Prevention of Cardio-renal Outcomes in Chronic Kidney Disease in Denmark 2011-2023: A Nationwide Observational Study

Rationale & Objective Chronic kidney disease (CKD) increases risk of hospitalization, cardiovascular disease, end-stage kidney disease, and death. We aimed to investigate use of cardio-renal protective treatment in Danish residents with incident CKD and evaluate associated benefit on renal and cardiovascular outcomes from 2011 to 2023. Study Design Observational cohort study Setting & Participants Adults with incident CKD (≥2 estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m 2 ≥90 days apart, no intervening eGFR ≥60 ml/min/1.73 m 2 , and ≥1 preceding eGFR ≥60 ml/min/1.73 m 2 ) were identified in Danish health care registers from 2011-2022 and followed through 2023. Outcome(s) One-year standardized probabilities of treatment with sodium-glucose Cotransporter-2 Inhibitors (SGLT2i), renin-angiotensin-system inhibitors (RASi), and lipid-lowering medications, and one-year standardized risks of progression of CKD, cardiovascular disease, heart failure, mortality, and a composite outcome. Analytical Approach Standardized probabilities and risks were evaluated using multiple logistic and cause-specific Cox regression models adjusted for relevant confounders. Results Among 183,956 individuals (median age 78 years, 46% male, median eGFR 53 ml/min/1.73 m 2 ) with median follow-up of 6.1 years, standardized one-year probability of treatment with SGLT2i and RASi increased (0.08% to 11.0% and 59.0% to 67.3%, p-trend 0.11 and 0.04), while lipid-lowering therapy remained stable (53.5% to 54.8%, p-trend 0.79). Standardized one-year risks of CKD progression and cardiovascular disease decreased (0.6% to 0.3% and 4.0% to 3.0%, p-trend 0.01 and 0.03), while risks of heart failure, death, and the composite outcome remained unchanged (8.8% to 9.2%, 12.2% to 11.1%, and 21.9% to 20.3%, p-trend 0.89, 0.19, and 0.42). Limitations Observational design limits causal inference. Misclassification of incident CKD and index eGFR, unmeasured testing indications, adherence and clinical/lifestyle factors may affect risk estimates. Conclusions From 2011 to 2023, implementation of cardio-renal protective treatment increased, while risk of CKD progression and cardiovascular events declined in individuals with incident CKD.