026| Volume 26, ISSUE 10, SUPPLEMENT , S12, October 2020

Cystatin C for Estimation of Renal Function and Valganciclovir Dosing in Heart Transplant Patients


      Accuracy of serum creatinine (sCr) in the estimation of renal function among heart transplant (HT) pts may be limited by changes in muscle mass. Cystatin C (CysC) is independent from muscle mass and provides an alternative measure of estimated glomerular filtration rate (eGFR). We hypothesized that: i) sCr would overestimate renal function due to muscle wasting; and ii) this would cause overdosing of valganciclovir (VGC) and, thereby, leukopenia. Herein, we aimed to: i) compare post-HT changes in CysC- and sCr-based eGFR; and ii) explore whether the use of CysC in lieu of sCr carries the potential to reduce the rate of VGC-induced leukopenia.


      Pts transplanted between 6/2016 and 4/2019 had serial measurements of CysC and sCr pre- and post-HT. eGFR was assessed using CKD-EPI-CysC (eGFRCysC) and MDRD (eGFRsCr). Linear mixed models were used to regress post-HT changes in eGFRCysC, eGFRsCr and sCr/CysC ratio (a validated marker of muscle mass). In a subgroup of patients receiving VGC, eGFR was assessed as a time-varying covariate at 1-, 3-, and 6-months post-HT. The primary endpoint was rate of VGC-induced leukopenia within 1-month of renal function assessment. Appropriateness of VGC dosing for renal impairment was assessed using, in addition to eGFRCysC and eGFRsCr, creatinine clearance (CrCl) as per manufacturer's recommendation.


      A total of 309 samples were collected in 83 pts. eGFRCysC was markedly lower than eGFRsCr early post-HT (Figure A). While eGFRsCr declined long-term, eGFRCysC showed an opposite trend with a gradual improvement. The decline in eGFRsCr mirrored the rise in sCr/CysC ratio, suggesting that increase in muscle mass may contribute to this decline. Among 57 pts who were on VGC at 1-, 3-, and 6-months post-HT, 117 samples were available. Based on sCr-based equations (eGFRsCr and CrCl), VGC was appropriately dosed in the majority of samples (72% and 64%, respectively). However, based on eGFRCysC, VGC was inappropriately dosed in 54 (46%) samples: 11 (9%) underdosed, 43 (37%) overdosed (Figure B). Among 31 episodes of VGC-induced leukopenia within 1-month of sampling, 15 (48%) occurred in samples with VGC overdosed by eGFRCysC. In adjusted models, higher CysC but not sCr was associated with increased risk for leukopenia (OR: CysC: 1.47, 95%CI 1.04-2.06; sCr: 1.19, 95%CI 0.79-1.79).


      eGFRCysC and eGFRsCr markedly differ early post-HT with critical implications in the dosing of VGC. The use of CysC in lieu of sCr may prevent VGC overdosing and reduce the rate of leukopenia in HT pts.
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