Protective effects of irbesartan and alpha lipoic acid in STZ-induced diabetic nephropathy in rats.

The aim of this study was designed to investigate the possible beneficial effects of the angiotensin (ang) II T(1) (AT(1)) receptor blocker, irbesartan (Irb), and the alpha lipoic acid (ALA) in streptozotocin (STZ)-induced diabetic nephropathy (DNP) in rats. The rats were randomly allotted into one of five experimental groups: A, control; B, diabetic untreated; C, diabetic treated with Irb; D, diabetic treated with ALA; and E, diabetic treated with Irb + ALA; each group contains 10 animals. B, C, D, and E groups received STZ. Diabetes was induced in four groups by a single intraperitoneal injection of STZ (50 mg/kg, freshly dissolved in 5 mmol/L citrate buffer, pH 4.5). The rats in Irb-, ALA-, and Irb + ALA-treated groups were given Irb (5 mg/kg), ALA (in a dose of 3 mg/kg), and Irb + ALA (in a dose of 2.5 + 1.5 mg/kg) once a day orally by using intragastric intubation for 12 weeks starting 2 days after STZ injection, respectively. Treatment with ALA and especially Irb reduced the glomerular size; thickening of capsular, glomerular, and tubular basement membranes; increased amounts of mesangial matrix and tubular dilatation as compared with diabetic-untreated rats. Notably, the better effects were obtained when Irb and ALA were given together. We conclude that Irb, ALA, and especially Irb + ALA therapy causes renal morphologic improvement after STZ-induced diabetes in rats. We believe that further preclinical research into the utility of Irb and ALA treatment, alone or its combination, may indicate its usefulness as a potential treatment in DNP.

L-Carnitine ameliorates glycerol-induced myoglobinuric acute renal failure in rats.

There is increasing evidence indicating that oxidative stress plays an important role in the pathogenesis of rhabdomyolysis-induced myoglobinuric acute renal failure (ARF). During times of war and natural disasters, myoglobinuric ARF can assume epidemic proportions. Thus, early and effective renoprotective treatments are of utmost importance. It has been shown that L-carnitine, used as a safe and effective nutritional supplement for more than three decades, is effective in preventing renal injury in many renal injury models involving oxidative stress. The present study was performed to investigate the effects of L-carnitine in an experimental model of myoglobinuric ARF. Four groups of rats were employed in this study: group 1 served as a control; group 2 was given glycerol (10 mL/kg, i.m.); group 3 was given glycerol plus L-carnitine (100 mg/kg, i.p.), starting at the same time as the glycerol injection; group 4 was given glycerol plus L-carnitine (100 mg/kg, i.p.), starting 48h before the glycerol injection. After glycerol injections, the i.p. injections of L-carnitine were repeated every 24h for four days. Ninety-six hours after glycerol injections, blood samples and kidney tissues were taken from the anesthetized rats. Urea and creatinine levels in plasma, N-acetyl-beta-D-glucosaminidase activity in urine, and malondialdehyde levels and catalase enzyme activity in kidney tissue were determined. Histopathological changes and iron accumulation in the kidney tissue were evaluated. In this study, glycerol administration led to marked renal oxidative stress, as well as severe functional and morphological renal deterioration. L-carnitine, possibly via its antioxidant properties, ameliorates glycerol-induced myoglobinuric kidney injury.

Experimental myoglobinuric acute renal failure: the effect of vitamin C.

