title: Evolution of allograft fibrosis and function in kidney transplant recipients: a retrospective analysis of stable patients under CNI and mTORi.
abstract: Histological 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 36 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, TGF-β1 expression, and allograft function decline were significantly lower after conversion to mTORi compared with 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.
authors: Division of Nephrology, University of Heidelberg, Heidelberg, Germany.
authors: Luis Eduardo
authors: LE
authors: Becker
authors: Bernhard
authors: B
authors: Weritz
authors: Xue
authors: X
authors: Yi
authors: Marie-Luise
authors: ML
authors: Gross-Weissmann
authors: Rüdiger
authors: R
authors: Waldherr
authors: Martin
authors: M
authors: Zeier
authors: Claudia
authors: C
authors: Sommerer
mesh_terms: D000328:Adult; D064591:Allografts / Q000473:pathology; D001706:Biopsy; D065095:Calcineurin Inhibitors / Q000627:therapeutic use*; D015935:Complement C4b / Q000378:metabolism; D018450:Disease Progression; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D005355:Fibrosis; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D007150:Immunohistochemistry; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007668:Kidney / Q000473:pathology*; D007676:Kidney Failure, Chronic / Q000601:surgery*; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000378:metabolism; D010982:Platelet-Derived Growth Factor / Q000378:metabolism; D012189:Retrospective Studies; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D065095:Calcineurin Inhibitors; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D007166:Immunosuppressive Agents; D010446:Peptide Fragments; D010982:Platelet-Derived Growth Factor; D053773:Transforming Growth Factor beta1; D042461:Vascular Endothelial Growth Factor A; D016222:Fibroblast Growth Factor 2; D015935:Complement C4b; C032261:complement C4d; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases
keywords: TGF-β; allograft fibrosis; calcineurin inhibitor; everolimus; kidney transplantation; mTORi