A pilot study linking endothelial injury in lungs and kidneys in chronic obstructive pulmonary disease

Francesca Polverino, Maria E. Laucho-Contreras, Hans Petersen, Vanesa Bijol, Lynette M. Sholl, Mary E. Choi, Miguel Divo, Victor Pinto-Plata, Alfredo Chetta, Yohannes Tesfaigzi, Bartolomé R. Celli, Caroline A. Owen

Research output: Contribution to journalArticlepeer-review

51 Scopus citations

Abstract

Rationale: Patients with chronic obstructive pulmonary disease (COPD) frequently have albuminuria (indicative of renal endothelial cell injury) associated with hypoxemia. Objectives: To determine whether (1) cigarette smoke (CS)- induced pulmonary and renal endothelial cell injury explains the association between albuminuria and COPD, (2) CS-induced albuminuria is linked to increases in the oxidative stress-advanced glycation end products (AGEs) receptor for AGEs (RAGE) pathway, and (3) enalapril (which has antioxidant properties) limits the progression of pulmonary and renal injury by reducing activation of the AGEs-RAGE pathway in endothelial cells in both organs. Methods: In 26 patients with COPD, 24 ever-smokers without COPD, 32 nonsmokers who underwent a renal biopsy or nephrectomy, and in CS-exposed mice, we assessed pathologic and ultrastructural renal lesions, andmeasured urinary albumin/creatinine ratios, tissue oxidative stress levels, and AGEs and RAGE levels in pulmonary and renal endothelial cells. The efficacy of enalapril on pulmonary and renal lesions was assessed in CS-exposed mice. Measurements and Main Results: Patients with COPD and/or CS-exposed mice had chronic renal injury, increased urinary albumin/creatinine ratios, and increased tissue oxidative stress and AGEs-RAGE levels in pulmonary and renal endothelial cells. Treating mice with enalapril attenuated CS-induced increases in urinary albumin/creatinine ratios, tissue oxidative stress levels, endothelial cell AGEs and RAGE levels, pulmonary and renal cell apoptosis, and the progression of chronic renal and pulmonary lesions. Conclusions: Patients with COPD and/or CS-exposed mice have pulmonary and renal endothelial cell injury linked to increased endothelial cell AGEs and RAGE levels. Albuminuria could identify patients with COPD in whom angiotensin-converting enzyme inhibitor therapy improves renal andlung functionby reducing endothelial injury.

Original languageEnglish (US)
Pages (from-to)1464-1476
Number of pages13
JournalAmerican journal of respiratory and critical care medicine
Volume195
Issue number11
DOIs
StatePublished - Jun 1 2017
Externally publishedYes

Keywords

  • Cigarette smoke
  • Comorbidities
  • COPD
  • Endothelium
  • Kidney

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine

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