Mechanisms and mediators of lung injury after acute kidney injury

Faubel, Sarah; Edelstein, Charles L.

doi:10.1038/nrneph.2015.158

Cited by 155 publications

(133 citation statements)

References 137 publications

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“…AKI-mediated lung injury is well described in animal models and is predominantly characterized by lung inflammation, as judged by increased cytokines, chemokines, and neutrophils by 4 hours post-AKI 12 . Non-cardiogenic pulmonary edema is variably present 12 . By 24 hours, T cell infiltration, necroptosis, parthanatos, apoptosis, and increased caspase-3 activity are present 13,14 .…”

Section: Discussionmentioning

confidence: 99%

Early peritoneal dialysis reduces lung inflammation in mice with ischemic acute kidney injury

Altmann

Ahuja

Kiekhaefer

et al. 2017

Kidney International

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Although dialysis has been used in the care of patients with acute kidney injury (AKI) for over 50 years, very little is known about the potential benefits of uremic control on systemic complications of AKI. Since the mortality of AKI requiring renal replacement therapy (RRT) is greater than half in the intensive care unit a better understanding of the potential of RRT to improve outcomes is urgently needed. Therefore, we sought to develop a technically feasible and reproducible model of RRT in a mouse model of AKI. Models of low and high dose peritoneal dialysis (PD) were developed and their effect on AKI, systemic inflammation, and lung injury after ischemic AKI was examined. High dose PD had no effect on AKI, but effectively cleared serum IL-6, and dramatically reduced lung inflammation while low dose PD had no effect on any of these three outcomes. Both models of RRT using PD in AKI in mice reliably lowered urea in a dose dependent fashion. Thus, use of these models of PD in mice with AKI has great potential to unravel the mechanisms by which RRT may improve the systemic complications that have led to increased mortality in AKI. In light of recent data demonstrating reduced serum IL-6 and improved outcomes with prophylactic PD in children, we believe our results are highly clinically relevant.

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Section: Discussionmentioning

confidence: 99%

Early peritoneal dialysis reduces lung inflammation in mice with ischemic acute kidney injury

Altmann

Ahuja

Kiekhaefer

et al. 2017

Kidney International

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“…Circulating cytokines may have deleterious effects on other organs and higher levels have been shown to be associated with adverse clinical outcomes, including prolonged duration of mechanical ventilation, intensive care and hospital length of stay [26, 40, 41]. IL-8 is a potent neutrophil cytokine that promotes lung neutrophil accumulation and lung tissue injury [42]. Liu et al demonstrated that serum IL-6 and IL-8 are predictive of AKI and prolonged duration of mechanical ventilation in children following cardiac surgery [30].…”

Section: Discussionmentioning

confidence: 99%

A Decline in Intraoperative Renal Near-Infrared Spectroscopy Is Associated With Adverse Outcomes in Children Following Cardiac Surgery

Gist

Kaufman

Cruz

et al. 2016

Pediatric Critical Care Medicine

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Objective Renal near infrared spectroscopy (NIRS) is known to be predictive of acute kidney injury (AKI) in children following cardiac surgery using a series of complex equations and area under the curve. This study was performed to determine if a ≥ 20% reduction in renal NIRS for 20 consecutive minutes intra-operatively or within the first 24 post-operative hours is associated with 1) AKI, 2) increased AKI biomarkers, or 3) other adverse clinical outcomes in children following cardiac surgery. Design Prospective single center observational study Setting Pediatric cardiac intensive care unit Patients Children less than or equal to age 4 years who underwent cardiac surgery with the use of cardiopulmonary bypass during the study period (June 2011 to July 2012). Interventions None Measurements and Main Results A reduction in NIRS was not associated with AKI. 9/12 (75%) of patients with a reduction in renal NIRS did not develop AKI. The remaining 3 patients had mild AKI (pRIFLE-R). A reduction in renal NIRS was associated with the following adverse clinical outcomes: 1) a longer duration of mechanical ventilation (p = 0.05), 2) longer intensive care length of stay (p = 0.05), and 3) longer hospital length of stay (p < 0.01). A decline in renal NIRS in combination with an increase in serum IL-6 and serum IL-8 was associated with a longer intensive care length of stay, and the addition of urine IL-18 to this was associated with a longer hospital length of stay. Conclusions In this cohort, the rate of AKI was much lower than anticipated thereby limiting the evaluation of a reduction in renal NIRS as a predictor of AKI. A ≥ 20% reduction in renal NIRS was significantly associated with adverse outcomes in children following cardiac surgery. The addition of specific biomarkers to the model was predictive of worse outcomes in these patients. Thus, real time evaluation of renal NIRS using the specific levels of change of a 20% reduction for 20 minutes may be useful in predicting prolonged mechanical ventilation and other adverse outcomes in children undergoing cardiac surgery.

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“…Data also support that after the initial 24 hours of critical illness, the maintenance of a net even fluid balance is important. 26 On the other hand, tubular epithelial cells may directly contribute to the production of inflammatory mediators that may propagate the injury locally or in distant organs. 7,23 Pulmonary congestion and oedema may also occur without fluid overload in patients with AKI.…”

Section: Husain-syed Et Almentioning

confidence: 99%

“…7,23 Pulmonary congestion and oedema may also occur without fluid overload in patients with AKI. 26,30 In addition, animal models have demonstrated that during AKI, the integrity of the alveolar-capillary barrier is impaired by various factors, which causes fluid accumulation in the lung. Recent findings indicate a direct interaction between the lung and kidney.…”

Section: Husain-syed Et Almentioning

confidence: 99%

Distant organ dysfunction in acute kidney injury

2019

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Acute kidney injury (AKI) is a common complication in critically ill patients and it is associated with increased morbidity and mortality. Epidemiological and clinical data show that AKI is linked to a wide range of distant organ injuries, with the lungs, heart, liver, and intestines representing the most clinically relevant affected organs. This distant organ injury during AKI predisposes patients to progression to multiple organ dysfunction syndrome and ultimately, death. The strongest direct evidence of distant organ injury occurring in AKI has been obtained from animal models. The identified mechanisms include systemic inflammatory changes, oxidative stress, increases in leucocyte trafficking and the activation of proapoptotic pathways.Understanding the pathways driving AKI-induced distal organ injury are critical for the development and refinement of therapies for the prevention and attenuation of AKI-related morbidity and mortality. The purpose of this review is to summarize both clinical and preclinical studies of AKI and its role in distant organ injury.

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Mechanisms and mediators of lung injury after acute kidney injury

Cited by 155 publications

References 137 publications

Early peritoneal dialysis reduces lung inflammation in mice with ischemic acute kidney injury

Early peritoneal dialysis reduces lung inflammation in mice with ischemic acute kidney injury

A Decline in Intraoperative Renal Near-Infrared Spectroscopy Is Associated With Adverse Outcomes in Children Following Cardiac Surgery

Distant organ dysfunction in acute kidney injury

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