Association of remnant cholesterol with kidney outcomes in adults with type 2 diabetes: a systematic review and meta-analysis

Abstract

Remnant cholesterol (RC) reflects the cholesterol carried by triglyceride-rich lipoprotein remnants and may capture lipid-related kidney risk not fully represented by conventional lipid measures. We evaluated the associations between RC and kidney outcomes in adults with type 2 diabetes mellitus (T2DM). Following PRISMA 2020, PubMed/MEDLINE, Scopus, the Cochrane Library, Google Scholar, Wiley Online Library, and ScienceDirect were searched for longitudinal and cross-sectional observational studies evaluating circulating RC and kidney outcomes in adults with T2DM. Studies of mixed populations were eligible only when T2DM-specific data could be extracted. Adjusted effect estimates were pooled separately by study design and kidney outcome using restricted maximum likelihood random-effects models with Hartung–Knapp adjustment. Seventeen articles contributed 18 independent estimates from 2,817,820 participants with T2DM. The exploratory all-study model showed an association between higher RC and adverse kidney outcomes (association ratio 1.50, 95% CI 1.32–1.72, P  < 0.001; I 2  = 87.6%). The longitudinal model, comprising 12 independent estimates from 11 articles, showed a similar association (HR 1.27, 95% CI 1.17–1.37, P  < 0.001; I 2  = 42.9%). Outcome-specific analyses showed an association with incident diabetic kidney disease (DKD; HR 1.27, 95% CI 1.15–1.41, P  = 0.0029). The estimate for kidney failure/end-stage kidney disease was positive but not statistically significant (HR 1.56, 95% CI 0.82–2.97, P  = 0.115). The association with DKD progression also did not reach statistical significance (HR 1.17, 95% CI 1.00–1.37, P  = 0.052), while one study reported an association with incident albuminuria (HR 1.23, 95% CI 1.06–1.43, P  = 0.007). Six cross-sectional studies showed an association between higher RC and prevalent or early DKD in adults with T2DM (OR 2.03, 95% CI 1.71–2.42, P  < 0.001; I 2  = 2.5%). The longitudinal association remained after restricting the analysis to estimates adjusted for blood pressure, glycemia, and adiposity (HR 1.28, 95% CI 1.21–1.37, P  < 0.001). A smaller subset that included continuous estimates showed that a 0.1 mmol/L increase in RC was not associated with incident DKD (HR 1.02, 95% CI 0.98–1.07, P  = 0.197). Higher RC was associated with incident and prevalent DKD and with adverse longitudinal kidney outcomes overall in adults with T2DM. RC may serve as a complementary kidney-risk marker, but the observational evidence does not establish causality or a clinical threshold. Systematic review registration : https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD420261475085 , identifier CRD420261475085.