Distant effects of experimental renal ischemia/reperfusion injury

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Abstract

Acute renal failure results in significant morbidity and mortality, yet renal failure is not the usual cause of death in the clinical situation. We have previously reported systemic increases in the inflammatory mediators tumor necrosis factor-α (TNF-α) and interleukin-1 (IL-1) after renal ischemia in the mouse. In the present study, an animal model of bilateral renal ischemia was used to test the hypothesis that cytokines released with renal ischemia have effects on other organ systems. Increased levels of immunoreactive TNF-α and IL-1 and intercellular adhesion molecule-1 mRNA were found in the heart after renal ischemia in the rat. This was accompanied by increases in myeloperoxidase activity, an index of tissue leukocyte infiltration, in the heart as well as the liver and lung. Functional changes in the heart 48 h after renal ischemia included increases in left ventricular end diastolic diameter, left ventricular end systolic diameter, and decreased fractional shortening by echocardiography. Evidence of apoptosis of cardiac cells was also found 48 h after an abbreviated period of renal ischemia insufficient to induce azotemia but not bilateral nephrectomy (which resulted in significant renal failure), suggesting that renal ischemia but not uremia is necessary for the apoptosis observed. It was also found that blocking the action of TNF-α limited cardiac apoptosis. Renal ischemia results in distant effects and the alterations observed in the heart may be important in the morbidity and mortality observed clinically.

Original languageEnglish
Pages (from-to)1549-1558
Number of pages10
JournalJournal of the American Society of Nephrology
Volume14
Issue number6
DOIs
StatePublished - Jun 1 2003

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Reperfusion Injury
Ischemia
Kidney
Tumor Necrosis Factor-alpha
Apoptosis
Interleukin-1
Renal Insufficiency
Morbidity
Azotemia
Mortality
Uremia
Intercellular Adhesion Molecule-1
Nephrectomy
Acute Kidney Injury
Peroxidase
Echocardiography
Cause of Death
Leukocytes
Animal Models
Cytokines

ASJC Scopus subject areas

  • Nephrology

Cite this

Distant effects of experimental renal ischemia/reperfusion injury. / Kelly, Katherine.

In: Journal of the American Society of Nephrology, Vol. 14, No. 6, 01.06.2003, p. 1549-1558.

Research output: Contribution to journalArticle

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