Blood volume and chronic kidney disease in heart failure – Can volume expansion help balance the Cardio-Renal Axis for better clinical outcomes?

Intravascular volume is largely regulated by the kidneys but how differences in intravascular volume profiles interact with chronic kidney disease (CKD) to influence outcomes in chronic heart failure (HF) has not been explored. Our hypothesis was that a greater degree of volume expansion (VE) would moderate the impact of CKD on HF-related clinical outcomes. Quantitative blood volume (BV) data were available in 137 patients at the time of hospital discharge using a nuclear medicine radiolabeled albumin indicator-dilution technique. The study patients were stratified by the cohort median glomerular filtration rate (GFR, 44 ml/min/1.73 m²). An a priori cut-point of ≥+25% above normal BV was then used to further stratify the two GFR subgroups and prospectively analyzed for 1-year HF-related mortality or 1st re-hospitalization. Persistent BV expansions ≥+25% were present in 51% of the cohort. In the subgroup with GFR above the median (N = 68) greater or lesser BV expansion from +25% did not differentiate outcomes. However, in the subgroup with GFR below the median (N = 69), BV expansion-stratified risk (log-rank p = 0.022) with <+25% VE associated with poorer outcomes, while VE ≥ + 25% was associated with lower risk and comparable to GFR above the median. In patients with chronic HF, significant intravascular VE and CKD are common co-existing conditions. The presence of larger VE, however, appears to be a factor mitigating the impact of declining renal function on clinical outcomes, and as an element of volume pathophysiology warrants further study.