Risk improvement and adverse kidney outcomes in patients with chronic kidney disease: findings from KNOW-CKD

Background: Many trials have attempted to slow the progression of chronic kidney disease (CKD) by modifying specific risk factors, but without achieving satisfactory results. We aimed to evaluate the association between the degree of improvement in multiple risk factors and adverse kidney outcomes. Methods: This was a prospective observational study of 839 patients with CKD G3-G4. The main predictors were the number of improved risk factors between baseline and year one as follows: a decrease in proteinuria, systolic blood pressure, phosphate, and uric acid, and an increase in hemoglobin and bicarbonate from the baseline status to out of the target range. The primary outcome was a composite one, including CKD progression (50% decline in eGFR or kidney replacement therapy) and all-cause death. Results: Patients whose risk factors eventually improved had more unfavorable baseline profiles of the six considered factors. During 3097.8 person-years of follow-up (median 3.5 years per patient), the composite outcome occurred in 48.0% of patients (incidence rate, 13.0 per 100 person-years). Compared with an improvement of no risk factors, the adjusted HRs (95% CI) for improvement of 1 and ≥ 2 risk factors were 0.96 (0.76–1.22) and 0.53 (0.37–0.75), respectively. The association was not affected by diabetic status or CKD severity. Among the risk factors, proteinuria accounted for the greatest contribution to CKD progression. Conclusions: In patients with CKD G3-G4, improvement in multiple factors was associated with a decreased risk of CKD progression, suggesting the importance of multifactorial risk management. Graphical abstract: [Figure not available: see fulltext.]