Amira Awadalla

Activation of nuclear factor erythroid 2-related factor 2 (Nrf2) and Nrf-2-dependent genes by ischaemic pre-conditioning and post-conditioning: new adaptive endogenous protective responses against renal ischaemia/reperfusion injury

To investigate the impact of ischaemic pre‐conditioning (Ipre) and post‐conditioning (Ipost) on expression of nuclear factor erythroid 2‐related factor 2 (Nrf2) gene and its dependent genes, haem oxygenase‐1 (HO‐1) and NADPH‐quinone oxidoreductase‐1 (NQO‐1); inflammatory cytokines TNF‐α, IL1β and ICAM‐1; and apoptotic markers such as caspase‐3 in renal ischaemia/reperfusion (I/R) injury.

Protection against renal ischaemia/reperfusion injury: A comparative experimental study of the effect of ischaemic preconditioning vs. postconditioning

Abstract Objective: To compare the effect of ischaemic preconditioning (Ipre) vs. ischaemic postconditioning (Ipost) on renal ischaemia/reperfusion (I/R) injury in rats. Materials and methods: In all, 120 male Sprague–Dawley rats were classified into four groups of 30 rats each, designated sham, control, Ipre and Ipost. Renal function, including serum creatinine, blood urea nitrogen (BUN), creatinine clearance (CrCl), fractional Na excretion (FENa) and renal histopathology were measured at 2, 24 and 48 h after ischaemia. Markers of lipid peroxidation (malondialdehyde, MDA), superoxide dismutase (SOD) and reduced glutathione (GSH) were measured in kidney tissues during the same intervals. Results: Ipre caused a significant improvement in renal function, as indicated by a significant decrease in serum creatinine, BUN and FENa, with a significant increase in CrCl. However, Ipost caused no significant improvement in renal function. Morphologically Ipre caused a marked significant improvement in the renal tubular damage score compared to Ipost. Also, Ipre caused a significant decrease in MDA, and significant increase in GSH and SOD when compared to Ipost. Conclusion: Ipre is more potent than Ipost for improving the renal injury induced by I/R. Ipre caused a marked improvement in renal function and morphology, while Ipost caused a minimal improvement in morphology only. Moreover, Ipre caused a marked and significant reduction in oxidative stress in kidney tissues, while Ipost caused a minimal reduction.

Role of combination of l-arginine and α-tocopherol in renal transplantation ischaemia/reperfusion injury: a randomized controlled experimental study in a rat model

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Systemic and renal haemodynamic changes in renal schemia/reperfusion injury: impact of erythropoietin

The objective of this study was to investigate the effects of erythropoietin (EPO) on systemic and renal hemodynamics in a rat model of renal ischemic/reperfusion (I/R) injury. We used 30 male Sprague-Dawley rats distributed among the following 3 groups (10 rats per group): (i) the sham-operated group, (ii) the control group (I/R injury only), and (iii) the EPO-treated group (I/R injury with 1500 U EPO·(kg body mass)⁻¹ on day 0, and 500 U·kg⁻¹ on days 2 and 4 after ischemia). Renal function, arterial blood pressure (ABP), renal plasma flow (RPF), renal blood flow (RBF), and renal vascular resistance (RVR) were measured on days 1, 2, and 7 after ischemia. The expression of endothelial NO synthase (eNOS) and histopathology of kidney were evaluated on day 7. The contractility of aortic strips was recorded from the different groups. The results show that renal function and histopathology were significantly improved after treatment with EPO. Compared with the control group, the EPO-treated group showed a significant increase in RPF, RBF, haematocrite, ABP, eNOS expression, and a decrease in RVR (p < 0.05).The response of aortic strips to the relaxant effect of acetylcholine was improved in the EPO-treated group. In conclusion, treatment with EPO improves renal function and renal haemodynamics in renal I/R injury, and causes significant rise of ABP and haematocrite value.

A randomised controlled trial evaluating renal protective effects of selenium with vitamins A, C, E, verapamil, and losartan against extracorporeal shockwave lithotripsy‐induced renal injury

To evaluate the protective effects of selenium with vitamins A, C and E (selenium ACE, i.e. antioxidants), verapamil (calcium channel blocker), and losartan (angiotensin receptor blocker) against extracorporeal shockwave lithotripsy (ESWL)‐induced renal injury.

Impact of Hepatitis C Virus (HCV) infection on biomolecular markers influencing the pathogenesis of bladder cancer

ObjectiveThe present study was designed to determine the possible impact of hepatitis C virus (HCV) infection on the expression of telomerase (TERT), retinoblastoma (RB1), E2F3, TP53, CDKN1A (p21) and fibroblast growth factor receptor- 3 (FGFR3) genes in patients with bladder cancer (BC).Materials and methods100 patients with bladder cancer (15 female and 85 male) were divided into 2 groups; Group I: 50 HCV negative subjects (age range 36–79), and Group II: 50 HCV positive subjects (age range 42–80). Expressions of the telomerase, retinoblastoma (Rb), E2F3, TP53 and FGFR3 genes were tested by immunohistochemistry and real time PCR in tumour tissues and healthy bladder tissues. Also, telomerase activity was assessed by telomeric repeats amplification protocol (TRAP).ResultsBladder tumors associated with HCV infection were of high grade and invasive squamous cell carcinomas (SCCs). Expressions of hTERT, Rb, E2F3, TP53 and FGFR3 as well as telomerase activity were significantly higher in bladder tissues of HCV-infected patients compared with bladder tissues of non infected patients (p<0.05). On the contrary, CDKN1A (p21) expression was significantly lower in bladder tissues of HCV-infected patients compared to bladder tissues of non infected patients (p<0.05).ConclusionThe expressions of hTERT, Rb, E2F3, TP53 and FGFR3 as well as the activity of telomerase were significantly high in malignant bladder tissues associated with HCV infection. On the other hand, CDKN1A (p21) expression was low in bladder tissues of HCV-infected subjects. Moreover, there was a positive correlation between HCV infection and expression of telomerase, E2F3, TP53 and FGFR3. There was a negative correlation between HCV infection and expression of Rb and p21.