During times of war and natural disasters, rhabdomyolysis-induced myoglobinuric acute renal failure (ARF) can assume epidemic proportions. Free radicals play an important role in the pathogenesis of myoglobinuric ARF. Vitamin C is a major antioxidant, scavenging free radicals. We have not found any studies on the effect of vitamin C on myoglobinuric ARF. Thus, we aimed to investigate the effects of vitamin C on the myoglobinuric ARF formed by glycerol in rats. Three groups of rats were employed in this study. Group 1 served as control, group 2 was given 50% glycerol (10 mL/kg, i.m.), and group 3 was given glycerol plus vitamin C (20 mg/kg, i.p. for four days). Ninety-six hours after glycerol injections, blood samples and kidney tissues were taken from the anesthetized rats. Urea and creatinine levels in plasma; N-acetyl-beta-D-glucosaminidase activity in urine; malondialdehyde levels, superoxide dismutase and catalase enzyme activity in kidney tissue were determined. Histopathological changes and iron accumulation in the kidney tissue were evaluated. In this study, glycerol administration led to marked renal oxidative stress and severe renal functional and morphological deterioration. The treatment of animals with vitamin C partially corrected the renal dysfunction and morphological impairment. In this respect, vitamin C appears to be a promising candidate for the prevention of rhabdomyolysis-induced ARF. Higher dosages of vitamin C than in 20 mg/kg may be beneficial for better functional and morphological recovery in this model ARF.

Effect of angiotensin-converting enzyme inhibition and angiotensin II type 1 receptor blockade on streptozotocin-induced diabetic nephropathy.

The aim of this study was designed to investigate the possible beneficial effects of the angiotensin-converting enzyme (ACE) inhibitor, Quinapril (Q) and, the angiotensin (ang) II T(1) (AT1) receptor blocker, irbesartan (Irb), in streptozotocin (STZ)-induced diabetes in rats. The rats were randomly allotted into one of five experimental groups: A (control), B (diabetic untreated), C (diabetic treated with Q), D (diabetic treated with Irb), and E (diabetic treated with Q&Irb), each group containing 10 animals. Groups B-E received STZ. Diabetes was induced in four groups by a single intraperitoneal (i.p) injection of STZ (50 mg/kg, freshly dissolved in 5 mmol/L citrate buffer, pH 4.5). Two days after STZ treatment, development of diabetes in four experimental groups was confirmed by measuring blood glucose levels in a tail vein blood samples. Rats with blood glucose levels of 250 mg/dL or higher were considered to be diabetic. The rats in Q-, Irb-, and Q&Irb-treated groups were given Q (in a dose of 3 mg/kg body weight), Irb (5 mg/kg body weight), and Q&Irb (in a dose of 1.5 mg/kg + 2.5 mg/kg body weight) once a day orally by using intra-gastric intubation for 12 weeks starting two days after STZ injection. Treatment of Q and especially Irb reduced the glomerular size and thickening of capsular, glomerular, and tubular basement membranes; and increased amounts of mesangial matrix and tubular dilatation and renal function as compared with diabetics untreated. Notably, the better effects were obtained when Q and Irb given together. We conclude that Q, Irb, and especially Q+Irb therapy causes renal morphologic and functional improvement after STZ-induced diabetes in rats. We believe that further preclinical research into the utility of Q and Irb treatment, alone or its combination, may indicate its usefulness as a potential treatment in diabetic nephropathy (DNp).

Effect of vitamin E therapy on oxidative stress and erythrocyte osmotic fragility in patients on peritoneal dialysis and hemodialysis.

BACKGROUND: Several medications have been tested with the aim of decreasing oxidative stress and erythrocyte osmotic fragility in patients on dialysis. The aim of the present study was to assess the influence of vitamin E therapy on oxidative stress and erythrocyte osmotic fragility in patients on hemodialysis (HD) and peritoneal dialysis (PD). METHODS: This was a placebo-controlled study. The study was performed on 34 HD patients, 13 PD patients and 22 healthy volunteers with a mean age of 45.57 +/- 8.54 years. HD patients were divided into 2 groups: treatment (n=19) and control (n=15). Vitamin E was administered, 300 mg/day, to the HD treatment group and PD patients for 20 weeks. Lipid peroxidation, antioxidant condition and erythrocyte osmotic fragility (EOF) were examined before and after treatment. RESULTS: Before the treatment, the levels of EOF (p<0.001) and malondialdehyde (MDA) (p<0.001) were significantly lower, and erythrocyte superoxide dismutase (SOD) (p=0.001) and vitamin E levels (p<0.001) were significantly higher in the healthy group than PD and HD groups. Serum vitamin E increased from 0.93 +/- 0.16 to 1.09 +/- 0.14 mg/dL (p=0.001), EOF decreased from 0.49% +/- 0.03% to 0.42% +/- 0.04% NaCl (p<0.001), and plasma MDA values decreased from 2.77 +/- 0.87 to 2.20 +/- 0.767 nmol/mL (p=0.018) in the HD treatment group after vitamin E treatment. Levels of EOF decreased from 0.51% +/- 0.09% to 0.43% +/- 0.03% NaCl in the PD treatment group after vitamin E treatment (p=0.021). CONCLUSION: Vitamin E therapy is effective in decreasing the levels of EOF in patients on HD and PD, and it is also effective in decreasing lipid peroxidation in patients on HD.

