Pharmacological intervention for renal ischemia-reperfusion injury with dose-matched glucocorticoids

Ischemia-reperfusion injury (IRI) lacks a clear pharmacological target, despite being a leading cause of acute kidney injury. We evaluated the protective effects of dose-equivalent glucocorticoids as a potential therapy for renal IRI.

A 60-minute bilateral renal IRI model was established in male Sprague Dawley rats. Animals were randomly assigned to sham, IRI, IRI plus hydrocortisone (IRI-HCT), or IRI plus dexamethasone (IRI-Dexa) groups. An equivalent dose of hydrocortisone (26.7 mg/kg) or dexamethasone (1 mg/kg) was administered intravenously immediately after reperfusion. Rats were sacrificed 24 hours postreperfusion for blood collection and kidney harvesting. In vitro analyses evaluating the protective effects of glucocorticoids included periodic acid-Schiff staining, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, tumor necrosis factor alpha (TNF-α) immunofluorescence, and quantitative polymerase chain reaction.

Renal IRI led to significant renal dysfunction and histological damage, demonstrated by elevated serum creatinine levels, reduced estimated glomerular filtration rate, and marked tubular injury. Dexamethasone treatment lowered creatinine levels and reduced injury scores compared with the IRI and IRI-HCT groups. TUNEL staining confirmed reduced apoptosis with dexamethasone; hydrocortisone had no significant effect. TNF-α expression was attenuated in both steroid-treated groups, with near-baseline levels in the IRI-Dexa group. Heme oxygenase-1 expression remained suppressed across IRI groups, regardless of steroid treatment; however, ATPase H⁺ transporting V0 subunit D2 expression was significantly restored by both steroids.

Dexamethasone appears more effective than hydrocortisone in reducing acute renal IRI, underscoring the need for context-specific steroid selection in clinical settings.