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      Association of the Estimated Glomerular Filtration Rate With vs Without a Coefficient for Race With Time to Eligibility for Kidney Transplant

      research-article
      , PhD 1 , , , MD 2 , , MD, MPH 1 , 3 , , MD, MAS 1
      JAMA Network Open
      American Medical Association

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          Abstract

          This cohort study assesses the association between estimated glomerular filtration rate (eGFR) calculated with vs without a coefficient for race and time to achievement of an eGFR less than 20 mL/min/1.73 m 2.

          Key Points

          Question

          Is adjusting for Black race in estimating equations for glomerular filtration rate in patients with chronic kidney disease associated with a delay in kidney transplant eligibility?

          Findings

          In this cohort study of 1658 self-identified Black adults with chronic kidney disease, commonly used estimates of kidney function did not correspond well with directly measured kidney function. Estimating kidney function not including a coefficient for race (vs including a race coefficient) was significantly associated with a shorter time to achieving an estimated glomerular filtration rate less than 20 mL/min/1.73 m 2, a key threshold of kidney function for referral and listing for kidney transplant.

          Meaning

          The findings suggest that biases in race-based glomerular filtration rate estimates may be associated with delays in potential kidney transplant eligibility.

          Abstract

          Importance

          Kidney transplant is associated with improved survival and quality of life among patients with kidney failure; however, significant racial disparities have been noted in transplant access. Common equations that estimate glomerular filtration rate (eGFR) include adjustment for Black race; however, how inclusion of the race coefficient in common eGFR equations corresponds with measured GFR and whether it is associated with delayed eligibility for kidney transplant listing are unknown.

          Objective

          To compare eGFR with measured GFR and evaluate the association between eGFR calculated with vs without a coefficient for race and time to eligibility for kidney transplant.

          Design, Setting, and Participants

          This prospective cohort study used data from the Chronic Renal Insufficiency Cohort, a multicenter cohort study of participants with chronic kidney disease (CKD). Self-identified Black participants from that study were enrolled between April 2003 and September 2008, with follow-up through December 2018. Statistical analyses were completed on November 11, 2020.

          Exposure

          Estimated GFR, measured annually and estimated using the creatinine-based Chronic Kidney Disease-Epidemiology (CKD-EPI) equation with and without a race coefficient.

          Main Outcomes and Measures

          Iothalamate GFR (iGFR) measured in a subset of participants (n = 311) and time to achievement of an eGFR less than 20 mL/min/1.73 m 2, an established threshold for kidney transplant referral and listing.

          Results

          Among 1658 self-identified Black participants, mean (SD) age was 58 (11) years, 848 (51%) were female, and mean (SD) eGFR was 44 (15) mL/min/1.73 m 2. The CKD-EPI eGFR with the race coefficient overestimated iGFR by a mean of 3.1 mL/min/1.73 m 2 (95% CI, 2.2-3.9 mL/min/1.73 m 2; P < .001). The mean difference between CKD-EPI eGFR without the race coefficient and iGFR was of smaller magnitude (−1.7 mL/min/1.73 m 2; 95% CI, −2.5 to −0.9 mL/min/1.73 m 2). For participants with an iGFR of 20 to 25 mL/min/1.73 m 2, the mean difference in eGFR with vs without the race coefficient and iGFR was 5.1 mL/min/1.73 m 2 (95% CI, 3.3-6.9 mL/min/1.73 m 2) vs 1.3 mL/min/1.73 m 2 (95% CI, −0.3 to 2.9 mL/min/1.73 m 2). Over a median follow-up time of 4 years (interquartile range, 1-10 years), use of eGFR calculated without vs with the race coefficient was associated with a 35% (95% CI, 29%-41%) higher risk of achieving an eGFR less than 20 mL/min/1.73 m 2 and a shorter median time to this end point of 1.9 years.

          Conclusions and Relevance

          In this cohort study, inclusion of the race coefficient in the estimation of GFR was associated with greater bias in GFR estimation and with delayed achievement of a clinical threshold for kidney transplant referral and eligibility. These findings suggest that nephrologists and transplant programs should be cautious when using current estimating equations to determine kidney transplant eligibility.

          Related collections

          Most cited references25

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          A new equation to estimate glomerular filtration rate.

