Abstract Background and Aims To evaluate the quality of evidence, potential biases, and validity of all available studies on dietary intervention and diabetic nephropathy (DN). Method We conducted an umbrella review of existing meta-analyses of randomized controlled trials (RCTs) that focused on the effects of dietary intervention on DN. Literature searching was performed via PubMed, Embase, Web of Science, Cochrane Database of Systematic Reviews, and hand searching of the reference lists. Systematic reviews and meta-analyses of RCTs that evaluated the effects of any dietary intervention on clinical outcomes of DN were included. Two reviewers evaluated the methodological quality of the included articles through AMSTAR score. In addition, according to the Grading of Recommendations, Assessment, Development and Evaluation (GRADE), evidence of each outcome was evaluated and graded as “high”, “moderate”, “low” or “very low” quality to draw conclusions. Additionally, we classified evidence of outcomes into 4 categories (class I to IV and non-significant (NS)). Results We identified 36 meta-analyses of RCTs and 55 clinical outcomes of DN from 395 unique articles (Fig. 1). Moderate quality evidence suggested that probiotics supplementation could significantly improve blood urea nitrogen (BUN), total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) in DN patients. Low quality evidence indicated that probiotics supplementation significantly improved serum creatinine, urinary albumin creatinine ratio (UACR), fasting blood glucose (FBG), HbA1c and high-density lipoprotein cholesterol (HDL-C) in DN patients. In addition, low quality evidence suggested that a salt restriction diet could significantly improve creatinine clearance rate (CrCl) in patients with DN. Low quality evidence suggested that vitamin D supplementation could significantly improve UACR in patients with DN. Besides, low quality evidence indicated that soy isoflavone supplementation could significantly improve BUN, FBG, TC, triglycerides (TG) and LDL-C in patients with DN. Furthermore, low quality evidence suggested that coenzyme Q10 supplementation could significantly improve HbA1c, TC and HDL-C in patients with DN, and dietary polyphenols also significantly improved HbA1c in patients with DN. Finally, low quality evidence suggested supplementation of antioxidant vitamins could significantly improve serum creatinine, systolic blood pressure, and HbA1c in patients with DN. The remaining outcomes were rated as very low quality due to significant risk of bias, significant heterogeneity, imprecision, and publication bias. Given the small sample size, all significantly associated outcomes were evaluated as class IV evidence (Fig. 2). Conclusion Moderate to low evidence suggests that supplementation with probiotics, vitamin D, soy isoflavones, coenzyme Q10, dietary polyphenols, antioxidant vitamins, and salt-restricted diets may significantly improve clinical outcomes in patients with DN.
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