Abstract Body: Introduction: By 30d post renal ischemia-reperfusion injury (IRI) in female Sprague Dawley rats, many indicators of normal physiology return to baseline while other markers of subclinical renal injury persist, e.g., rats exhibit compromised natriuresis in response to a saline bolus suggesting persistent changes in renal salt handling.

Hypothesis: IRI provokes changes in kidney Na⁺ transporters along the nephron that persists post-IRI.

Methods: 45 min warm bilateral renal IRI or sham surgery was followed by kidney collection after 1d or 30d IRI. Abundance of ~ 40 kidney transporters, channels, claudins, and metabolic markers were assessed in kidney cortex “c” and medulla “m” homogenates by semi-quantitative immunoblot; results are expressed relative to baseline shams = 100%.

Results:
Cortical NHE3, SGLT2, villin, megalin, and AQP1 abundance decrease ≥50% at 1d, and return to sham at 30d; SGLT1 increases 200% at 1d and returns to sham by 30d.

mNKCC2 decreases 90% at 1d and returns to 85% at 30d; mNa,K-ATPase subunit abundance and ATPase activity decrease 65% and 50% respectively at 1d, and recover to 80% at 30d.

cNKCC2 and cNCC decrease > 50% at 1d and recover to 75% and 90% of sham at 30d. ENaC α and γ subunits increase 130 and 150%, while cleaved α and γ decrease 30%, and claudin8 decreases 50% at 1d; all return to baseline at 30d. Both cNa,K-ATPase subunits and ATPase activity fell 20-30% at 1d and restored to sham at 30d.

AKI markers: c&mHIF1α increases ≥ 200% at 1d and remain ≥140% at 30 d. HO-1 decreases 50% at 1d and returns to sham by 30d. Electron transport chain proteins (by OXPHOS) decrease 20-30% in cortex, but not medulla at 1d, and returned to sham at 30d. Cortical cytokines fall 67% (IL-6) and 50% (IL1β) at 1d and return to sham at 30d. cKIM1, and cAlbumin increase >15-fold at day1and return toward baseline at 30d.

Conclusions: Transporters and markers along entire nephron are impacted differentially by IRI in female rats. Most decrease at 1d and recover; SGLT1 doubles reflecting glycolytic alteration; ENaC increases then recovers; HIF1α increases and remains elevated 30d post-IRI. These IRI provoked changes potentially impact the aberrant fluid homeostasis observed post-IRI, including during pregnancy, and warrant investigation.