Sluiten Added to My program.
Sluiten Removed from My program.
Back Home

Bootcongres

Thu, March 27th, 2014, 9:30 - 9:40

Circulating MicroRNAs Correlate with Diabetic Nephropathy and Systemic Microvascular Damage and Normalize after Simultaneous Pancreas-Kidney Transplantation

R. Bijkerk, J.M.G.J. Duijs, M. Khairoun, C.J.H. ter Horst, M.J.K. Mallat, J.I. Rotmans, A.P.J. de Vries, E.J.P. de Koning, J.W. de Fijter, T.J. Rabelink, A.J. van Zonneveld, M.E.J. Reinders

Moderator(s): M.H.L. Christiaans en E.J.P. de Koning

Location(s): Grote zaal

Category:

Objective: As microvascular disease is one of the most important drivers of diabetic complications, early noninvasive monitoring of the microvasculature may be of clinical value. By assessing microRNA (miRNA) profiles in healthy controls and diabetic nephropathy (DN) patients before and following simultaneous pancreas-kidney transplantation (SPK), we aimed to identify differentially expressed subsets of miRNAs that associate with microvascular destabilization. Methods: Thirteen miRNAs, which were selected based on a pilot study, were determined, using TaqMan® Human MicroRNA Array Card, in plasma of healthy controls (n=19), DN (n=21) and SPK patients (n=37). To be able to distinguish between kidney or pancreas contribution to miRNA levels, also DM1 patients with good renal function (n=15) and DN patients that only received a kidney transplant (KTx, n=15) were included. Furthermore, 14 DN patients were studied longitudinally up to 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), insulin-like growth factor (IGF) and soluble thrombomodulin (sTM) were measured using ELISA. Results: We demonstrated differential expression of miR-25, -27a, -130b, -152, -223, -320, -326, -340, -574-3p, and -660 as a result of diabetic nephropathy. All investigated miRNAs clearly associated with renal function, except for miR-574-3p, that showed a striking association with hyperglycaemia. Furthermore we demonstrate a strong association between miRNA levels and systemic microvascular destabilization, in particular miR-130b and -340, as they correlate with Angiopoietin-2/1 ratio, sTM, IGF and capillary tortuosity.

Conclusion: Circulating miRNAs correlate with DN and systemic microvascular destabilization. Following SPK these profiles normalized concomitant with microvascular stabilization supporting the potential use of miRNA profiles to assess disease progression in DN.