Mitochondrial calcium accumulation and respiration in ischemic acute renal failure in the rat

• DOI: 10.1038/ki.1984.48
• Publication Date: 2007-06-16T13:10:04Z
• Authors: Douglas R. Wilson; Patricia E. Arnold; Thomas J. Burke; Robert W. Schrier
• Keywords: Male; Rats, Inbred Strains; Acute Kidney Injury; Kidney; Mitochondria; Rats; Microscopy, Electron; 03 medical and health sciences; Oxygen Consumption; 0302 clinical medicine; Nephrology; Ischemia; Creatinine; Animals; Calcium; Magnesium

Changes in mitochondrial (Mito) calcium (Ca++) and Mito respiration have been demonstrated 24 hr after a renal ischemic insult. The Ca++ accumulation has been suggested to contribute to impaired Mito function; alternatively, the Mito Ca++ accumulation could be a late event resulting from cell death. The present aim was, therefore, to determine the sequence of changes in Mito function in ischemic acute renal failure (ARF) induced by 45 min of bilateral renal pedicle clamping in the rat. Animals were studied at the end of clamping, 1, 4, and 24 hr after reflow. By 24 hr, the serum creatinine level had risen progressively to almost ten times control values and fractional excretion of sodium and water were increased. Mito respiration (state 3, adenosine diphosphate-stimulated; acceptor control ratio, state 3/state 4; and uncoupled, FCCP) was severely depressed immediately after 45 min of clamping but improved significantly at 1 and 4 hr after reflow although remaining below sham-operated controls. At 24 hr, when ischemic ARF was established, Mito respiration was again severely depressed. Mito Ca++ was increased slightly but significantly at the end of clamping and increased progressively at 1, 4, and 24 hr after reflow. The Mito Ca++ accumulation was not only demonstrated to occur very early after the ischemic insult, but was relatively selective since it was not associated with Mito Mg++ accumulation. Moreover, the increased Mito Ca++ during reperfusion (1, 4, and 24 hr) demonstrated a significant correlation with the decreased state 3 respiration and the rising serum creatinine level (P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)