Differential effects of kidney–lung cross-talk during acute kidney injury and bacterial pneumonia

Singbartl, Kai; Bishop, Jeffery V.; Wen, Xiang; Murugan, Raghavan; Chandra, Satya V.; Filippi, Marie Dominique; Kellum, John A.

doi:10.1038/ki.2011.201

Cited by 70 publications

(76 citation statements)

References 50 publications

(69 reference statements)

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“…8 Because infection leading to sepsis is the most common cause of AKI, a vicious cycle can occur in which sepsis-induced immune dysfunction is exacerbated and prolonged by sepsis-induced AKI.…”

Section: S Ome Forms Of Acute Vital Organ Injury Leadingmentioning

confidence: 99%

Kidney Attack

Kellum¹,

Bellomo²,

Ronco³

2012

JAMA

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Section: S Ome Forms Of Acute Vital Organ Injury Leadingmentioning

confidence: 99%

Kidney Attack

Kellum¹,

Bellomo²,

Ronco³

2012

JAMA

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“…Experimental administration of LPS, both systemically and intratracheally, has been used to induce pulmonary inflammation in animal models of ALI [8][9][10][11]. The acute lung inflammation may have deleterious effects on remote organs such as kidney and may involve crosstalk between the lung and kidney [12]. Survival decreases drastically when acute kidney injury (AKI) and ALI occur together [13,14].…”

Section: Introductionmentioning

confidence: 99%

PARP inhibitor, olaparib ameliorates acute lung and kidney injury upon intratracheal administration of LPS in mice

et al. 2014

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We have previously shown that PARP-1 inhibition provides protection against lung inflammation in the context of asthma and acute lung injury. Olaparib is a potent new generation PARP inhibitor that has been approved for human testing. The present work was designed to evaluate its beneficial potential against LPS-induced acute lung injury and acute kidney injury upon intratracheal administration of the endotoxin in mice. Administration of olaparib at different doses, 30 min after LPS treatment showed that single intraperitoneal injection of the drug at 5 mg/kg b.wt. reduced the total number of inflammatory cells particularly neutrophils in the lungs. This was associated with reduced pulmonary edema as the total protein content in the bronchoalveolar fluid was found to be decreased substantially. Olaparib provided strong protection against LPS-mediated secondary kidney injury as reflected by restoration of serum levels of urea, creatinine, and uric acid toward normal. The drug restored the LPS-mediated redox imbalance toward normal in lung and kidney tissues as assessed by measuring malondialdehyde and GSH levels. Finally, RT-PCR data revealed that olaparib downregulates the LPS-induced expression of NF-κB-dependent genes namely TNF-α, IL-1β, and VCAM-1 in the lungs without altering the expression of total p65NF-κB. Overall, the data suggest that olaparib has a strong potential to protect against LPS-induced lung injury and associated dysfunctioning of kidney in mice. Given the fact that olaparib is approved by FDA for human testing, our findings can pave the way for testing of the drug on humans inflicted with acute lung injury.

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“…Animal and human data seem to be conflicting, indicating that AKI both is an intensely inflammatory event [10][11][12] and may also have immunosuppressive effects. 13 Ischemia-reperfusion injury (IRI) of native kidneys may also perturb systemic immune responses. AKI is associated with acute respiratory distress syndrome and synergistically increases patient mortality because of sepsis and multiorgan dysfunction syndrome.…”

mentioning

confidence: 99%

Renal Ischemia-Reperfusion Injury Amplifies the Humoral Immune Response

Fuquay

Renner²,

Kulik

et al. 2013

Journal of the American Society of Nephrology

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Renal transplant recipients who experience delayed graft function have increased risks of rejection and long-term graft failure. Ischemic damage is the most common cause of delayed graft function, and although it is known that tissue inflammation accompanies renal ischemia, it is unknown whether renal ischemia affects the production of antibodies by B lymphocytes, which may lead to chronic humoral rejection and allograft failure. Here, mice immunized with a foreign antigen 24-96 hours after renal ischemia-reperfusion injury developed increased levels of antigen-specific IgG 1 compared with sham-treated controls. This amplified IgG 1 response did not follow unilateral ischemia, and it did not occur in response to a T-independent antigen. To test whether innate immune activation in the kidney after ischemia affects the systemic immune response to antigen, we repeated the immunization experiment using mice deficient in factor B that lack a functional alternative pathway of complement. Renal ischemia-reperfusion injury did not cause amplification of the antigen-specific antibodies in these mice, suggesting that the increased immune response requires a functional alternative pathway of complement. Taken together, these data suggest that ischemic renal injury leads to a rise in antibody production, which may be harmful to renal allografts, possibly explaining a mechanism underlying the link between delayed graft function and longterm allograft failure.

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Differential effects of kidney–lung cross-talk during acute kidney injury and bacterial pneumonia

Cited by 70 publications

References 50 publications

Kidney Attack

Kidney Attack

PARP inhibitor, olaparib ameliorates acute lung and kidney injury upon intratracheal administration of LPS in mice

Renal Ischemia-Reperfusion Injury Amplifies the Humoral Immune Response

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