          Equations to estimate glomerular filtration rate (GFR) are routinely used to assess kidney function. Current equations have limited precision and systematically underestimate measured GFR at higher values. To develop a new estimating equation for GFR: the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. Cross-sectional analysis with separate pooled data sets for equation development and validation and a representative sample of the U.S. population for prevalence estimates. Research studies and clinical populations ("studies") with measured GFR and NHANES (National Health and Nutrition Examination Survey), 1999 to 2006. 8254 participants in 10 studies (equation development data set) and 3896 participants in 16 studies (validation data set). Prevalence estimates were based on 16,032 participants in NHANES. GFR, measured as the clearance of exogenous filtration markers (iothalamate in the development data set; iothalamate and other markers in the validation data set), and linear regression to estimate the logarithm of measured GFR from standardized creatinine levels, sex, race, and age. In the validation data set, the CKD-EPI equation performed better than the Modification of Diet in Renal Disease Study equation, especially at higher GFR (P < 0.001 for all subsequent comparisons), with less bias (median difference between measured and estimated GFR, 2.5 vs. 5.5 mL/min per 1.73 m(2)), improved precision (interquartile range [IQR] of the differences, 16.6 vs. 18.3 mL/min per 1.73 m(2)), and greater accuracy (percentage of estimated GFR within 30% of measured GFR, 84.1% vs. 80.6%). In NHANES, the median estimated GFR was 94.5 mL/min per 1.73 m(2) (IQR, 79.7 to 108.1) vs. 85.0 (IQR, 72.9 to 98.5) mL/min per 1.73 m(2), and the prevalence of chronic kidney disease was 11.5% (95% CI, 10.6% to 12.4%) versus 13.1% (CI, 12.1% to 14.0%). The sample contained a limited number of elderly people and racial and ethnic minorities with measured GFR. The CKD-EPI creatinine equation is more accurate than the Modification of Diet in Renal Disease Study equation and could replace it for routine clinical use. National Institute of Diabetes and Digestive and Kidney Diseases.
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            Estimating glomerular filtration rate from serum creatinine and cystatin C.

            Estimates of glomerular filtration rate (GFR) that are based on serum creatinine are routinely used; however, they are imprecise, potentially leading to the overdiagnosis of chronic kidney disease. Cystatin C is an alternative filtration marker for estimating GFR. Using cross-sectional analyses, we developed estimating equations based on cystatin C alone and in combination with creatinine in diverse populations totaling 5352 participants from 13 studies. These equations were then validated in 1119 participants from 5 different studies in which GFR had been measured. Cystatin and creatinine assays were traceable to primary reference materials. Mean measured GFRs were 68 and 70 ml per minute per 1.73 m(2) of body-surface area in the development and validation data sets, respectively. In the validation data set, the creatinine-cystatin C equation performed better than equations that used creatinine or cystatin C alone. Bias was similar among the three equations, with a median difference between measured and estimated GFR of 3.9 ml per minute per 1.73 m(2) with the combined equation, as compared with 3.7 and 3.4 ml per minute per 1.73 m(2) with the creatinine equation and the cystatin C equation (P=0.07 and P=0.05), respectively. Precision was improved with the combined equation (interquartile range of the difference, 13.4 vs. 15.4 and 16.4 ml per minute per 1.73 m(2), respectively [P=0.001 and P 30% of measured GFR, 8.5 vs. 12.8 and 14.1, respectively [P<0.001 for both comparisons]). In participants whose estimated GFR based on creatinine was 45 to 74 ml per minute per 1.73 m(2), the combined equation improved the classification of measured GFR as either less than 60 ml per minute per 1.73 m(2) or greater than or equal to 60 ml per minute per 1.73 m(2) (net reclassification index, 19.4% [P<0.001]) and correctly reclassified 16.9% of those with an estimated GFR of 45 to 59 ml per minute per 1.73 m(2) as having a GFR of 60 ml or higher per minute per 1.73 m(2). The combined creatinine-cystatin C equation performed better than equations based on either of these markers alone and may be useful as a confirmatory test for chronic kidney disease. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases.).
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              Comparison of mortality in all patients on dialysis, patients on dialysis awaiting transplantation, and recipients of a first cadaveric transplant.

