ObjectivesIschemia-reperfusion injury (IRI) is a major cause of acute kidney injury and chronic kidney disease. Two promising preconditioning methods for the kidney, intermittent arterial clamping (IC) and treatment with the hypoxia mimetic cobalt chloride, have never been directly compared. Furthermore, the protective efficacy of the chemically related transition metal Zn2+ against renal IRI is unclear. Although Co2+ ions have been shown to protect the kidney via hypoxia inducible factor (HIF), the effect of Zn2+ ions on the induction of HIF1α, HIF2α and HIF3α has not been investigated previously.Materials and methodsThe efficacy of different preconditioning techniques was assessed using a Sprague-Dawley rat model of renal IRI. Induction of HIF proteins following Zn2+ treatment of the human kidney cell lines HK-2 (immortalized normal tubular cells) and ACHN (renal cancer) was measured using Western Blot.ResultsFollowing 40 minutes of renal ischemia in rats, cobalt preconditioning offered greater protection against renal IRI than IC as evidenced by lower peak serum creatinine and urea concentrations. ZnCl2 (10 mg/kg) significantly lowered the creatinine and urea concentrations compared to saline-treated control rats following a clinically relevant 60 minutes of ischemia. Zn2+ induced expression of HIF1α and HIF2α but not HIF3α in HK-2 and ACHN cells.ConclusionZnCl2 preconditioning protects against renal IRI in a dose-dependent manner. Further studies are warranted to determine the possible mechanisms involved, and to assess the benefit of ZnCl2 preconditioning for clinical applications.

Ischaemia-reperfusion injury (IRI) during various surgical procedures, including partial nephrectomy for kidney cancer or renal transplantation, is a major cause of acute kidney injury and chronic kidney disease. Currently there are no drugs or methods for protecting human organs, including the kidneys, against the peril of IRI. The aim of this study was therefore to investigate the reno-protective effect of Zn preconditioning in a clinically relevant large animal sheep model of IRI. Further the reno-protective effectiveness of Zn preconditioning was tested on normal human kidney cell lines HK-2 and HEK293. Anaesthetised sheep were subjected to uninephrectomy and 60 min of renal ischaemia followed by reperfusion. Sheep were preconditioned with intravenous injection of zinc chloride prior to occlusion. Serum creatinine and urea were measured before ischaemia and for 7 days after reperfusion. HK-2 and HEK293 cells were subjected to in vitro IRI using the oxygen- and glucose-deprivation model. Zn preconditioning reduced ischaemic burden determined by creatinine and urea rise over time by ~ 70% in sheep. Zn preconditioning also increased the survival of normal human kidney cells subjected to cellular stress such as hypoxia, hydrogen peroxide injury, and serum starvation. Overall, our protocol incorporating specific Zn dosage, number of dosages (two), time of injection (24 and 4 h prior), mode of Zn delivery (IV) and testing of efficacy in a rat model, a large preclinical sheep model of IRI and cells of human origin has laid the foundation for assessment of the benefit of Zn preconditioning for human applications.

The aim of the study was to evaluate the effect of pelvic floor muscle (PFM) assessment and training before and after robot-assisted laparoscopic radical prostatectomy (RARP) in improving PFM strength and urinary continence. We performed an analysis of a database of patients who underwent robot-assisted laparoscopic radical prostatectomy (RARP) performed by two urologists from 2011 to 2013. Pelvic floor muscle (PFM) activation and strength were graded by a trained pelvic floor physiotherapist. Patients were given an exercise program, grouped according to the strength of their pelvic floor as graded by assessment, to complete before and after surgery. PFM strength was recorded preoperatively, 4 days post-catheter removal and 4 weeks post-catheter removal. Continence was recorded at 4 weeks postop and was defined as the requirement of no continence aids. A total of 98 patients had RARP and a preoperative physiotherapy assessment plus postoperative appointments at around 1 and 4 weeks post-RARP. The majority of men improved their PFM strength regardless of preoperative strength with no significant predictors of postoperative strength found. Age was the only significant predictor of postoperative incontinence. In this pilot study, a majority of patients increased their pelvic floor strength with time. Pelvic floor physiotherapy is an important modifiable patient factor, which does have an impact in improving patients' urinary continence by strengthening the pelvic floor muscles. Patient age influences response to pelvic floor physiotherapy.