Role of the Nervous System in Acute Kidney Injury

Although its parasympathetic innervation has not been elucidated, the sympathetic innervation of the kidney is well studied. Renal sympathetic overactivity has been observed in essential hypertension and chronic kidney disease. Renal sympathetic nerve activation decreases glomerular filtration rate and increases sodium absorption, which further deteriorates renal function. Sympathetic overactivity presents without uremia, suggesting that the cause is intrinsic to the diseased kidney itself. By disrupting signaling from the injured kidney, renal nerve denervation is expected to be beneficial in patients with kidney disease. Additionally, the immune system mediates an indirect association between the kidney and nervous system via the cholinergic anti-inflammatory pathway (CAP), whose main players include the vagus nerve, spleen, α7 acetylcholine receptor-positive macrophages, CD4+ T cells, and β2-adrenergic receptors. In animal models, AKI attenuation was achieved via CAP activation induced by vagus nerve stimulation or ultrasound treatment, although the exact mechanism remains unclear. Novel techniques, such as optogenetics, may help elucidate the CAP mechanisms and promote the clinical use of CAP-targeted immunomodulating therapy for prevention and treatment of kidney disease. Here, we provide an overview of kidney innervation and discuss the relationship between the kidney and the nervous system, including the CAP, in the context of acute kidney injury.