---

Introduction: In diabetes mellitus the increase of AgII (Angiotensin II), IGF-1(insulin like growth factor-1) and growth hormone induce kidney lesions especially changes in content and thickness of GBM and widening and fusion of podocyte pedicles. In this research for the first time the combination of Losartan (AT1 receptor blocker) and Octreotide (Somatostatin analogue) were used in order to prevent glomerular epithelial lesions.
Materials & Methods: In this experimental study 15 male rats (2 months age) were uninephrectomised from left flank and divided in 5 groups (3 per group). 7 days later diabetes was induced in 2th, 3th, 4th and 5th group by Alloxan (120mg/kg) subcutaneously. 5 days after diabetes induction, the third group received Losartan (5mg/kg/day) orally, 4th group Octretide (10 ŭg/day) subcutaneously and 5th group both two drugs with the mentioned doses for 8 weeks. The 2th group was served as diabetic non treatment group. Kidneys of all groups were fixed by perfusion technique. After second fixation of 1 mm3 cortex parts in Osmium Tetroxide, they were processed in TAAB812 resin for embedding. Thin sections (600 nm thickness) were prepared and investigated by transmission electron microscope qualitatively.
Results: Losartan inhibited fusion and thickening of podocyte pedicles but in some cases couldn,t maintain the 3 layer form of GBM. Octreotide had little effect on inhibition of fusion and thickening of podocyte pedicles and no effect in 3 layer form maintaining of GBM. Combined therapy inhibited fusion and thickening of podocyte pedicles and maintained 3 layer form of GBM but in some cases the lamina rara near endothelium was not seen.
Conclusion: Octreotide have little effect on prevention of glomerular epithelium lesions. However Losartan could prevent glomerular epithelium lesions well, but combined drug therapy showed better results comparing Losartan.

---

Introduction: The acute response to renal ischemia-reperfusion injury involves attenuation of glomerular filtration rate, as well as reduced tubular function. The possible mediators involved in ischemia-reperfusion injury include vasoconstrictor agents including angiotensin II (Ang II). Inhibition of the angiotensin II receptor type 1 (AT1) diminishes the deleterious effects of ischemia-reperfusion on glomerular function. This study is done to investigate the effect of angiotensin II receptor type 1 antagonist on renal hemodynamic and tubular responses to ischemia-reperfusion injury in rat. Materials and Methods: In this experimental study, acute renal failure was induced by 30 minutes clamping of both renal arteries in male Sprague-Dawley rats. Renal hemodynamic and excretory function was followed for 120 minutes reperfusion, while saline or the selective AT1 receptor antagonist (Losartan) was infused. In plasma and urine samples, Cr level was measured. Also plasma and urine content of Sodium was measured. Data was analyzed using ANOVA and Duncan tests. Results: Renal ischemia for 30 minutes decreased glomerular filtration rate during reperfusion and increased urine flow and Sodium excretion up to three fold. Losartan (10 mg/kg i.v.) did not change glomerular filtration rate prior to ischemia but improved it during reperfusion and there were progressive increases in urine flow. Losartan caused a lowering of ischemia-induced rise in Sodium excretion. Conclusion: The ischemic challenge may cause release of angiotensin II, which acts on AT1 receptors to decrease perfusion.

---

Background: The renin-angiotensin system(RAS) has a major role in development of diabetic nephropathy and blocking of RAS by inhibitors and blocking of angiotesin receptors is standard treatment for preventing kidney disease and proteinuria. It is reported that VIT-D analogues are able to suppress renin exertion and improve proteinuria. The aim of this study is to evaluate the effect of VitD analogue (calitriol) on reducing proteinuria in patients with diabetic nephropathy.

Materials and Methods: In this clinical trial study, 132 eligible patients that had diabetic nephropathy and hadn’t vit D deficiency were selected. The patients were divided into two equal groups. First group received the combination of losartan 25mg twice daily and calcitriol 0.25mg and second group received losartan 25 mg twice daly alone for 3 months. The FBS, lipid profile, ESR-CRP BUN, Cr, HbA1c, Ca, P, and 24 hours urine protein were evaluated in all patients at beginning and end of study and the results were statistcally compared.

Results: The 24-hour urine protein in losartan and calitriol group was improved compared to losartan. This difference was statistically significant (p=0.003). As well as, in kidney function (BUN, Cr) in the losartan and calcitriol group compared to losartan alone was significantly improved(p<0.05).

Conclusion: Combination of calcitriol with angiotesin receptor blockers(ARBs) is more effective than ARBs alone in improvement of proteinuria and real function.