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Kidney Week

Abstract: TH-PO935

Circulating Long Noncoding RNAs Are Associated with Diabetic Nephropathy and Normalize After Simultaneous Pancreas-Kidney Transplantation

Session Information

Category: Diabetic Kidney Disease

  • 602 Diabetic Kidney Disease: Clinical

Authors

  • Groeneweg, Koen, Leiden University Medical Center, Leiden, Netherlands
  • Au, Yu wah, Leiden University Medical Center, Leiden, Netherlands
  • De Fijter, Johan W., Leiden University Medical Center, Leiden, Netherlands
  • Van Zonneveld, Anton Jan, Leiden University Medical Center, Leiden, Netherlands
  • Reinders, Marlies, Leiden University Medical Center, Leiden, Netherlands
  • Bijkerk, Roel, Leiden University Medical Center, Leiden, Netherlands
Background

Diabetes mellitus can lead to end-stage renal disease and cardiovascular injury. Simultaneous pancreas kidney transplantation (SPKT) replaces kidney function and restores endogenous insulin secretion. Circulating long noncoding RNAs (lncRNAs) are promising biomarkers in (cardiovascular) disease and can provide insight into pathogenesis. However little is known about these markers in vascular injury in the context of diabetic nephropathy (DN) and after SPKT.

Methods

We performed a pilot study of 40.173 lncRNAs in plasma of healthy controls and patients with diabetic nephropathy. Based on these results, as well as a dedicated literature search, we assessed 14 candidate lncRNAs of which 9 were detectable in plasma samples in DN (n=14), SPKT (n=35) and healthy controls (n=15). All DN patients were studied longitudinally before and 1, 6 and 12 months after SPKT. LncRNAs that were detected in less than 95% of the samples were excluded from the study. Angiopoietin-2 and soluble thrombomodulin (sTM) were measured using ELISA as a markers for vascular injury.

Results

MALAT1 was significantly higher (p=0.002) in patients with DN (median 13.8, IQR 2.9-16.3) compared with healthy controls (median 0.16, IQR 0.1-1.3). The first month after SPKT MALAT1 normalized from 13.8 to 0.3 (p=0.012). EPHA6, LIPCAR and G003293 showed a similar pattern with significant decline after SPKT (resp. p=0.01, p=0.01 and p=0.04). Interestingly we observed a strong correlation between MALAT1, EPHA6 and LIPCAR with blood pressure and vascular injury marker sTM.

Conclusion

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