Endothelial damage and hemostatic markers in patients with uncomplicated mild-to-moderate hypertension and relationship with risk factors.

Endothelial damage, high fibrinogen levels, and platelet activity are the important accelerating factors for the development of hypertension (HT). von Willebrand factor (vWF; endothelial damage marker), fibrinogen levels, and platelet aggregability were compared between patients with uncomplicated, mild-to-moderate hypertension and healthy subjects. The relationship between traditional cardiovascular risk factors and endothelial damage and prothrombotic state was evaluated. One hundred sixty-nine (54 males, 115 females) patients with untreated and uncomplicated mild-to-moderate HT, and age, gender, and body mass index-matched 124 (58 males, 83 females) healthy subjects were enrolled in this study. Plasma vWF, fibrinogen levels, adenosine diphosphate-induced platelet aggregability, insulin, glucose, serum lipids, and uric acid were measured. Patients with HT had significantly increased fibrinogen, vWF, platelet number and aggregability induced by adenosine diphosphate, triglycerides, total/HDL-C, glucose, uric acid levels, and insulin resistance than control group. vWF and hemostatic markers were comparable between smoker and nonsmoker subjects. Platelet aggregability was positively related to systolic and diastolic blood pressure, and vWF. Fibrinogen was positively associated with body mass index (BMI), systolic and diastolic blood pressure, total cholesterol (TC), uric acid, vWF, and insulin resistance. vWF was significantly related to age, systolic blood pressure, TC, LDL-C, and total/HDL-C. Systolic blood pressure was independently related to vWF. vWF and diastolic blood pressure were significant predictors for adenosine diphosphate-induced platelet aggregability. Systolic blood pressure and vWF were independent predictors for fibrinogen levels. Uncomplicated mild-to-moderate HT had endothelial damage and is associated with a prothrombotic state. Traditional cardiovascular risk factors such as age, BMI, dyslipidemia, and insulin resistance are important contributors to the development of endothelial damage and a prothrombotic state. Therefore, it is important to control these cardiovascular risk factors along with proper treatment of HT for preventing target organ damage in mild-to-moderate HT.

99mTc(V)-DMSA scintigraphy in monitoring the response of bone disease to vitamin D3 therapy in renal osteodystrophy.

Renal osteodystrophy (ROD) is a common and serious complication for uremic patients and patients are treated with 1,25-dihydroxyvitamin D3. The bone scanning agent 99mTc-phosphate has also been used to evaluate in ROD but it is not clear that bone scintigraphy has a role in the follow-up of treatment. In this study 99mTc(V)-DMSA scintigraphy was performed in eleven patients [age 40.7 +/- 17.3 (mean +/- SD) yr] with ROD before and after vitamin D3 therapy. Images were obtained after hemodialysis performed following tracer injection to maintain normal blood levels of the radiopharmaceutical and to reduce soft tissue activity. Lumbar vertebra-to-soft tissue uptake ratios (LUR) were quantified with the planar 99mTc(V)-DMSA images. Alkaline phosphatase and parathyroid hormone levels after treatment had significantly decreased compared with pre-therapy. In all patients there was visually decreased uptake in bone structures after treatment. After treatment the mean LUR ratio was significantly lower than those of before treatment (3.59 +/- 2.63 vs. 1.65 +/- 0.62; p = 0.01). LUR values were correlated with pre-therapy alkaline phosphatase and parathyroid hormone. These findings indicate that 99mTc(V)-DMSA scintigraphy is sensitive in evaluating the response of ROD to vitamin D3 therapy.

