Performance of glomerular filtration rate estimating equations in a community-based sample of Blacks and Whites: the multiethnic study of atherosclerosis.
ABSTRACT: Background:The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations are recommended for glomerular filtration rate (GFR) estimation in the general population. They have not been evaluated in community-based populations, including Blacks at higher levels of GFR, but are commonly applied in such populations. Methods:In an ancillary study of Multi-Ethnic Study of Atherosclerosis conducted at one site, we evaluated the performance of the CKD-EPI equations for creatinine (eGFRcr), cystatin C (eGFRcys) or the combination (eGFRcr-cys) compared with GFR measured as plasma clearance of iohexol. Results:Among 294 participants, the mean age was 71 (SD 9) years, 47% were Black, 48% were women and the mean measured GFR (mGFR) was 72.6 (SD 18.8) mL/min/1.73 m2. The CKD-EPI equations overestimated mGFR with a larger median bias for eGFRcr and eGFRcr-cys than eGFRcys [-8.3 (95% confidence interval -9.7, -6.5), -7.8 (-9.2, -6.2) and -3.7 (-5.0, -1.8) mL/min/1.73 m2, respectively], with smaller bias for those with lower compared with higher eGFR and by race compared with sex. Conclusion:The small differential bias of the CKD-EPI equation between races suggests that they can be used in Blacks as well as Whites in older community-based adults. The large differential bias in women versus men in all equations is in contrast to other studies and is unexplained. Further studies are required in multiracial and multiethnic community-based cohorts, taking into account differences in GFR measurement methods.
Project description:Current guidelines recommend reporting eGFR using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations unless other equations are more accurate, and recommend the combination of creatinine and cystatin C (eGFRcr-cys) as more accurate than either eGFRcr or eGFRcys alone. However, preferred equations and filtration markers in elderly individuals are debated. In 805 adults enrolled in the community-based Age, Gene/Environment Susceptibility (AGES)-Reykjavik Study, we measured GFR (mGFR) using plasma clearance of iohexol, standardized creatinine and cystatin C, and eGFR using the CKD-EPI, Japanese, Berlin Initiative Study (BIS), and Caucasian and Asian pediatric and adult subjects (CAPA) equations. We evaluated equation performance using bias, precision, and two measures of accuracy. We first compared the Japanese, BIS, and CAPA equations with the CKD-EPI equations to determine the preferred equations, and then compared eGFRcr and eGFRcys with eGFRcr-cys using the preferred equations. Mean (SD) age was 80.3 (4.0) years. Median (25th, 75th) mGFR was 64 (52, 73) ml/min per 1.73 m(2), and the prevalence of decreased GFR was 39% (95% confidence interval, 35.8 to 42.5). Among 24 comparisons with the other equations, CKD-EPI equations performed better in 9, similar in 13, and worse in 2. Using the CKD-EPI equations, eGFRcr-cys performed better than eGFRcr in four metrics, better than eGFRcys in two metrics, and similar to eGFRcys in two metrics. In conclusion, neither the Japanese, BIS, nor CAPA equations were superior to the CKD-EPI equations in this cohort of community-dwelling elderly individuals. Using the CKD-EPI equations, eGFRcr-cys performed better than eGFRcr or eGFRcys.
Project description:<h4>Background</h4>Glomerular filtration rate (GFR) estimating equations using the combination of creatinine and cystatin C (eGFRcr-cys) are more accurate than equations using either alone (eGFRcr or eGFRcys). New guidelines suggest measuring cystatin C as a confirmatory test when eGFRcr may be inaccurate, but do not specify demographic or clinical conditions in which eGFRcys or eGFRcr-cys are more accurate than eGFRcr nor which estimate to use in such circumstances.<h4>Methods</h4>We compared the performance of the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations in 1119 subjects in the CKD-EPI cystatin C external validation dataset. Subgroups were defined by eGFRcr, age, sex, diabetes status and body mass index (BMI). The reference test was GFR measured using urinary or plasma clearance of exogenous filtration markers. Cystatin C and creatinine assays were traceable to primary reference materials. Accuracy was defined as the absolute difference in eGFR compared with mGFR.<h4>Results</h4>The mean mGFR was 70 ± 41 (SD) mL/min/1.73 m(2). eGFRcys was more accurate than eGFRcr at lower BMI and less accurate at higher BMI, especially at higher levels of eGFRcr. There were small differences in accuracy in people according to the diabetes status. eGFRcr-cys was as accurate or more accurate than eGFRcr or eGFRcys in these and all other subgroups.<h4>Conclusions</h4>eGFRcr-cys, but not eGFRcys, is more accurate than eGFRcr in most subgroups we studied, suggesting preferential use of eGFRcr-cys when serum cystatin C is measured as a confirmatory test to obtain more accurate eGFR. Further studies are necessary to evaluate diagnostic strategies for using eGFRcys and eGFRcr-cys.
