Conversion to low-dose tacrolimus or rapamycin 3 months after kidney transplantation

A prospective, protocol biopsy-guided study

O. Pankewycz, N. Leca, R. Kohli, E. Weber-Shrikant, M. Said, Muna A Alnimri, L. Feng, S. Patel, M. R. Laftavi

Research output: Contribution to journalArticle

14 Citations (Scopus)

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; 46 ng/mL) or sirolimus (SRL; 610 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 (1015 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.

Original languageEnglish (US)
Pages (from-to)519-523
Number of pages5
JournalTransplantation Proceedings
Volume43
Issue number2
DOIs
StatePublished - Mar 2011
Externally publishedYes

Fingerprint

Tacrolimus
Sirolimus
Kidney Transplantation
Atrophy
Biopsy
Fibrosis
Kidney
Allografts
Mycophenolic Acid
Antilymphocyte Serum
Random Allocation
Drug-Related Side Effects and Adverse Reactions
Glomerular Filtration Rate
Immunosuppression
Histology
Transplantation
Steroids
Rabbits
Transplants
Therapeutics

ASJC Scopus subject areas

  • Surgery
  • Transplantation

Cite this

Conversion to low-dose tacrolimus or rapamycin 3 months after kidney transplantation : A prospective, protocol biopsy-guided study. / Pankewycz, O.; Leca, N.; Kohli, R.; Weber-Shrikant, E.; Said, M.; Alnimri, Muna A; Feng, L.; Patel, S.; Laftavi, M. R.

In: Transplantation Proceedings, Vol. 43, No. 2, 03.2011, p. 519-523.

Research output: Contribution to journalArticle

Pankewycz, O. ; Leca, N. ; Kohli, R. ; Weber-Shrikant, E. ; Said, M. ; Alnimri, Muna A ; Feng, L. ; Patel, S. ; Laftavi, M. R. / Conversion to low-dose tacrolimus or rapamycin 3 months after kidney transplantation : A prospective, protocol biopsy-guided study. In: Transplantation Proceedings. 2011 ; Vol. 43, No. 2. pp. 519-523.
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AU - Said, M.

AU - Alnimri, Muna A

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