Long‐term effects on renal function of dose‐reduced calcineurin inhibitor and sirolimus in cardiac transplant patients

Abstract

One hundred and fifty-five patients (79 sirolimus and 76 controls) were included and had similar baseline characteristics. Sirolimus was started a mean of 1429 d post-CTX and maintained for a mean of 823 d. Reason for conversion to sirolimus was renal insufficiency (34%), vasculopathy (29%), recurrent rejection (19%), and other (18%). The eGFR was not different between groups at baseline (44.7 mL/min/1.73 m(2) vs. 46.0, p = 0.64) or at any point during follow-up: 90 d, 180 d, 1 yr, 2 yr, and 3 yr. conclusion: Patients converted to a regimen of sirolimus and a dosed-reduced CNI have stable renal function over the following three yr, but do not have an improvement in renal outcomes compared to patients maintained on full dose CNI.

Sirolimus Immunoprophylaxis and Renal Histological Changes in Long-Term Cardiac Transplant Recipients

“…In contrast to these reports, recent publications by Gonzalez-Vilchez et al 10 failed to report long-term improvement (28 months) of renal function in SIR-treated cardiac transplant recipients 9 ± 4 years following the procedure. Similar neutral observations were recently reported by Khandhar et al 11 These observations are also in agreement with the report from Gustafsson et al 39 In that study, a shorter time from transplantation to conversion was associated with a greater improvement in renal function at 6 months.…”

“…SIR therapy has also yielded increased triglyceride levels and proteinuria with limited change in blood pressure in most of the investigations. 8-12,29-34…”

“…The effects of SIR substitution for CNI on renal function have shown some encouraging yet controversial effects in cardiac transplant patients with suspected renal dysfunction caused by CNI toxicity. 7-14 The characterization of renal structural and functional abnormalities in patients with suspected CNI-induced nephrotoxicity, together with the evaluation of changes in renal function long term following SIR substitution have not been investigated in the same study. Accordingly, the primary objective of this clinical investigation was to assess the impact of SIR as a substitution for CNI on GFR at 6 months in stable long-term cardiac transplant recipients.…”

Immunosuppressive therapies after heart transplantation — The balance between under- and over-immunosuppression

“…Initial randomized trials by Eisen et al [54], and Keogh et al [55], indicated that EVL and SRL actually potentiate the nephrotoxic side effects of CNIs unless the doses of the CNIs are reduced. Several studies have, subsequently, studied HT patients in whom an m-TOR inhibitor has been introduced together with a CNI-reduction [56][57][58][59][60][61][62][63][64][65][66][67][68][69][70][71][72][73] or a CNI-withdrawal . Altogether, it appears as if both of the two strategies have beneficial effects on renal function, although questions remain regarding the safety and efficacy compared with ordinary CNI-therapy.…”