treatment, a sig-
nificant proportion of patients will be refractory to this
regime.
MMF in lupus nephritis 3939
© The Author 2010. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.
For Permissions, please e-mail: journals.permissions@oxfordjournals.org
    • "For example, the CKD-EPI formula is not validated for adolescents below the age of 18 years or for pregnant women, whereas the 4vMDRD-formula is not validated for the very old (beyond 85 years). Both formulas were developed from cohorts consisting of mainly Caucasians or Blacks with uncertain accuracy in other ethnical groups1011121314. Moreover, in normal to mild impairment of kidney function, the estimations are highly scattered compared to gold standard methods [6, 15, 16]. "
    [Show abstract] [Hide abstract] ABSTRACT: Background Creatinine clearance (CrCl) based on 24 h urine collection is an established method to determine glomerular filtration rate (GFR). However, its measurement is cumbersome and the results are frequently inaccurate. The aim of this study was to develop an alternative method to predict CrCl and urinary protein excretion based on plasma creatinine and the quantification of muscle mass through bioimpedance analysis (BIA). Methods In 91 individuals with normal and impaired renal function CrCl was measured from 24 h urine excretion and plasma creatinine concentration. A model to predict 24 h-creatininuria was developed from various measurements assessing muscle mass such as body cell mass (BCM) and fat free mass (FFM) obtained by BIA, skinfold caliper and other techniques (training group, N = 60). Multivariate regression analysis was performed to predict 24 h-creatininuria and to calculate CrCl. A validation group (N = 31) served to compare predicted and measured CrCl. Results Overall (accuracy, bias, precision, correlation) the new BIA based prediction model performed substantially better compared with measured CrCl (P15 = 87 %, bias = 0, IQR of differences = 7.9 mL/min/1.73 m2, R = 0.972) versus established estimation formulas such as the 4vMDRD (P15 = 26 %, bias = -8.3 mL/min/1.73 m2, IQR = 13.7 mL/min/1.73 m2, R = 0.935), CKD-EPI (P15 = 29 %, bias = -7.0 mL/min/1.73 m2, IQR = 12.1 mL/min/1.73 m2, R = 0.932, Cockcroft-Gault equations (P15 = 55 %, bias = -4.4 mL/min/1.73 m2, IQR = 9.0 mL/min/1.73 m2, R = 0.920). The superiority of the new method over established prediction formulas was most obvious in a subgroup of individuals with BMI > 30 kg/m2 and in a subgroup with CrCl > 60 mL/min/1.73 m2. Moreover, 24 h urinary protein excretion could be estimated accurately by normalization with 24 h-creatininuria derived from BIA based BCM. Conclusion Prediction of CrCl based on estimated urinary creatinine excretion determined from measurement of BCM by BIA technique is both accurate and convenient to quantify renal function in normal and diseased states. This new method may become particularly helpful for the evaluation of patients with borderline renal insufficiency and/or with abnormal body composition.
    Full-text · Article · Dec 2015
    • "Finally, the MDRD and CKD-EPI equations were developed in patients with chronic kidney disease stage 4–5. The study of Peralta et al. [24] strongly suggests that even in a cohort of African-American, the race correction factors of 1.21 for the MDRD-v4 et 1.16 for the CKD-EPI equations are probably too high for young patients with CKD-EPI estimated GFR comprised between 60 and 80 mL/min/1.73 m2 and should rather be 1.12. "
    [Show abstract] [Hide abstract] ABSTRACT: Sickle cell disease (SCD) leads to tissue hypoxia resulting in chronic organ dysfunction including SCD associated nephropathy. The goal of our study was to determine the best equation to estimate glomerular filtration rate (GFR) in SCD adult patients. We conducted a prospective observational cohort study. Since 2007, all adult SCD patients in steady state, followed in two medical departments, have had their GFR measured using iohexol plasma clearance (gold standard). The Cockcroft-Gault, MDRD-v4, CKP-EPI and finally, MDRD and CKD-EPI equations without adjustment for ethnicity were tested to estimate GFR from serum creatinine. Estimated GFRs were compared to measured GFRs according to the graphical Bland and Altman method. Sixty-four SCD patients (16 men, median age 27.5 years [range 18.0-67.5], 41 with SS-genotype were studied. They were Sub-Saharan Africa and French West Indies natives and predominantly lean (median body mass index: 22 kg/m2 [16-33]). Hyperfiltration (defined as measured GFR >110 mL/min/1.73 m2) was detected in 53.1% of patients. Urinary albumin/creatinine ratio was higher in patients with hyperfiltration than in patients with normal GFR (4.05 mg/mmol [0.14-60] versus 0.4 mg/mmol [0.7-81], p = 0.01). The CKD-EPI equation without adjustment for ethnicity had both the lowest bias and the greatest precision. Differences between estimated GFRs using the CKP-EPI equation and measured GFRs decreased with increasing GFR values, whereas it increased with the Cockcroft-Gault and MDRD-v4 equations. We confirm that SCD patients have a high rate of glomerular hyperfiltration, which is frequently associated with microalbuminuria or macroalbuminuria. In non-Afro-American SCD patients, the best method for estimating GFR from serum creatinine is the CKD-EPI equation without adjustment for ethnicity. This equation is particularly accurate to estimate high GFR values, including glomerular hyperfiltration, and thus should be recommended to screen SCD adult patients at high risk for SCD nephropathy.
    Full-text · Article · Aug 2012
  • Article · Mar 2011
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