Functional and molecular evaluation of using aliskiren during acute and chronic partial ureteral obstruction in rat solitary kidney.

AIMS: To study the effect of direct renin inhibitor (aliskiren) on the renal function during acute and chronic partial ureteral obstruction (PUO) in rat solitary kidney. MAIN METHODS: Sixty male Sprague-Dawley rats were randomly allocated into three groups (20 rats each); sham, PUO and aliskiren groups. Right nephrectomy was performed in all groups. Rats in PUO and aliskiren groups were subjected to left PUO and received no treatment and aliskiren (10 mg/kg, orally, once per day till sacrification), respectively. Blood samples were then collected for biochemical measurements. Ten rats from each group were sacrificed after two weeks, while the remaining rats were sacrificed after four weeks. Left kidneys were harvested for histopathological examination, BCL-2, interleukin (IL)-6, transforming growth factor (TGF)-ß1, collagen I and fibronectin relative gene expression and assessment of glutathione (GSH), superoxide dismutase (SOD), malondialdehyde (MDA) and nitric oxide (NO) activity. KEY FINDINGS: After two and four weeks of PUO, aliskiren significantly recompensed the rise of serum creatinine (Scr) and blood urea nitrogen (BUN). Aliskiren also revealed significantly better histopathological results regarding cortical and medullary necrosis, regeneration and inflammatory cell infiltration. Aliskiren group showed statistically significant up-regulation of BCL-2 and down-regulation of IL-6, TGF-ß1, collagen I and fibronectin relative gene expression. Aliskiren significantly increased GSH and SOD activity and reduced MDA and NO activity. Moreover, aliskiren administration for four weeks after PUO significantly yielded more renoprotective effect compared to its administration for two weeks. SIGNIFICANCE: Aliskiren ameliorates the deterioration of the renal function during acute and chronic PUO in a solitary kidney.

Ischaemia-reperfusion injury in renal transplantation: the role of nitric oxide in an experimental rat model.

OBJECTIVE: to investigate the role of nitric oxide (NO) in ischaemia-reperfusion (I/R) injury in a renal transplant rat model, as I/R injury is a common consequence of renal transplantation and NO has many protective properties that might protect the kidney after I/R injury. MATERIALS AND METHODS: in all, 30 male Sprague-Dawley rats weighing 350-400 g and aged 4-6 months underwent renal transplantation and received FK506 (an immunosuppressant) to overcome early acute rejection episodes. The rats were divided randomly into three groups (10 rats each): Group I, treated with FK506 (2 mg/kg body weight [bw], once daily), served as the control group; Group II, treated with FK506 2 mg/kg bw and L-arginine 300 mg/kg bw; and Group III, treated with FK506 (2 mg/kg bw) and, n-omega-nitro-l-arginine methyl ester (L-NAME; 50 mg/kg bw). Urine and blood samples were taken at 0 (before operation), 2, 7, and 14 days after transplantation for estimation of urine sodium, creatinine, fractional excretion of sodium, serum creatinine, sodium, and blood urea nitrogen (BUN). Kidney specimens were taken for histological examination by light microscopy. RESULTS: serum creatinine and BUN levels significantly decreased in the L-arginine-treated group (both P < 0.001) while they were significantly increased in the L-NAME-treated group (P < 0.005 and P < 0.001, respectively) compared with the control group at all time intervals. Light microscopic examination of the renal biopsies in the control group showed acute tubular necrosis, which was minimal in kidneys transplanted and treated with L-arginine and more markedly with L-NAME. CONCLUSION: I/R injury impaired graft function during the first week after transplantation. Injection of L-arginine before ischaemia antagonized graft deterioration and improved morphological appearance.

Co-administration of ketoconazole and tacrolimus therapy: a transplanted rat model.

BACKGROUND/AIM: The aim of this work is to study the safety and the effect of addition of ketoconazole to experimental kidney transplanted rat treated with tacrolimus and predicts the percentage of tacrolimus dose reduction. MATERIAL AND METHODS: The material of this work included 60 male Sprague Dawely rats subjected to renal allotransplantation. They were equally divided into five groups: Group I: served as control group, Group II: received FK506 3.2 mg/kg/bw, Group III: received FK506 2 mg/kg/bw, Group IV: received FK506 1 mg/kg/bw, Group V: received FK506 1 mg/kg/bw plus Ketoconazole 20 mg/kg/day. FK506 trough level and laboratory investigations were determined at 0, 3, 7, 10, 14, and 27 days post-transplantation. RESULTS: In all groups loss of body weight was observed at day 27 after treatment compared to that before transplantation. Serum creatinine significantly increased at day 27 compared to the basal level in groups treated with 1.0 and 3.2 mg FK506 (1.80 +/- 0.50 versus 0.39 +/- 0.06 P = 0.001) and (1.03 +/- 0.26 versus 0.50 +/- 0.07 P = 0.001) respectively, while for 2.0 mg or 1.0 mg plus keto groups, no significant differences in serum creatinine levels over time (0.56 +/- 0.22 versus 0.44 +/- 0.10 P = 0.106) and (0.55 +/- 0.30 versus 0.42 +/- 0.08 P=0.160) were observed. CONCLUSION: Concomitant administration of Ketoconazole and FK506 in transplanted rat model is safe and results in increase of blood trough level concentration of FK506 with 50% reduction of its dose.