Y-RNAs and their fragments reflect kidney injury in diabetic kidney disease.

Diabetic kidney disease (DKD) affects one-third of patients with diabetes mellitus (DM). Y-RNAs (RNYs) are a type of highly abundant non-coding RNA that could potentially serve as disease biomarkers. This study investigated whether circulating RNYs associate with DKD that may facilitate early detection and intervention of DKD. Patients were categorized into three groups: healthy controls (HCs), patients with type 1 DM without DKD, and those with DKD. We examined the levels of RNYs and their fragments using RT-qPCR. Levels of RNYs were determined in three main non-coding RNA carriers (extracellular vesicles [EVs], AGO2, and HDL). Serum expression of full-length RNYs mainly decreased in the DKD group, while RNY fragments were elevated in the DM group compared to the HC group and decreased in the DKD group compared to the DM group. While we observed circulating RNYs to be attached to AGO2 and HDL, the majority is present in EVs. In addition, the subtype ratio of full-length RNY3/RNY4 associated with kidney injury, while RNY1, RNY3, RNY3/RNY4 ratio and all fragment RNYs strongly associated with markers of vascular injury. Circulating RNYs and their fragments associate with (vascular injury in) DKD show potential as biomarkers for kidney injury in DM.