Acute renal failure leads to dysregulation of lung salt and water channels

Hamid Rabb, Zhaohui Wang, Takashi Nemoto, John Hotchkiss, Naoko Yokota, Manoocher Soleimani

Research output: Contribution to journalArticlepeer-review

183 Scopus citations


Background. Renal ischemia/reperfusion (I/R) injury and the acute respiratory distress syndrome (ARDS) frequently coexist in the intensive care setting, and this combination is associated with a high mortality. Recent experimental data demonstrate that renal I/R injury leads to an increase in pulmonary vascular permeability, similar to that observed in ARDS. However, the effects of renal I/R injury on alveolar fluid clearance - of potential importance in the setting of increased permeability - are unknown. We investigated the effects of renal I/R injury on pulmonary epithelial sodium channel (ENaC), Na,K-ATPase and aquaporin expression as a first step in addressing this question. Methods. Sprague Dawley rats were subjected to four protocols: (1) surgery for bilateral I/R injury, (2) sham surgery, (3) surgery for unilateral I/R injury, or (4) bilateral nephrectomy. Lung tissue was examined for Na channel, Na,K-ATPase, aquaporin-1, and aquaporin-5 expression. Northern and Western blots were performed. Results. Renal I/R injury and bilateral nephrectomy both led to marked down-regulation of pulmonary ENaC, Na,K-ATPase and aquaporin-5 but not aquaporin-1 compared to sham surgery. These changes were not influenced by the animals' volume status. In contrast, unilateral I/R with an intact contralateral kidney did not lead to down-regulation of channel down-regulation. Conclusions. Ischemic acute renal failure leads to down regulation of pulmonary ENaC, Na,K-ATPase and aquaporin-5, but not aquaporin-1. Since bilateral nephrectomy but not single kidney I/R injury also leads to lung changes, these changes are likely mediated by systemic effects of acute renal failure (ARF), such as "uremic toxins", rather than reperfusion products. These changes may modulate lung dysfunction, susceptibility to lung injury, or both.

Original languageEnglish (US)
Pages (from-to)600-606
Number of pages7
JournalKidney international
Issue number2
StatePublished - 2003


  • Acute renal failure
  • Aquaporin-5
  • Ischemia
  • Sodium channel
  • Sodium potassium ATPase

ASJC Scopus subject areas

  • Nephrology


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