Recoverability of renal functions after relief of partial ureteric obstruction of solitary kidney: impact of ferulic acid

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MP06-09 LOCAL SILDENAFIL ACCELERATE RENAL REGENERATION AFTER ISCHEMIA/ REPERFUSION INJURY IN CANINE MODEL.

INTRODUCTION AND OBJECTIVES: As the waiting time increases for listed renal failure patients, it is becoming common to encounter patients with minimal or no urine output with small shrunken bladders at the time of transplant. Mirabegron has proven benefit in treating overactive bladder(OAB) symptoms by relaxing the bladder through beta-3-adrenergic receptors. Our aim is to evaluate the efficacy of Mirabegron following kidney transplantation on patients with small bladder capacity. METHODS: Kidney transplant recipients with small bladder volumes who experienced OAB symptoms and were started on Mirabegron therapy within 3 months after transplant were included in this study. Patients were excluded if they had evidence of urinary tract infection or a history of complex urologic surgeries preceding transplantation. We used the OAB-symptom score (OAB-SS; Journal of Urology, 2007), a simple self-report questionnaire evaluating OAB symptoms. The minimum OAB-SS score for inclusion was 12. Patient demographics and OAB-SS pre and post-Mirabegron were collected and compared using paired t-test analysis. RESULTS: The 36 participants were predominantly male (83%) anddeceased-donor kidney transplant recipients (86%).Medianagewas 48 years (IQR 36.5-60). 47% of patients reported pre-transplant urinary symptoms, most commonly recurrent UTI (28%). BPH-lower urinary tract symptoms (LUTS) reported by 30% of males may contribute to the sample sex imbalance. Before Mirabegron initiation, 44% of patients had failed trials of at least one pharmacologic agent and over 20% had failed trials of at least two medications. After starting Mirabegron therapy, 86% reported a decrease in OAB-SS. Overall mean score change was -4.7 points (p<0.001). Mean score on each OAB-SS survey question also decreased significantly (p<0.001, Table 2). CONCLUSIONS: Mirabegron effectively reduces severity of symptoms related to small bladder volume following renal transplantation by increasing bladder relaxation and storage capacity.

Modulation of renal ischemia/reperfusion in rats by a combination of ischemic preconditioning and adipose-derived mesenchymal stem cells (ADMSCs)

The present study investigated the effects of combination of ischemic preconditioning (Ipre) and adipose-derived mesenchymal stem cells (ADMSCs) on renal ischemia-reperfusion (I-R) injury in rats. 90 male Sprague Dawley rats were divided into 5 equal groups; sham operated, control (45 min left renal ischemia), Ipre group as control group with 3 cycles of Ipre just before renal ischemia, ADMSCs-treated group (as control with ADMSCs 10(6) cells in 0.1 mL via penile vein 60 min before ischemia time), and Ipre + ADMSCs group as ADMCs group with 3 cycles of Ipre. Ipre and ADMSCs groups showed significant decrease in serum creatinine and blood urea nitrogen (BUN) and caspase-3 and CD45 expression in kidney and significant increase in HIF-1α, SDF-1α, CD31, and Ki67 expressions in kidney compared with the control group (p < 0.05). Moreover, the Ipre + ADMSCs group showed significant decrease in serum BUN and caspase-3 and CD45 expression in kidney with significant increase in HIF-1α, SDF-1α, CD31, and Ki67 expression in kidney compared with the Ipre and ADMCs groups (p < 0.05). We concluded that Ipre potentiates the renoprotective effect of ADMSCs against renal I/R injury probably by upregulation of HIF-1α, SDF-1α, CD31, and Ki67 and downregulation of caspase-3 and CD45.

MP79-10 SILDENAFIL ACTIVATES NRF2 DEPENDENT ANTI-OXIDANT GENES AND ANTI-APOPTOTIC BCL-2 GENE AND INHIBITS PRO-INFLAMMATORY CYTOKINES GENES IN RAT MODEL OF RENAL ISCHEMIA/REPERFUSION INJURY

complication rates were 28.0% (95% CI 15.4 to 42.7%) for anticoagulants, compared to 12.13% (95% CI 0.8 to 33.93%) for aspirin þ anticoagulant, 0.31% (95% CI 0.0001 to 1.32%) for aspirin, and 6.1% (95% CI 2.2 to 11.7%) for the control group. CONCLUSIONS: Aspirin is more effective in reducing allograft thrombosis, after kidney transplantation, whether alone or in association with an anticoagulant, when compared to no drug prophylaxis, and without higher hemorrhagic complication rates. Anticoagulants, when used alone, do not show a beneficial effect on thrombosis rates, additionally yielding higher bleeding rates.