Adrenoceptors of the medial septal area modulate water intake and renal excretory function induced by central administration of angiotensin II

We investigated the role of a-adrenergic antagonists and clonidine injected into the medial septal area (MSA) on water intake and the decrease in Na+, K+ and urine elicited by ANGII injection into the third ventricle (3rdV). Male Holtzman rats with stainless steel cannulas implanted into the 3rdV and MSA were used. ANGII (12 nmol/µl) increased water intake (12.5 ± 1.7 ml/120 min). Clonidine (20 nmol/µl) injected into the MSA reduced the ANGII-induced water intake (2.9 ± 0.5 ml/120 min). Pretreatment with 80 nmol/µl yohimbine or prazosin into the MSA also reduced the ANGII-induced water intake (3.0 ± 0.4 and 3.1 ± 0.2 ml/120 min, respectively). Yohimbine + prazosin + clonidine injected into the MSA abolished the ANGII-induced water intake (0.2 ± 0.1 and 0.2 ± 0.1 ml/120 min, respectively). ANGII reduced Na+ (23 ± 7 µEq/120 min), K+ (27 ± 3 µEq/120 min) and urine volume (4.3 ± 0.9 ml/120 min). Clonidine increased the parameters above. Clonidine injected into the MSA abolished the inhibitory effect of ANGII on urinary sodium. Yohimbine injected into the MSA also abolished the inhibitory effects of ANGII. Yohimbine + clonidine attenuated the inhibitory effects of ANGII. Prazosin injected into the MSA did not cause changes in ANGII responses. Prazosin + clonidine attenuated the inhibitory effects of ANGII. The results showed that MSA injections of a1- and a2-antagonists decreased ANGII-induced water intake, and abolished the Na+, K+ and urine decrease induced by ANGII into the 3rdV. These findings suggest the involvement of septal a1- and a2-adrenergic receptors in water intake and electrolyte and urine excretion induced by central ANGII.

Detection of renal dysfunction based on serum creatinine levels in a Brazilian community: the Bambuí Health and Ageing Study

There are few population-based studies of renal dysfunction and none conducted in developing countries. In the present study the prevalence and predictors of elevated serum creatinine levels (SCr > or = 1.3 mg/dl for men and 1.1 mg/dl for women) were determined among Brazilian adults (18-59 years) and older adults (>60 years). Participants included all older adults (N = 1742) and a probabilistic sample of adults (N = 818) from Bambuí town, MG, Southeast Brazil. Predictors were investigated using multiple logistic regression. Mean SCr levels were 0.77 ± 0.15 mg/dl for adults, 1.02 ± 0.39 mg/dl for older men, and 0.81 ± 0.17 mg/dl for older women. Because there were only 4 cases (0.48%) with elevated SCr levels among adults, the analysis of elevated SCr levels was restricted to older adults. The overall prevalence of elevated SCr levels among the elderly was 5.09% (76/1494). The prevalence of hypercreatinemia increased significantly with age (chi² = 26.17, P = 0.000), being higher for older men (8.19%) than for older women (5.29%, chi² = 5.00, P = 0.02). Elevated SCr levels were associated with age 70-79 years (odds ratio [OR] = 2.25, 95% confidence interval [CI]: 1.15-4.42), hypertension (OR = 3.04, 95% CI: 1.34-6.92), use of antihypertensive drugs (OR = 2.46, 95% CI: 1.26-4.82), chest pain (OR = 3.37, 95% CI: 1.31-8.74), and claudication (OR = 3.43, 95% CI: 1.30-9.09) among men, and with age >80 years (OR = 4.88, 95% CI: 2.24-10.65), use of antihypertensive drugs (OR = 4.06, 95% CI: 1.67-9.86), physical inactivity (OR = 2.11, 95% CI: 1.11-4.02) and myocardial infarction (OR = 3.89, 95% CI: 1.58-9.62) among women. The prevalence of renal dysfunction observed was much lower than that reported in other population-based studies, but predictors were similar. New investigations are needed to confirm the variability in prevalence and associated factors of renal dysfunction among populations.

Lymphocyte subpopulations during cytomegalovirus disease in renal transplant recipients

We have determined the number of circulating T, B and natural killer cells in renal transplant recipients in order to detect changes during cytomegalovirus (CMV) infections. Serial blood samples were taken from 61 patients on standard triple immunosuppression therapy (cyclosporin A, azathioprine and prednisone). Using two-color flow cytometry analysis, the absolute number of CD3+, CD4+, CD8+, CD19+, CD3+HLA-DR+ and CD16+56+ cells was determined. Forty-eight patients (78.7%) developed active CMV infection, and all of them subsequently recovered. Twenty of the infected patients (32.8%) presented symptoms compatible with CMV disease during the infectious process. The number of lymphocytes and their main subpopulations were normal before the onset of CMV disease. During the disease there was a decrease followed by a significant increase (P<0.005) in the number of CD3+, CD4+, CD8+ and CD3+HLA-DR+ cells. No significant changes were observed in natural killer cells or B lymphocytes during the disease. We conclude, as observed in all viremic patients recovering from infection, that recovery is associated with an increase in the number of T cell subsets. The monitoring of different lymphocyte subsets along with antigenemia can be extremely useful in the detection of patients at high risk of developing CMV symptoms, allowing the early introduction of antiviral therapy or the reduction of immunosuppression therapy.

