Date Published: June 17, 2019
Publisher: Public Library of Science
Author(s): Martin Russ, Sascha Ott, Janis R. Bedarf, Michael Kirschfink, Bernhard Hiebl, Juliane K. Unger, Nick Ashton.
Acute kidney injury (AKI) corrupts the outcome of about 50% of all critically ill patients. We investigated the possible contribution of the pathology acidemia on the development of AKI. Pigs were exposed to acidemia, acidemia plus hypoxemia or a normal acid-base balance in an experimental setup, which included mechanical ventilation and renal replacement therapy to facilitate biotrauma caused by extracorporeal therapies. Interestingly, extensive histomorphological changes like a tubular loss of cell barriers occurred in the kidneys after just 5 hours exposure to acidemia. The additional exposure to hypoxemia aggravated these findings. These ‘early’ microscopic pathologies opposed intra vitam data of kidney function. They did not mirror cellular or systemic patterns of proinflammatory molecules (like TNF-α or IL 18) nor were they detectable by new, sensitive markers of AKI like Neutrophil gelatinase-associated lipocalin. Instead, the data suggest that the increased renal proton excretion during acidemia could be an ‘early’ first hit in the multifactorial pathogenesis of AKI.
Acute kidney injury (AKI) complicates the course of disease of up to 50% of all patients admitted to an intensive care unit [1–3] and contributes to the failure of further organs, especially the lungs . This ‘kidney-lung cross-talk’ seems to take place bidirectional [5–9] and the pathophysiological mechanisms include the release of proinflammatory mediators due to mechanical ventilation, impaired circulation due to positive end-expiratory airway pressure (PEEP), as well as hypercapnia and hypoxia due to acute lung injury (ALI) or lung protective low tidal volume ventilation (LTVV) . The implementation of LTVV and adequate PEEP levels reduce the mortality due to ALI [11, 12], but the combination of lung injury and LTVV can cause respiratory acidosis. In patients, respiratory acidosis is usually tolerated to facilitate lung protective ventilation regimes as long as arterial pH remains above 7.2; this approach is called ‘permissive hypercapnia’. [13, 14].
Clinically, urinary output and laboratory measurements like serum creatinine are used to evaluate kidney function. Even immunological mediator levels, advanced hemodynamic monitoring and medical imaging can only give an indirect reflection of kidney perfusion, morphology and function. The hardest criterion of kidney cell damage is a biopsy and histopathological examination, which is almost never achievable in the critically ill patient. Thus, experimental investigations are necessary to identify conditions that result in cell damage and in turn AKI. To our knowledge, this was the first time that the impact of mixed acidemia on kidney function and histomorphology was investigated in large animals under clinical conditions.
An exposure to a mixed acidemia of 5 hours resulted in histomorphological changes like a tubular loss of cell barriers in the kidneys of anesthetized healthy pigs. An exposure to an additional hypoxemia aggravated these histomorphological changes. The experimental model did not result in a systemic or local inflammation which could be correlated to histomorphology or kidney function. Kidney function as well as systemic perfusion were not compromised in this experimental setup. Instead, the additional energy-depending secretion of protons through the kidneys may have caused the histomorphological changes. Further investigations are needed about the exact pathomechanism and its possible relevance in critically ill patients.