Renal function in heart transplant patients after switch to combined mammalian target of rapamycin inhibitor and calcineurin inhibitor therapy

Helmschrott, Matthias; Rivinius, Rasmus; Brückner, Thomas; Katus, Hugo A.; Doesch, Andreas O.

doi:10.2147/dddt.s135503

Cited by 7 publications

(14 citation statements)

References 48 publications

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“…Compared with studies in Western countries, the decline in renal function for 1 year after HTx was slightly worse or almost the same in the present study. [32][33][34] Furthermore, although the protocols of immunosuppressive regimens vary among each affiliation of HTx centres, the data in the present study were similar to those in the national database. 31 Despite differences in the impact of polymorphisms on TAC and CsA pharmacokinetics, studies comparing Japanese patients with other ethnicities with regard to renal function and other clinical outcomes are scarce.…”

Section: Limitationssupporting

confidence: 74%

Impact of tacrolimus versus cyclosporin A on renal function during the first year after heart transplant

et al. 2020

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Aims Nephrotoxicity of calcineurin inhibitors (CNIs) is associated with adverse events in patients undergoing heart transplant (HTx), although studies directly comparing tacrolimus (TAC) versus cyclosporin A (CsA), especially in combination with everolimus and low-dose CNIs approach, are limited. Thus, we sought to investigate the associations of TAC and CsA with clinical outcomes in HTx recipients, with specific focus on renal function. Methods and results From August 2007 to February 2017, 72 consecutive patients (39 treated with TAC vs. 33 with CsA) receiving de novo HTx in a single transplant centre were retrospectively evaluated. We used the instrumental variable method to account for unmeasured confounding. The study outcomes were percentage change in estimated glomerular filtration rates (eGFR) (safety endpoint) and biopsy-proven acute rejection (efficacy endpoint) within the first year after HTx. The enrolled patients (median age 40 years) were predominantly men (68%). There were no significant differences in baseline characteristics, including eGFR (64.8 [45.7-96.4] mL/min/1.73 m 2 in TAC vs. 65.6 [57.9-83.0] mL/min/1.73 m 2 for CsA; P = 0.48), other than sex (male, 49% for TAC vs. 91% for CsA; P < 0.001) between the two groups. Within the first year after HTx, 23 (59%) in the TAC group switched mycophenolate mofetil to everolimus, whereas 16 (48%) in the CsA group (P = 0.52). At 12 months, the rates of mortality and end-stage renal disease requiring renal replacement therapies were both 0%. In the instrumental variable analysis, no differences in renal function as well as graft rejection for 1 year after HTx existed between the TAC and CsA groups. These results were similar when taking into account of everolimus use. Conclusions Irrespective of everolimus use with low-dose CNIs, our analysis using the instrumental variable method showed no differences in renal function as well as graft rejection during the first year after HTx between HTx recipients who received TAC or CsA.

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Section: Limitationssupporting

confidence: 74%

Impact of tacrolimus versus cyclosporin A on renal function during the first year after heart transplant

et al. 2020

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“…Routine follow-up appointments comprised anamnesis, physical examination, electrocardiography, blood tests, dose adjustment of immunosuppressive drug therapy, and performance of echocardiography. 25 – 30 …”

Section: Methodsmentioning

confidence: 99%

Chronic digitalis therapy in patients before heart transplantation is an independent risk factor for increased posttransplant mortality