Project description:BACKGROUND:The Kidney Disease Improving Global Outcomes (KDIGO) guideline recommends use of a cystatin C-based estimated glomerular filtration rate (eGFR) to confirm creatinine-based eGFR between 45 and 59 mL · min(-1) · (1.73 m(2))(-1). Prior studies have demonstrated that comorbidities such as solid-organ transplant strongly influence the relationship between measured GFR, creatinine, and cystatin C. Our objective was to evaluate the performance of cystatin C-based eGFR equations compared with creatinine-based eGFR and measured GFR across different clinical presentations. METHODS:We compared the performance of the CKD-EPI 2009 creatinine-based estimated GFR equation (eGFRCr) and the newer CKD-EPI 2012 cystatin C-based equations (eGFRCys and eGFRCr-Cys) with measured GFR (iothalamate renal clearance) across defined patient populations. Patients (n = 1652) were categorized as transplant recipients (n = 568 kidney; n = 319 other organ), known chronic kidney disease (CKD) patients (n = 618), or potential kidney donors (n = 147). RESULTS:eGFRCr-Cys showed the most consistent performance across different clinical populations. Among potential kidney donors without CKD [stage 2 or higher; eGFR >60 mL · min(-1) · (1.73 m(2))(-1)], eGFRCys and eGFRCr-Cys demonstrated significantly less bias than eGFRCr; however, all 3 equations substantially underestimated GFR when eGFR was <60 mL · min(-1) · (1.73 m(2))(-1). Among transplant recipients with CKD stage 3B or greater [eGFR <45 mL · min(-1) · (1.73 m(2))(-1)], eGFRCys was significantly more biased than eGFRCr. No clear differences in eGFR bias between equations were observed among known CKD patients regardless of eGFR range or in any patient group with a GFR between 45 and 59 mL · min(-1) · (1.73 m(2))(-1). CONCLUSIONS:The performance of eGFR equations depends on patient characteristics that are readily apparent on presentation. Among the 3 CKD-EPI equations, eGFRCr-Cys performed most consistently across the studied patient populations.
Project description:BACKGROUND:Clinical practice guidelines recommend estimation of glomerular filtration rate (eGFR) using validated equations based on serum creatinine (eGFRcr), cystatin C (eGFRcys), or both (eGFRcr-cys). However, when compared with the measured GFR (mGFR), only eGFRcr-cys meets recommended performance standards. Our goal was to develop a more accurate eGFR method using a panel of metabolites without creatinine, cystatin C, or demographic variables. METHODS:An ultra-performance liquid chromatography-tandem mass spectrometry assay for acetylthreonine, phenylacetylglutamine, pseudouridine, and tryptophan was developed, and a 20-day, multiinstrument analytical validation was conducted. The assay was tested in 2424 participants with mGFR data from 4 independent research studies. A new GFR equation (eGFRmet) was developed in a random subset (n = 1615) and evaluated in the remaining participants (n = 809). Performance was assessed as the frequency of large errors [estimates that differed from mGFR by at least 30% (1 - P30); goal <10%]. RESULTS:The assay had a mean imprecision (?10% intraassay, ?6.9% interassay), linearity over the quantitative range (r 2 > 0.98), and analyte recovery (98.5%-113%). There was no carryover, no interferences observed, and analyte stability was established. In addition, 1 - P30 in the validation set for eGFRmet (10.0%) was more accurate than eGFRcr (13.1%) and eGFRcys (12.0%) but not eGFRcr-cys (8.7%). Combining metabolites, creatinine, cystatin C, and demographics led to the most accurate equation (7.0%). Neither equation had substantial variation among population subgroups. CONCLUSIONS:The new eGFRmet equation could serve as a confirmatory test for GFR estimation.
