Association between eGFRcystatin C-to-eGFRcreatinine Ratio and the Nonkidney Factors Muscle Mass, Muscle Strength, and Sarcopenia

Background: Selective glomerular hypofiltration syndromes (SGHS), are linked to cardiovascular disease and mortality, and defined by a low eGFRcysC/eGFRcreat ratio. To correctly define SGHS, non-renal factors potentially affecting creatinine and cystatin C should be accounted for. The aim of our study was to investigate the association between muscle mass, muscle strength, sarcopeni and eGFRcysC/eGFRcreat ratio. Methods: This study was based on 1044 females from the Osteoporosis Prospective Risk Assessment (OPRA) cohort, all aged 75 at inclusion with additional investigations after 5 (n=683) and 10 (n=355) years. Estimated glomerular filtration rate (eGFR) was based on creatinine and cystatin C using the CKD-EPI equation, and eGFRcysC/eGFRcreat ratio was determined. Muscle strength was measured as maximal knee extension and muscle mass measured by dual-energy x-ray absorptiometry (DXA). Sarcopenia was defined according to European Working Group on Sarcopenia in Older People (EWGSOP)2, defined as low muscle strength plus low muscle mass. Linear regression models examined the association between the dependent variable, low eGFR ratio, and the independent variables, muscle mass, muscle strength and sarcopenia. Analyses were adjusted for inflammation (CRP), smoking and glucocorticoid treatment. Results are presented as regression coefficients with 95 % confidence intervals (CI), p-value and partial explained variation (R2). Results: Sarcopenia was present in 32, 33 and 36 individuals at ages 75, 80 and 85 years respectively. At age 75, sarcopenia was significantly associated with the eGFR ratio (βadj=-0,09, 95% CI = -0,2 to -0,02, p=0,012, R2=4,9%) (Table). Similar results were observed at age 85, but not at 80. Muscle mass was associated with the eGFR ratio at age 75 (βadj=0,03, 95% CI = 0,01 to 0,05, p=0,008, R2= 4,7%) and at age 80, but not at 85. Muscle strength showed a significant association across all ages, with the explained variation decreasing with age (9%, 7,8%, 4,1%). Conclusion: While the eGFRcysC/eGFRcreat ratio was associated with non-renal factors such as muscle mass, muscle strength and sarcopenia, these parameters explained only a small portion of the variation in the ratio, suggesting limited clinical impact. Further investigations in older populations are warranted to confirm these findings.