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Background: Diabetic kidney disease (DKD) lacks a simple and relatively accurate predictor. The Triglyceride–Glucose (TyG) Index is a proxy of insulin resistance, but the association between the TyG Index and DKD is less certain. We investigated if the TyG Index can predict DKD onset effectively. Materials and Methods: Cross-sectional and longitudinal analyses were undertaken. In total, 1432 type-2 diabetes mellitus (T2DM) patients were included in the cross-sectional analysis. The TyG Index (calculated by ln [fasting triglycerides (mg/dL) × fasting glucose (mg/dL)/2]) was split into three tertiles. Associations of the TyG Index with microalbuminuria and estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2 were calculated. Longitudinally, 424 patients without DKD at baseline were followed up for 21 (range, 12– 24) months. The main outcome was DKD prevalence as defined with eGFR < 60 mL/min/1.73 m2 or continuously increased urinary microalbuminuria: creatinine ratio (> 30 mg/mL) over 3 months. Cox regression was used to analyze the association between the TyG Index at baseline and DKD. Receiver operating characteristics curve (ROC) analysis was used to assess the sensitivity and specificity of the TyG Index in predicting DKD. Results: In cross-sectional analysis, patients with a higher TyG Index had a higher risk of microalbuminuria (OR = 2.342, 95% CI = 1.744– 3.144, p < 0.001), and eGFR < 60 mL/min/1.73 m2 (1.696, 95% CI =1.096– 2.625, p = 0.018). Longitudinally, 94 of 424 participants developed DKD. After confounder adjustment, patients in the high tertile of the TyG Index at baseline had a greater risk to developing DKD than those in the low tertile (HR = 1.727, 95% CI = 1.042– 2.863, p = 0.034). The area under the ROC curve was 0.69 (0.63– 0.76). Conclusion: The TyG Index is a potential predictor for DKD in T2DM patients. Clinical Trial: Clinical Trials identification number = NCT03692884. [ABSTRACT FROM AUTHOR]

Renin-independent aldosteronism (RIA) describes the spectrum of autonomous aldosterone secretion from mild to overt. We aimed to explore whether RIA is causally associated with chronic kidney disease (CKD) in patients with diabetes. We cross-sectionally included 1027, 402 and 39,709 patients with any type of diabetes from cohorts of EIMDS, CONPASS and UK Biobank, respectively. In EIMDS, we defined RIA and renin-dependent aldosteronism based on plasma aldosterone and renin concentrations. We performed captopril challenge test to confirm renin-dependent or independent aldosteronism in CONPASS. In UK Biobank, we generated genetic instruments for RIA based on the genome-wide association studies (GWAS). We extracted the corresponding single nucleotide polymorphisms (SNPs) information from the GWAS data of CKD in diabetes. We harmonized the SNP-RIA and SNP-CKD data to conduct the two-sample Mendelian randomization analyses. In EIMDS and CONPASS, when compared to subjects with normal aldosterone concentration or renin-dependent aldosteronism, participants with RIA had a lower estimated glomerular filtration rate, a higher prevalence of CKD, and a higher multivariate-adjusted odds ratio (OR) of CKD (OR 2.62 [95%CI 1.09–6.32] in EIMDS, and 4.31 [1.39–13.35] in CONPASS). The two-sample Mendelian randomization analysis indicated that RIA was significantly associated with a higher risk of CKD (inverse variance weighted OR 1.10 [95 % CI 1.05–1.14]), with no evidence of significant heterogeneity or substantial directional pleiotropy. Among patients with diabetes, renin-independent aldosteronism is causally associated with a higher risk of CKD. Targeted treatment of autonomous aldosterone secretion may benefit renal function in diabetes. • Diabetic patients with RIA had a higher risk of CKD compared to normal aldosterone or renin-dependent aldosteronism. • Two-sample Mendelian randomization analysis indicated that RIA was causally associated with CKD in diabetic patients. • Targeted treatment of autonomous aldosterone secretion may benefit renal function in diabetic patients. [ABSTRACT FROM AUTHOR]