Project description:BackgroundBeta-2 microglobulin (B2M) and cystatin C are novel glomerular filtration markers that have a stronger association with adverse outcomes than creatinine. The B2M-based glomerular filtration rate (GFR) estimating equation was built in 2016. Several new creatinine and cystatin C equations were developed in 2019 in China. However, external validation of these new equations remains to be seen.MethodsThis is a prospective cohort study. The equations were validated in a population totaling 830 participants (median age 62 years). These equations include the B2M-based equation (built in 2016), three CKD-EPI equations (built in 2009 and 2012), three Yang-Du equations (C-CKD-EPIscr, C-CKD-EPIcys, and C-CKD-EPIscr-cys equations, all of which were Chinese-modified CKD-EPI equations developed by Yang et al. in 2019), and a Xiangya equation (a creatinine-based equation built in the Third Xiangya Hospital in 2019). The estimated GFR (eGFR) calculated separately by 8 equations (B2M GFR, CKD-EPIscr, CKD-EPIcys, CKD-EPIscr-cys, C-CKD-EPIscr, C-CKD-EPIcys, C-CKD-EPIscr-cys, and Xiangya equations) was compared with the reference GFR (rGFR) measured by the 99mTc-DTPA renal dynamic imaging method. Participants were divided into CKD stage 1-5 specific subgroups. The primary outcomes of this study were bias, precision (interquartile range of difference, IQR), and accuracy (the proportion of eGFR within 30% of rGFR [P30] and root mean square error [RMSE]) of eGFR versus rGFR.ResultsThe B2M-based equation was worse than CKD-EPI equations and Yang-Du equations in most outcomes. CKD-EPIscr and C-CKD-EPIscr equations had a larger area under the receiver operating characteristic curve (ROCAUC). The CKD-EPIscr equation had the highest sensitivity (83.3%) and the Xiangya equation the highest specificity (89.5%) to diagnose CKD. The bias was the lowest in CKD-EPIcys and C-CKD-EPIscr-cys equations by median and mean difference (1.23 and -1.42, respectively). The Xiangya equation yielded the highest bias by both median and mean difference (8.29 and 6.52, respectively). The C-CKD-EPIscr equation was the most accurate with the highest P30 value (68.1%) and most precise with the lowest IQR (19). The Xiangya equation had the best RMSE (lowest RMSE, 0.56), and gave the best performance in the CKD stage 2 subgroup. The C-CKD-EPIscr-cys equation achieved the lowest bias in CKD stage 3-5 (p = 0.663, 0.104, and 0.130, respectively, compared with rGFR).ConclusionThe B2M-based equation was worse than CKD-EPI and Yang-Du equations on the whole. CKD-EPIcys and C-CKD-EPIscr-cys equations had the lowest bias, whereas the Xiangya equation yielded the highest bias. The Xiangya equation gave the best performance in the CKD stage 2 subgroup, while the C-CKD-EPIscr-cys equation achieved the lowest bias in CKD stage 3-5. Further work to improve the performance of the GFR estimating equation is needed.

Project description:Background In 2021, the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) validated a new equation for estimated glomerular filtration rate (eGFR). However, this new equation is not ethnic-specific, and prevalence of CKD in Asians is known to differ from other ethnicities. This study evaluates the impact of the 2009 and 2021 creatinine-based eGFR equations on the prevalence of CKD in multiple Asian cohorts. Methods Eight population-based studies from China, India, Russia (Asian), Singapore and South Korea provided individual-level data (n = 67,233). GFR was estimated using both the 2009 CKD-EPI equation developed using creatinine, age, sex, and race (eGFRcr [2009, ASR]) and the 2021 CKD-EPI equation developed without race (eGFRcr [2021, AS]). CKD was defined as an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73m2 (G3-G5). Prevalence of eGFR categories was compared within each study and within subgroups of age, sex, body mass index (BMI), diabetes, and hypertension status. The extent of reclassification was examined using net reclassification improvement (NRI). Findings Of 67,233 adults, CKD prevalence was 8.6% (n = 5800/67,233) using eGFRcr (2009, ASR) and 6.4% (n = 4307/67,233) using eGFRcr (2021, AS). With the latter, CKD prevalence was reduced across all eight studies, ranging from −7.0% (95% CI −8.5% to −5.4%) to −0.4% (−1.3% to 0.5%), and across all subgroups except those in the BMI < 18.5% subgroup. Net reclassification index (NRI) was significant at −2.33% (p < 0.001). No individuals were reclassified as a higher (more severe) eGFR category, while 1.7%−4.2% of individuals with CKD were reclassified as one eGFR category lower when eGFRcr (2021, AS) rather than eGFRcr (2009, ASR) was used. Interpretation eGFRcr (2021, AS) consistently provided reduced CKD prevalence and higher estimation of GFR among Asian cohorts than eGFRcr (2009, ASR). Based on current risk-stratified approaches to CKD management, more patients reclassified to lower-risk GFR categories could help reduce inappropriate care and its associated adverse effects among Asian renal patients. Comparison of both equations to predict progression to renal failure or adverse outcomes using prospective studies are warranted. Funding National Medical Research Council, Singapore.

