Intravascular Volume Modulates the Outcome Predictive Capacity of Clinical Renal Function Biomarkers in Clinically "Euvolemic" Chronic Heart Failure Patients.

ABSTRACT

BACKGROUND: Cardiorenal interconnections are complex and may in part be mediated by the extent of intravascular volume expansion. The impact of subclinical volume excess on outcomes in heart failure (HF) patients with chronic kidney disease (CKD) has not been examined previously. OBJECTIVES: To assess the impact of volume-kidney interactions on outcomes in clinically "euvolemic" chronic HF patients (NYHA class II) with coexisting CKD. METHODS: Plasma volume (PV) was prospectively measured in 110 stable HF patients with different degrees of renal function using a standardized radiolabeled albumin indicator-dilution technique. To examine the interactive roles of volume expansion and biomarkers of CKD, the cohort was dichotomized by median PV and then further stratified by cohort median serum creatinine, eGFR, and BUN, and analyzed for outcomes of HF-related mortality and 1st hospitalization. RESULTS: PV was expanded above normal in 76% of the cohort. Over 1.5 years of follow-up, sCr and BUN above and eGFR below cohort median stratified higher risks for the composite endpoint only in ambulatory HF patients with a severe degree of PV expansion (median PV expansion ≥+26%; p = 0.02). With less expansion (<+26% expansion), these biomarkers reflecting worse renal function did not discriminate risk (p = 0.578). The percentage of subjects experiencing composite outcome events was, however, comparable for both greater and lesser degrees of PV expansion in HF patients with stable clinical status. CONCLUSIONS: In clinically stable chronic HF patients with coexisting CKD, substantial subclinical PV expansion is common even when patients are considered clinically to be euvolemic, and, importantly, the extent of PV expansion impacts outcomes including early HF mortality. Better kidney function appears to mitigate the effects of excess PV expansion, while less volume expansion appears to limit the risk of worse renal function as reflected by clinical biomarkers of renal function. Thus, the extent of volume expansion impacts the capacity of standard clinical biomarkers of CKD to differentiate outcome risk in ambulatory chronic (NYHA class II) HF patients.