Serum Long Non-Coding RNAs in Diabetic Kidney Disease

Abstract

Background: Diabetic kidney disease (DKD) afflicts almost 40% of type 2 diabetes mellitus (T2DM) patients and may progress to end-stage renal disease despite multifactorial management. Urinary albumin/creatinine ratio (UACR) and estimated glomerular filtration rate (eGFR) are not sufficiently sensitive or specific for early diagnosis or recognition of patients at higher risk of cardiorenal complications. Long non-coding RNAs (lncRNAs) emerged as key regulators of major DKD signaling pathways. Their potential role as novel biomarkers or therapeutic targets in DKD remains to be established. Methods: We studied 4 groups of 25 adults each. G1, 2, 3 had T2DM and normal, moderately-increased, and severely-increased UACR, respectively. G4 were healthy controls. Participants underwent clinical assessment and analysis of blood picture, fasting serum glucose, glycated hemoglobin, lipid profile, hepatic transaminases, albumin, urea, and creatinine. By real-time quantitative polymerase chain reaction, we assessed relative serum expression levels of the lncRNAs plasmacytoma variant translocation-1 gene (PVT1), metastasis-associated lung adenocarcinoma transcript-1 (MALAT1), and cancer susceptibility candid-2 gene (CASC2). Results: Serum PVT1 was significantly higher in diabetic patients compared with controls, and significantly higher in G2 compared with the other patients’ groups. Serum MALAT1 and CASC2 showed no statistically significant association with the occurrence of T2DM, DKD, or other major diabetic complications. Increased serum creatinine was the only significant predictor of increased UACR. Conclusions: Increased serum PVT1 is a reliable early biomarker of DKD progression. It may provide a plausible therapeutic approach. The involvement of MALAT1 and CASC2 in DKD pathogenesis is less established. Further large-scale prospective studies are warranted.