Outcomes and Risk Factors of Widened Difference in Estimated Glomerular Filtration Rate by Creatinine or Cystatin C: Adjust Model Development with More than 300,000 UK Biobank Participants

Background: Recent studies have highlighted the significance of discrepancies between cystatin C-based(eGFRcys) and creatinine-based(eGFRcr) CKD-EPI eGFR. This study explores the implications of differences between eGFRcys and eGFRcr(eGFRdiff) on clinical outcomes and develops an adjusted model using eGFRcr and variables. Methods: Using data from the UK Biobank cohort of 343,854 participants, we stratified them into three groups based on eGFRdiff: lower(eGFRcys-eGFRcr<-15), middle(-15≤eGFRcys-eGFRcr≤15), and upper(eGFRcys-eGFRcr>15). We analyzed the risks of death, MI, and ischemic stroke in the eGFRdiff<-15 and eGFRdiff>15 groups using Cox regression models. Logistic regression identified variables associated with eGFRdiff. And we developed and validated a regression model using eGFRcr and associated variables to approximate eGFRcys. Results: Individuals with eGFRdiff<-15 had increased risks of death (HR:1.37[1.30-1.44]), MI (HR:1.23[1.15-1.33]), and ischemic stroke (HR:1.19[1.08-1.31]). Variables associated with eGFRdiff<-15 included high waist/hip circumference, high body weight, low fat-free mass, high total food intake, low protein intake, diabetes, and larger kidney volumes. A regression model was developed using eGFRcr, sex, age, height, weight, and BMI. In the validation set, this model achieved an adjusted R^2 of 0.47, improved from the initial R^2 of 0.32 between eGFRcys and eGFRcr. The adjusted model improved clinical outcome prediction. Conclusion: This study confirmed that eGFRdiff<-15 is associated with increased risks of clinical outcomes and identified factors associated with eGFRdiff. We developed an adjusted model, demonstrating superior clinical outcome association.ROC and AUROC of adjust models.