Effect of glycine and hypertrophy on renal outer medullary hypoxic injury in ischemia reflow and contrast nephropathy.
Glycine preserves tubular cell integrity under hypoxic and toxic conditions in vitro. It also ameliorates cisplatin nephrotoxicity in vivo. We studied the effect of glycine on tubular necrosis from ischemia reflow and on inner stripe injury in an animal model of radiocontrast nephropathy. In all experiments, glycine (75 mg/100 g/h) increased tubular damage in the inner stripe. In the model of radiocontrast nephropathy, the percentage of medullary thick ascending limb (mTAL) necrosis at 24 hours increased from 22% +/- 6% to 41% +/- 9% or 55% +/- 7% with glycine infusion of 75 or 135 minutes, respectively (mean +/- SE, P less than 0.05, analysis of variance [ANOVA]). Renal function was not significantly affected. In rat kidneys subjected to ischemia reflow, mTAL injury following glycine increased from 1% +/- 0% to 12% +/- 6% (P less than 0.05) and from 8% +/- 5% to 49% +/- 8% (P less than 0.01) 24 hours after 30 minutes and 45 minutes ischemia, respectively. Tubular injury in the inner stripe was maximal in the deep interbundle zone, typical of hypoxic, rather than reperfusion, injury. Prior uninephrectomy increased inner stripe damage, but protected the proximal tubules. Both uninephrectomy and glycine infusion were found to contribute to mTAL necrosis. The infusion of glycine for 1 hour in intact rats increased renal blood flow by 44% and tripled urine volume (P less than 0.01). A parallel increase in glomerular filtration rate GFR; by 22% over 90 minutes) fell short of statistical significance.(ABSTRACT TRUNCATED AT 250 WORDS)
Heyman
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Charles A. Dana Research Institute, Department of Medicine, Harvard Medical School, Boston, MA.
Brezis
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Epstein
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Spokes
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Rosen
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D000818:Animals; D015687:Cell Hypoxia / Q000187:drug effects; D005998:Glycine / Q000494:pharmacology*; D006984:Hypertrophy; D007483:Iothalamic Acid / Q000009:adverse effects*; D007679:Kidney Medulla / Q000187:drug effects / Q000473:pathology*; D007683:Kidney Tubular Necrosis, Acute / Q000209:etiology* / Q000473:pathology / Q000517:prevention & control; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D015427:Reperfusion Injury / Q000473:pathology* / Q000517:prevention & control
D007483:Iothalamic Acid; D005998:Glycine