The Difference in eGFR by Cystatin C vs. Creatinine Is Strongly Associated with Mortality Independent of Measured GFR

Background: In preliminary work, we have shown that the difference in glomerular filtration rate (eGFR) estimated by cystatin C [eGFRCys] and creatinine [eGFRCr], was associated with risk of frailty, hospitalization, cardiovascular events and mortality. Prior studies lacked directly measured GFR so it remained uncertain if associations were influenced by kidney function. Methods: 567 participants of the Berlin Initiative Study (BIS) had baseline GFR measured by iohexol clearance (mGFR), as well as serum creatinine and cystatin C levels. eGFRCr and eGFRCys were calculated using CKD-EPI equations, and eGFRDiff was defined as eGFRCys - eGFRCr. Mortality was recorded during up to 8 years follow-up. The association between eGFRDiff and mortality was assessed using Cox regression. Results: Average (SD) age was 79 (±6) years, eGFRCys 63 (±21), and eGFRCr 69 (±17) for an eGFRDiff of -6 (±12) mL/min/1.73m2. Compared to participants with minimal differences in eGFR, those with a substantially positive difference eGFRDiff (≥10 mL/min/1.73m2) were younger (76 vs. 78 years), less were diabetic (17% vs. 24%) and fewer took antihypertensives (59% vs 76%). Those with a substantially negative eGFRDiff (≤ -10 mL/min/1.73m2) were at much higher death risk which was minimally influenced with or without adjustment for measured GFR, age, sex, and urine albumin/creatinine ratio (Table).Table.: Association of eGFRDiff with Mortality in Older Adults in the Berlin Initiative StudyConclusions: In BIS, an eGFRCys estimate that was substantially less than an eGFRCr estimate was associated with significantly higher risk of death. This association remained after adjusting for mGFR. Important clinical information beyond kidney function is embedded in eGFRDiff. Funding: Private Foundation Support