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Diabetic kidney disease (DKD) is the leading attributable cause of chronic kidney disease worldwide, occurring in approximately 30%-40% of people with diabetes. Therefore, early identification of high-risk population of DKD hold paramount significance in public health. Estimated glomerular filtration rate (eGFR) are wildly used in the realm of medical practice as an essential indicator of DKD diagnosis and prognosis, which is clinically calculated using serum creatinine or cystatin C. Nevertheless, it has been observed that difference between cystatin C- and creatinine- based eGFR (eGFRdiff) can exhibit significant. Negative eGFRdiff is associated with increased risk of a range of adverse outcomes, including falls, hospital admission, kidney failure, cardiovascular events, and mortality. However, the association of eGFRdiff and incident diabetic kidney disease (DKD) remains unknown. We aimed to prospectively investigate the associations of eGFRdiff with risk of incident DKD.
This prospective cohort study included 25,825 participants (mean age 59.1 years, 60.4% men) with diabetes free of microvascular complications at baseline (2006 to 2010) from the UK Biobank. eGFRdiff was calculated using both absolute difference between cystatin C- and creatinine-based calculations (eGFRabdiff), and the ratio between them (eGFRrediff). eGFRabdiff was further stratified by three categories: (1) less than -15 ml/min/1.73 m2 (negative eGFRabdiff), (2) -15 to 15 ml/min/1.73 m2 (midrange eGFRabdiff), and (3) 15 ml/min/1.73 m2 or greater (positive eGFRabdiff), while the eGFRrediff was categorized into two groups: less than 0.6, and 0.6 or greater. Incidence of DKD was ascertained using electronic health records. Cox proportional hazards regression models were used to evaluate the associations of eGFRdiff with incident DKD.
Altogether, 38.9% of participants exhibited negative eGFRabdiff at baseline. During a median of 13.6 years of follow-up, 3203 participants developed DKD. In comparisons with participants with midrange eGFRabdiff, participants with negative eGFRabdiff had a multivariable adjusted hazard ratio (95% confidence interval) of 1.63 (1.50, 1.76) for DKD. Each SD increment of eGFRabdiff was associated with a 36% lower risk of incident DKD. For each 10-percent increment in eGFRrediff, the corresponding hazard ratio (95% confidence interval) were 0.77 (0.75, 0.79) for DKD. The magnitude of associations was not materially altered in all sensitivity analyses.
Larger negative eGFRdiff was associated with an increased risk of incident DKD. Our findings suggest additional attention on monitoring cystatin C and eGFRdiff could provide potentially beneficial for risk stratification of DKD.