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

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-C 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-C (target 3-7 ng/ml) and standard MMF dose (750 mg bid). Subclinical inflammation, adjusted for confounders, was associated with low TAC-C 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-C 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-C or MMF dose in the multivariate analysis. Our data suggest that in TAC- and MMF-based regimens, TAC-C levels are associated with subclinical inflammation in patients receiving reduced MMF dose.

Subclinical inflammation phenotypes and long-term outcomes after pediatric kidney transplantation

“…This difference from our study may be attributable to their conversion from tacrolimus to sirolimus and a lower maintenance MMF dose in patients with NOMOA. 28–30 Finally, the steroid-based arm (n = 70) of the multicenter SNS01-NIH-CCTPT study found a 35% lower rate of subclinical inflammation in 6-month surveillance biopsies, but was also less racially diverse than our study. 26 Our data from a diverse pediatric cohort provide a significant addition to the existing literature on outcomes after surveillance biopsies.…”

Optimizing Mycophenolic Acid Exposure in Kidney Transplant Recipients: Time for Target Concentration Intervention

“…140-145 In contrast, while some studies have linked the use of mycophenolate to reduced dnDSA formation, 146,147 the impact of MPA dose or exposure on dnDSA formation is largely absent. Torres et al 141 linked tubulointerstitial inflammation in low-risk recipients with combination of low tacrolimus concentrations and reduced MMF dosing, while Filler et al 148 reported a significant association between minimum MPA trough concentrations and dnDSA formation in pediatric renal transplant recipients.…”

Proposed Definitions of T Cell-Mediated Rejection and Tubulointerstitial Inflammation as Clinical Trial Endpoints in Kidney Transplantation

“…Since tacrolimus and mycophenolate were introduced, the prevalence of tubulointerstitial inflammation in the first 2 years (subclinical aTCMR and borderline changes) has fallen from >50% to ∼10% of transplant recipients ( 71 ). In addition, severity of inflammation has decreased to the point that subclinical aTCMR in protocol biopsies constitutes an uncommon diagnosis ( 63 ).…”