Selective glomerular hypofiltration syndrome: a novel renal phenotype associated with cardiovascular disease and adverse outcomes in diabetic kidney disease.

INTRODUCTION: Selective glomerular hypofiltration syndrome (SGHS), defined by a low ratio of estimated glomerular filtration rate using cystatin C (eGFRcys) to estimated glomerular filtration rate using creatinine (eGFRcr), has emerged as a novel kidney dysfunction phenotype. Its role in diabetic kidney disease (DKD) remains unknown. This study aimed to investigate the association between SGHS and the prevalence of cardiovascular disease (CVD) at the time of renal biopsy-diagnosed DKD, as well as its association with long-term renal outcomes. RESEARCH DESIGN AND METHODS: This study included 182 patients with biopsy-proven DKD. SGHS was defined as eGFRcys/eGFRcr ratio <0.60. Predictive value of the SGHS for the prevalence of CVD was assessed using receiver operating characteristic (ROC) curves. Independent risk factors for CVD prevalence were identified by logistic regression and used to construct a nomogram. ROC curves, calibration curves, decision curve analysis, and clinical impact curves were used for assessment of model performance. The impact of SGHS on renal outcomes was assessed using Kaplan-Meier curves and Cox regression. Subgroup analyses stratified by gender and body mass index categories were performed. Sensitivity analysis was conducted by redefining SGHS as eGFRcys/eGFRcr ratio <0.70. RESULTS: Of 182 patients, 41 (22.5%) had SGHS. The eGFRcys/eGFRcr ratio better predicted CVD (area under the curve (AUC) 0.730, 95% CI 0.643 to 0.816) than eGFRcr (AUC 0.602, 95% CI 0.507 to 0.697), eGFRcys (AUC 0.701, 95% CI 0.615 to 0.786), estimated glomerular filtration rate based on creatinine and cystatin C (AUC 0.685, 95% CI 0.595 to 0.774), and urinary albumin-to-creatinine ratio (AUC 0.633, 95% CI 0.540 to 0.725). SGHS was independently associated with CVD after adjustment (OR 9.27, 95% CI 3.20 to 26.84; p<0.001). A nomogram incorporating SGHS demonstrated good discrimination (AUC 0.834; bias-corrected C-index 0.808) and calibration. Over a median follow-up of 30.1 months, patients with SGHS had higher cumulative DKD progression probability (log-rank test: χ²=11.79, p<0.001), and SGHS was an independent risk factor for DKD progression (HR 2.645, 95% CI 1.564 to 4.472; p<0.001). Subgroup analyses and sensitivity analysis confirmed the robustness of these findings. CONCLUSIONS: SGHS is independently associated with the prevalence of CVD at the time of DKD diagnosis, and independently predicts adverse renal outcomes in patients with DKD. As an easily obtainable parameter, the eGFRcys/eGFRcr ratio may serve as a valuable risk assessment tool in patients with DKD.