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Effect of Calcineurin Inhibitor-Free Everolimus-Based Immunosuppressive Regimen on Albuminuria and Glomerular Filtration Rate after Heart Transplantation.

Effect of Calcineurin Inhibitor-Free Everolimus-Based Immunosuppressive Regimen on Albuminuria and Glomerular Filtration Rate after Heart Transplantation.
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Nelson LM, Andreassen AK, Andersson B, Gude E, Eiskjær H, Rådegran G, Dellgren G, Gullestad L, Gustafsson F,


Nelson LM, Andreassen AK, Andersson B, Gude E, Eiskjær H, Rådegran G, Dellgren G, Gullestad L, Gustafsson F, (click to view)

Nelson LM, Andreassen AK, Andersson B, Gude E, Eiskjær H, Rådegran G, Dellgren G, Gullestad L, Gustafsson F,

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Transplantation 2017 02 23() doi 10.1097/TP.0000000000001706
Abstract
BACKGROUND
Albuminuria in maintenance heart transplantation (HTx) is associated with poor renal response when switching to a calcineurin inhibitor (CNI)-lowered or free immunosuppressive regimen using everolimus (EVR), but the significance of albuminuria associated with EVR treatment after early CNI withdrawal in de novo HTx is unknown.

METHODS
We tested if glomerular filtration rate (mGFR, measured by CrEDTA clearance) was associated with urine albumin/creatinine ratio (UACR) post-HTx in a subgroup of patients included in the SCHEDULE trial, where de novo HTx patients (n=115) were randomized to EVR with complete CNI elimination 7-11 weeks post-HTx or standard CNI immunosuppression.

RESULTS
In 66 patients UACR measures were available at 1 year. In 7 patients in the EVR group a CNI was reintroduced within 12 months. Median mGFR was significantly higher in the EVR group both 1 and 3 years post-HTx (p=0.0004, p=0.03). Median UACR at 1 year was significantly higher in the EVR group (p=0.002). There was no correlation between log(UACR) at 1 year and mGFR at 1 or 3 years (r=-0.01, p=0.9; r=0.15, p=0.26), and in the EVR group nor between log(UACR) at 1 year and change in mGFR (Δ1-3 years) (r=0.27, p=0.14). Excluding patients in the EVR group in whom a CNI was reintroduced did not significantly change the results.

CONCLUSIONS
The effects of EVR with early CNI withdrawal after HTx on albuminuria and renal function appear dissociated; hence the clinical significance of albuminuria in this setting is uncertain and should not necessarily rule out EVR-based immunosuppression.

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