Aim: Simultaneous pancreas-kidney transplantation (SPK) is an advanced treatment option for patients 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 microRNAs 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 were studied longitudinally before, 1, 6 and 12 months after SPK. Microvascular morphology and mean capillary density were visualized using sidestream darkfield imaging of the oral mucosa. Furthermore, circulating levels of angiogenic factors, including angiopoietin-1 (Ang1), angiopoietin-2 (Ang2), VEGF and 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 also showed a strong correlation with increased tortuosity of the microvasculature and sTM levels.
Conclusion: Circulating microRNAs profiles correlate with DN and systemic microvascular destabilization. Following SPK these profiles normalized concomitant with microvascular stabilization supporting the potential use of microRNA profiles to assess disease progression in DN.
To cite this abstract in AMA style:Bijkerk R, Khairoun M, Duijs J, Horst Kter, Vries Ade, Koning Ede, Fijter Jde, Rabelink T, Zonneveld Avan, Reinders M. Circulating MicroRNAs Correlate with Diabetic Nephropathy and Systemic Microvascular Damage and Normalize after Simultaneous Pancreas-Kidney Transplantation [abstract]. Am J Transplant. 2013; 13 (suppl 5). https://atcmeetingabstracts.com/abstract/circulating-micrornas-correlate-with-diabetic-nephropathy-and-systemic-microvascular-damage-and-normalize-after-simultaneous-pancreas-kidney-transplantation/. Accessed July 24, 2021.
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