Renal protection of losartan 50 mg in normotensive Chinese patients with nondiabetic chronic kidney disease.

AIMS: Nondiabetic chronic kidney disease (CKD) is the leading major cause of end-stage renal disease in developing countries including China. Among the 5 stages of CKD, it is critical to retard the progression of stage 3 because renal disorder could accelerate aggravation behind that stage. Data suggest that high dosages of angiotensin receptor blockers (ARBs) could retard the progression of renal disease in hypertensive and/or diabetic patients. Nevertheless, in daily practice of nephrology, quite a number of nondiabetic patients with CKD who are normotensive do not tolerate even moderate dosages of ARBs because of adverse effects such as systemic hypotension, epically for Chinese patients. The aim of this study was to investigate the renoprotective effects of relatively low dosages of ARBs in normotensive Chinese patients with nondiabetic stage 3 CKD. METHODS: A prospective, randomized, parallel-group, open-label study was performed over a period of 12 months. A total of 238 enrolled patients were randomly allocated to treatment with losartan 50 mg (n = 119) or placebo (n = 119). All patients were followed up at 2-month intervals. At each visit, blood pressure was measured, and urinalysis and serum biochemistry tests were performed. RESULTS: Finally, 112 patients given losartan and 114 patients given placebo completed the study. In the losartan group, there was a significant and biphasic time-dependent decline in proteinuria during therapy (1.72 ± 0.47 to 0.99 ± 0.48 g/d; P < 0.001). Conversely, placebo did not simultaneously change the amount of proteinuria (1.73 ± 0.49 to 1.64 ± 0.50 g/d; P = 0.337). Estimated glomerular filtration rate remained stable during the entire study period in the patients given losartan (44.8 ± 8.1 to 44.1 ± 7.7 mL/min per 1.73 m; P = 0.120) but were significantly reduced in the placebo group (44.5 ± 8.5 to 39.1 ± 7.4 mL/min per 1.73 m, P < 0.001). The changes in blood pressure were kept constant in the 2 groups. All adverse events were minimal and nonfatal. CONCLUSIONS: For normotensive patients with nondiabetic stage 3 CKD, therapy with a daily dose of losartan, 50 mg, may perform effective renoprotection without changing blood pressure and be generally safe and well tolerated.

[Effects of Jianpi Qinghua Recipe on oxygen radicals and transforming growth factor beta1 in renal tissue in a rat model of chronic renal failure with hyperlipidemia].

OBJECTIVE: To evaluate the effects of Jianpi Qinghua Recipe (JPQHR) on oxygen radicals and transforming growth factor beta1 (TGFbeta1) in renal tissue in a rat model of chronic renal failure with hyperlipidemia. METHODS: Chronic renal failure with hyperlipidemia was induced in rats in untreated group and JPQHR-treated group by 5/6 nephrectomy and high fat diet. Then the rats in these two groups were fed distilled water and JPQHR respectively for eight weeks. The rats in normal control group received no specific interventions. After eight weeks of treatment, the levels of 24 h urine protein (Upr), blood urea nitrogen (BUN) and serum creatinine (Cr), cholesterol (Ch), triglycerides (TG), high-density lipoprotein (HDL) and low-density lipoprotein (LDL) of rats in these three groups were examined. The activity of superoxide dismutase (SOD), contents of malondialdehyde (MDA) and non-esterified fatty acids (NEFA) and expression level of TGFbeta1 mRNA in renal tissue of rats in each groups were also determined. RESULTS: The levels of 24 Upr, BUN and serum Cr, Ch, TG and LDL in the JPQHR-treated group were significantly lower than those in the untreated group. The contents of MDA and NEFA and the expression level of TGFbeta1 mRNA in the JPQHR-treated group were also significantly lower than those in the untreated group, while the activity of SOD was significantly increased in the JPQHR-treated group as compared with that in the untreated group. CONCLUSION: The results indicate that JPQHR can improve the renal function of rats with chronic renal failure and hyperlipidemia by regulating lipid metabolism, maintaining balance between prooxidants and antioxidants and reducing expression of TGFbeta1 mRNA in renal tissue.

[Changes of SOD, GSH and MDA in renal tissues of diabetic hyperlipidemia rats].

OBJECTIVE: To study the changes of SOD, GSH and MDA in the renal tissues of diabetes rat models through the comparison of their metabolic features. METHODS: Two types of diabetes rat models were established by feeding high-lipid food along with small dose injecting of streptozotocin (STZ) (model group 1) and repeated small dose injecting of STZ with complete Freund's adjuvant (CFA) (model group 2). And changes of the following were observed: body weight, urine volume, blood sugar, blood lipid, serum insulin, insulin sensitive index (ISI),superoxide dismutase (SOD), glutathione (GSH) and malondialdehyde (MDA) of the renal tissues. RESULTS: The body weight of the two model groups of rats decreased, while the urine volume and the blood sugar increased predominantly. These indexes of the two model groups were significantly different from those of the normal group (P<0.05). The renal tissue MDA level increased while the SOD and GSH level decreased in both model group 1 and model group 2, but the changes in model group 1 were more obvious than those in the model group 2. The serum insulin level which decreased in model group 2 did not decrease significantly in model group 1, but the ISI in model group 1 decreased more significantly than that in model group 2 (P<0.05). CONCLUSION: The antioxidase activity decreased in renal tissues of diabetes rats and hyperlipidemia was the main cause of the corresponding oxidations.

[Effect and mechanism of Tangshenning Recipe on micro-albuminuria in rats with early diabetic nephropathy].

OBJECTIVE: To study the modifying effect and mechanism of Tangshenning Recipe on micro-albuminuria in rats with early diabetic nephropathy (DN). METHODS: Male Wistar rats were randomly divided into the normal group (n=8) and model group (n=24). Intraperitoneal injecting of streptozotocin (STZ) plus complete Freund's adjuvant (CFA) was applied once a week for 3 times to induce the DN rats model. Three weeks later, the model group rats were randomly divided into pathologic group (n=8), monopril group (n=8) and Tangshenning Recipe group(n=8) according to the 24 h U-Alb. Each group's renal hemodynamics index and SOD, GSH, MDA in renal tissue were determined by radioimmunoassay (RIA) and colorimetric method respectively. RESULTS: The levels of plasmatic TXB(2), the ratio of TXB(2) and 6-keto-PGF1alpha, and the CGRP in pathologic group were significantly higher than those in normal group. The levels of plasmatic ET decreased obviously, SOD decreased and MDA increased significantly in the rats' renal tissue of pathologic group. The levels of plasmatic TXB(2), the ratio of TXB(2) and 6-keto-PGF1alpha decreased significantly in both Tangshenning Recipe group and monopril group, and the therapeutic effect of Tangshenning Recipe group was better than that of monopril group. SOD was higher and MDA was lower in Tangshenning Recipe group than that in pathologic group. CONCLUSION: The results indicates that Tangshenning Recipe can lower the micro-albuminuria in early DN rats, the mechanism of which probably lies in the modification of glycometabolism, the ratio of TXB(2) and 6-keto-PGF1alpha, the plasmatic CGRP and the renal lipid preoxidation.