Project description:CONTEXT:The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation more accurately estimates glomerular filtration rate (GFR) than the Modification of Diet in Renal Disease (MDRD) Study equation using the same variables, especially at higher GFR, but definitive evidence of its risk implications in diverse settings is lacking. OBJECTIVE:To evaluate risk implications of estimated GFR using the CKD-EPI equation compared with the MDRD Study equation in populations with a broad range of demographic and clinical characteristics. DESIGN, SETTING, AND PARTICIPANTS:A meta-analysis of data from 1.1 million adults (aged ? 18 years) from 25 general population cohorts, 7 high-risk cohorts (of vascular disease), and 13 CKD cohorts. Data transfer and analyses were conducted between March 2011 and March 2012. MAIN OUTCOME MEASURES:All-cause mortality (84,482 deaths from 40 cohorts), cardiovascular mortality (22,176 events from 28 cohorts), and end-stage renal disease (ESRD) (7644 events from 21 cohorts) during 9.4 million person-years of follow-up; the median of mean follow-up time across cohorts was 7.4 years (interquartile range, 4.2-10.5 years). RESULTS:Estimated GFR was classified into 6 categories (?90, 60-89, 45-59, 30-44, 15-29, and <15 mL/min/1.73 m(2)) by both equations. Compared with the MDRD Study equation, 24.4% and 0.6% of participants from general population cohorts were reclassified to a higher and lower estimated GFR category, respectively, by the CKD-EPI equation, and the prevalence of CKD stages 3 to 5 (estimated GFR <60 mL/min/1.73 m(2)) was reduced from 8.7% to 6.3%. In estimated GFR of 45 to 59 mL/min/1.73 m(2) by the MDRD Study equation, 34.7% of participants were reclassified to estimated GFR of 60 to 89 mL/min/1.73 m(2) by the CKD-EPI equation and had lower incidence rates (per 1000 person-years) for the outcomes of interest (9.9 vs 34.5 for all-cause mortality, 2.7 vs 13.0 for cardiovascular mortality, and 0.5 vs 0.8 for ESRD) compared with those not reclassified. The corresponding adjusted hazard ratios were 0.80 (95% CI, 0.74-0.86) for all-cause mortality, 0.73 (95% CI, 0.65-0.82) for cardiovascular mortality, and 0.49 (95% CI, 0.27-0.88) for ESRD. Similar findings were observed in other estimated GFR categories by the MDRD Study equation. Net reclassification improvement based on estimated GFR categories was significantly positive for all outcomes (range, 0.06-0.13; all P < .001). Net reclassification improvement was similarly positive in most subgroups defined by age (<65 years and ?65 years), sex, race/ethnicity (white, Asian, and black), and presence or absence of diabetes and hypertension. The results in the high-risk and CKD cohorts were largely consistent with the general population cohorts. CONCLUSION:The CKD-EPI equation classified fewer individuals as having CKD and more accurately categorized the risk for mortality and ESRD than did the MDRD Study equation across a broad range of populations.

Project description:BACKGROUND: Black individuals are far more likely than white individuals to develop end stage renal disease (ESRD). However, earlier stages of chronic kidney disease (CKD) have been reported to be less prevalent among blacks. This disparity remains poorly understood. The objective of this study was to evaluate whether the lower prevalence of CKD among blacks in early stages of CKD might be due in part to an inability of the MDRD equation to accurately determine early stages of CKD in both the black and white population. METHODS: We conducted a retrospective cohort study of 97, 451 patients seen in primary care clinic in Veterans Integrated Service Network 2 (VISN 2) over a 7 year period to determine the prevalence of CKD using both the Modification of Diet in Renal Disease (MDRD) Study equation and the more recently developed CKD Epidemiology Collaboration (CKD-EPI) equation. Demographic data, comorbid conditions, prescription of medications, and laboratory data were recorded. Logistic regression and quantile regression models were used to compare the prevalence of estimated glomerular filtration rate (eGFR) categories between black and white individuals. RESULTS: The overall prevalence of CKD was lower when the CKD-EPI equation was used. Prevalence of CKD in whites was 53.2% by MDRD and 48.4% by CKD-EPI, versus 34.1% by MDRD and 34.5% by CKD-EPI in blacks. The cumulative logistic regression and quantile regression showed that when eGFR was calculated by the EPI method, blacks were as likely to present with an eGFR value less than 60 mL/min/1.73 m2 as whites. Using the CKD-EPI equation, blacks were more likely than white individuals to have stage 3b, 4 and 5 CKD. Using the MDRD method, the prevalence in blacks was only higher than in whites for stage 4 and 5 CKD. Similar results were obtained when the analysis was confined to patients over 65 years of age. CONCLUSIONS: The MDRD equation overestimates the prevalence of CKD among whites and underestimates the prevalence of CKD in blacks compared to the CKD-EPI equation.

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Impact of Removing Race Variable on CKD Classification Using the Creatinine-Based 2021 CKD-EPI Equation.

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