Disordered aldosterone-volume relationship in end-stage kidney disease

Abstract

Introduction. Sodium loading, and subsequent volume expansion, suppresses aldosterone levels in individuals with normal renal function. We hypothesised that loss of renal function impairs this volume-aldosterone relationship. Materials and methods. With multifrequency bioimpedance spectroscopy, we measured total body water (TBW), extracellular volume (ECV), and intracellular volume in five haemodialysis patients at varied states of hydration and in five healthy volunteers during low-, normal-, and high-salt diets. Serum aldosterone, potassium, and C-reactive protein were measured simultaneously. Scatterplots and general estimating equations were used to examine the relationship among these variables. Results. In healthy volunteers with salt loading, and in haemodialysis subjects with increased inter-dialytic weight gain, expansion of ECV led to reciprocal declines in serum aldosterone concentrations. The relationship was more profound in healthy volunteers (p<0.001) than in haemodialysis subjects (p=0.1). Notably, haemodialysis subjects posted consistently higher levels of ECV (median 49.6% TBW, IQR 43.9—51.8% compared to 41.1%, 39.9—42.8% in volunteers) and serum aldosterone (median 26.7 ng/dl, IQR 19.8—29.6 compared to 12.4 ng/dl, 8.8—16.0 in volunteers). Serum potassium did not appear to influence aldosterone concentration (p=0.9). Conclusions. The shift of the volume-aldosterone curve in haemodialysis subjects suggests that end-stage kidney disease is a state of high volume and inappropriately high aldosterone. These data have important clinical implications, as dialysis patients may benefit from both volume reduction and mineralocorticoid receptor blockade.