Creatinine- versus cystatin C-based renal function assessment in the Northern Manhattan Study

S Ali Husain,Clinton B Wright,Yeseon Park Moon,Myles Wolf,Ralph L Sacco,Joshua Z Willey,Sumit Mohan,Ken Cheung,Mitchell S V Elkind,Petter Bjornstad

doi:10.1371/journal.pone.0206839

Abstract

BackgroundAccurate 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.MethodsThe 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.ResultsParticipants (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.ConclusionsIn 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.

Highlights

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’ chronic kidney disease (CKD) status was discordant, and only 28% maintained the same CKD stage by both measures
Multiethnic, elderly cohort, we found a highly discrepant prevalence of CKD with eGFRcys versus eGFRcr
Kidney Disease Improving Global Outcomes (KDIGO) guidelines recommend confirming creatininebased chronic kidney disease (CKD) diagnosis using an alternative method of glomerular filtration rate (GFR) estimation in select groups.[9]

Summary

Introduction

Accurate and reliable glomerular filtration rate (GFR) estimation has enabled the identification and classification of renal dysfunction in a manner that could not be done with the use of serum creatinine values in isolation.[1,2,3] The calculation of estimated GFR (eGFR) using creatinine, an endogenous amino acid derivative of muscle cells, can inform drug dosing and guide risk stratification.[4,5,6] By taking into account factors that impact creatinine generation, eGFR equations are able to provide an assessment of GFR without the cost or complexity associated with GFR “measurement” using exogenous substances such as inulin or iohexol.[7]the use of creatinine is imperfect: because creatinine generation is dependent on muscle mass, factors that influence body composition, including age, sex, and race, adversely impact the reliability of creatinine-based GFR estimation.[8]. Accurate and reliable glomerular filtration rate (GFR) estimation has enabled the identification and classification of renal dysfunction in a manner that could not be done with the use of serum creatinine values in isolation.[1,2,3] The calculation of estimated GFR (eGFR) using creatinine, an endogenous amino acid derivative of muscle cells, can inform drug dosing and guide risk stratification.[4,5,6] By taking into account factors that impact creatinine generation, eGFR equations are able to provide an assessment of GFR without the cost or complexity associated with GFR “measurement” using exogenous substances such as inulin or iohexol.[7]. 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

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