Rivinius

Helmschrott

Ruhparwar

et al. 2017

TCRM

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ObjectivesDigitalis therapy (digoxin or digitoxin) in patients with heart failure is subject to an ongoing debate. Recent data suggest an increased mortality in patients receiving digitalis. This study investigated the effects of chronic digitalis therapy prior to heart transplantation (HTX) on posttransplant outcomes.Patients and methodsThis was a retrospective, observational, single-center study. It comprised 530 adult patients who were heart-transplanted at Heidelberg University Hospital between 1989 and 2012. Patients with digitalis prior to HTX (≥3 months) were compared to those without (no or <3 months of digitalis). Patients with digitalis were further subdivided into patients receiving digoxin or digitoxin. Primary outcomes were early posttransplant atrial fibrillation and mortality.ResultsA total of 347 patients (65.5%) had digitalis before HTX. Of these, 180 received digoxin (51.9%) and 167 received digitoxin (48.1%). Patients with digitalis before HTX had a significantly lower 30-day (P=0.0148) and 2-year (P=0.0473) survival. There was no significant difference between digoxin and digitoxin in 30-day (P=0.9466) or 2-year (P=0.0723) survival. Multivariate analysis for posttransplant 30-day mortality showed pretransplant digitalis therapy as an independent risk factor (hazard ratio =2.097, CI: 1.036–4.248, P=0.0397). Regarding atrial fibrillation in the early posttransplant period, there was neither a statistically significant difference between patients with and without digitalis (P=0.1327) nor between patients with digoxin or digitoxin (P=0.5867).ConclusionDigitalis in patients before HTX is an independent risk factor for increased posttransplant mortality.

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“…After discharge, patients were followed up monthly within the first 6 months after HTX, then bimonthly between months 6 and 12 after HTX, and thereafter usually three to four times annually. [28][29][30][31][32][33][34][35][36]…”

Section: Follow-upmentioning

confidence: 99%

“…Steroids (prednisolone) were tapered incrementally during the first post-transplant months and were finally discontinued (if clinically possible) 6 months after HTX. [28][29][30][31][32][33][34][35][36]…”

Section: Post-transplant Medicationmentioning

confidence: 99%

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Elevated pre‐transplant pulmonary vascular resistance is associated with early post‐transplant atrial fibrillation and mortality

et al. 2020

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Aims Severely elevated pre‐transplant pulmonary vascular resistance (PVR) has been linked to adverse effects after heart transplantation (HTX). The impact of a moderately increased PVR before HTX on post‐transplant outcomes remains uncertain. The aim of this study was to investigate the effects of an elevated pre‐transplant PVR ≥ 300 dyn·s·cm−5 (≥3.75 Wood units) on outcomes after HTX. Methods and results This observational retrospective single‐centre study included 561 patients receiving HTX at Heidelberg Heart Center between 1989 and 2015. Patients were stratified by degree of pre‐transplant PVR. Analyses covered demographics, post‐transplant medication, mortality and causes of death after HTX, early post‐transplant atrial fibrillation (AF), and length of the initial hospital stay after HTX. Ninety‐four patients (16.8%) had a PVR ≥ 300 dyn·s·cm−5 (≥3.75 Wood units). These patients had a higher rate of early post‐transplant AF [20.2 vs. 10.7%, difference: 9.5%, 95% confidence interval (CI): 0.9–18.1%, P = 0.01] and an increased 30 day post‐transplant mortality (25.5 vs. 6.4%, hazard ratio: 4.4, 95% CI: 2.6–7.6, P < 0.01), along with a higher percentage of death due to transplant failure (21.2 vs. 4.1%, difference: 17.1%, 95% CI: 8.7–25.5%, P < 0.01). Multivariate analysis revealed a PVR ≥ 300 dyn·s·cm−5 (≥3.75 Wood units) as a significant risk factor for increased 30 day mortality after HTX (hazard ratio: 4.4, 95% CI: 2.5–7.6, P < 0.01). Kaplan–Meier estimator showed a lower 2 year survival after HTX (P < 0.01) in patients with a PVR ≥ 300 dyn·s·cm−5 (≥3.75 Wood units). Conclusions Elevated pre‐transplant PVR ≥ 300 dyn·s·cm−5 (≥3.75 Wood units) is associated with early post‐transplant AF and increased mortality after HTX.

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Renal function in heart transplant patients after switch to combined mammalian target of rapamycin inhibitor and calcineurin inhibitor therapy

Cited by 7 publications

References 48 publications

Impact of tacrolimus versus cyclosporin A on renal function during the first year after heart transplant

Impact of tacrolimus versus cyclosporin A on renal function during the first year after heart transplant

Chronic digitalis therapy in patients before heart transplantation is an independent risk factor for increased posttransplant mortality

Elevated pre‐transplant pulmonary vascular resistance is associated with early post‐transplant atrial fibrillation and mortality

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