Everolimus Associated With Low-Dose Calcineurin Inhibitors, an Option in Kidney Transplant Recipients of Very Old Donors

Furian, Lucrezia; Silvestre, Carlos; Vallese, L.; Baldan, N; Donato, P.; Bonfante, Luciana; Cavallin, Francesco; Marchini, Francesco; Rigotti, Paolo

doi:10.1016/j.transproceed.2014.08.044

Cited by 10 publications

(5 citation statements)

References 29 publications

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“…From 2003 to 2007, the recipients of ECD grafts were treated with mTOR inhibitors (sirolimus at the target serum level of 10-15 ng/mL in the first 3 months and then 5-10 ng/mL) plus mycophenolic acid. From 2008, the protocol was slightly changed as previously described 15,16 with low dosage of calcineurin inhibitor plus low dosage of everolimus.…”

Section: Immunosuppressive Therapymentioning

confidence: 99%

How does age affect the outcome of kidney transplantation in elderly recipients?

Neri

Furian

Cavallin

et al. 2017

Clinical Transplantation

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The aging of the on-dialysis population raises the issue of whether to propose elderly patients for kidney transplantation and how to manage their immunosuppression. This study aimed to analyze the outcome of kidney transplantation on an Italian series of elderly recipients. We included in this retrospective study all patients over 60 years, receiving a deceased-donor kidney transplantation from January 2004 to December 2014 in two north Italian Centers. We analyzed the correlation of recipient age with graft's and patient's survival, delayed graft function, acute cellular rejection (ACR), surgical complications, infections, and glomerular filtration rate. Four hundred and fifty-two patients with a median age of 65 years were included in the study. One-, 3-, and 5-year patient's and graft's survival were, respectively, of 98.7%, 93%, 89% and 94.4%, 87.9%, 81.4%. The increasing recipient age was an independent risk factor only for the patient's (P=.008) and graft's survival (P=.002). ACR and neoplasia were also associated to a worse graft survival. The reduced graft survival in elderly kidney recipients seems to be related more to the increasing recipient's age than to the donor's features. In this population, the optimization of organ allocation and immunosuppression may be the key factors to endorse improvements.

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Section: Immunosuppressive Therapymentioning

confidence: 99%

How does age affect the outcome of kidney transplantation in elderly recipients?

Neri

Furian

Cavallin

et al. 2017

Clinical Transplantation

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“…Moreover, everolimus is used in combination with other medications for the treatment of a wide spectrum of diseases (for review, Calimeri and Ferreri 2017;Pelletier et al 2016;Blair et al 2017). Several papers reported about the usage of everolimus to treat different diseases in old patients (Donati et al 2017;Furian et al 2014;Wei and Lai 2015). However, there are no reports published about long-term treatment of seizure-prone old patients or old experimental animals by mTORC1 inhibitors.…”

Section: Discussionmentioning

confidence: 99%

RHEB1 insufficiency in aged male mice is associated with stress-induced seizures

et al. 2017

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The mechanistic target of rapamycin (mTOR), a protein kinase, is a central regulator of mammalian metabolism and physiology. Protein mTOR complex 1 (mTORC1) functions as a major sensor for the nutrient, energy, and redox state of a cell and is activated by ras homolog enriched in brain (RHEB1), a GTP-binding protein. Increased activation of mTORC1 pathway has been associated with developmental abnormalities, certain form of epilepsy (tuberous sclerosis), and cancer. Clinically, those mTOR-related disorders are treated with the mTOR inhibitor rapamycin and its rapalogs. Because the effects of chronic interference with mTOR signaling in the aged brain are yet unknown, we used a genetic strategy to interfere with mTORC1 signaling selectively by introducing mutations of Rheb1 into the mouse. We created conventional knockout (Rheb1 ) and gene trap (Rheb1 ) mutant mouse lines. Rheb1-insufficient mice with different combinations of mutant alleles were monitored over a time span of 2 years. The mice did not show any behavioral/neurological changes during the first 18 months of age. However, after aging (> 18 months of age), both the Rheb1 and Rheb1 hybrid males developed rare stress-induced seizures, whereas Rheb1 and Rheb1 females and Rheb1 and Rheb1 mice of both genders did not show any abnormality. Our findings suggest that chronic intervention with mTORC1 signaling in the aged brain might be associated with major adverse events.

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“…Patients received standard dose of calcineurin inhibitors (CNIs), mycophenolate and steroids or, as alternative treatment, low dose CNI, mTORi, and steroids. The choice of using mTORi in combination with low dose CNI was essentially based on donor characteristics: a low dose CNI-based therapy was prescribed to reduce renal toxicity and benefit recipients of graft from extended criteria donors [26]. Immunosuppressive drug levels were also monitored according to clinical practice of the Transplant Center.…”

Section: Methodsmentioning

confidence: 99%

Physical Fitness as a Prognostic Marker for Infectious Events in Kidney Transplant Recipients

et al. 2021

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Introduction: Infectious events are one of the leading causes of death in kidney transplant recipients (KTRs). KTRs have reduced cardiorespiratory fitness (CRF), a predictor for infections in other populations. The aim of this study was to investigate whether CRF and muscle strength are prognostic markers for infectious events in KTRs. Methods: In this retrospective cohort study, 155 KTRs underwent an incremental, maximal cardiopulmonary exercise test (CPET) 3 months after transplantation. CRF was analyzed with peak oxygen consumption (VO2 peak) while muscle strength with isometric handgrip (HG) test. Laboratory blood samples and drug therapy were collected. The median follow-up period was 54 (interquartile range 38–62) months. Cox regression analyses were performed to evaluate predictors of infectious events adjusting for potential confounders. Results: During this study, severe infectious events occurred in 41 subjects (26.5%). 15.5% (n = 24) of patients had a severely reduced CRF, defined as a VO2 peak below the 5th percentile of the reference values reported for a matched healthy population. The hazard ratio for infectious events in this subgroup was 2.389 (95% CI = 1.188–4.801, p = 0.014), independently of gender, age, BMI, time on dialysis, hemoglobin concentration, eGFR, diabetes, and immunosuppressive regimen. On the contrary, no significant association of HG strength and infections was found. Conclusion: Therefore, low CRF may be considered as a modifiable predictor of severe infectious events in KTRs. A CPET should thus be recommended for cardiovascular screening, evaluation of CRF, and tailored exercise prescription to reduce the risk of infections and potentially improve long-term outcomes of transplantation.

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Everolimus Associated With Low-Dose Calcineurin Inhibitors, an Option in Kidney Transplant Recipients of Very Old Donors

Cited by 10 publications

References 29 publications

How does age affect the outcome of kidney transplantation in elderly recipients?

How does age affect the outcome of kidney transplantation in elderly recipients?

RHEB1 insufficiency in aged male mice is associated with stress-induced seizures

Physical Fitness as a Prognostic Marker for Infectious Events in Kidney Transplant Recipients

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