12. Diabetic nephropathy alters circulating long noncoding RNA levels that normalize following simultaneous pancreas-kidney transplantation

K.E. Groeneweg, Y.W. Au, C. van Kooten, J.W. de Fijter, M.E.J. Reinders, R. Bijkerk, A.J. van Zonneveld

Wednesday 4 march 2020

0:00 - 0:00h at Toon Hermans Foyer

Parallel session: Postersessie 3 – Klinische abstracts

Background: Simultaneous pancreas kidney transplantation (SPKT) replaces kidney function and restores endogenous insulin secretion in patients with insulin-dependent diabetes mellitus and its vascular complication diabetic nephropathy (DN). Circulating long noncoding RNAs (lncRNAs) have emerged as promising biomarkers in (cardio)vascular disease and may provide insight into pathogenesis. Here, we aimed to identify lncRNAs that are associated with DN and vascular injury in the context of SPKT.

Methods: We first performed a pilot study of 40.173 lncRNAs in plasma of healthy controls and patients with DN. Based on these results, as well as on a literature based-selection of vascular injury related lncRNAs, we assessed 14 candidate lncRNAs in plasma samples of DN (n=14), SPKT (n=35), healthy controls (n=15) and renal transplant recipients (KTx; n=13). DN patients were also studied longitudinally before and 1, 6 and 12 months after SPKT. Markers of vascular injury angiopoietin-2 and soluble thrombomodulin(sTM) were measured using ELISA, while angiogenic microRNAs were assessed using RT-qPCR.

Results: Out of 14 selected lncRNAs, we found MALAT1 and LIPCAR to be significantly higher in patients with DN compared with healthy controls, while we found a similar trend for LNC-EPHA6. SPKT caused MALAT1, LIPCAR and LNC-EPHA6 to normalize to levels of healthy controls (p=0.012). The longitudinal study demonstrated that MALAT1, LNC-EPHA6 and LIPCAR levels significantly declined within one month after SPKT (p=0.01, p=0.01 and p=0.04, respectively). In addition, we observed a strong association between MALAT1, LNC-EPHA6 and LIPCAR and the vascular injury marker sTM and a subset of angiogenic microRNAs (miR-27a, miR-130b, miR-152 and miR-340).

Conclusions: Specific circulating lncRNAs associate with DN and vascular injury and normalize after SPKT. As such, lncRNAs are potentially interesting biomarkers for disease progression in DN and may provide insight into the underlying pathophysiology.