Project description:The US prevalence of reduced estimated glomerular filtration rate (eGFR) based on serum creatinine level increased during the decade ending in 2002. National Health and Nutrition Examination Survey (NHANES) cystatin C measurements recently were calibrated to the international standard, allowing for an independent test of the trend in prevalence of reduced eGFR using cystatin C level.Cross-sectional surveys performed during 2 periods.Nationally representative subsamples of adult participants from NHANES III (1988-1994) and the NHANES 1999-2002 surveys.Survey period.Prevalence of reduced GFR, defined as eGFR <60 mL/min/1.73 m² based on levels of serum creatinine, cystatin C, or both (eGFRcr, eGFRcys, and eGFRcr-cys), using estimating equations developed by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI).Serum cystatin C level, measured from stored samples in 2006, calibrated to the international standard in 2012.Between 1988-1994 and 1999-2002, the prevalence of reduced eGFRcr, eGFRcys, and eGFRcr-cys increased from 4.7% (95% CI, 4.1%-5.3%) to 6.5% (95% CI, 5.9%-7.1%) (P < 0.001), from 5.5% (95% CI, 4.6%-6.5%) to 8.7% (95% CI, 7.5%-10.0%) (P < 0.001), and from 4.4% (95% CI, 3.7%-5.2%) to 7.1% (95% CI, 6.2%-8.0%) (P < 0.001), respectively. The higher prevalence of reduced GFR in the later period was observed in all subgroups of age, race, sex, and GFR categories. After adjusting for changes in the US population by age, sex, race, diabetes, hypertension, and body mass index, prevalence ratios of reduced GFR in the later versus earlier survey were 1.24 (95% CI, 1.09-1.45), 1.34 (95% CI, 1.15-1.67), and 1.33 (95% CI, 1.17-1.65) using eGFRcr, eGFRcys, and eGFRcr-cys, respectively.Likely underascertainment of persons with GFR <15 mL/min/1.73 m²; GFR was estimated and not measured; comparability of laboratory assays based on a calibration subsample.The prevalence of reduced eGFRcys in the US civilian noninstitutionalized population increased between 1988-1994 and 1999-2002, confirming the increase observed in the prevalence of reduced eGFRcr.
Project description:In the estimation of glomerular filtration rate (GFR), ethnicity is an important determinant. However, all existing equations have been built solely from Caucasian and Afro-American populations and they are potentially inaccurate for estimating GFR in African populations. We therefore evaluated the performance of different estimated GFR (eGFR) equations in predicting measured GFR (mGFR).In a cross-sectional study, 93 healthy adults were randomly selected in the general population of Kinshasa, Democratic Republic of the Congo, between June 2015 and April 2016. We compared mGFR by plasma clearance of iohexol with eGFR obtained with the Modified Diet in Renal Disease (MDRD) equation with and without ethnic factor, the Chronic Kidney Disease Epidemiology (CKD-EPI) serum creatinine (SCr)-based equation, with and without ethnic factor, the cystatin C-based CKD-EPI equation (CKD-EPI SCys) and with the combined equation (CKD-EPI SCrCys) with and without ethnic factor. The performance of the equations was studied by calculating bias, precision and accuracy within 30% (P30) of mGFR.There were 48 women and 45 men. Their mean age was 45.0±15.7 years and the average body surface area was 1.68±0.16m2. Mean mGFR was 92.0±17.2 mL/min/1.73m2 (range of 57 to 141 mL/min/1.73m2). Mean eGFRs with the different equations were 105.5±30.1 and 87.2±24.8 mL/min/1.73m2 for MDRD with and without ethnic factor, respectively; 108.8±24.1 and 94.3x20.9 mL/min/1.73m2 for CKD-EPI SCr with and without ethnic factor, respectively, 93.5±18.6 mL/min/1.73m2 for CKD-EPI SCys; 93.5±18.0 and 101±19.6 mL/min/ 1.73m2 for CKD-EPI SCrCys with and without ethnic factor, respectively. All equations slightly overestimated mGFR except MDRD without ethnic factor which underestimated by -3.8±23.0 mL/min /1.73m2. Both CKD-EPI SCr and MDRD with ethnic factors highly overestimated mGFR with a bias of 17.9±19.2 and 14.5±27.1 mL/min/1.73m2, respectively. There was a trend for better P30 for MDRD and CKD-EPI SCr without than with the ethnic factor [86.0% versus 79.6% for MDRD (p = 0.21) and 81.7% versus 73.1% for the CKD-EPI SCr equations (p = 0.057)]. CKD-EPI SCrCys and CKD-EPI SCys were more effective than creatinine-based equations.In the Congolese healthy population, MDRD and CKD-EPI equations without ethnic factors had better performance than the same equations with ethnic factor. The equations using Cys C (alone or combined with SCr) performed better than the creatinine-based equations.
