title: Experimental chronic kidney disease attenuates ischemia-reperfusion injury in an ex vivo rat lung model.
abstract: Lung ischemia reperfusion injury (LIRI) is one of important complications following lung transplant and cardiopulmonary bypass. Although patients on hemodialysis are still excluded as lung transplant donors because of the possible effects of renal failure on the lungs, increased organ demand has led us to evaluate the influence of chronic kidney disease (CKD) on LIRI. A CKD model was induced by feeding Sprague-Dawley rats an adenine-rich (0.75%) diet for 2, 4 and 6 weeks, and an isolated rat lung in situ model was used to evaluate ischemia reperfusion (IR)-induced acute lung injury. The clinicopathological parameters of LIRI, including pulmonary edema, lipid peroxidation, histopathological changes, immunohistochemistry changes, chemokine CXCL1, inducible nitric oxide synthase (iNOS), proinflammatory and anti-inflammatory cytokines, heat shock protein expression, and nuclear factor-κB (NF-κB) activation were determined. Our results indicated that adenine-fed rats developed CKD as characterized by increased blood urea nitrogen and creatinine levels and the deposition of crystals in the renal tubules and interstitium. IR induced a significant increase in the pulmonary arterial pressure, lung edema, lung injury scores, the expression of CXCL1 mRNA, iNOS level, and protein concentration of the bronchial alveolar lavage fluid (BALF). The tumor necrosis factor-α levels in the BALF and perfusate; the interleukin-10 level in the perfusate; and the malondialdehyde levels in the lung tissue and perfusate were also significantly increased by LIRI. Counterintuitively, adenine-induced CKD significantly attenuated the severity of lung injury induced by IR. CKD rats exhibited increased heat shock protein 70 expression and decreased activation of NF-κB signaling. In conclusion, adenine-induced CKD attenuated LIRI by inhibiting the NF-κB pathway.
authors.affiliation: Division of Pulmonary and Critical Care, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, Republic of China.
authors.forename: Chung-Kan
authors.identifier: http://orcid.org/0000-0003-3666-9833
authors.initials: CK
authors.lastname: Peng
authors.affiliation: Institute of Undersea and Hyperbaric Medicine, National Defense Medical Center, Taipei, Taiwan, Republic of China.
authors.forename: Kun-Lun
authors.initials: KL
authors.lastname: Huang
authors.affiliation: Division of Pulmonary Medicine, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Taipei, Taiwan, Republic of China.|School of Medicine, Tzu Chi University, Hualien, Taiwan, Republic of China.
authors.forename: Chou-Chin
authors.initials: CC
authors.lastname: Lan
authors.affiliation: Division of Nephrology, Department of Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, Republic of China.
authors.forename: Yu-Juei
authors.initials: YJ
authors.lastname: Hsu
authors.affiliation: Division of Pulmonary Medicine, Department of Internal Medicine, Taoyuan Armed Forces General Hospital, Lungtan, Taoyuan, Taiwan, Republic of China.
authors.forename: Geng-Chin
authors.initials: GC
authors.lastname: Wu
authors.affiliation: Division of Clinical Nutrition, Taoyuan Armed Forces General Hospital, Lungtan, Taoyuan, Taiwan, Republic of China.
authors.forename: Chia-Hui
authors.initials: CH
authors.lastname: Peng
authors.affiliation: Department of Critical Care Medicine, Li-Shin Hospital, Taoyuan, Taiwan, Republic of China.
authors.forename: Chin-Pyng
authors.initials: CP
authors.lastname: Wu
authors.affiliation: Department of Critical Care Medicine, Chi-Mei Medical Center, Tainan, Taiwan Republic of China.
authors.forename: Khee-Siang
authors.initials: KS
authors.lastname: Chan
mesh_terms: D000818:Animals; D054360:Chemokine CXCL1 / Q000378:metabolism; D016207:Cytokines / Q000096:biosynthesis; D066298:In Vitro Techniques; D018836:Inflammation Mediators / Q000378:metabolism; D007676:Kidney Failure, Chronic / Q000378:metabolism / Q000503:physiopathology*; D015227:Lipid Peroxidation; D008171:Lung Diseases / Q000473:pathology*; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000517:prevention & control*; D015398:Signal Transduction
chemical_list: D054360:Chemokine CXCL1; C513297:Cxcl1 protein, rat; D016207:Cytokines; D018836:Inflammation Mediators; D016328:NF-kappa B; D052247:Nitric Oxide Synthase Type II