A wandering path toward prevention for acute kidney injury

Abstract

A wandering path toward prevention for acute kidney injury Simon J. AtkinsonDepartment of Biology, Indiana University-Purdue University Indianapolis, Indianapolis, Indiana, USA. Acute kidney injury: challenges for therapy developmentAcute kidney injury (AKI) remains a serious complication in hospitalized patients, especially those that are critically ill (1, 2), and results in significant mortality and morbidity in this population. Those individuals that develop AKI and survive are at extremely high risk of progressing to chronic kidney disease. AKI is almost invariably diagnosed in conjunction with a set of comorbid conditions, such as multiorgan sepsis or congestive heart failure, or in the aftermath of major cardiothoracic surgery. Basic research on AKI is complicated by the challenge of isolating and dissecting the mechanisms of AKI in animal or in vitro models while retaining relevance to the typically complicated clinical presentation seen in patients in the ICU. This fundamental challenge has limited progress in the identification of novel preventative measures or treatments for AKI that might improve upon the largely supportive measures that are currently employed (3). Researchers, physicians, and patients could sorely use some serendipitous findings that, like those of the three princes of Serendip (4), might advance their quest and put an end to their wanderings in search of an answer. In this issue, Inoue, Abe, and colleagues (5) build on just such a finding and suggest a new path forward. Specifically, these authors have uncovered neuroimmunomodulatory mechanisms that are amenable to therapeutic intervention and have potential to contribute additional strategies for limiting AKI. This line of research by Mark Okusa and colleagues began (6) with the hypothesis that preconditioning the renal vasculature with contrast-enhanced ultrasound would stimulate increased blood flow to the kidney and thereby attenuate ischemia-reperfusion injury (IRI) and consequent AKI. Surprisingly, the amelioration of IRI by prior ultrasound exposure did not require the introduction of contrast, nor did it require that the kidney itself be targeted with the ultrasound probe. Instead, exposure of the spleen was determined to be key to the protective effect, and a correlation between spleen enlargement and the ability to recruit CD4 + T cells to the spleen was found. Together, these results suggested that ultrasound stimulation might invoke an antiinflammatory response, leading Okusa and colleagues to propose that this protective effect was due to the known ability of certain ultrasound frequencies to stimulate nerves. The proposed mechanism of action ( Figure 1) involves ultrasound activation of adrenergic neurons innervating the spleen, stimulation of CD4 + cells via β-adrenergic receptors, consequent release of acetylcholine by T cells, and then stimulation of nicotinic cholinergic receptors on myeloid/macrophage cells. Pharmacologic studies have implicated stimulation of α7 nicotinic acetylcholine receptors (α7nAChRs) prese...

R1 autonomic nervous system in acute kidney injury

“…Acute kidney injury occurs in a variety of clinical scenarios with diverse manifestations ranging from a slight and sustained elevation in serum creatinine levels to anuric renal failure . AKI is commonly diagnosed in conjunction with a set of comorbid conditions including multiple organ sepsis, congestive heart failure or resulting major cardiothoracic surgery . AKI requiring dialysis is associated with a mortality rate ranging from 40% to 50%, and increasing to 60‐80% if combined with distant organ dysfunction states such as cardiac and respiratory failure.…”

“…Research on AKI is challenging as differentiation of underlying mechanisms in animal or in vitro models may differ to the complicated clinical presentation of patients in the intensive care units . Nevertheless, recent years have seen several exciting advancements in the field.…”

Vagus Nerve Stimulation Alleviates Hepatic Ischemia and Reperfusion Injury by Regulating Glutathione Production and Transformation

“…Hence, IAPs may involve in protective function of VNS and the inhibition of apoptosis when glutathione exerts antioxidant function. VNS has also been applied to IRI of the kidney [42], and the results of our proteomic analysis suggested that this regulatory approach is related to glutathione metabolism. We assumed that VNS could serve as a pretreatment before reperfusion, which might reduce inflammation and injury by adjusting the antioxidant capacity of the liver itself.…”

LncTCONS_00058568 is involved in the pathophysiologic processes mediated by P2X7R in the lower thoracic spinal cord after acute kidney injury

“…AKI is often caused by factors such as renal ischemia, severe infection and nephrotoxic drugs, of which the proportion of AKI induced by renal ischemia is as high as 50% 28 . Multiple mechanisms may explain the deterioration of AKI and its advancement towards chronic kidney disease (CKD), encompassing inflammation, angiotensin II, 29 renal nerves, 30 vagus nerves, 31 and neuro‐immunomodulatory mechanisms 31,32 . The kidney is innervated by an abundant assortment of efferent and afferent sympathetic nerves 33 .…”