Login to Access Video or Poster Abstract: MP19-09
Sources of Funding: Canadian Institute of Health Research_x000D_

Introduction

Renal injury acquired during prolonged ureteral obstruction (UO) can lead to permanent renal dysfunction. Treatments aimed at mitigating renal injury during UO are limited. Hydrogen sulfide (H₂S), an endogenous gasotransmitter, has been shown to ameliorate tissue injury. We have previously demonstrated that daily H₂S treatment can reduce the histopathological markers of renal injury following 30 days of unilateral ureteral obstruction (UUO). The current study employs UUO followed by reimplantation to investigate the effects of daily H₂S on renal function following the relief of obstruction.

Methods

The left ureter of male Lewis rats were ligated at the ureterovesical junction. Starting on post-operative day (POD) 1 and every day for 13 days, rats received either daily intraperitoneal (IP) injection of phosphate buffered saline (PBS) vehicle or 200µmol/kg of GYY4137 (slow-releasing H₂S donor) in PBS. On POD 14, the ligature was removed and the left ureter was reimplanted into the bladder, and a right nephrectomy performed so that the rat is solely dependent on the left kidney. Urine and serum samples were collected to monitor renal function. On POD 30, the left kidney was removed and tissue sections were stained with hematoxylin and eosin (H&E) to measure cortical thickness.

Results

67% of control rats, compared to 100% of H₂S-treated rats, lived until POD 30. Histological analysis showed a significant decrease in cortical thickness (P<0.0001) in control rats when compared to Sham rats, which was significantly rescued upon treatment with H₂S (P<0.0001). Serum creatinine (SCr) in control rats, but not H₂S-treated rats, was significantly increased when compared to Sham animals on POD 3 and 7 (P<0.05). Following reimplantation (PODs 17, 21, 24 and 30), SCr in both control and treatment groups were significantly elevated when compared to Sham. Interestingly, H₂S treatment drastically decreased SCr levels when compared to control animals on all PODs after reimplantation. Proteinuria continued to be higher in both control and treatment groups following reimplantation compared to Sham (P<0.05), however, H₂S treatment group showed markedly reduced proteinuria compared to the control group.

Conclusions

We show, for the first time, that daily H₂S therapy rescues renal function and preserves renal architecture following UO. H₂S may one day become a clinically viable pre-emptive therapy against renal injury associated with UO and contribute to improved renal function in patients with UO.

Funding

Canadian Institute of Health Research_x000D_