Histological progression of chronic renal allograft injury comparing sirolimus and mycophenolate mofetil-based protocols. A single-center, prospective, randomized, controlled study.

In an effort to mitigate progression of IF/TA associated with chronic renal allograft injury, we hypothesize that adjuvant immunosuppression with sirolimus (SRL) will delay progression compared with MMF. Subjects 5-17 yr old, >1-yr post-transplant with mild or moderate IF/TA (Banff criteria) and tacrolimus dose minimization were randomized to continue MMF or convert to SRL and followed for two yr. For the entire cohort (n = 20), there was significant progression of %GGS, ci, ct, cv, and ah scores over the follow-up period (p < 0.05). There was no difference in rates of progression of Banff scores, %GGS, or % IF over two yr between the two groups, though power was low. Both groups exhibited similar rates of eGFR decline (MMF: -12.3 vs. SRL: -11.8 mL/min/1.73 m²/yr), which was correlated with ct score (p < 0.05). The SRL group had more episodes of acute allograft dysfunction and oral ulcers. Proteinuria at 24 months was significantly increased in the SRL group (6/9 subjects) but was not correlated with eGFR or %GGS. We conclude that neither MMF nor SRL, combined with low-dose tacrolimus, was effective at mitigating progressive histological changes or functional decline associated with chronic renal allograft injury.

RCT Entities:   Population Interventions Outcomes