Cardiovascular Autonomic Dysfunction in Chronic Kidney Disease: a Comprehensive Review

Cardiovascular autonomic dysfunction is a major complication of chronic kidney disease (CKD), likely contributing to the high incidence of cardiovascular mortality in this patient population. In addition to adrenergic overdrive in affected individuals, clinical and experimental evidence now strongly indicates the presence of impaired reflex control of both sympathetic and parasympathetic outflow to the heart and vasculature. Although the principal underlying mechanisms are not completely understood, potential involvements of altered baroreceptor, cardiopulmonary, and chemoreceptor reflex function, along with factors including but not limited to increased renin-angiotensin-aldosterone system activity, activation of the renal afferents and cardiovascular structural remodeling have been suggested. This review therefore analyzes potential mechanisms underpinning autonomic imbalance in CKD, covers results accumulated thus far on cardiovascular autonomic function studies in clinical and experimental renal failure, discusses the role of current interventional and therapeutic strategies in ameliorating autonomic deficits associated with chronic renal dysfunction, and identifies gaps in our knowledge of neural mechanisms driving cardiovascular disease in CKD.