Analysis of Factors Associated with Diabetic Kidney Disease and the Value of Methylenetetrahydrofolate Reductase (MTHFR) in the Diagnosis of Diabetic Kidney Disease

Abstract

Background: There are reports on the early diagnosis of diabetic kidney disease (DKD) with a single serum index, but all of them have certain limitations. The role of methylenetetrahydrofolate reductase (MTHFR) gene promoter methylation in DKD still lacks evidence-base. The aim of this study was to analyze the factors associated with DKD and the value of MTHFR gene promoter methylation in the diagnosis of DKD. Methods: The study included a diabetes mellitus (DM) group (n = 138) and DKD group (n = 82). Clinical data, such as age, gender, disease duration, body mass index (BMI), serum indicators, and urine biochemical indicators were collected, and logistic regression was used to analyze the independent risk factors affecting the occurrence of DKD. Receiver operating curve (ROC) was used to analyze the diagnostic value of biochemical indicators individually and in combination for the detection of DKD. Results: The levels of glycosylated hemoglobin (HbA1c), serum creatinine (SCr), homocysteine (Hcy), cysteine (Cysc), urinary microalbumin and blood urea nitrogen (BUN) in the DKD group were significantly higher than those in the DM group, while MTHFR gene promoter methylation and glomerular filtration rate (eGFR) levels were significantly lower than those in the DM group (p < 0.05). Elevated levels of Hcy and urinary microalbumin were independent risk factors for DKD in patients with DM (p < 0.05). MTHFR gene promoter methylation level and elevated eGFR were protective factors affecting DKD in patients with DM. The methylation level of MTHFR gene promoter negatively correlated with the severity of DKD (p < 0.05). The area under the curve (AUC) of Hcy, urinary microalbumin, MTHFR gene promoter methylation and eGFR level for diagnosis of DKD were 0.617 (0.483–0.751), 0.720 (0.594–0.846), 0.657 (0.526–0.788) and 0.792 (0.688–0.896) respectively. The AUC of combined risk factors for diagnosis of DKD was 0.845 (0.758–0.932). Conclusions: Elevated levels of Hcy and urinary microalbumin were independent risk factors for DKD in patients with DM. The methylation level of MTHFR gene promoter negatively correlated with the severity of DKD. Therefore, attention should be paid to the changes of the methylation level of MTHFR gene promoter in clinical work.