Race, Genetic Ancestry, and Estimating Kidney Function in CKD

Hsu, Chi‐yuan; Yang, Wei; Parikh, Rishi; Anderson, Amanda H.; Chen, Teresa K.; Cohen, Debbie L.; He, Jiang; Mohanty, Madhumita Jena; Lash, James P.; Mills, Katherine T.; Muiru, Anthony N.; Parsa, Afshin; Saunders, Milda R.; Shafi, Tariq; Townsend, Raymond R.; Waikar, Sushrut S.; Wang, Jianqiao; Wolf, Myles; Tan, Thida C.; Feldman, Harold I.; Go, Alan S.

doi:10.1056/nejmoa2103753

Cited by 164 publications

(168 citation statements)

References 34 publications

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“… 8 , 9 , 10 , 11 , 12 , 13 Recently, the National Kidney Foundation (NKF) and American Society of Nephrology (ASN) recommended the increased use of cystatin C to estimate GFR because cystatin C is less affected than creatinine by non-GFR determinants and is not associated with race or genetic ancestry. 7 , 14 , 15 , 16 The NKF and ASN also recommended using the combined eGFR equation, which includes both cystatin C and creatinine to balance the potential confounding by their non-GFR determinants. 15 However, a large eGFRdiff cys-cr indicates that non-GFR factors are associated with substantial change in 1 biomarker; therefore, use of the combined eGFR equation among persons with large eGFRdiff cys-cr may mask the differential influence of these non-GFR factors.…”

Section: Introductionmentioning

confidence: 99%

Association of Intraindividual Difference in Estimated Glomerular Filtration Rate by Creatinine vs Cystatin C and End-stage Kidney Disease and Mortality

et al. 2022

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IMPORTANCEAs cystatin C is increasingly adopted to estimate glomerular filtration rate (eGFR), clinicians will encounter patients in whom cystatin C-based eGFR (eGFRcys) and creatinine-based eGFR (eGFRcr) differ widely. The clinical implications of these differences, eGFRdiff cys-cr , are unknown. OBJECTIVE To evaluate the associations of eGFRdiff cys-cr with end-stage kidney disease (ESKD) and mortality among individuals with chronic kidney disease (CKD). DESIGN, SETTING, AND PARTICIPANTSThis is a prospective cohort study of 4956 individuals with mild to moderate CKD from 7 clinical centers in the United States who enrolled in the Chronic Renal Insufficiency Cohort (CRIC) Study between 2003 to 2018. Statistical analyses were completed in December 2021.EXPOSURES eGFRdiff cys-cr (eGFRcys − eGFRcr) was calculated at baseline and annually thereafter for 3 years. Because 15 mL/min/1.73 m 2 represents a clinically meaningful difference in eGFR that also distinguishes CKD stages, eGFRdiff cys-cr was categorized as: less than −15 mL/min/1.73 m 2 , −15 to 15 mL/min/1.73 m 2 , and 15 mL/min/1.73 m 2 or greater. MAIN OUTCOMES AND MEASURESThe outcomes of ESKD, defined as initiation of maintenance dialysis or receipt of a kidney transplant, and all-cause mortality were adjudicated from study entry until administrative censoring in 2018. RESULTS Among 4956 participants with mean (SD) age of 59.5 (10.5) years, 2152 (43.4%) were Black, 515 (10.4%) were Hispanic, and 2113 (42.6%) were White. There were 2156 (43.5%) women and 2800 (56.5%) men. At baseline, eGFRcys and eGFRcr values differed by more than 15 mL/min/ 1.73 m 2 in one-third of participants (1638 participants [33.1%]). Compared with participants with similar baseline eGFRcys and eGFRcr (eGFRdiff cys-cr −15 to 15 mL/min/1.73 m 2 ), those in whom eGFRcys was substantially lower than eGFRcr (eGFRdiff cys-cr < −15 mL/min/1.73 m 2 ) had a higher risk of mortality (hazard ratio [HR], 1.86; 95% CI, 1.40-2.48) while those with eGFRdiff cys-cr of 15 mL/min/1.73 m 2 or greater had lower risks of ESKD (subHR [SHR], 0.73; 95% CI, 0.59-0.89) and mortality (HR, 0.68; 95% CI, CI 0.58-0.81). In time-updated analyses, participants with eGFRdiff cys-cr less than −15 mL/min/1.73 m 2 had higher risks of ESKD (SHR, 1.83; 95% CI, 1.10-3.04) and mortality (HR, 3.03; 95% CI,) compared with participants with similar eGFRcys and eGFRcr.Conversely, participants with eGFRdiff cys-cr of 15 mL/min/1.73 m 2 or greater had lower risks of ESKD (SHR, 0.50; 95% CI, 0.35-0.71) and mortality (HR, 0.58; 95% CI, 0.45-0.75). Longitudinal changes in eGFRdiff cys-cr were associated with mortality risk. Compared with participants who had similar slopes by eGFRcys and eGFRcr, those with smaller eGFRcr declines had an 8-fold increased mortality risk (continued) Key Points Question Are differences between estimated glomerular filtration rate by cystatin C (eGFRcys) vs creatinine (eGFRcr) associated with the risk of end-stage kidney disease (ESKD) and mortality among individuals with chronic kidney disease (CKD)? F...

