Abstract: TH-PO208
Kidney Hypoplasia Increases Kidney Injury following Reversal of Unilateral Ureteral Obstruction
Session Information
- Hypertension and CVD: Basic Research Findings
October 24, 2024 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Hypertension and CVD
- 1601 Hypertension and CVD: Basic
Authors
- Goorani, Samaneh, University of Arkansas for Medical Sciences, Little Rock, Arkansas, United States
- Imig, John D., University of Arkansas for Medical Sciences, Little Rock, Arkansas, United States
Background
Studies have found that short-term kidney injury by unilateral ureteral obstruction (UUO) results in long-term consequences of hypertension and CKD. Not known is whether renal hypoplasticity and low nephron number increases the long-term consequences.
Methods
Male and female renal hypoplastic ROP Os/+ and wild type ROP +/+ mice underwent UUO, or sham surgery followed ureter clip removal on day 7 (RUUO). BP was measured by telemetry to determine SBP, MAP, and HR weekly. Renal artery resistive index (RI) was evaluated by ultrasound. Urine was collected at the end to assess CysC and NGAL. A terminal kidney tissue collection was conducted for gene expression, and histology.
Results
At baseline, ROP +/+ and ROP Os/+ MAP, SBP, and HR were not different in either sex of mice. SBP and MAP increased, and HR decreased in RUUO ROP Os/+ and RUUO ROP +/+ mice compared to sham mice groups. Interestingly, RUUO ROP Os/+ mice demonstrated 35-40 mmHg higher SBP and 100-150 beats lower HR than RUUO ROP +/+ mice 35 days following clip removal. RI was higher in RUUO ROP Os/+ and RUUO ROP +/+ mice compared to sham mice. Moreover, RUUO ROP Os/+ had a higher RI than RUUO ROP +/+ mice indicating a greater reduction in renal blood flow in RUUO ROP Os/+ mice. CysC and NGAL were 2-fold higher in RUUO ROP Os/+ than RUUO ROP +/+ mice. Fibrotic PCR pathway array demonstrated higher fibrotic markers in RUUO ROP Os/+ than RUUO ROP+/+ mice. RT-PCR confirmed markedly higher expressions of Fn1, collagen1, vimentin in RUUO ROP Os/+ than RUUO ROP +/+ mice. Renal tubular cast formation in RUUO ROP Os/+ and RUUO ROP +/+ mice was higher compared to sham mice. The increase in renal tubular cast formation was higher in RUUO ROP Os/+ than RUUO ROP+/+. Similarly, α-SMA deposition was higher (3 vs 2-fold) in RUUO ROP Os/+ compared to RUUO ROP +/+ mice. Mac2+ inflammatory cells were increased in RUUO ROP Os/+ to a greater extent than RUUO ROP +/+ mice. There were no differences between male and female mice for all groups and parameters measured.
Conclusion
These data demonstrate renal hypoplasia and low nephron number ROP Os/+ mice had increased blood pressure, renal inflammation, and kidney injury compared to ROP +/+ mice 35 days following ureter clip removal.
Funding
- NIDDK Support