Introduction
Renal involvement in type 2 diabetes (T2DM) can be due to diabetes (diabetic kidney disease, DKD) or other causes (non-DKD, NDKD) or both (mixed kidney disease). Available clinical and laboratory parameters have limitations in predicting a diagnosis (gold standard renal biopsy). Long non-coding RNAs (lncRNAs) evaluated in preclinical models but unexplored in biopsy-proven kidney disease in T2DM. We aimed to determine whether there is differential expression of lncRNAs in DKD (compared with NDKD).
Research design and methods
lncRNAs preselected through database search for evaluation in humans.
Discovery cohort: Preselected lncRNAs () evaluated in three components of urine (urinary cell, urinary exosome, and cell-free urine) from biopsy-proven DKD, NDKD, T2DM without kidney disease and healthy subjects (n=40/group). lncRNAs found consistently significant in all components were checked in kidney tissue. Receiver operating characteristic curves were performed to evaluate diagnostic performance.
Validation cohort: Best performing lncRNA (in discovery cohort) evaluated in independent cohort.
Clinical utility: The utility of identified lncRNAs was further assessed for clinical decision-making.
Results
Discovery cohort: Level of MALAT1 and PVT1 differed in all urinary components of DKD and elevated in kidney biopsy tissue. MALAT1 showed the most consistent results. Urinary cell-derived MALAT1 showed the most consistent results (Ct <8.3, sensitivity 90%, specificity 89.6% OR 53.9, p<0.0001) to differentiate DKD from NDKD
Validation cohort: Urinary cell-derived MALAT1 showed sensitivity (90%) and specificity (88.5%).
Clinical utility: Addition of MALAT1 to currently existing clinical/biochemical discriminators of DKD from NDKD helps improve clinical decision making, with a net reclassification improvement (NRI) of 0.53, 64% of DKD cases were correctly reclassified to a higher probability of disease (NRI+ = 0.280), and 62.5% of NDKD controls were correctly reclassified to a lower probability of disease (NRI– = 0.250).
Conclusions
Urinary cell-derived MALAT1 improves the ability to differentiate DKD from NDKD over and above currently used clinical and biochemical parameters.
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