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Section: Introductionmentioning

confidence: 99%

Association of Intraindividual Difference in Estimated Glomerular Filtration Rate by Creatinine vs Cystatin C and End-stage Kidney Disease and Mortality

et al. 2022

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“…The eGFR findings seem inconsistent with the higher prevalence of CKD in ethnic minorities 6 , 7 , 8 and may imply that eGFR-based screening tools, such as the KDIGO, have important limitations in multiethnic populations. 14 , 15 , 23 , 24 An alternative interpretation of the higher eGFR in the ethnic minority groups may reflect the presence of hyperfiltration—a biological factor that is considered to be an early sign of microvascular kidney alterations. A higher GFR is thought to be a sign of increased intraglomerular hydrostatic pressure and precedes development of proteinuria, progressive kidney function decline, and overt CKD.…”

Section: Discussionmentioning

confidence: 99%

“… 24 More recently, comparison between pair-matched African Europeans and Europeans also demonstrated a positive bias of CKD-EPI eGFR in the African population, 14 whereas in African Americans having CKD omission of race in this equation resulted in more underestimation of the GFR. 15 In South Asians living in Pakistan, it was found that CKD-EPI eGFR overestimates true GFR. 23 Data with regard to the other ethnic groups included our cohort remain limitedly reported.…”

Section: Discussionmentioning

confidence: 99%

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Discrepancies in estimated glomerular filtration rate and albuminuria levels in ethnic minority groups – The multiethnic HELIUS cohort study

et al. 2022

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“…It has been argued that to exclude race from the eGFR equations would provoke a systematic under interpretation of measured GFR. To disclosure about the use of race when estimating GFR, or to accept denial to identify race from the patient, or to use a cystatin C confirmatory test has been proposed as a way to overcome the conflict ( 41 , 42 ). In September 2021, the National Kidney Foundation and the American Society of Nephrology Joint Task Force on Reassessing the Inclusion of Race in Diagnosing Kidney Diseases recommended a new 2021 CKD-EPI creatinine eGFR equation which does not include race to estimate GFR ( Table 1 ).…”

Section: Introductionmentioning

confidence: 99%

The Glomerular Filtration Rate: From the Diagnosis of Kidney Function to a Public Health Tool

Cusumano

Tzanno-Martins²,

Rosa-Díez

2021

Front. Med.

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The prevalence of chronic kidney disease (CKD) continues to increase worldwide, as well as the associated morbidity and mortality and the consequences on the patients' quality of life and countries' economies. CKD often evolves without being recognized by patients and physicians, although the diagnosis is based on two simple laboratory data: the estimated glomerular filtration rate (eGFR) and urine analysis. To measure GFR, the knowledge about the physiologic processes at the nephron level, the concept of clearance, and the identification of creatinine as a suitable endogenous marker for measuring the creatinine clearance (CrCl) had to be previously developed. On those bases, different equations to calculate CrCl (Cockcroft and Gault, 1976), or estimated GFR (four variables MDRD, 1999; CKD-Epi, 2009, among others) were generated. They all include creatinine and some demographic data, such as sex and age. However, to compare results throughout life or among laboratories, the creatinine determination must be standardized. In addition, the accuracy of these equations remains controversial in certain subgroups of patients. For these reasons, other mathematical models to improve CrCl estimation have been developed, such as when urine cannot be collected, in debilitated elderly patients and patients with trauma, diabetes, or obesity. Currently, eGFR in adults can be measured and reported immediately, using isotope dilution mass spectrometry traceable creatinine-based equations. In conclusion, based on knowledge obtained from renal physiology, eGFR can be used in the clinic for the diagnosis and early treatment of CKD, as well as a public instrument to estimate the prevalence.

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Race, Genetic Ancestry, and Estimating Kidney Function in CKD

Cited by 164 publications

References 34 publications

Association of Intraindividual Difference in Estimated Glomerular Filtration Rate by Creatinine vs Cystatin C and End-stage Kidney Disease and Mortality

Association of Intraindividual Difference in Estimated Glomerular Filtration Rate by Creatinine vs Cystatin C and End-stage Kidney Disease and Mortality

Discrepancies in estimated glomerular filtration rate and albuminuria levels in ethnic minority groups – The multiethnic HELIUS cohort study

The Glomerular Filtration Rate: From the Diagnosis of Kidney Function to a Public Health Tool

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