Risk Factors for Progressive Cardiorenal Syndrome in CKD Patients

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Background: Cardiorenal syndrome (CRS) is linked with poor outcomes. We studied the incidence and risk factors for progressive CRS (pCRS) in CKD patients. Methods: 3,557 CKD patients in the Chronic Renal Insufficiency Cohort (CRIC) Study were included in this analysis after excluding those with heart failure (HF) at baseline. The mean follow-up was 10.5 years. pCRS was defined as development of both HF and renal failure (RF) (ESKD) within 12 months of each other. Cox proportional hazards models were used to examine the association of risk factors and pCRS. Risk factors for CRS type 2 (HF preceded RF) and CRS type 4 (RF preceded HF) were also analyzed. Results: The average age was 59 years for those with pCRS and 57 years for those without. Age-adjusted incidence was 4.5/1000 person years, and was 5.0 in Men and 5.9 in Black. Traditional risk factors [multivariable-adjusted hazard ratios (95% CI)] for pCRS were less than high school education [1.82 (1.21, 2.73)], history of CVD [1.48 (1.03, 2.12)], lower eGFR [per 1SD,1.83 (1.40, 2.39)], and higher uACR [per 1SD, 2.26 (1.78, 2.86)]. The significant multivariable-adjusted HRs associated with novel risk factors are presented in Table. The risk factor associated with both CRS type 2 and 4 were kidney dysfunction, albuminuria, and mineral bone disorder (higher alkaline phosphatase and FGF23), inflammation (TNF-α), and fibrotic factor (GDF-15). Conclusions: This study indicates that education level, history of CVD, kidney dysfunction, albuminuria, mineral bone disorder, diabetes control, anemia, volume overload, inflammation, and fibrotic factor are associated with pCRS. Further studies are warranted to assess the benefits of specific interventions to improve CRS outcomes. Funding: NIDDK Support Multivariable-Adjusted Hazard Ratios of Progressive Cardiorenal Syndrome Associated with Novel Risk Factors - Variables (per SD) Multivariable-adjusted* HR (95% CI) P-value Hemoglobin (1.77 g/dL) 0.82 (0.68, 0.99) 0.049 Hemoglobin AIC(1.53 %) 1.31 (1.14, 1.52) 0.001 Log (alkaline phosphatase, 0.32 U/L) 1.18 (1.00, 1.38) 0.045 Log (brain natriuretic peptide, 1.25 pg/mL) 1.32 (1.10, 1.57) 0.002 *Adjusted for age, sex, race, clinic sites, and significant traditional risk factors

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