Diabetic nephropathy alters circulating long noncoding RNA levels that normalize following simultaneous pancreas–kidney transplantation

Koen E. Groeneweg, Yu Wah Au, Jacques M.G.J. Duijs, Barend W. Florijn, Cees van Kooten, Johan W. de Fijter, Marlies E.J. Reinders, Anton Jan van Zonneveld, Roel Bijkerk*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

6 Citations (Scopus)
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Abstract

Simultaneous pancreas–kidney transplantation (SPKT) replaces kidney function and restores endogenous insulin secretion in patients with diabetic nephropathy (DN). Here, we aimed to identify circulating long noncoding RNAs (lncRNAs) that are associated with DN and vascular injury in the context of SPKT. Based on a pilot study and a literature-based selection of vascular injury–related lncRNAs, we assessed 9 candidate lncRNAs in plasma samples of patients with diabetes mellitus with a kidney function >35 mL/min/1.73 m2 (DM; n = 12), 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. Of 9 selected lncRNAs, we found MALAT1, LIPCAR, and LNC-EPHA6 to be higher in DN compared with healthy controls. SPKT caused MALAT1, LIPCAR, and LNC-EPHA6 to normalize to levels of healthy controls, which was confirmed in the longitudinal study. In addition, we observed a strong association between MALAT1, LNC-EPHA6, and LIPCAR and vascular injury marker soluble thrombomodulin and a subset of angiogenic microRNAs (miR-27a, miR-130b, miR-152, and miR-340). We conclude that specific circulating lncRNAs associate with DN-related vascular injury and normalize after SPKT, suggesting that lncRNAs may provide a promising novel monitoring strategy for vascular integrity in the context of SPKT.

Original languageEnglish
Pages (from-to)3451-3461
Number of pages11
JournalAmerican Journal of Transplantation
Volume20
Issue number12
Early online date30 Apr 2020
DOIs
Publication statusPublished - Dec 2020
Externally publishedYes

Bibliographical note

Funding Information:
Dr Bijkerk is supported by a grant from the Dutch Kidney Foundation (16OKG16), and Drs Bijkerk and van Zonneveld are supported by a grant from the European Foundation for the Study of Diabetes (EFSD).

Funding information:
Dutch Kidney Foundation, Grant/Award
Number: 16OKG16; European Foundation
for the Study of Diabetes

Publisher Copyright:
© 2020 The Authors. American Journal of Transplantation published by Wiley Periodicals LLC on behalf of The American Society of Transplantation and the American Society of Transplant Surgeons

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