Histologic evaluations of renal allograft biopsies are essential for diagnosis, but still show a low predictive value for long-term allograft function. One limitation relies on the fact that the analysis is usually based on a single biopsy sample and, therefore, no dynamic changes are considered. Using two distinct approaches, we evaluated the evolution of fibrosis and related markers in thirty-six stable kidney transplant patients under calcineurin inhibitor therapy with two indication biopsies each, prior and at least 6 months after substitution by mTORi (N=18), or maintenance on CNI (N=18). In the method comparison, both Banff Chronicity Score and the digitally assessed fibrosis were correlated with allograft function at biopsy (r=−0.36 and r=−0.72, P=0.002 and P<0.0001, respectively). However, only the progression of fibrosis digitally assessed was correlated with allograft function loss, not only within the time between biopsies (r=−0.47, P=0.004) but also in the 60 month follow-up (r=−0.47, P=0.006). In the group analysis, despite of a higher incidence of C4d positivity (P=0.05), progression of fibrosis, TGFß1 expression and allograft function decline were significantly lower after conversion to mTORi compared to maintenance on CNI (P=0.05, P=0.02 and P=0.01, respectively). PDGF, VEGF, b-FGF and HIF1A expressions remained stable over time regardless of therapy.
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Alberto Reino Buelvas