Kidney-Lung Crosstalk in the Critically Ill Patient

Ko, Gang Jee; Rabb, Hamid; Hassoun, Heitham T.

doi:10.1159/000218087

Cited by 94 publications

(77 citation statements)

References 125 publications

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“…AKI alters the host innate and adaptive immune response, and experimental data have identified both soluble and cellular mediators of organ crosstalk activated by the postischemic kidney (4,20). Organ crosstalk involves a complex interplay between numerous biochemical, cellular, and tissuespecific factors that incite remote pulmonary proinflammatory and proapoptotic signaling (6,8,14).…”

Section: Discussionmentioning

confidence: 99%

“…Clinical observations suggest an association between AKI and dysfunction of extrarenal organs, such as the heart, lung, and brain, and new experimental data have emerged that focus on the interactive effects of concomitant kidney and distant organ dysfunction (4,5). These studies have highlighted (1) the pathophysiological importance of proinflammatory and proapoptotic pathways as contributors to the complex nature of this interorgan crosstalk, and (2) the involvement of both soluble and cellular-based mediators in this altered immune response during AKI.…”

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confidence: 99%

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Lung T Lymphocyte Trafficking and Activation during Ischemic Acute Kidney Injury

Lie

White

Santora

et al. 2012

The Journal of Immunology

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Despite advances in renal replacement therapy, the mortality rate for acute kidney injury (AKI) remains unacceptably high, likely owing to extrarenal organ dysfunction. Kidney ischemia–reperfusion injury (IRI) activates cellular and soluble mediators that facilitate organ crosstalk and induce caspase-dependent lung apoptosis and injury through a TNFR1-dependent pathway. Given that T lymphocytes mediate local IRI in the kidney and are known to drive TNFR1-mediated apoptosis, we hypothesized that T lymphocytes activated during kidney IRI would traffic to the lung and mediate pulmonary apoptosis during AKI. In an established murine model of kidney IRI, we identified trafficking of CD3+ T lymphocytes to the lung during kidney IRI by flow cytometry and immunohistochemistry. T lymphocytes were primarily of the CD3+CD8+ phenotype; however, both CD3+CD4+ and CD3+CD8+ T lymphocytes expressed CD69 and CD25 activation markers during ischemic AKI. The activated lung T lymphocytes did not demonstrate an increased expression of intracellular TNF-α or surface TNFR1. Kidney IRI induced pulmonary apoptosis measured by caspase-3 activation in wild-type controls, but not in T cell-deficient (Tnu/nu) mice. Adoptive transfer of murine wild-type T lymphocytes into Tnu/nu mice restored the injury phenotype with increased cellular apoptosis and lung microvascular barrier dysfunction, suggesting that ischemic AKI-induced pulmonary apoptosis is T cell dependent. Kidney–lung crosstalk during AKI represents a complex biological process, and although T lymphocytes appear to serve a prominent role in the interorgan effects of AKI, further experiments are necessary to elucidate the specific role of activated T cells in modulating pulmonary apoptosis.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Lung T Lymphocyte Trafficking and Activation during Ischemic Acute Kidney Injury

Lie

White

Santora

et al. 2012

The Journal of Immunology

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“…Mechanisms of AKI-induced ALI include dysregulation of inflammatory reaction, innate immune response, oxidative stress, apoptosis, and soluble mediator metabolism. 7 Rodent models of bilateral nephrectomy (BNx) and renal ischemia reperfusion have been used to investigate the role of AKI in the pathogenesis of ALI. 8 -11 Ischemic AKI engenders increased pulmonary vascular permeability by down-regulating pulmonary epithelial sodium channel, Na,K-ATPase, and aquaporin-5.…”

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confidence: 99%

Neutrophil Elastase Contributes to Acute Lung Injury Induced by Bilateral Nephrectomy

