Background: A major obstacle in the management of kidney transplant recipients is a lack of non-invasive, cost-effective, specific biomarkers critically needed for monitoring graft performance post-kidney transplantation.

Methods: Total RNA was isolated from urinary cell pellets and miRNA profiles between chronic allograft dysfunction with interstitial fibrosis and tubular atrophy (IF/TA, N=6) and normal functioning allografts (NFA, N=10) patients were compared using the GeneChip miRNA 3.0 Array to generate an initial urine signature. Two miRNAs were selected for further validation in an independent set of samples (NFA=10 and IF/TA=7) and prospective evaluation of urinary cell pellets (N=132) of kidney transplant recipients (KTRs, N=66). A set of 25 KTRs with urine samples collected at two time (3 and 6-mo) post-KT and classified by graft function at 2 years post-KT were also evaluated urine miRNA arrays to test if diagnostic markers of CAD were also useful at early disease stages. Moreover, only 59 miRNAs were differentially expressed between the two time points for KTRs with poor function with 8 miRNAs continuously affected in relation with graft function.

Results: Twenty-two microRNAs were identified as significantly altered between CAD with IF/TA and NFA. Two down-regulated microRNAs, miR-125b and miR-203, were selected for further validation. At 3-mo post-KT 126 miRNA were differentially expressed between groups while 89 were differentially expressed at 6-mo post-KT between groups with good vs. poor graft function at 2 years post-KT. A total of 8 miRNAs were continuously differentially expressed in the poor function group post-KT.

Conclusions: We have identified miRNAs differentially expressed in IF/TA samples that can be useful for diagnosis and monitoring post kidney transplantation. Moreover, we identified a panel of urine miRNA that are continuously affected during progression to CAD. These markers have high potential as non-invasive markers of CAD progression.

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