Differential Impact of Hospitalization on Cystatin C– and Creatinine-Based Estimated GFR

Background: Cystatin C has entered mainstream clinical care as a measure of kidney function, joining serum creatinine which has been used for almost a century. But many physicians notice that eGFRCr and eGFRCys values can differ considerably. Hospitalization with critical illness is known to acutely decrease eGFRdiff (eGFRCys – eGFRCr). However, whether this effect occurs in all-cause hospitalizations and persists after hospitalization is unknown. Methods: Among 5,599 adult participants in the Chronic Renal Insufficiency Cohort (CRIC) study with serum creatinine and cystatin C measurements, we estimated the association of six categories of total days of hospitalization between annual study visits (never hospitalized, hospitalized <7 days, 7-<14 days, 14-<28 days, 28-<42 days, and ≥ 42 days) and changes in eGFRCr, eGFRCys, and eGFRdiff between those study visits. Results: Compared to no hospitalization between study visits, increasing days of hospitalization were associated with decreases in eGFRCys (e.g., -3.30 [95% CI -5.48, -1.13] ml/min/1.73m 2 for ≥ 42 days of hospitalization, test for trend p<0.001), while eGFRCr remained relatively stable (e.g., -1.12 [-2.77, 0.53] ml/min/1.73m 2 for ≥ 42 days of hospitalization, test for trend p=0.21). The differential effect resulted in eGFRdiff becoming progressively more negative with more total days of hospitalization (test for trend p<0.001). Conclusions: Prolonged or repeated hospitalization was associated with larger decreases in eGFRCys compared to eGFRCr on measurements months after hospital discharge.