Ishii

Doi

Okamoto

et al. 2010

The American Journal of Pathology

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Acute kidney injury (AKI) is a serious problem in critically ill patients of intensive care units. It has been reported previously that AKI can induce acute lung injury (ALI), as well as cause injuries to other remote organs , including the lungs. Patients with AKI complicated by ALI show remarkably high mortality. ALI is characterized by neutrophil infiltration into the lung. Neutrophil elastase (NE) is a key enzyme for tissue injury caused by activated neutrophils , such as occurs in ALI. Therefore , this study investigated the role of NE in AKI-induced ALI using a specific NE inhibitor , sivelestat sodium hydrate (ONO-5046), in a mouse bilateral nephrectomy model. Bilateral nephrectomy showed not only a remarkable increase in blood urea nitrogen levels, but also demonstrated neutrophil infiltration into the lung, increased pulmonary inflammatory cytokine expression [interleukin-6, neutrophil chemokine keratinocyte-derived chemokine, and tumor necrosis factor-␣], and protein leakage with early increases in both systemic and pulmonary NE activity. ONO-5046 treatment reduced NE activity and improved these pulmonary inflammatory responses. Additionally, ONO-5046-treated animals had longer survival times. These data demonstrate that increasing NE activity induces pulmonary inflammatory damage in a bilateral nephrectomy model. Blockade of NE activity will be a useful therapeutic strategy for ALI complications in AKI patients. Acute lung injury (ALI) is a life-threatening condition that is frequently complicated with acute kidney injury (AKI), which is a serious condition in intensive care units. The ALI mortality is higher than 50% and increases with the development of other organ failure including AKI.1 One report described a mortality rate higher than 80% for patients with AKI complicated with ALI.2 Current prevention and treatment strategies for AKI cannot sufficiently improve the mortality of these severely ill patients. Although many basic and clinical researchers are investigating novel therapies for AKI, 3 targeting of other organ damages caused by AKI is also necessary for improving AKI outcomes.Recently, it has been suggested that AKI influences other remote organs including the lungs.4 -6 Experimental evidence indicates that AKI-induced ALI occurs not only by volume overload, but also through deleterious kidneylung interactions. Mechanisms of AKI-induced ALI include dysregulation of inflammatory reaction, innate immune response, oxidative stress, apoptosis, and soluble mediator metabolism.7 Rodent models of bilateral nephrectomy (BNx) and renal ischemia reperfusion have been used to investigate the role of AKI in the pathogenesis of ALI. 8 -11 Ischemic AKI engenders increased pulmonary vascular permeability by down-regulating pulmonary epithelial sodium channel, Na,K-ATPase, and aquaporin-5. 10 Ischemic AKI induced leukocyte accumulation and activation of inflammatory transcription factors such as nuclear factor-B and p38 mitogen-activated protein kinase in the lung, which was attenuated by an anti-infla...

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“…Interest in this area has been growing due to the high morbidity and mortality rates associated with AKI. Despite recent improvements in supportive care, these rates have remained unchanged over the past two decades 12,13 . Both experimental and clinical studies have pointed to an association between AKI and extrarenal organ injury.…”

Section: Discussionmentioning

confidence: 99%

Analysis of the effects of topical renal hypothermia on lung tissue after kidney ischemia and reperfusion in rats

et al. 2015

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PURPOSE:To evaluate whether topical renal hypothermia (TRH) at different levels of temperature has protective effects on lung tissue after renal I/R, through an analysis of organ histology and inflammatory markers in lung tissue. METHODS:Twenty-eight male Wistar rats were randomly allocated across four groups and subjected to renal ischemia at different levels of topical renal temperature: normothermia (no cooling, 37°C), mild hypothermia (26°C), moderate hypothermia (15°C), and deep hypothermia (4°C). To induce I/R, the vessels supplying the left kidney of each animal were clamped for 40 minutes, followed by reperfusion. After four hours, another procedure was performed to harvest the tissues of interest. TNF-α, IL-1β and myeloperoxidase activity were measured in lung tissue. Histological analysis was performed in hematoxylin and eosin-stained lung specimens. RESULTS:Induction of renal I/R under deep topical hypothermia resulted in a significant decrease in lung concentrations of TNF-α compared with normothermic I/R (p<0.05). A trend toward significant correlation was found between lung IL-1β concentration and intensity of hypothermia p=0.055). No difference was found in myeloperoxidase activity or histologic injury between groups. CONCLUSION:Topical renal hypothermia reduces activation of the inflammatory cascade in the lung parenchyma. However, tissueprotective effects were not observed.

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Kidney-Lung Crosstalk in the Critically Ill Patient

Cited by 94 publications

References 125 publications

Lung T Lymphocyte Trafficking and Activation during Ischemic Acute Kidney Injury

Lung T Lymphocyte Trafficking and Activation during Ischemic Acute Kidney Injury

Neutrophil Elastase Contributes to Acute Lung Injury Induced by Bilateral Nephrectomy

Analysis of the effects of topical renal hypothermia on lung tissue after kidney ischemia and reperfusion in rats

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