Rapamycin use and rapid withdrawal of calcineurin inihibitors in pediatric renal transplantation

Vilalta, R.; Vila, Amparo Marquina; Nieto, Juliana Serrano; Callı́s, L

doi:10.1016/s0041-1345(03)00055-1

Cited by 13 publications

(24 citation statements)

References 4 publications

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“…16,17,21,23 The few patients in this review who were started on sirolimus specifically for renal dysfunction had improved renal function at follow-up. This was reflected in the group as a whole where renal function either demonstrated stability or improvement on serial annual GFR studies.…”

Section: Discussionmentioning

confidence: 92%

“…6,[12][13][14] Sirolimus has also been used as a renal sparing agent by allowing for use of lower doses of calcineurin inhibitors (CNIs). [15][16][17] Although the positive effects of sirolimus are promising, dose-dependent side effects, including hematologic abnormalities, hyperlipidemia, gastrointestinal disturbances, interstitial lung disease and mouth ulcers, have been reported in the adult population. 18 -20 Few studies of the effects of sirolimus have been done on pediatric kidney, intestine and liver transplant recipients.…”

mentioning

confidence: 99%

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Sirolimus immunosuppression in pediatric heart transplant recipients: A single-center experience

Lobach

Pollock-BarZiv

West

et al. 2005

The Journal of Heart and Lung Transplantation

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Section: Discussionmentioning

confidence: 92%

mentioning

confidence: 99%

Sirolimus immunosuppression in pediatric heart transplant recipients: A single-center experience

Lobach

Pollock-BarZiv

West

et al. 2005

The Journal of Heart and Lung Transplantation

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“…SRL represents an alternative to CNIs, which are still the standard of care for preventing AR after kidney tx. Both TAC and SRL have the same intracellular target, namely FKBP12 protein (6, 7). However, this does not cause an antagonism between TAC and SRL, as there is usually a sufficient FKBP12 reserve to support simultaneous effects of these two drugs (6).…”

Section: Mechanism Of Actionmentioning

confidence: 99%

“…Inhibition of calcineurin, which is a serine–threonine phosphatase, blocks the G0 to G1 transition (7). On the other hand, SRL interferes with the consequences of the signals from IL‐2 (6). When SRL binds to FKBP12, the resulting complex blocks the activation of mTOR, which is a cell cycle‐specific kinase activating p70 ribosomal S6 kinase.…”

Section: Mechanism Of Actionmentioning

confidence: 99%

Sirolimus in pediatric renal transplantation

Kasap

2011

Pediatric Transplantation

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SRL, an mTOR inhibitor that inhibits cell cycle progression, represents an important alternative to CNIs, which are still the cornerstones of pediatric solid organ tx. Because there are still limited data on SRL use among pediatric solid organ recipients, further studies are needed to verify the efficacy and safety of SRL. It has unique pharmacokinetic characteristics concerning dosing intervals and reduction of the dose in combination with other immunosuppressants. SRL also has antineoplastic, antiviral, and antiatherogenic advantages over other immunosuppressive agents. The adverse effects of SRL including thrombocytopenia, hyperlipidemia, proteinuria, impaired wound healing, mouth ulcers, edema, male hypogonadism, TMA, and interstitial pneumonitis must be considered carefully in pediatric population. This article reviews the most recent data on SRL application in the field of pediatric renal tx.

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“…Albeit only proven in experimental systems the antiproliferative effects of sirolimus might be of additional benefit in such high‐risk populations with regards to abnormal cellular proliferation such as scarring and neoplasms (reviewed in 4–6). When sirolimus was added to standard immunosuppression in children, withdrawal of the CNI resulted in improved renal function without effects on rejection or graft survival (17–20). To our knowledge no prospective data regarding conversion to sirolimus in children with CAN have been published.…”

Section: Discussionmentioning

confidence: 99%

Conversion from calcineurin inhibitor to sirolimus in pediatric chronic allograft nephropathy

Falger¹,

Mueller²,

Arbeiter³

et al. 2006

Pediatric Transplantation

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CAN is a major cause for allograft loss in renal transplantation. Sirolimus was recently introduced as a potent non-nephrotoxic alternative to CNIs. In the present study, effects of a conversion protocol were investigated in pediatric CAN with declining GFR, defined by a Schwartz formula clearance below 60 mL/1.73 m2/min, steadily increasing SCr and allograft biopsy. In eight children with a median age of 12.8 yr, sirolimus was started at median 32 months after transplantation with a loading dose of 0.24 mg/kgBW, followed by 0.2 mg/kgBW/day, aimed at trough levels of 15-20 ng/mL. CNIs were reduced to 50% at start of sirolimus and discontinued at median seven days when target levels of sirolimus were reached. Following conversion, changes of GFR significantly stabilized (-2.9 vs. +0.4 mL/min/1.73 m2/month, p = 0.025). Individual GFR increased in five of eight patients (p = 0.026), only one child exhibited unaltered progression of graft failure. In the responders, mean SCr improved by 0.3 mg/dL (p = 0.043). Effects were not dependent on GFR at conversion, nor time post-transplantation. Blood pressure, hematological parameters and proteinuria remained stable during the observation period, serum lipids transiently increased. About half of the children suffered from infectious complications. No child had to be taken off sirolimus; there was no graft loss during the observation period. In conclusion, conversion from CNIs to sirolimus is an effective protocol with tolerable side effects to stabilize renal graft function for at least one yr in the majority of children with biopsy proven CAN.

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Rapamycin use and rapid withdrawal of calcineurin inihibitors in pediatric renal transplantation

Cited by 13 publications

References 4 publications

Sirolimus immunosuppression in pediatric heart transplant recipients: A single-center experience

Sirolimus immunosuppression in pediatric heart transplant recipients: A single-center experience

Sirolimus in pediatric renal transplantation

Conversion from calcineurin inhibitor to sirolimus in pediatric chronic allograft nephropathy

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