Dose-response Association of Diabetic Kidney Disease with Routine Clinical Parameters in Patients with Type 2 Diabetes Mellitus: a Systematic Review and Meta-analysis

Background: Diabetic kidney disease (DKD) is a leading cause of end-stage kidney disease and is associated with high mortality rates. The influence of routine clinical parameters on DKD onset in patients with type 2 diabetes mellitus (T2DM) remains uncertain.

Methods: In this systematic review and meta-analysis, we searched multiple databases, including PubMed, Embase, Scopus, Web of Science, and Cochrane Library, for studies published from each database inception until January 11, 2024. We included cohort studies examining the association between DKD onset and various clinical parameters, including body mass index (BMI), hemoglobin A1c (HbA1c), systolic blood pressure (SBP), diastolic blood pressure (DBP), total cholesterol (TC), triglycerides (TG), low-density lipoprotein (LDL), high-density lipoprotein (HDL), and serum uric acid (UA). Random-effect dose-response meta-analyses utilizing one-stage and/or cubic spline models, were used to estimate correlation strength. This study is registered in PROSPERO (CRD42022326148).

Findings: This analysis of 46 studies involving 317,502 patients found that in patients with T2DM, the risk of DKD onset increased by 3% per 1 kg/m increase in BMI (relative risk (RR) = 1.03, confidence interval (CI) [1.01-1.04], I = 70.07%; GRADE, moderate); a 12% increased risk of DKD onset for every 1% increase in HbA1c (RR = 1.12, CI [1.07-1.17], I = 94.94%; GRADE, moderate); a 6% increased risk of DKD onset for every 5 mmHg increase in SBP (RR = 1.06. CI [1.03-1.09], I = 85.41%; GRADE, moderate); a 2% increased risk of DKD onset per 10 mg/dL increase in TG (RR = 1.02, CI [1.01-1.03], I = 78.45%; GRADE, low); an 6% decreased risk of DKD onset per 10 mg/dL increase in HDL (RR = 0.94, CI [0.92-0.96], I = 0.33%; GRADE, high), and a 11% increased risk for each 1 mg/dL increase in UA (RR = 1.11, CI [1.05-1.17], I = 79.46%; GRADE, moderate). Subgroup analysis revealed a likely higher risk association of clinical parameters (BMI, HbA1c, LDL, and UA) in patients with T2DM for less than 10 years.

Interpretation: BMI, HbA1c, SBP, TG, HDL and UA are potential predictors of DKD onset in patients with T2DM. Given high heterogeneity between included studies, our findings should be interpreted with caution, but they suggest monitoring of these clinical parameters to identify individuals who may be at risk of developing DKD.

Funding: Shenzhen Science and Innovation Fund, the Hong Kong Research Grants Council, and the HKU Seed Funds, and Scientific and technological innovation project of China Academy of Chinese Medical Sciences.