Risk Factors for Progressive Cardiorenal Syndrome Events in Patients with Chronic Kidney Disease: The CRIC Study

Background: Cardiorenal syndrome (CRS) is associated with poor outcomes. Risk factors for progressive CRS are not understood in patients with chronic kidney disease (CKD). Objectives: This study aimed to determine the incidence of progressive CRS and risk factors in individuals with CKD. Methods: Adults with CKD in the Chronic Renal Insufficiency Cohort (CRIC) study excluding those with heart failure (HF) at baseline were included (n = 3,557). We defined progressive CRS as developing HF and end-stage kidney disease (ESKD) within 12 months. ESKD was defined as needing renal replacement therapy or renal transplant. The associations of baseline risk factors with progressive CRS were examined using Cox proportional hazards models. A sensitivity analysis assessed risk factors in those who developed HF before ESKD and vice versa. Results: 161 patients (4.5%) developed progressive CRS. Traditional risk factors [multivariable-adjusted hazard ratios (HR) (95% CI)] associated with progressive CRS in multivariable models included lower education [1.90 (1.28,2.83)], cardiovascular disease [1.53 (1.07,2.18)], lower estimated glomerular filtration rate [0.64 (0.51,0.82)] and higher albumin to creatinine ratio [2.44 (1.98,3.02)]. Novel risk factors associated included higher levels of alkaline phosphatase, brain natriuretic peptide (BNP), tumor necrosis factor alpha (TNF-?), growth differentiation factor 15 (GDF-15), hemoglobin A1C, and lower hemoglobin. Risk factors associated with both ESKD before HF and HF before ESKD were kidney dysfunction, albuminuria, and mineral bone disorder (higher alkaline phosphatase and PTH), inflammation (TNF-?), fibrotic factor (GDF-15), and anemia. Diabetes, CVD, systolic blood pressure, waist circumference, HbA1c, and BNP were more strongly associated when HF preceded ESKD. Conclusions: Both traditional risk factors and novel risk factors associated with inflammation, mineral bone disorder, anemia, diabetes control, albuminuria, worse kidney function, and fibrotic factors are associated with progressive CRS in individuals with CKD. Many of these risk factors are modifiable representing potential areas for intervention.