Kidney Week

Abstract: SA-PO976

Decreasing T-Cell Activation Inhibits Progressive Renal Injury in Obese Dahl Salt-Sensitive Rats Before Puberty

Session Information

• CKD: Pathobiology - II
  November 05, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
  Abstract Time: 10:00 AM - 12:00 PM

Category: CKD (Non-Dialysis)

• 2203 CKD (Non-Dialysis): Mechanisms

Authors

• Ekperikpe, Ubong S., The University of Mississippi Medical Center, Jackson, Mississippi, United States

Ubong S. Ekperikpe,

• Cornelius, Denise C., The University of Mississippi Medical Center, Jackson, Mississippi, United States

Denise C. Cornelius,

• Williams, Jan Michael, The University of Mississippi Medical Center, Jackson, Mississippi, United States

Jan Michael Williams,

Background

Childhood obesity is growing at an alarming rate and is now considered a risk factor for renal injury and the development of chronic kidney disease later in life. Recently, we reported that the obese Dahl salt-sensitive leptin receptor mutant (SS^LepRmutant) rat develops renal injury before puberty that was associated with increased T-cell infiltration and activation. The current study investigated the effect of abatacept on renal inflammation and the progression of renal injury in SS^LepRmutant rats before puberty.

Methods

Four-week-old SS and SS^LepRmutant rats were treated with either vehicle (PBS) or abatacept (1 mg/kg; ip, every other day) for 4 weeks. Proteinuria was measured every two weeks until the rats reached 8 weeks of age. At the end of the study, MAP (via chronic catheter) was measured, and the kidneys were collected to measure renal cytokine levels and the infiltration of immune cells (via ELISA and flow cytometry). Renal histopathology analysis was performed as well to determine glomerular/tubular injury and renal fibrosis.

Results

We did not observe any differences in MAP across the groups. While proteinuria rose from 8±3 to 47±18 mg/day in SS rats, proteinuria markedly increased from 68±17 to 434±73 mg/day in SS^LepRmutant rats. Treatment with abatacept decreased proteinuria by almost 50% in SS^LepRmutant rats (265±47 mg/day; p<0.05) without affecting SS rats (26±7 mg/day). We observed a significant increase in T-cell infiltration and activation in SS^LepRmutant rats versus SS rats, and treatment with abatacept significantly reduced this response. Renal macrophage inflammatory protein-3 alpha (MIP-3α) was significantly increased, while interleukin-4 (IL-4) was markedly decreased in SS^LepRmutant vs SS rats (20±2 vs 6±1 pg/mg, and 15±2 vs 42±6 pg/mg, respectively; p<0.05), and treatment with abatacept significantly decreased renal MIP-3α, while increasing IL-4 in SS^LepRmutant rats, without affecting SS rats. We observed significant increases in glomerular and tubular injury and renal fibrosis in SS^LepRmutant rats compared to SS rats, and treatment with abatacept decreased these renal parameters in SS^LepRmutant rats.

Conclusion

These data suggest that anti-inflammatory strategies may be beneficial in managing renal injury associated with childhood obesity.

Funding

• NIDDK Support