Contrast nephropathy may be partly mediated by autonomic dysfunction: Renal failure considered as a modern maladaptation of the prehistoric trauma response

Abstract

The mechanism behind iodinated radiocontrast nephropathy remains elusive. Direct oxidative damage is the prevailing hypothesis, but the apparent protective effect of iodine against oxidation contradicts this view. We propose that autonomic dysfunction participates in the pathogenesis of radiocontrast nephropathy and may account for other contrast-associated reactions previously attributed to allergy. Iodine, through its effects on thyroid function and chemoreceptor response to metabolic acidosis, may induce hyperadrenergia and consequently diminish renovascular flow and urine output. The renal response to adrenergia likely served an adaptive function during prehistoric evolution when trauma was a dominant source of hypovolemia and adrenergia, but the response may behave maladaptively today as evolutionarily nai ve triggers for adrenergia have emerged. Autonomic dysfunction can further impair renal function by deranging renovascular autoregulation and inducing oxidative reperfusion injury as a secondary phenomenon. Many other causes of acute renal failure such as drug toxicity, surgery, hospitalization, and diabetes may operate through hyperadrenergia, impaired renovascular autoregulation, and oxidative reperfusion injury. Dialysis, a volume reduction therapy for renal failure, can counterintuitively worsen renal dysfunction by exacerbating adrenergia, which may explain its association with accelerated atherosclerosis, inflammation, and cancer. Other examples of vicious cycles that perpetuate renal dysfunction may include renal artery stenosis, carotid stenosis, and atherosclerosis as well as the cardio-renal, hepato-renal, and pulmonary-renal syndromes. The benefits of hydration and bicarbonate in protecting renal function may operate in part through baroreceptor- and chemoreceptor-mediated reduction of sympathovagal ratio, respectively. New treatment paradigms for renal failure including pharmacologic and electro-mechanical therapies are envisioned based on autonomic remodeling, reduced sympathovagal ratio, and neuromodulation of pathways typically associated with trauma such as renin, angiotensin, vasopressin, and aldosterone.