The Difference Between Cystatin C– and Creatinine-Based Estimated GFR and Incident Frailty: An Analysis of the Cardiovascular Health Study (CHS)

Potok, O. Alison; Katz, Ronit; Bansal, Nisha; Siscovick, David S.; Odden, Michelle C.; Ix, Joachim H.; Shlipak, Michael G.; Rifkin, Dena E.

doi:10.1053/j.ajkd.2020.05.018

Cited by 46 publications

(60 citation statements)

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“…Particularly when creatinine-based eGFR presents an implausibly high value in contrast to the cystatin C–based eGFR, we recommend to interpret the creatinine-based result with caution [ 64 ]. Potok et al [ 65 , 66 ] hypothesize that prognostic information about frailty and mortality is embedded in the difference between cystatin C and creatinine, i.e that frailty would be less prevalent in older adults with a higher value of cystatin C–based eGFR as compared with creatinine-based eGFR.…”

Section: Discrepancies Between Creatinine-based and Cystatin C–based Egfrmentioning

confidence: 99%

Assessment of kidney function: clinical indications for measured GFR

Ebert

Bevc

Bökenkamp

et al. 2021

Clinical Kidney Journal

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In the vast majority of cases, glomerular filtration rate (GFR) is estimated using serum creatinine, which is highly influenced by age, sex, muscle mass, body composition, severe chronic illness and many other factors. This often leads to misclassification of patients or potentially puts patients at risk for inappropriate clinical decisions. Possible solutions are the use of cystatin C as an alternative endogenous marker or performing direct measurement of GFR using an exogenous marker such as iohexol. The purpose of this review is to highlight clinical scenarios and conditions such as extreme body composition, black race, disagreement between creatinine- and cystatin C-based estimated GFR (eGFR), drug dosing, liver cirrhosis, advanced chronic kidney disease and the transition to kidney replacement therapy, non-kidney solid organ transplant recipients, and living kidney donors where creatinine-based GFR estimation may be invalid. In contrast to the majority of literature on measured GFR (mGFR), this review does not include aspects of mGFR for research or public health settings but aims to reach practicing clinicians and raise their understanding of the substantial limitations of creatinine. While including cystatin C as a renal biomarker in GFR estimating equations has been shown to increase the accuracy of the GFR estimate, there are also limitations to eGFR based on cystatin C alone or the combination of creatinine and cystatin C in the clinical scenarios described above that can be overcome by measuring GFR with an exogenous marker. We acknowledge that mGFR is not readily available in many centres but hope that this review will highlight and promote the expansion of kidney function diagnostics using standardized mGFR procedures as an important milestone towards more accurate and personalized medicine.

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Section: Discrepancies Between Creatinine-based and Cystatin C–based Egfrmentioning

confidence: 99%

Assessment of kidney function: clinical indications for measured GFR

Ebert

Bevc

Bökenkamp

et al. 2021

Clinical Kidney Journal

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“…5,6,17 As efforts advance to improve CKD detection and monitoring and to eliminate the use of race in estimating kidney function, cystatin C will be increasingly incorporated into routine clinical care, and clinicians will commonly encounter persons with large eGFRdiff cys-cr . 5,6,18,19 Persons with large eGFRdiff cys-cr may have different risk profiles from those with similar eGFRcys and eGFRcr values. Furthermore, the eGFRdiff cys-cr would evolve if eGFRcys and eGFRcr changed at different rates over time, thus potentially offering further prognostic information.…”

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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“…This is consistent with findings in our previous work in other cohorts. 6,7 The present study aimed at understanding the determinants of this difference. We hypothesized that muscle J o u r n a l P r e -p r o o f quantity would account for the association between eGFRDiff and poor functional status and we were surprised to find this was not the case.…”

Section: Discussionmentioning

confidence: 99%

Cystatin C- and Creatinine-Based Glomerular Filtration Rate Estimation Differences and Muscle Quantity and Functional Status in Older Adults: The Health, Aging, and Body Composition Study

Potok

Shlipak

et al. 2022

Kidney Medicine

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This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

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The Difference Between Cystatin C– and Creatinine-Based Estimated GFR and Incident Frailty: An Analysis of the Cardiovascular Health Study (CHS)

Cited by 46 publications

References 10 publications

Assessment of kidney function: clinical indications for measured GFR

Assessment of kidney function: clinical indications for measured GFR

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

Cystatin C- and Creatinine-Based Glomerular Filtration Rate Estimation Differences and Muscle Quantity and Functional Status in Older Adults: The Health, Aging, and Body Composition Study

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