Sirolimus rescue of renal failure in children after combined liver-kidney transplantation

Vester, Udo; Kranz, Birgitta; Nadalin, Silvio; Paul, Andreas; Becker, Jan U.; Hoyer, Peter F.

doi:10.1007/s00467-004-1733-4

Cited by 11 publications

(12 citation statements)

References 24 publications

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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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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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“…In a case series, three children who underwent combined liver and kidney transplant were switched to sirolimus because of prolonged renal failure requiring dialysis and acute calcineurin inhibitor toxicity on biopsy. All three demonstrated improved renal function with cessation of dialysis [34]. These studies suggest that decreasing calcineurin inhibitor exposure by adding MMF or eliminating long-term exposure by switching to sirolimus can have beneficial effects on renal function in children after liver transplantation.…”

Section: Introductionmentioning

confidence: 99%

Chronic kidney disease after liver, cardiac, lung, heart–lung, and hematopoietic stem cell transplant

Hingorani

2008

Pediatr Nephrol

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Patient survival after cardiac, liver, and hematopoietic stem cell transplant (HSCT) is improving; however, this survival is limited by substantial pretransplant and treatmentrelated toxicities. A major cause of morbidity and mortality after transplant is chronic kidney disease (CKD). Although the majority of CKD after transplant is attributed to the use of calcineurin inhibitors, various other conditions such as thrombotic microangiopathy, nephrotic syndrome, and focal segmental glomerulosclerosis have been described. Though the immunosuppression used for each of the transplant types, cardiac, liver and HSCT is similar, the risk factors for developing CKD and the CKD severity described in patients after transplant vary. As the indications for transplant and the long-term survival improves for these children, so will the burden of CKD. Nephrologists should be involved early in the pretransplant workup of these patients. Transplant physicians and nephrologists will need to work together to identify those patients at risk of developing CKD early to prevent its development and progression to end-stage renal disease.

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“…Furthermore, enzyme localization in native pancreas tissue may play a role (12,13). Commercial enzymes represent the greatest reagent costs for human islet isolation, yet little is known about their uptake into the pancreas.…”

mentioning

confidence: 99%

“…This case also illustrates that it is possible to preserve kidney allograft function in some patients with PH. Furthermore, replacing Cyclosporin A with a mammalian target of rapamycin inhibitor may reduce oxalate deposition and contribute to improved graft outcomes (12).…”

mentioning

confidence: 99%

Long-Term Renal Allograft Survival After Posttransplantation Diagnosis of Primary Hyperoxaluria

et al. 2013

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Sirolimus rescue of renal failure in children after combined liver-kidney transplantation

Abstract: Prolonged renal failure after transplantation with severe CNI toxicity may be salvaged successfully with sirolimus-based immunosuppression.

Cited by 11 publications

References 24 publications

Conversion from calcineurin inhibitor to sirolimus in pediatric chronic allograft nephropathy

Conversion from calcineurin inhibitor to sirolimus in pediatric chronic allograft nephropathy

Chronic kidney disease after liver, cardiac, lung, heart–lung, and hematopoietic stem cell transplant

Long-Term Renal Allograft Survival After Posttransplantation Diagnosis of Primary Hyperoxaluria

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