Impact of Everolimus-based Immunosuppression on Renal Function in Liver Transplant Recipients

López, Ferran Campillo i; Alfocea, Patricia Abellán; Suazo, Eva Julissa Ortega; Garrido, María Ángeles López; Massare, A. Becerra; Medina, Ana Maria; Redondo–Cerezo, Eduardo; Aguilar, M.D. Espinosa

doi:10.1016/j.transproceed.2019.12.012

Cited by 3 publications

(3 citation statements)

References 15 publications

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“…Если конверсия ИС у таких реципиентов проводилась в первый год после ТП, улучшение функции почек было более значительным [6]. Однако в течение первого года более ранняя конверсия ИС (первые 3 мес после ТП) не приводила к столь выраженным различиям в изменении СКФ по сравнению с более поздним назначением эверолимуса [7].…”

Section: Discussionunclassified

The effect of early everolimus administration on the renal function while reducing the dosage of calcineurin inhibitors in liver transplant recipients in a long-term follow-up

Сюткин¹,

Салиенко²,

Олисов³

et al. 2021

Transplantologiâ (Mosk.)

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Introduction. The lifelong use of calcineurin inhibitors in liver transplant recipients leads to an increased incidence of chronic kidney disease.Objective. To compare the changes in glomerular filtration rate over five years in liver transplant recipients between those on everolimus with a reduced exposure to calcineurin inhibitors and those on standard doses of calcineurin inhibitors.Material and methods. Fourteen liver transplant recipient switched to everolimus with a minimization of calcineurin inhibitors exposure in the first months after liver transplantation from February 2009 to February 2015 who had received that therapy continuously for at least 60 months were included in the case-control study. Twenty eight liver transplant recipients (matched by sex, etiology of the underlying disease, calcineurin inhibitors) who were followed-up for at least 60 months after liver transplantation, who had received no dose of everolimus, in whom the glomerular filtration rate could be calculated at all points of analysis were selected as a comparison group (1:2). Glomerular filtration rate was calculated immediately before liver transplantation; 12, 24, 36, 48, and 60 months after liver transplantation. The glomerular filtration rate after liver transplantation was also calculated for liver transplant recipients from the main group immediately before the conversion to everolimus.Results. Before liver transplantation, the median of glomerular filtration rate in the main group of liver transplant recipients was lower (81.2 ml/min) than in the comparison group (97.5 ml/min, p=0.01). After liver transplantation, the renal function worsened in both groups of patients. In a pairwise comparison, the medians of glomerular filtration rate were statistically significantly lower after 12 months, 24 months, 36 months, 48 months after liver transplantation, than before liver transplantation. The median of glomerular filtration rate at the time of immunosuppression conversion was 44.3 ml/min. After the conversion of immunosuppression, the median of glomerular filtration rate gradually increased, and after 36 months the differences in glomerular filtration rate reached statistical significance compared with the level before conversion (69.4 ml/min;p=0.048). These differences still increased after 60 months after conversion (72.3 ml/min; p=0.041).Conclusion. Long-term administration of everolimus with minimization of calcineurin inhibitors exposure with the early conversion to this immunosuppression regime provides a steady improvement in renal function in liver transplant recipients with a low glomerular filtration rate in the preoperative and early post-transplant period.

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Section: Discussionunclassified

The effect of early everolimus administration on the renal function while reducing the dosage of calcineurin inhibitors in liver transplant recipients in a long-term follow-up

Сюткин¹,

Салиенко²,

Олисов³

et al. 2021

Transplantologiâ (Mosk.)

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“…Currently, two principal calcineurin inhibitors (CNIs) used for immunosuppressive treatment after LT are tacrolimus (TAC) and cyclosporin, and they have been emphasized as the etiology of acute and chronic kidney disease (CKD) in LT patients. CKD has an annual incidence of 8%, affecting 18% of patients 5 years after LT ( Nogueras Lopez et al, 2020 ). CKD can be categorized in relation to the estimated glomerular filtration rate (eGFR) using the Modification of Diet in Renal Disease (MDRD) equation (<60 ml/min/1.73 m 2 ) ( Bilbao et al, 2015 ).…”

Section: Introductionmentioning

confidence: 99%

“…After CKD develops, frequently prescribed alternatives to TAC include anti-metabolites, such as mycophenolic acid derivatives, and mammalian target of rapamycin (mTOR) inhibitors ( Saliba et al, 2011 ). Among these drugs, mTOR inhibitors have been shown to have a favorable adverse event profile and to be effective in preventing acute cellular rejection while protecting kidney function in LT patients to whom immunosuppressants are usually administered in the outpatient clinic ( De Simone et al, 2009 ; Saliba et al, 2011 ; De Simone et al, 2012 ; Bilbao et al, 2015 ; Saliba et al, 2017 ; Saliba et al, 2019 ; Nogueras Lopez et al, 2020 ; Saliba et al, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

