title: Protocol biopsy findings in living donor kidney transplant patients treated with once-daily or twice-daily tacrolimus formulation.
abstract: BACKGROUND
  Once-daily extended-release tacrolimus (Tac-QD) has been shown to have equivalent efficacy and safety to the twice-daily formulation (Tac-BID) in kidney transplant patients. However, detailed comparison of allograft pathology found on a protocol biopsy (PB) in Tac-QD- versus Tac-BID-based regimens has not been described.
  
  
  METHODS
  We retrospectively investigated 119 de novo living donor kidney transplant patients treated with Tac-QD (n = 90) or Tac-BID (n = 29) and their 3- and 12-month PB results. Other immunosuppressive drugs administered included basiliximab, mycophenolate mofetil, and methylprednisolone. We evaluated daily doses and trough levels of Tac and serum creatinine levels, and compared pathologic findings.
  
  
  RESULTS
  Daily doses were higher in the Tac-QD group, but trough levels and serum creatinine levels were comparable. On 3- and 12-month PB, the frequency of subclinical rejection was similar between the groups, whereas interstitial fibrosis and tubular atrophy (IF/TA) were less common in the Tac-QD group at 12 months (42.2% vs 20.6%, P = .04). Univariate and multivariate logistic regression analyses revealed that allograft rejection (borderline changes or higher) was associated with IF/TA (odds ratio 4.09, 95% confidence interval 1.76-10.10, P = .001). The Tac-QD-based regimen showed a trend toward the absence of IF/TA but it did not reach statistical significance. Tubular vacuolization and arteriolar hyaline changes were also comparable in the two groups.
  
  
  CONCLUSIONS
  We found a trend toward milder IF/TA, but no significant differences in kidney allograft pathology in patients who were administered Tac-QD- versus Tac-BID-based regimens at 12 months. The effects of Tac-QD on chronic allograft injury must be studied by longer observation.
authors.affiliation: Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. Electronic address: kosukemasutani@yahoo.co.jp.
authors.forename: K
authors.initials: K
authors.lastname: Masutani
authors.affiliation: Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Tsuchimoto
authors.affiliation: Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Haruyama
authors.affiliation: Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Kitada
authors.affiliation: Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Okabe
authors.affiliation: Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Noguchi
authors.affiliation: Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Tanaka
authors.affiliation: Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan; Department of Integrated Therapy for Chronic Kidney Disease, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Tsuruya
authors.affiliation: Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Kitazono
mesh_terms: D000328:Adult; D001706:Biopsy; D002985:Clinical Protocols; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D016030:Kidney Transplantation; D019520:Living Donors; D008297:Male; D008875:Middle Aged; D016559:Tacrolimus / Q000008:administration & dosage*; D055815:Young Adult
chemical_list: D007166:Immunosuppressive Agents; D016559:Tacrolimus