Mechanisms Underlying Combined Acute Renal Failure and Acute Lung Injury in the Intensive Care Unit

Chien, Chu Chun; King, Landon S.; Rabb, H.

doi:10.1159/000078877

Cited by 19 publications

(8 citation statements)

References 62 publications

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“…In multiple organ dysfunction syndrome, ARF is an additional independent risk factor for mortality (28). It has been repeatedly demonstrated that there is a strong correlation between ARF and ARDS (6).…”

Section: Discussionmentioning

confidence: 99%

Leptospirosis leads to dysregulation of sodium transporters in the kidney and lung

Andrade¹,

Rodrigues²,

Sanches³

et al. 2007

American Journal of Physiology-Renal Physiology

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Leptospirosis is a public health problem worldwide. Severe leptospirosis manifests as pulmonary edema leading to acute respiratory distress syndrome and polyuric acute renal failure (ARF). The etiology of leptospirosis-induced pulmonary edema is unclear. Lung edema clearance is largely affected by active sodium transport out of the alveoli rather than by reversal of the Starling forces. The objective of this study was to profile leptospirosis-induced ARF and pulmonary edema. We inoculated hamsters with leptospires and collected 24-h urine samples on postinoculation day 4. On day 5, the animals were killed, whole blood was collected, and the kidneys and lungs were removed. Immunoblotting was used to determine expression and abundance of water and sodium transporters. Leptospirosis-induced ARF resulted in natriuresis, lower creatinine clearance, and impaired urinary concentrating ability. Renal expression of the sodium/hydrogen exchanger isoform 3 and of aquaporin 2 was lower in infected animals, whereas that of the Na-K-2Cl cotransporter NKCC2 was higher. Leptospirosis-induced lesions, predominantly in the proximal tubule, were responsible for the polyuria and natriuresis observed. The polyuria might also be attributed to reduced aquaporin 2 expression and the attendant urinary concentrating defect. In the lungs, expression of the epithelial sodium channel was lower, and NKCC1 expression was upregulated. We found that leptospirosis profoundly influences the sodium transport capacity of alveolar epithelial cells and that impaired pulmonary fluid handling can impair pulmonary function, increasing the chance of lung injury. Greater knowledge regarding sodium transporter dysregulation in the lungs and kidneys can provide new perspectives on leptospirosis treatment.

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Section: Discussionmentioning

confidence: 99%

Leptospirosis leads to dysregulation of sodium transporters in the kidney and lung

Andrade¹,

Rodrigues²,

Sanches³

et al. 2007

American Journal of Physiology-Renal Physiology

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“…27 When ARF and acute lung injury are combined, the mortality rate exceeds 80%. 28 Experimentally, ARF has been reported to induce caspase-dependent pulmonary apoptosis. 29 Patients with various renal diseases are particularly vulnerable to the adverse effects of PAP.…”

Section: Introductionmentioning

confidence: 99%

The effect of thymoquinone treatment on the combined renal and pulmonary toxicity of cisplatin and diesel exhaust particles

Ali

Za’abi

Shalaby

et al. 2015

Exp Biol Med (Maywood)

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Particulate air pollution (PAP) exposure is associated with increased morbidity and mortality, particularly in patients with renal disease. However, there are only a few studies on the interaction between PAP and renal injury, and none on agents that may ameliorate it. We studied the interaction between cisplatin (CP) nephrotoxicity and a single exposure to diesel exhaust particle (DEP) in rats 24 h before sacrifice, and assessed the effect of co-treatment with the active ingredient in Nigella Sativa seed oil, thymoquinone (TQ) thereon. Rats were injected intraperitoneally with CP (6 mg/kg) and four days later, they were exposed intratracheally to DEP (0.5 mg/kg), and were sacrificed 24 h later. Oral TQ (20 mg/kg) was given daily throughout the experimental period. CP alone caused several physiological, biochemical, and histopathological changes that included reduced growth and creatinine clearance, and raised plasma neutrophil gelatinase-associated lipocalin (NGAL), interleukin 6 (IL-6) and C-reactive protein (CRP), creatinine and urea concentrations, and urinary N-acetyl-b-D-glucosaminidase (NAG) activities. It adversely affected several indices of oxidative damage in the kidneys, and induced renal tubular necrosis. Most of these actions were significantly potentiated in rats given both CP and DEP. TQ significantly abrogated many of the effects of CP and DEP, given alone and in combination. These results provide experimental evidence that subjects with renal diseases can be at higher risk from PAP, and that TQ, pending further pharmacological and toxicological studies, can be considered a useful agent in patients with renal diseases and exposed to PAP.

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“…AKI and ARDS frequently coexist in critically ill patients, suggesting a shared pathophysiology (Chien et al. ; Liu et al. ; Vincent ).…”

Section: Introductionmentioning

confidence: 99%

“…Similar to ARDS, sepsis-induced acute kidney injury (AKI) is common and of great clinical significance, yet remains poorly understood (Uchino et al 2005;Zarjou and Agarwal 2011). AKI and ARDS frequently coexist in critically ill patients, suggesting a shared pathophysiology (Chien et al 2004;Liu et al 2007;Vincent 2011). We therefore hypothesized that sepsis is associated with activation of glomerular heparanase, contributing to the early onset of septic AKI.…”

Section: Introductionmentioning

confidence: 99%

Heparanase mediates renal dysfunction during early sepsis in mice

et al. 2013

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Heparanase, a heparan sulfate-specific glucuronidase, mediates the onset of pulmonary neutrophil adhesion and inflammatory lung injury during early sepsis. We hypothesized that glomerular heparanase is similarly activated during sepsis and contributes to septic acute kidney injury (AKI). We induced polymicrobial sepsis in mice using cecal ligation and puncture (CLP) in the presence or absence of competitive heparanase inhibitors (heparin or nonanticoagulant N-desulfated re-N-acetylated heparin [NAH]). Four hours after surgery, we collected serum and urine for measurement of renal function and systemic inflammation, invasively determined systemic hemodynamics, harvested kidneys for histology/protein/mRNA, and/or measured glomerular filtration by inulin clearance. CLP-treated mice demonstrated early activation of glomerular heparanase with coincident loss of glomerular filtration, as indicated by a >twofold increase in blood urea nitrogen (BUN) and a >50% decrease in inulin clearance (P < 0.05) in comparison to sham mice. Administration of heparanase inhibitors 2 h prior to CLP attenuated sepsis-induced loss of glomerular filtration rate, demonstrating that heparanase activation contributes to early septic renal dysfunction. Glomerular heparanase activation was not associated with renal neutrophil influx or altered vascular permeability, in marked contrast to previously described effects of pulmonary heparanase on neutrophilic lung injury during sepsis. CLP induction of renal inflammatory gene (IL-6, TNF-α, IL-1β) expression was attenuated by NAH pretreatment. While serum inflammatory indices (KC, IL-6, TNF-α, IL-1β) were not impacted by NAH pretreatment, heparanase inhibition attenuated the CLP-induced increase in serum IL-10. These findings demonstrate that glomerular heparanase is active during sepsis and contributes to septic renal dysfunction via mechanisms disparate from heparanase-mediated lung injury.

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Mechanisms Underlying Combined Acute Renal Failure and Acute Lung Injury in the Intensive Care Unit

Cited by 19 publications

References 62 publications

Leptospirosis leads to dysregulation of sodium transporters in the kidney and lung

Leptospirosis leads to dysregulation of sodium transporters in the kidney and lung

The effect of thymoquinone treatment on the combined renal and pulmonary toxicity of cisplatin and diesel exhaust particles

Heparanase mediates renal dysfunction during early sepsis in mice

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