Warm renal
ischemia performed during partial
nephrectomy has been found to be associated with
kidney disease. Since endogenous
ouabain (EO) is a neuro-endocrine
hormone involved in renal damage, we evaluated the role of EO in renal
ischemia-reperfusion injury (IRI). We measured plasma and renal EO variations and markers of glomerular and tubular damage (nephrin, KIM-1, Kidney-Injury-Molecule-1, α1 Na-K ATPase) and the protective effect of the
ouabain inhibitor,
rostafuroxin. We studied five groups of rats: (1) normal; (2) infused for eight weeks with
ouabain (30 µg/kg/day, OHR) or (3) saline; (4)
ouabain; or (5) saline-infused rats orally treated with 100 µg/kg/day
rostafuroxin for four weeks. In group 1, 2-3 h after IRI, EO increased in ischemic kidneys while decreased in plasma.
Nephrin progressively decreased and KIM-1
mRNA increased starting from 24 h.
Ouabain infusion (group 2) increased blood pressure (from 111.7 to 153.4 mmHg) and
ouabain levels in plasma and kidneys. In OHR ischemic kidneys at 120 h from IRI,
nephrin, and KIM-1 changes were greater than those detected in the controls infused with saline (group 3). All these changes were blunted by
rostafuroxin treatment (groups 4 and 5). These findings support the role of EO in IRI and suggest that
rostafuroxin pre-treatment of patients before partial
nephrectomy with
warm ischemia may reduce IRI, particularly in those with high EO.