Real-Life Experience of mTOR Inhibitors in Liver Transplant Recipients in a Region Where Living Donation Is Predominant

et al. 2021

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Background: Mammalian target of rapamycin (mTOR) inhibitors, such as everolimus and sirolimus, may be efficacious in preserving renal function in liver transplantation (LT) recipients while preventing hepatocellular carcinoma (HCC) recurrence.Materials and Methods: In this study, we retrospectively evaluated the safety, efficacy, and renoprotective effects of mTOR inhibitors in LT recipients. Among the 84 patients enrolled, mTOR inhibitor was commenced during the first year after LT. Renal function was measured by estimated glomerular filtration rate (eGFR) using the Modification of Diet in Renal Disease equation.Results: Regarding the type of mTOR inhibitor, everolimus was used in 71 patients and sirolimus in 13 patients. Concomitant tacrolimus was used in 63 patients (75.0%). For total enrolled patients, kidney function did not significantly change during 12 months after initiation of mTOR inhibitors, although tacrolimus-withdrawn patients (n = 21) showed better kidney function compared to tacrolimus-minimized patients (n = 63) after conversion. However, a significant improvement in kidney function was observed in the eGFR <60 ml/min/1.73 m2 group (n = 19) 12 months after initiation of mTOR inhibitors, for both patient groups with early + mid starters (n = 7, stating within 1 year after LT) and late starters (n = 12, starting over 1 year after LT). mTOR inhibitors were safely administered without serious adverse events that led to drug discontinuation.Conclusion: We demonstrated that patients with renal impairment showed significant improvement in renal function regardless of the timing of mTOR inhibitor start, suggesting that switch to mTOR inhibitors may be beneficial when renal function declines.

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Changes in glomerular filtration rate in liver recipients after reduced exposure to calcineurin inhibitors with concomitant everolimus administration within the first year after immunosuppression conversion

Syutkin

Салиенко

Zhuravel

et al. 2021

RJTAO

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Objective: to compare changes in estimated glomerular filtration rate (eGFR) in liver recipients with initially normal and impaired eGFR within the first year after immunosuppression conversion.Materials and methods. Enrolled in the study were 215 recipients of deceased-donor livers from February 2009 to February 2020, who received everolimus with dose reduction or complete withdrawal of calcineurin inhibitors (immunosuppression conversion, ISxC) for varying periods of time. GFR was measured using the MDRD-4 formula immediately before ISxC, then 3, 6, and 12 months after orthotopic liver transplantation (LTx). One month was considered an acceptable temporary deviation from the corresponding point.Results. At the time of ISxC, 32 (15%) of 215 recipients had normal renal function. Chronic kidney disease (CKD) increased in 60% of the recipients with normal eGFR by the end of the first year following ISxC; the fall in eGFR was particularly pronounced in older recipients. In the group with a baseline eGFR of 60–89 mL/min/1.73 m2, eGFR normalized in 62% of cases within 12 months; 28% of cases had no changes in renal function. In the subgroup with a pronounced decrease in eGFR at the time of ISxC, increased eGFR was observed as early as 1 month after ISxC, and the maximum was recorded after 3–6 months. The mean eGFR relative to baseline by month 3 after eGFR were higher for ISxC that was done in the first 2 months after LTx (19.7 ± 15.7 ml/minute/1.73 m2) than for ISxC done in the long-term period after LTx (10.1 ± 8.7 ml/minute/1.73 m2, p < 0.05).Conclusion. Changes in eGFR in liver recipients receiving EVR plus low-dose calcineurin inhibitor (CNI) depend on baseline eGFR and are multidirectional. The use of ISxC in the early post-LTx period led to a more pronounced improvement in eGFR. Maximal changes in eGFR were observed by 3–6 months after ISxC.

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Impact of Everolimus-based Immunosuppression on Renal Function in Liver Transplant Recipients

Cited by 3 publications

References 15 publications

The effect of early everolimus administration on the renal function while reducing the dosage of calcineurin inhibitors in liver transplant recipients in a long-term follow-up

The effect of early everolimus administration on the renal function while reducing the dosage of calcineurin inhibitors in liver transplant recipients in a long-term follow-up

Real-Life Experience of mTOR Inhibitors in Liver Transplant Recipients in a Region Where Living Donation Is Predominant

Changes in glomerular filtration rate in liver recipients after reduced exposure to calcineurin inhibitors with concomitant everolimus administration within the first year after immunosuppression conversion

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