Kidney functional reserve assessment in healthy young adults and cancer survivors: A cross-sectional study using cystatin C

Purpose: Kidney functional reserve (KFR) is a compensatory increase of glomerular filtration rate (GFR) in response to physiologic or pathologic stress. Cystatin C is a novel biomarker of GFR that has not previously been used to calculate KFR in cancer survivors. The study aims were to: (1) explore cystatin C-derived KFR (CysC-KFR) in healthy adolescents and young adults (AYAs), and (2) compare CysC-KFR between AYA cancer survivors with nephrotoxic chemotherapy exposure but normal glomerular filtration rate (GFR) at study entry and healthy AYAs. Methods: For this single-center cross-sectional pilot study, AYA cancer survivors were recruited and included if they received nephrotoxic chemotherapy during treatment, had normal GFR at study entry, and had no serious chronic medical conditions. Healthy AYAs were recruited from the general population. After drinking an oral protein load, hourly blood samples were collected from participants to measure creatinine and cystatin C for calculation of KFR. Survivors’ KFR values were compared to age- and sex-matched healthy AYAs in our cohort using Student’s t-testing and Pearson correlation. Results: The average CysC-KFR in 15 healthy AYAs and 7 cancer survivors was 12.3% and 14.2%, respectively. KFR was lower in older participants. KFR was not impacted by the type of nephrotoxic chemotherapy used. Conclusions: This study demonstrates potential feasibility of a cystatin C-based protocol for KFR assessments. Our methodology yielded similar results to prior KFR studies in healthy AYAs though the results need to be validated in larger studies as the small sample size and selective population significantly limit interpretation and generalizability of the findings. Implications for Cancer Survivors: This study demonstrates a potentially feasible approach for KFR measurement in cancer survivors, but further work is needed in order to evaluate the validity and reproducibility of a cystatin C-based KFR assessment and its association to age and cancer treatment-related factors.