Sarcopenia, adiposity, and discrepancies in cystatin C versus creatinine-based eGFR in patients with cancer: a cross-sectional study
medRxiv (Cold Spring Harbor Laboratory)(2023)
Abstract
Purpose Creatinine-based estimated glomerular filtration rate (eGFRCRE) may overestimate kidney function in patients with sarcopenia. While Cystatin C-based eGFR (eGFRCYS) is less affected by muscle mass, it may underestimate kidney function in patients with obesity. We sought to evaluate the relationship between body composition and discrepancies between creatinine and eGFRCRE and eGFRCYS in patients with cancer.
Methods We conducted a cross-sectional study of consecutive adults with cancer who had an abdominal CT scan performed within 90 days of simultaneous eGFRCRE and eGFRCYS measurements between May 2010-January 2022. Sarcopenia was defined using independent sex-specific cutoffs for skeletal muscle index (SMI) at the level of the third lumbar vertebral body (<39 cm2/m2 for women,<55 cm2/m2 for men). High adiposity was defined as the highest sex-specific quartile of total (visceral plus subcutaneous) adiposity index in the cohort. The primary outcome was eGFR discrepancy, defined by eGFRCYS >30% lower than eGFRCRE. We estimated the odds of eGFR discrepancy using multivariable logistic regression modeling.
Results Of 545 included patients (mean age 63 ±14 years, 300 [55%] females, 440 [80.7%] non-Hispanic white), 320 (58.7%) met the criteria for sarcopenia and 136 (25%) had high adiposity. After adjustment for potential confounders, sarcopenia and high adiposity were both associated with >30% eGFR discrepancy (adjusted odds ratio [aOR] 1.90, 95% confidence interval [CI] 1.12–3.24; aOR 2.01, 95% CI 1.15–3.52, respectively).
Conclusion Discrepancies in eGFRCRE and eGFRCYS are common in adult patients with cancer, and sarcopenia and high adiposity are both independently associated with large eGFR discrepancies.
Significance statement Serum creatinine may overestimate glomerular filtration rate (GFR) in patients with muscle loss, which is particularly common among patients with cancer. Serum cystatin C may perform better than creatinine in such patients, but its accuracy is affected by obesity. We performed body composition analysis using computed tomography scans in 545 adult patients with cancer and found that both sarcopenia and high adiposity were independently associated with greater discrepancies in serum creatinine-vs. cystatin C-based estimated GFR. These findings highlight the need for future studies to improve and personalize GFR assessment in patients with cancer, particularly in those who will receive renally cleared medications and anti-neoplastic therapies with a narrow therapeutic index.
### Competing Interest Statement
Conflicts of interest: S. Gupta reports research support from BTG International and GE Healthcare. She is a member of GlaxoSmithKlines Global Anemia Council, a consultant for Secretome, and founder of the American Society of Onconephrology. MES: Reports research funding from Gilead, Merck, EMD Serono, and Angion. She has served as a scientific advisory board member to Mallinckrodt, Travere, and Novartis. DEL reports research support from BioPorto, BTG International, and Metro International Biotech LLC. FJF received unrelated research funding from the William M. Wood Foundation, has a related patent WO2019051358A1, and is a consultant for Pfizer. JFG has served as a compensated consultant or received honoraria from Bristol-Myers Squibb, Genentech/Roche, Takeda, Loxo/Lilly, Blueprint Medicine, Gilead, Moderna, AstraZeneca, Curie Therapeutics, Mirati, Merus Pharmacueticals, Nuvalent, Pfizer, Novartis, Merck, iTeos, Karyopharm, Silverback Therapeutics, and GlydeBio; research support from Novartis, Genentech/Roche, and Takeda; institutional research support from Bristol-Myers Squibb, Tesaro, Moderna, Blueprint, Jounce, Array Biopharma, Merck, Adaptimmune, Novartis, and Alexo; and has an immediate family member who is an employee with equity at Ironwood Pharmaceuticals. All remaining authors have no conflict of interest.
### Funding Statement
MES is funded by NIH grant R01DK130839 SG is funded by NIH grant K23DK125672 DEL is funded by NIH grants R01HL144566, R01DK125786, and R01DK126685 SJS is funded by NIH/NIA (K76AG074919) outside the submitted work
### Author Declarations
I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.
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The details of the IRB/oversight body that provided approval or exemption for the research described are given below:
The Massachusetts General Brigham Institutional Review Board approved this study and waived the need for informed consent.
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I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).
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I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.
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De-identified data produced in the present study are available upon reasonable request to the corresponding author.
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Key words
egfr,adiposity,cancer,creatinine-based,cross-sectional
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