Near-drowning: new perspectives for human hypoxic acute kidney injury

• Published in: Nephrology, dialysis, transplantation Vol. 35; no. 2; pp. 206 - 212
• Main Authors: Heyman, Samuel N, Gorelik, Yuri, Zorbavel, Danny, Rosenberger, Christian, Abassi, Zaid, Rosen, Seymour, Khamaisi, Mogher
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 01-02-2020
• Subjects: hypoxia; acute kidney injury; medullary thick ascending limb; animal model; human
• ISSN: 0931-0509; 1460-2385
• DOI: 10.1093/ndt/gfz016

Abstract
Concepts regarding hypoxic acute kidney injury (AKI) are derived from widely used warm ischemia-reflow (WIR) models, characterized by extensive proximal tubular injury and associated with profound inflammation. However, there is ample clinical and experimental data indicating that hypoxic AKI may develop without total cessation of renal blood flow, with a different injury pattern that principally affects medullary thick limbs in the outer medulla. This injury pattern likely reflects an imbalance between blood and oxygen supply and oxygen expenditure, principally for tubular transport. Experimental models of hypoxic AKI other than WIR are based on mismatched oxygen delivery and consumption, particularly within the physiologically hypoxic outer medulla. However, evidence for such circumstances in human AKI is lacking. Recent analysis of the clinical course and laboratory findings of patients following near-drowning (ND) provides a rare glimpse into such a scenario. This observation supports the role of renal hypoxia in the evolution of AKI, as renal impairment could be predicted by the degree of whole-body hypoxia (reflected by lactic acidosis). Furthermore, there was a close association of renal functional impairment with indices of reduced oxygen delivery (respiratory failure and features of intense sympathetic activity) and of enhanced oxygen consumption for active tubular transport (extrapolated from the calculated volume of consumed hypertonic seawater). This unique study in humans supports the concept of renal oxygenation imbalance in hypoxic AKI. The drowning scenario, particularly in seawater, may serve as an archetype of this disorder, resulting from reduced oxygen delivery, combined with intensified oxygen consumption for tubular transport.