Use of Serum Creatinine and Cystatin C Improves Risk Stratification for Mannitol Therapy in Patients with Intracerebral Hemorrhage

Abstract Objectives: An accurate assessment of renal function is key to the hyperosmolar mannitol therapy of patients after intracerebral hemorrhage (ICH), yet a comprehensive report of this safety concern is not available. This study aims to investigate the risk stratification of patients with ICH receiving mannitol treatment using the measurements of serum creatinine, cystatin C, or both in real-world settings. Methods: This population-based, observational, retrospective study was conducted with patients with an acute ICH admitted to a tertiary care university hospital from October 2010 to December 2018. Admission cystatin C and creatinine levels were measured in serum samples; these data were used to calculate the estimated glomerular filtration rate (eGFR). An eGFR value less than 90 mL/min/1.73 m2 of body-surface area was considered abnormal. Mannitol doses were recorded by the mean dose range per day (≤50, 51–100, 101–150, and >150 g/day). Results: A total of 1,946 patients (mean age 59 years; 68.6% male) were included in the present analysis. Among patients with abnormal eGFR values calculated from serum creatinine, cystatin C, or both creatinine and cystatin C, moderate-dose (101–150 g/day) and high-dose (>150 g/day) mannitol use were associated with an increased risk of all-cause in-hospital mortality compared with a mannitol dose of ≤50 g/day in analyses adjusted for ICH risk factors. For patients exhibiting normal eGFR values estimated based on serum creatinine and cystatin C, high-dose mannitol administration was also independently associated with death during hospitalization. However, this association was not observed among patients with a normal eGFR derived from combined creatinine and cystatin C measurements. Conclusions: The findings in this study provide encouraging support that eGFR use based on a combination of creatinine and cystatin C measurements for risk stratification among patients with ICH receiving hyperosmolar mannitol treatment in clinical practice.