Tacrolimus and mycophenolate regimen and subclinical tubulo-interstitial inflammation in low immunological risk renal transplants

Transpl Int. 2017 Nov;30(11):1119-1131. doi: 10.1111/tri.13002. Epub 2017 Jul 27.

Abstract

The aim was to evaluate the relationship between maintenance immunosuppression, subclinical tubulo-interstitial inflammation and interstitial fibrosis/tubular atrophy (IF/TA) in surveillance biopsies performed in low immunological risk renal transplants at two transplant centers. The Barcelona cohort consisted of 109 early and 66 late biopsies in patients receiving high tacrolimus (TAC-C0 target at 1-year 6-10 ng/ml) and reduced MMF dose (500 mg bid at 1-year). The Oslo cohort consisted of 262 early and 237 late biopsies performed in patients treated with low TAC-C0 (target 3-7 ng/ml) and standard MMF dose (750 mg bid). Subclinical inflammation, adjusted for confounders, was associated with low TAC-C0 in the early (OR: 0.75, 95% CI: 0.61-0.92; P = 0.006) and late biopsies (OR: 0.69, 95% CI: 0.50-0.95; P = 0.023) from Barcelona. In the Oslo cohort, it was associated with low MMF in early biopsies (OR: 0.90, 95% CI: 0.83-0.98; P = 0.0101) and with low TAC-C0 in late biopsies (OR: 0.77, 95% CI: 0.61-0.97; P = 0.0286). MMF dose was significantly reduced in Oslo between early and late biopsies. IF/TA was not associated with TAC-C0 or MMF dose in the multivariate analysis. Our data suggest that in TAC- and MMF-based regimens, TAC-C0 levels are associated with subclinical inflammation in patients receiving reduced MMF dose.

Keywords: calcineurin antagonists; immunosuppression clinical; kidney clinical; mycophenolate mofetil; subclinical rejection; tacrolimus.

Publication types

  • Multicenter Study

MeSH terms

  • Adult
  • Aged
  • Cohort Studies
  • Female
  • Humans
  • Immunosuppression Therapy
  • Kidney / pathology
  • Kidney Transplantation*
  • Male
  • Middle Aged
  • Mycophenolic Acid / administration & dosage*
  • Nephritis, Interstitial / pathology
  • Nephritis, Interstitial / prevention & control*
  • Postoperative Complications / pathology
  • Postoperative Complications / prevention & control*
  • Tacrolimus / administration & dosage*

Substances

  • Mycophenolic Acid
  • Tacrolimus