              The extent to which renal allotransplantation - as compared with long-term dialysis - improves survival among patients with end-stage renal disease is controversial, because those selected for transplantation may have a lower base-line risk of death. In an attempt to distinguish the effects of patient selection from those of transplantation itself, we conducted a longitudinal study of mortality in 228,552 patients who were receiving long-term dialysis for end-stage renal disease. Of these patients, 46,164 were placed on a waiting list for transplantation, 23,275 of whom received a first cadaveric transplant between 1991 and 1997. The relative risk of death and survival were assessed with time-dependent nonproportional-hazards analysis, with adjustment for age, race, sex, cause of end-stage renal disease, geographic region, time from first treatment for end-stage renal disease to placement on the waiting list, and year of initial placement on the list. Among the various subgroups, the standardized mortality ratio for the patients on dialysis who were awaiting transplantation (annual death rate, 6.3 per 100 patient-years) was 38 to 58 percent lower than that for all patients on dialysis (annual death rate, 16.1 per 100 patient-years). The relative risk of death during the first 2 weeks after transplantation was 2.8 times as high as that for patients on dialysis who had equal lengths of follow-up since placement on the waiting list, but at 18 months the risk was much lower (relative risk, 0.32; 95 percent confidence interval, 0.30 to 0.35; P<0.001). The likelihood of survival became equal in the two groups within 5 to 673 days after transplantation in all the subgroups of patients we examined. The long-term mortality rate was 48 to 82 percent lower among transplant recipients (annual death rate, 3.8 per 100 patient-years) than patients on the waiting list, with relatively larger benefits among patients who were 20 to 39 years old, white patients, and younger patients with diabetes. Among patients with end-stage renal disease, healthier patients are placed on the waiting list for transplantation, and long-term survival is better among those on the waiting list who eventually undergo transplantation.
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                Author and article information

                Journal
                JAMA Netw Open
                JAMA Netw Open
                JAMA Netw Open
                JAMA Network Open
                American Medical Association
                2574-3805
                14 January 2021
                January 2021
                14 January 2021
                : 4
                : 1
                : e2034004
                Affiliations
                [1 ]Kidney Research Institute, Division of Nephrology, University of Washington, Seattle
                [2 ]Division of Nephrology, University of Washington, Seattle
                [3 ]Puget Sound Veterans Affairs Health Care System, Seattle, Washington
                Author notes
                Article Information
                Accepted for Publication: November 29, 2020.
                Published: January 14, 2021. doi:10.1001/jamanetworkopen.2020.34004
                Open Access: This is an open access article distributed under the terms of the CC-BY License. © 2021 Zelnick LR et al. JAMA Network Open.
                Corresponding Author: Leila R. Zelnick, PhD, Kidney Research Institute, Division of Nephrology, University of Washington, 325 9th Ave, PO Box 359606, Seattle, WA 98104 ( lzelnick@ 123456uw.edu ).
                Author Contributions : Dr Zelnick had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
                Concept and design: All authors.
                Acquisition, analysis, or interpretation of data: Zelnick, Leca, Bansal.
                Drafting of the manuscript: Zelnick, Leca, Bansal.
                Critical revision of the manuscript for important intellectual content: Leca, Young.
                Statistical analysis: Zelnick, Bansal.
                Obtained funding: Bansal.
                Administrative, technical, or material support: Bansal.
                Supervision: Bansal.
                Conflict of Interest Disclosures: Dr Leca reported receiving grants from Novartis, Angion, CaredX, Natera, Veloxis, and TGI Institution outside the submitted work. Dr Young reported receiving support from the Veterans Affairs Puget Sound Health Care System. No other disclosures were reported.
                Funding/Support: This work supported by an unrestricted fund from the Northwest Kidney Centers and by grant 1R01HG007879-01A1 from the National Human Genomes Research Institute, National Institutes of Health (Dr Young).
                Role of the Funder/Sponsor: The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.
                Disclaimer: This article was not prepared in collaboration with investigators of the Chronic Renal Insufficiency Cohort Study (CRIC) study and does not necessarily reflect the opinions or views of the CRIC study investigators, the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) central repositories, or the NIDDK. The Veterans Health Administration does not endorse any of the statements or opinions advocated by this article.
                Additional Information: The CRIC was conducted by the CRIC study investigators and supported by the NIDDK. The data from the CRIC reported here were supplied by the NIDDK central repositories.
                Article
                zoi201034
                10.1001/jamanetworkopen.2020.34004
                7809586
                33443583
                885bd97a-ac9b-42a8-94ea-c3febf03ebb5
                Copyright 2021 Zelnick LR et al. JAMA Network Open.

                This is an open access article distributed under the terms of the CC-BY License.

                History
                : 20 October 2020
                : 29 November 2020
                Categories
                Research
                Original Investigation
                Online Only
                Nephrology

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