Conversion to Low-Dose Tacrolimus or Rapamycin 3 Months After Kidney Transplantation: A Prospective, Protocol Biopsy-Guided Study

Abstract Long-term survival of kidney allografts is primarily limited by a progressive decline in function characterized by the presence of interstitial fibrosis (IF) and tubular atrophy (TA) on biopsy. Since chronic calcineurin-inhibitor (CNI) drug toxicity has been implicated as a significant caus...

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Bibliographic Details
Published in:Transplantation proceedings 2011-03, Vol.43 (2), p.519-523
Main Authors: Pankewycz, O, Leca, N, Kohli, R, Weber-Shrikant, E, Said, M, Alnimri, M, Feng, L, Patel, S, Laftavi, M.R
Format: Article
Language:English
Subjects:
Adult
Aged
Animals
Antibacterial agents
Antibiotics. Antiinfectious agents. Antiparasitic agents
Antilymphocyte Serum - chemistry
Biological and medical sciences
Biopsy - methods
Female
Fundamental and applied biological sciences. Psychology
Fundamental immunology
Glomerular Filtration Rate
Humans
Immunosuppressive Agents - pharmacology
Immunosuppressive Agents - therapeutic use
Kidney Transplantation - methods
Male
Medical sciences
Middle Aged
Pharmacology. Drug treatments
Prospective Studies
Rabbits
Sirolimus - therapeutic use
Surgery
Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases
Surgery of the urinary system
Tacrolimus - therapeutic use
Time Factors
Tissue, organ and graft immunology
Transplantation, Homologous
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Summary:Abstract Long-term survival of kidney allografts is primarily limited by a progressive decline in function characterized by the presence of interstitial fibrosis (IF) and tubular atrophy (TA) on biopsy. Since chronic calcineurin-inhibitor (CNI) drug toxicity has been implicated as a significant cause of IF/TA, a major effort in transplantation has been to decrease or eliminate CNI therapy. We now report the clinical and histological consequences of converting renal transplant recipients at 3 months to either very low levels of tacrolimus (TAC; 4–6 ng/mL) or sirolimus (SRL; 6–10 ng/mL) therapy. Fifty-eight enrollees in this prospective randomized trial received low-dose (2.9 ± 0.6 mg/kg) rabbit antithymocyte globulin induction followed by standard doses of TAC (10–15 ng/mL), mycophenolic acid, and low-dose steroids for 3 months. Protocol biopsies were performed at implantation and 3 and 12 months. Six patients had evidence of either borderline changes ( n = 5) or grade 1A rejection ( n = 1) on the 3-month protocol biopsy and were not randomized. Only one patient had clinically evident rejection that occurred after randomization to SRL. One patient in each group had borderline changes at 12 months. Renal function (estimated glomerular filtration rate) was equivalent in both groups at 12 months (TAC 74 ± 15 vs SRL 66 ± 18 mL/min, P = .22). Chronic allograft damage index scores at 1 year were similar in both groups (TAC 2.8 ± 2.4 vs SRL 2.0 ± 2.7, P = .71). The percentage of patients with IF/TA scores greater than 2 at 1 year was low in both groups (TAC 12% vs SRL 9%, P = .78). Therefore, in a low-risk population defined as having a normal 3-month protocol biopsy, TAC levels can be successfully decreased to very low concentrations. One-year graft function and histology were equally well maintained with either low-dose TAC or SRL immunosuppression.
ISSN:0041-1345
1873-2623
DOI:10.1016/j.transproceed.2011.01.033