Stage-specific elevation of MPO and NE mRNA expression in diabetic kidney disease and their independent associations with albuminuria.

BACKGROUND: Myeloperoxidase (MPO) and neutrophil elastase (NE) are key neutrophil enzymes involved in oxidative stress, inflammation, and neutrophil extracellular trap formation, all of which have been implicated in the pathogenesis of diabetic kidney disease (DKD). However, MPO and NE mRNA expression in peripheral blood leukocytes (PBL) across DKD stages remains insufficiently characterized. This study evaluates the association between DKD severity and MPO and NE mRNA expression in PBL. METHODS AND RESULTS: Seventy patients with type 2 diabetes were categorized into A1 DKD (normoalbuminuria), A2 DKD (moderately increased albuminuria), and A3 DKD (severely increased albuminuria) based on urine albumin-to-creatinine ratio (ACR). MPO and NE mRNA levels were quantified by qPCR from total RNA extracted from PBL. The groups were comparable in age, sex, BMI, diabetes duration, fasting glucose, lipid profile, and leukocyte counts. Systolic blood pressure and serum creatinine were significantly higher in A3 DKD compared with A1 DKD. MPO and NE expression did not differ between A1 and A2 DKD. In contrast, both MPO and NE mRNA levels were significantly elevated in A3 DKD compared with A1 and A2 DKD. Both markers correlated positively with urine albumin and ACR. Multivariable regression confirmed that the associations between MPO and NE expression and albuminuria were independent of clinical covariates. CONCLUSIONS: MPO and NE mRNA expression selectively increases in A3 DKD and is independently associated with albuminuria, indicating enhanced neutrophil activation in advanced DKD. These findings highlight MPO and NE as potential mechanistic markers of severe DKD and warrant further validation in larger, longitudinal studies.