Project description:OBJECTIVE Serum cystatin C is an alternative to serum creatinine for estimating glomerular filtration rate (GFR), since cystatin C is less influenced by age and muscle mass. Among persons with diabetes, we compared the performance of GFR estimated using cystatin C (eGFRcys) with that using creatinine (eGFRcr) for the identification of reduced kidney function and its association with diabetes complications. RESEARCH DESIGN AND METHODS We analyzed data from adult participants from the 1999-2002 National Health and Nutrition Examination Survey with available cystatin C (N = 4,457). Kidney function was dichotomized as preserved (eGFR ?60 mL/min/1.73 m(2)) or reduced (eGFR <60 mL/min/1.73 m(2)) using the 2012 Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) cystatin C and the 2009 CKD-EPI creatinine equations. RESULTS Among 778 persons with diabetes, the prevalence of reduced kidney function was 16.5% using eGFRcr and 22.0% using eGFRcys. More persons with diabetes were reclassified from preserved kidney function by eGFRcr to reduced kidney function by eGFRcys than persons without diabetes (odds ratio 3.1 [95% CI 1.9-4.9], P < 0.001). The associations between lower eGFR and higher prevalence of albuminuria, retinopathy, peripheral arterial disease, and coronary artery disease were robust regardless of filtration marker. Similarly, the risk of all-cause mortality increased with lower eGFRcr and eGFRcys. Only lower eGFRcys was significantly associated with cardiovascular mortality. CONCLUSIONS More persons with diabetes had reduced kidney function by eGFRcys than by eGFRcr, and lower eGFRcys was strongly associated with diabetes complications. Whether eGFRcys is superior to eGFRcr in approximating true kidney function in a diabetic population requires additional study.
Project description:Cystatin C could improve chronic kidney disease (CKD) classification in HIV-infected women relative to serum creatinine.Retrospective cohort analysis.Cystatin C and creatinine were measured from specimens taken and stored during the 1999-2000 examination among 908 HIV-infected participants in the Women's Interagency HIV study (WIHS). Mean follow-up was 10.2 years. Predictors of differential glomerular filtration rate (GFR) estimates were evaluated with multivariable linear regression. The associations of baseline categories (<60, 60-90, and >90?ml/min per 1.73?m) of creatinine estimated GFR (eGFRcr), cystatin C eGFR (eGFRcys), and combined creatinine-cystatin C eGFR (eGFRcr-cys) with all-cause mortality were evaluated using multivariable Cox regression. The net reclassification index (NRI) was calculated to evaluate the effect of cystatin C on reclassification of CKD staging.CKD risk factors were associated with lower eGFRcys and eGFRcr-cys values compared with eGFRcr. Relative to eGFR more than 90, the eGFR less than 60 category by eGFRcys (Adjusted hazard ratio: 2.56; 95% confidence interval: 1.63-4.02), eGFRcr-cys (3.11; 1.94-5.00), and eGFRcr (2.34; 1.44-3.79) was associated with increased mortality risk. However, the eGFR 60-90 category was associated with increased mortality risk for eGFRcys (1.80; 1.28-2.53) and eGFRcr-cys (1.91; 1.38-2.66) but not eGFRcr (1.20; 0.85-1.67). The overall NRI for mortality was 26% when reclassifying from eGFRcr to eGFRcys (P?<?0.001) and was 20% when reclassifying from eGFRcr to eGFRcr-cys (P?<?0.001).The addition of cystatin C may improve mortality risk prediction by stages of kidney function relative to creatinine. CKD risk factors are associated with an overestimate of GFR by serum creatinine relative to cystatin C.
