Background: Arteriolar hyalinosis (ah) is characterized by deposition of hyaline material in the vascular wall that may be caused by different insults including diabetes, hypertension and chronic exposure to calcineurin inhibitors. It is not clear if immune-mediated mechanisms play a role in its pathogenesis. We aim to investigate the molecular features of biopsy samples from patients with isolated arteriolar hyalinosis.

Methods: We studied the clinical, histopathological and molecular characteristics of 18 patients with isolated ah and non-specific interstitial fibrosis/tubular atrophy (IFTA) comparing to those of 22 patients with non-specific IFTA but without ah. All biopsies were negative in terms of Banff t, v and C4d scores. The gene expression profiles were studied by Affymetrix HuGene 1.0 ST expression arrays.

Results: Both groups were similar in terms of their age, gender, race, cause of renal failure, type of transplant, prior history of rejection, immunosuppressive regimen, serum creatinine and spot urine protein to creatinine ratio at the time of the biopsy, class I and II PRA levels, donor-specific antibody (DSA) frequency or mean fluorescence intensity values of DSA. At the histopathological level, both groups had similar Banff acute injury scores (g, ptc, i). Isolated ah group had lower ct and ci scores compared to the no ah group; (0.94±0.63 vs.1.8±0.85, p=0.0006) and (0.94±0.72 vs. 1.7±0.75, p=0.001), respectively. When gene expression profiles were compared, isolated ah group had 986 differentially expressed genes compared to the no ah group (FDR, p<0.05). When the differentially expressed genes were compared by gene ontology, the increased expression of gene transcripts was related to cellular metabolic functions and synthetic processes. Interestingly, the ah group had decreased expression of gene tarnscripts related to immune response (GO:0006955) and to regulation of immune system process (GO:0002682). In terms of intragraft pathogenesis based transcripts, there was no statistically significant difference in expression of transcripts related to interferon gamma, cytotoxic T cells, regulatory T cells, B cells, Natural killer cells, macrophages and endothelial cells between the 2 groups.

Conclusion: Kidney biopsies of patients with isolated ah demonstrated decreased expression of gene transcripts associated with immune response suggesting that immune-mediated mechanisms do not play role in its pathogenesis.

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