[Construction of evidence graph of modifiable risk factors for diabetic nephropathy]

Objective: Diabetic nephropathy (DN), a recognized public health problem worldwide, is an important cause of end-stage renal disease. Many non-genetic risk factors have been suggested, but their overall epidemiological reliability has not been evaluated. Therefore, the aim of this study was to provide the optimal available evidence of modifiable risks for the occurrence of DN risk. Methods: PubMed, Cochrane Library, CNKI, and Wanfang databases were used to retrieve Meta-analyses about various risk factors for DN published until June 2023. For each Meta analytic association, the effect size, 95%CI, heterogeneity, small-study effects, excess significance bias and 95% prediction intervals were calculated. The reliability and methodological quality of significant evidence was graded by using pre-defined criteria. Results: A total of 24 Meta-analyses (39 associations) were analyzed, covering a wide range of medication use, concomitant disease, biomarker, lifestyle, and physical measurement index. Continuous tumor necrosis factor receptor-1 (RR=2.79, 95%CI: 2.32-3.36), high level of TNFR-1 (RR=3.55, 95%CI: 2.78-4.54), high level of TNFR-2 (RR=4.69, 95%CI: 3.19-6.91), Helicobacter pylori infection (OR=2.15, 95%CI: 1.81-2.55), hypertension (OR=2.01, 95%CI: 1.73-2.34) and intensive glycemic control (RR=0.74, 95%CI: 0.67-0.84) were convincing evidence (gradeⅠ), and higher HbA1c variability (HR=1.18, 95%CI: 1.13-1.24), continuous TNFR-2 (RR=2.23, 95%CI: 1.68-2.94), higher total bilirubin level (OR=0.86, 95%CI: 0.82-0.90), depression (OR=1.18, 95%CI: 1.17-1.20), continuous waist circumference (standardized mean difference=0.18, 95%CI: 0.12-0.23), waist circumference (obesity: OR=1.56, 95%CI: 1.33-1.83) and ACEi use (RR=0.83, 95%CI: 0.77-0.88) were highly suggestive evidence (gradeⅡ). Moreover, higher blood uric acid (OR=2.05, 95%CI: 1.42-2.94), higher serum cystatin C (OR=51.14, 95%CI: 10.49-249.30), vitamin D deficiency (OR=2.05, 95%CI: 1.44-2.92), diabetic retinopathy (OR=2.19, 95%CI: 1.49-3.23), and higher visceral fat area (mean difference=11.65, 95%CI: 2.06-21.24) were the main risk factors for DN. Sodium-glucose cotransporter 2 inhibitors use had significant protective associations with DN (RR=0.49, 95%CI: 0.34-0.72). Conclusions: Intensive blood glucose control and rational drug use can significantly reduce the risk for DN in diabetes patients. Attention should be paid to the risk for hypertension, diabetic retinopathy, depression, obesity and other complications for DN, and daily monitoring and control of serum related biomarkers should be strengthened. The study results can be used as the evidence to identify populations at high-risk and suggest rational treatment options and healthy living interventions.