Login to Access Video or Poster Abstract: MP06-09
Sources of Funding: no funding

Introduction

The renoprotective effect of sildenafil has been proven in animal model. Also, it is reported to enhance expression of hepatocyte proliferating antigen after hepatic ischemia/ reperfusion injury (IR) in animal model. Yet this was not studied before in renal IR. We aim to investigate the role of local sildenafil administration in enhancement of renal recoverability and regenerative capacity after renal IR in canine model.

Methods

Seventy two male mongrel dogs were classified into 3 groups (each consists of 24 dogs): sham (right nephrectomy without left renal ischemia), local (LC) group (right nephrectomy, left renal ischemia for 6o minutes and local perfusion of ischemic kidney with saline and heparin for 5min immediately after ischemic induction) and local Sildenafil (LS) group (as LC and local perfusion with sildenafil 0.5 mg/kg). Each group is subdivided into 4 subgroups (6dogs each) according to time of scarification (1, 3, 7 and 14 days). Serum creatinine (Scr) and diuretic renography were performed for all dogs at the day of sacrification and compared with pre-ischemic values. Histopathological examination of the kidney was performed by un-informed pathologist. Renal cortex and medulla were examined for necrosis, interstitial fibrosis and regenerative indices (RI). Regenerative indices (RI) are mitosis, solid tubules, solid sheet, hyperchromatosis and prominent nucleoli. Also, immunohistochemical examination of renal tissue was done for assay of proliferative marker ki-67.

Results

Renal function tests were statistically significant lower in ischemic groups (LC and LS) in comparison to sham through the study period, where LS group showed statistically significant lower serum creatinine and higher GFR at all end point times than LC group. (Figure 1) Sildenafil-treated group showed statistically significant lower renal cortical and medullary necrosis and interstitial fibrosis than control group. Regarding RI, LS group showed statistically significant higher expression of all RI than other groups (p value <0.05). Also, LS group showed statistically significant higher expression of Ki-67 than both groups at 1, 3, 7 and 14 days post renal IR injury (p Values < 0.05). (Figure 2)

Conclusions

Local sildenafil administration; beside its role in renal protection against IR, enhances renal regenerative capacity after release of ischemic insult.

Funding

no funding