Plasma R-spondin 2 levels are associated with the progression of diabetic kidney disease

Abstract

Aims: Circulating factor R-spondin 2 (RSPO2) has been found to play a role in lipid metabolism and insulin resistance. However, its relationship with kidney injury and diabetic kidney disease (DKD) remains unclear. We aim to determine the expression levels of RSPO2 in patients with type 2 diabetes mellitus (T2DM) stratified by kidney disease risk, and analyze its correlations with the parameters of renal injury parameters, glucose and lipid profiles, and further investigate the association between plasma RSPO2 concentration and the prognosis risk of DKD. Methods: A total of 121 participants with T2DM were enrolled and categorized into four kidney disease risk groups (Low, Moderately Increased, High, and Very High Risk) based on estimated glomerular filtration rate (eGFR) and urine albumin-to-creatinine ratio (UACR). Relevant anthropometric and biochemical parameters were analyzed, and plasma RSPO2 concentrations were measured. Spearman’s correlation analysis and Multiple logistic regression analysis was conducted. Results: Plasma RSPO2 concentrations were significantly elevated in the High and Very High Risk groups compared to the Low and Moderately Increased Risk groups. In vitro, RSPO2 expression levels were elevated in kidney tissues of DKD mouse models. Spearman correlation analysis revealed that the plasma RSPO2 level was positively correlated with UACR, Urea, serum creatinine and history of hypertension, while negatively correlated with eGFR, diastolic blood pressure (DBP), drinking and metformin usage after adjusting for age. Multivariate logistic regression analysis demonstrated that a higher plasma RSPO2 concentration remained significantly associated with progression to a more severe kidney disease risk grade after adjusting for potential confounders. Conclusions: Elevated plasma RSPO2 concentration is independently associated with higher kidney disease risk in patients with T2DM and may serve as a potential biomarker for DKD progression. Further studies are needed to elucidate the role of RSPO2 in DKD and its underlying mechanisms.