Use of Serum Cystatin C versus Creatinine for Estimation of Renal Function and Valganciclovir Dosing in Heart Transplant Recipients

Abstract

Creatinine clearance (CrCl) is the accepted clinical standard for the assessment of renal function and dosing of renally-excreted medications such as valganciclovir (VGC) among heart transplant (HT) pts. Cystatin C (CysC) has recently shown superiority to serum creatinine (sCr) for the estimation of renal function in advanced diseases. We hypothesize that CysC-estimated glomerular filtration rate (Cys-eGFR) more accurately guides VGC dosing than CrCL, and thereby may prevents drug overdosing and leukopenia in HT pts. Pts transplanted between 11/2016 and 4/2019 who received VGC for CMV prophylaxis were included. eGFR was assessed using CrCl and CysC-eGFR as a time-varying covariate at 1-,3-, and 6-months post-HT. The primary endpoint was rate of leukopenia (WBC<4 × 103/uL) within 1-month of renal function assessment. Pts were otherwise censored at the time of: i) leukopenia due to other causes (eg, CMV, sepsis); ii) any change in VGC dose due to renal function; iii) end of CMV prophylaxis. Appropriateness of VGC dosing for renal impairment was assessed according to the manufacturer recommendation. Repeated measures logistic regression models were adjusted for baseline WBC, VGC dose, SMZ/TMP use, and mycophenolate dose. 119 samples were available in 58 pts (age 54±13 y, 20% female). Based on CrCl, VGC was inappropriately dosed in 43 samples: 21 underdosed, 22 overdosed. Based on CysC-eGFR, VGC was inappropriately dosed in 62 samples: 12 underdosed, 50 overdosed (Figure 1). 32 episodes of leukopenia were observed in 27 pts within 1-month of sampling. Half (n=16) of the events occurred in samples with VGC overdosed by CysC-eGFR. In adjusted models, CysC but not sCr was associated with a significant 1.48 times greater odds of leukopenia (per 0.3 mg/L CysC 95%CI 1.05-2.08; OR per 0.3 mg/dL sCr 1.17, 95%CI 0.78-1.73.) CONCLUSION: CysC-eGFR may more accurately estimate VGC dosing compared to CrCL thereby resulting in lower rates of leukopenia after HT.