Project description:BACKGROUND:Accurate glomerular filtration rate estimation informs drug dosing and risk stratification. Body composition heterogeneity influences creatinine production and the precision of creatinine-based estimated glomerular filtration rate (eGFRcr) in the elderly. We compared chronic kidney disease (CKD) categorization using eGFRcr and cystatin C-based estimated GFR (eGFRcys) in an elderly, racially/ethnically diverse cohort to determine their concordance. METHODS:The Northern Manhattan Study (NOMAS) is a predominantly elderly, multi-ethnic cohort with a primary aim to study cardiovascular disease epidemiology. We included participants with concurrently measured creatinine and cystatin C. eGFRcr was calculated using the CKD-EPI 2009 equation. eGFRcys was calculated using the CKD-EPI 2012 equation. Logistic regression was used to estimate odds ratios and 95% confidence intervals of factors associated with reclassification from eGFRcr?60ml/min/1.73m2 to eGFRcys<60ml/min/1.73m2. RESULTS:Participants (n = 2988, mean age 69±10yrs) were predominantly Hispanic, female, and overweight/obese. eGFRcys was lower than eGFRcr by mean 23mL/min/1.73m2. 51% of participants' CKD status was discordant, and only 28% maintained the same CKD stage by both measures. Most participants (78%) had eGFRcr?60mL/min/1.73m2; among these, 64% had eGFRcys<60mL/min/1.73m2. Among participants with eGFRcr?60mL/min/1.73m2, eGFRcys-based reclassification was more likely in those with age >65 years, obesity, current smoking, white race, and female sex. CONCLUSIONS:In a large, multiethnic, elderly cohort, we found a highly discrepant prevalence of CKD with eGFRcys versus eGFRcr. Determining the optimal method to estimate GFR in elderly populations needs urgent further study to improve risk stratification and drug dosing.
Project description:Background:The prevalence of chronic kidney disease (CKD) in African American individuals is high but whether this applies to native populations in sub-Saharan Africa is unclear. Methods:In a cross-sectional study, we assessed the prevalence and risk factors of CKD in rural and urban adults in South Kivu, Democratic Republic of Congo. Glomerular filtration rate (GFR) was estimated using the CKD-Epidemiology Collaboration (CKD-EPI) equations based on serum creatinine (eGFRcr), cystatin C (eGFRcys), or both markers (eGFRcr-cys), without ethnic correction factor. CKD was defined as an eGFR <60 ml/min per 1.73 m2 and/or albuminuria (albumin-to-creatinine ratio ?30 mg/g). Results:A total of 1317 participants aged 41.1 ± 17.1 years (730 rural, 587 urban) were enrolled. The prevalence of hypertension (20.2%; 95% confidence interval [CI], 18-22.3), diabetes mellitus (4.3%; 95% CI, 3.2-5.4) and obesity (8.9%; 95% CI, 7.4-10.5) was higher in urban than rural participants (all P < 0.05). HIV infection prevalence was 0.41% (95% CI, 0.05-0.78). The prevalence of eGFRcr <60 ml/min per 1.73 m2 was 5.4% (95% CI, 4.2-6.7). The prevalence of albuminuria was 6.6% (95 % CI, 5.1-8.1). The overall prevalence of CKD was 12.2% (95% CI, 10.2-14.2) according to CKD-EPIcr. Factors independently associated with CKD-EPIcr were older age (adjusted odds ratio [aOR], 1.05 [1.04-1.07]), urban residence (aOR 1.86 [1.18-2.95]), female sex (aOR 1.66 [1.04-2.66]), hypertension (aOR 1.90 [1.15-3.12]), diabetes (aOR 2.03 [1.02-4.06]), and HIV infection (10.21 [2.75-37.85]). The results based on eGFRcys or eGFRcr-cys were largely consistent with the preceding. Conclusion:Overall, the burden of CKD is substantial (>11%), predominantly in the urban area, and largely driven by classic risk factors (gender, aging, HIV, hypertension, and diabetes).