NIV Congres

Introduction Simultaneous pancreas-kidney transplantation (SPK) is an advanced treatment option forpatients with type I diabetes with extensive microvascular disease and nephropathy (DN). Circulating microRNAs (miRNAs) can be sensitive biomarkers and their functional properties could provide insight into disease state. By assessing miRNA profiles in healthy control subjects and patients with type 1 diabetes before and following SPK we aimed to identify differentially expressed subsets of miRNAs that associate with microvascular destabilization and disease state.

Methods Circulating miRNA expression was determined using TaqMan® Human MicroRNA Array Card in plasma of DN (n=8) and SPK patients(n=8) and compared with healthy controls (n=3). In addition, the SPK patients werestudied longitudinally before, 1, 6 and 12 months after SPK. Microvascular morphology and mean capillary density were visualized using sidestream darkfieldimaging of the oral mucosa. Furthermore, circulating levels ofangiogenic factors, including angiopoietin-1 (Ang1), angiopoietin-2 (Ang2), VEGFand soluble thrombomodulin (sTM) were measured using ELISA.

Results In our study we identified miR-25, miR-27a, miR-126, miR-130b, miR-132, miR-152, miR-181a, miR-320 and miR-660 to have elevated expression levels in plasma of DN patients as compared to healthy controls, whereas miR-223 and miR-574-3p expression was decreased. After SPK, expression levels of these miRNAs normalized and positively correlated with glomerular filtration rate and Hba1c levels. Interestingly, the expression of miR-126, miR-130b and miR-132, which are known to be pro-angiogenic, correlated with Ang2 levels. In addition, miR-130b showed a strong correlation with increased tortuosity of the microvasculature and sTM levels.

Conclusion Circulating miRNAs correlate with DN and systemic microvascular destabilization. Following SPK these profiles normalized concomitant with microvascular stabilization