Reduced Hypoxia-Dependent Signaling as a Potential Hemodynamic Mechanism of Anemia Following Acute Kidney Injury
Abstract
Anemia frequently develops after acute kidney injury (AKI), yet the mechanisms underlying its onset remain unclear. Our laboratory has shown that AKI produces disproportionate reductions in glomerular filtration rate relative to renal blood flow, potentially reducing renal oxygen demand more than delivery. We hypothesized that these hemodynamic alterations attenuate post-ischemic hypoxic signaling, leading to reduced hypoxia-inducible factor-1α (HIF-1α)-mediated erythropoietin (EPO) expression and anemia. This study examined whether increasing severity of renal ischemia-reperfusion (IR) injury promotes anemia and alters indices consistent with reduced hypoxic signaling during early AKI. Male rats underwent right uninephrectomy with sham IR (n=3) or left renal IR of 17.5 (n=4) or 35 minutes (n=4). Plasma creatinine (PCr) and hematocrit (Hct) were measured at baseline and 2 and 7 days post-IR. Kidney-to-body weight (KW/BW) ratio was assessed at study end. Longitudinal PCr and Hct were analyzed using mixed-effects modeling with time and IR duration as factors. KW/BW ratio was analyzed using Kruskal–Wallis with Dunn’s multiple comparisons. No differences in PCr or Hct were observed between groups at baseline or 7 days post-IR. At day 2, PCr increased in the 35-minute IR group (2.0±0.6 mg/dL) compared with 17.5-minute IR (0.70±0.06 mg/dL) and sham (0.63 mg/dL) groups, although differences were not statistically significant. Only animals in the 35-minute IR group developed Hct values <40%; however, variability within groups limited statistical detection. KW/BW ratio was greater in 35- vs. 17.5-min IR groups (7.1±0.8 vs. 4.2±0.8 g/kg, P<0.05), consistent with more severe AKI-induced injury. Despite variability inherent to small pilot cohorts, this graded IR model demonstrates differential injury severity and will support ongoing studies examining renal HIF-1α and erythropoietin expression to test whether post-AKI anemia is driven by hemodynamic alterations that reduce hypoxia-dependent signaling.
Start Time
15-4-2026 9:00 AM
End Time
15-4-2026 12:00 PM
Room Number
Culp Ballroom 316
Poster Number
51
Presentation Type
Poster
Presentation Subtype
Posters - Competitive
Presentation Category
Health
Student Type
Undergraduate Student
Faculty Mentor
Aaron Polichnowski
Reduced Hypoxia-Dependent Signaling as a Potential Hemodynamic Mechanism of Anemia Following Acute Kidney Injury
Culp Ballroom 316
Anemia frequently develops after acute kidney injury (AKI), yet the mechanisms underlying its onset remain unclear. Our laboratory has shown that AKI produces disproportionate reductions in glomerular filtration rate relative to renal blood flow, potentially reducing renal oxygen demand more than delivery. We hypothesized that these hemodynamic alterations attenuate post-ischemic hypoxic signaling, leading to reduced hypoxia-inducible factor-1α (HIF-1α)-mediated erythropoietin (EPO) expression and anemia. This study examined whether increasing severity of renal ischemia-reperfusion (IR) injury promotes anemia and alters indices consistent with reduced hypoxic signaling during early AKI. Male rats underwent right uninephrectomy with sham IR (n=3) or left renal IR of 17.5 (n=4) or 35 minutes (n=4). Plasma creatinine (PCr) and hematocrit (Hct) were measured at baseline and 2 and 7 days post-IR. Kidney-to-body weight (KW/BW) ratio was assessed at study end. Longitudinal PCr and Hct were analyzed using mixed-effects modeling with time and IR duration as factors. KW/BW ratio was analyzed using Kruskal–Wallis with Dunn’s multiple comparisons. No differences in PCr or Hct were observed between groups at baseline or 7 days post-IR. At day 2, PCr increased in the 35-minute IR group (2.0±0.6 mg/dL) compared with 17.5-minute IR (0.70±0.06 mg/dL) and sham (0.63 mg/dL) groups, although differences were not statistically significant. Only animals in the 35-minute IR group developed Hct values <40%; however, variability within groups limited statistical detection. KW/BW ratio was greater in 35- vs. 17.5-min IR groups (7.1±0.8 vs. 4.2±0.8 g/kg, P<0.05), consistent with more severe AKI-induced injury. Despite variability inherent to small pilot cohorts, this graded IR model demonstrates differential injury severity and will support ongoing studies examining renal HIF-1α and erythropoietin expression to test whether post-AKI anemia is driven by hemodynamic alterations that reduce hypoxia-dependent signaling.
