title: Sirolimus in chronic allograft nephropathy in pediatric recipients.
abstract: CAN is a common cause of late graft loss. Nephrotoxicity due to CNIs is known to contribute to CAN. We retrospectively evaluated the efficacy and safety of SRL in pediatric renal Tx recipients showing CAN in their allograft biopsy. Twenty-one patients aged 10.4 +/- 4.6 yr at Tx time receiving CNIs as primary immunosuppression were converted to SRL at 58.9 +/- 49.1 months after Tx, due to progressive decline of renal function and biopsy proven CAN. Mean follow-up after switch was 19.7 +/- 9.5 months. All patients received CsA as part of the immunosuppressive regimen, at a mean dose 4.4 +/- 1.2 mg/kg/day. Mean daily dose of SRL three month after conversion was 2.6 +/- 0.8 mg/body surface area/day and the mean through levels where 6.9 +/- 2.5 ng/mL. Graft biopsies showed Grade I CAN in 12 children and Grade II CAN in nine. After SRL introduction, there were neither acute rejection episodes nor graft losses. GFR improved at three months and was sustained thereafter only in children with Grade I CAN. Post-Tx time at conversion was the only significant variable between patients who had Grade I CAN and Grade II CAN (33.6 +/- 33.3 vs. 92.7 +/- 47.5 months, p = 0.003). Nine patients had no AEs, six patients had nine SAE: five diarrhea, one herpes zoster, one pancreatic pseudo cyst, one pneumonia, and one Influenza A infection; 11 patients had 13 AEs: six oral aphthous ulcers, three urinary tract infections, two herpes simplex, one lymphedema, and one nephrotic proteinuria. Significant improvement of GFR occurred in Grade I CAN group at three months from conversion and was sustained during follow-up. Those who had Grade II CAN experienced no change in GFR. The incidence of AEs and SAE is of concern and further studies are necessary to assess their relevance.
authors.affiliation: Nephrology Unit, Hospital de Pediatría Prof Dr Juan P Garrahan Buenos Aires, Argentina. juanibanez@sinectis.com.ar
authors.forename: J P
authors.initials: JP
authors.lastname: Ibáñez
authors.forename: M L
authors.initials: ML
authors.lastname: Monteverde
authors.forename: M A
authors.initials: MA
authors.lastname: Diaz
authors.forename: J
authors.initials: J
authors.lastname: Goldberg
authors.forename: A F
authors.initials: AF
authors.lastname: Turconi
mesh_terms: D001706:Biopsy; D002648:Child; D002784:Cholesterol / Q000097:blood; D004359:Drug Therapy, Combination; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D016030:Kidney Transplantation / Q000276:immunology* / Q000473:pathology* / Q000502:physiology; D010976:Platelet Count; D011183:Postoperative Complications / Q000188:drug therapy / Q000276:immunology; D011507:Proteinuria / Q000652:urine; D012189:Retrospective Studies; D012449:Safety; D020123:Sirolimus / Q000009:adverse effects / Q000627:therapeutic use*; D014184:Transplantation, Homologous; D014280:Triglycerides / Q000097:blood
chemical_list: D007166:Immunosuppressive Agents; D014280:Triglycerides; D002784:Cholesterol; D020123:Sirolimus