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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