Comparison of low versus high tacrolimus levels in kidney transplantation: assessment of efficacy by protocol biopsies

Transplantation. 2007 Feb 27;83(4):411-6. doi: 10.1097/


Background: The use of calcineurin inhibitors is generally guided by drug blood levels. However, those levels are chosen based on clinical experience, lacking adequate titration studies.

Methods: In these analyses, we compared clinical and histologic endpoints in two groups of kidney transplant recipients: in the first (HiTAC, January 2000 to June 2002, n=245) tacrolimus levels were significantly higher than in the second (LoTAC, July 2002 to September 2004, n=330). This change in drug levels (15% reduction) was made in an attempt to reduce the incidence of polyoma virus nephropathy (PVAN). Other immunosuppressive medications were unchanged during these two time periods.

Results: The recipient and donor demographics were not statistically different between the two groups. Compared to HiTAC, at one year posttransplant LoTAC had: 1) lower incidence of PVAN (10.5% vs. 2.5%, P<0.0001); 2) lower fasting glucose levels; 3) higher iothalamate glomerular filtration rate (52+/-19 vs. 59+/-17 ml/min/m, P<0.0001); and 4) on protocol one-year biopsies, lower incidence and severity of interstitial fibrosis (67% vs. 45%, P=0.003) and tubular atrophy (82% vs., 66%, P=0.01). The incidence and severity of acute rejection episodes was similar between both groups (7.8% versus 7.6%).

Conclusions: Modest reductions in tacrolimus exposure early posttransplant are associated with significant beneficial effects for the patient and the allograft without an increased immunologic risk.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biopsy
  • Clinical Protocols
  • Dose-Response Relationship, Drug
  • Female
  • Humans
  • Immunosuppressive Agents / administration & dosage*
  • Immunosuppressive Agents / pharmacology*
  • Kidney Transplantation / methods*
  • Male
  • Middle Aged
  • Polyomavirus Infections / pathology
  • Polyomavirus Infections / virology
  • Retrospective Studies
  • Tacrolimus / administration & dosage*
  • Tacrolimus / pharmacology*
  • Treatment Outcome


  • Immunosuppressive Agents
  • Tacrolimus