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Abstract: FR-PO108

Combined Effects of GSTM1 Deficiency and Podocyte-Specific APOL1 G0 and G2 Transgene on Blood Pressure and Albuminuria in a Mouse Model of CKD

Session Information

Category: CKD (Non-Dialysis)

  • 1903 CKD (Non-Dialysis): Mechanisms

Authors

  • Pourafshar, Shirin, University of Virginia, Charlottesville, Virginia, United States
  • Cechova, Sylvia, University of Virginia, Charlottesville, Virginia, United States
  • Keshavarz, Behnam, University of Virginia, Charlottesville, Virginia, United States
  • Chan, Rosa, University of Virginia, Charlottesville, Virginia, United States
  • Le, Thu H., University of Virginia, Charlottesville, Virginia, United States
Background

We reported that GSTM1 null allele (GSTM1(0)) is associated with accelerated kidney disease progression in the African Americans Study of Kidney Disease (AASK) participants, and those carrying both GSTM1(0) and APOL1 risk variants had the worst composite outcomes. This suggests a potential interaction between these 2 genes in CKD. Transgenic mice expressing the human APOL1 high risk variants in podocytes did not show kidney disease at baseline; however, females developed preeclampsia during pregnancy. The objective of this study was to investigate whether GSTM1 interacts with APOL1 to influence hypertension (HT) and kidney disease development in a mouse model of CKD.

Methods

We generated Gstm1 deficient mice on the FVB background. We crossed the FVB Gstm1-/- mice with FVB podocyte specific APOL1 G0 or G2 Transgenic mice (TgG0 and TgG2), respectively. The offspring were subjected to subtotal nephrectomy (Nx). Wild-type FVB were used as controls. After a 10-day training period, baseline systolic blood pressure (SBP) and SBP 6-8 weeks after Nx were measured using tail-cuff method. Urinary albumin and creatinine were measured using commercially available ELISA kits. Data are reported as means ± SD.

Results

There were no significant differences in albumin/creatinine ratios among groups. However, Gstm1-/-/APOL1TgG2 mice had significantly higher SBP compared to other groups and also higher than Gstm1-/-/APOL1TgG0 (P < 0.05) (see graph).

Conclusion

In experimental CKD, mice carrying podocyte specific APOL1 G2 Tg and deficient of GSTM1 enzyme have worst HT, independent of albuminuria. These results suggest a potential interaction between these two genes in the development of HT in CKD.

Gstm1-/-/APOL1TgG2 mice had significantly higher SBP compared to other groups.