Salivary function in patients with chronic renal failure undergoing hemodialysis.

PURPOSE: The aim of this study was to evaluate the changes in salivary gland function in patients with chronic renal failure (CRF) undergoing hemodialysis. METHODS: The group consisted of 23 patients with CRF (13 female, 10 male; mean age: 40 +/- 13 yr) and 14 healthy control subjects (mean age: 40 +/- 13 yr). All underwent dynamic salivary gland scintigraphy with gustatory stimulation. After intravenous administration of 99mTc pertechnetate, first, perfusion images at 2 seconds per frame were acquired for 1 minute, then dynamic images at 1 minute per frame were acquired for 45 minutes. At 30 minutes after injection, 10 ml lemon juice was given for 15 minutes as a gustatory stimulus. We obtained time-activity curves derived from regions of interest centered over the four major salivary glands. The following functional indices were calculated for each gland: the time of maximum radioactivity (Tmax) for the prestimulated period, the time of minimum radioactivity (Tmin), as an indicator of velocity of secretion after stimulation, and the Lem E5% value as an indicator of the secretion function. RESULTS: When the patients with CRF undergoing hemodialysis were compared to the controls, there were statistically significant differences in Tmax, Tmin and Lem E5% values for bilateral parotid glands, and Tmin values for bilateral submandibular glands (p < 0.05), there were no statistically significant differences in Tmax and Lem E5% values for bilateral submandibular glands. There were also significant differences in Tmax and Lem E5% values for bilateral parotid glands between mild oral problems and severe oral problems in patients with CRF (undergoing hemodialysis). CONCLUSION: In this study, prolonged Tmax and Tmin values, and decreased Lem E5% values for parotid glands and prolonged Tmin values for submandibular glands on salivary scintigraphy pointed out decreased parenchymatous and excretory function in patients with CRF undergoing hemodialysis.

A retrospective analysis for aetiology and clinical findings of 287 secondary amyloidosis cases in Turkey.

BACKGROUND: Secondary amyloidosis is the most frequent of the various types of systemic amyloidosis, the epidemiology of which is not yet fully known. The aim of our study was to evaluate retrospectively the collective data for the aetiological distribution, clinical findings and approaches to the management of secondary amyloidosis in Turkey. METHODS: Data from a simple questionnaire addressing aetiology, and demographic and clinical characteristics of patients with biopsy-proven secondary amyloidosis was retrospectively analysed. Eleven nephrology clinics contributed data for this study. RESULTS: The 11 contributing centres provided a total of 287 cases (102 female, 185 male). The aetiological distribution was as follows: familial Mediterranean fever (FMF) 64%, tuberculosis 10%, bronchiectasis and chronic obstructive lung disease 6%, rheumatoid arthritis 4%, spondylarthropathy 3%, chronic osteomyelitis 2%, miscellaneous 4%, unknown 7%. Oedema accompanied by proteinuria was present in 88% of the cases, hepatomegaly in 17%, and splenomegaly in 11%. The mean systolic and diastolic blood pressures were 115+/-26 and 73+/-15 mmHg respectively. The family history was positive in 16%; 73% of the cases were on colchicine treatment when the questionnaire was administered. Thirty-eight per cent of the cases had progressed to ESRD and were on renal replacement therapy. CONCLUSIONS: FMF is the leading cause of secondary amyloidosis in Turkey, followed by tuberculosis. Oedema accompanied by proteinuria is the most prominent presenting finding, and hypotension seems to be common among these patients.