Oral administration of L-arginine decreases blood pressure and increases renal excretion of sodium and water in renovascular hypertensive rats

The two-kidney, one-clip renovascular (2K1C) hypertension model is characterized by a reduction in renal flow on the clipped artery that activates the renin-angiotensin system. Endothelium dysfunction, including diminished nitric oxide production, is also believed to play a role in the pathophysiology of this model. Some studies have shown an effect of L-arginine (L-Arg, a nitric oxide precursor) on hypertension. In the present study we determined the ability of L-Arg (7 days of treatment) to reduce blood pressure and alter renal excretions of water, Na+ and K+ in a model of 2K1C-induced hypertension. Under ether anesthesia, male Wistar rats (150-170 g) had a silver clip (0.20 mm) placed around the left renal artery to produce the 2K1C renovascular hypertension model. In the experimental group, the drinking water was replaced with an L-Arg solution (10 mg/ml; average intake of 300 mg/day) from the 7th to the 14th day after surgery. Sham-operated rats were used as controls. At the end of the treatment period, mean blood pressure was measured in conscious animals. The animals were then killed and the kidneys were removed and weighed. There was a significant reduction of mean blood pressure in the L-Arg-treated group when compared to control (129 ± 7 vs 168 ± 6 mmHg, N = 8-10 per group; P<0.05). Concomitantly, a significant enhancement of water and Na+ excretion was observed in the 2K1C L-Arg-treated group when compared to control (water: 13.0 ± 0.7 vs 9.2 ± 0.5 ml/day, P<0.01; Na+: 1.1 ± 0.05 vs 0.8 ± 0.05 mEq/day, respectively, P<0.01). These results show that orally administered L-Arg acts on the kidney, possibly inducing changes in renal hemodynamics or tubular transport due to an increase in nitric oxide formation.

Ionic radiocontrast inhibits endothelium-dependent vasodilation of the canine renal artery in vitro: possible mechanism of renal failure following contrast medium infusion

To determine if radiocontrast impairs vascular relaxation of the renal artery, segments (4-5 mm in length) of canine renal artery were suspended in vitro in organ chambers to measure isometric force (95% O2/5% CO2, at 37ºC). Arterial segments with and without endothelium were placed at the optimal point of their length-tension relation and incubated with 10 µM indomethacin to prevent synthesis of endogenous prostanoids. The presence of nonionic radiocontrast (iohexol, Omnipaque 350, 1 ml in 25 ml control solution, 4% (v/v)) did not alter endothelium-dependent relaxation to acetylcholine in rings precontracted with both norepinephrine and prostaglandin F2alpha (N = 6). When the rings were precontracted with prostaglandin F2alpha, the presence of ionic contrast did not inhibit the relaxation of the arteries. However, in canine renal arteries contracted with norepinephrine, the presence of ionic radiocontrast (diatrizoate meglumine and diatrizoate sodium, MD-76, 1 ml in 25 ml control solution, 4% (v/v)) inhibited relaxation in response to acetylcholine, sodium nitroprusside (N = 6 in each group), and isoproterenol (N = 5; P < 0.05). Rings were relaxed less than 50% of norepinephrine contraction. Following removal of the contrast, vascular relaxation in response to the agonists returned to normal. These results indicate that ionic radiocontrast nonspecifically inhibits vasodilation (both cAMP-mediated and cGMP-mediated) of canine renal arteries contracted with norepinephrine. This reversible impairment of vasodilation could inhibit normal renal perfusion and act as a mechanism of renal failure following radiocontrast infusion. In the adopted experimental protocol the isoproterenol-induced relaxation of renal arteries precontracted with norepinephrine was more affected, suggesting a pivotal role of the cAMP system.

Chronic experimental myocardial infarction produces antinatriuresis by a renal nerve-dependent mechanism

The present study focused on the role of sympathetic renal nerve activity, in mediating congestive heart failure-induced sodium retention following experimental chronic myocardial infarction. Groups of male Wistar rats (240-260 g) were studied: sham-operated coronary ligation (CON3W, N = 11), coronary ligation and sham-operated renal denervation (INF3W, N = 19), 3 weeks of coronary ligation and sympathetic renal nerve denervation (INF3WDX, N = 6), sham-operated coronary ligation (N = 7), and 16 weeks of coronary ligation (INF16W, N = 7). An acute experimental protocol was used in which the volume overload (VO; 5% of body weight) was applied for 30 min after the equilibration period of continuous iv infusion of saline. Compared to control levels, VO produced an increase (P < 0.01, ANOVA) in urine flow rate (UFR; 570%) and urinary sodium excretion (USE; 1117%) in CON3W. VO induced a smaller increase (P < 0.01) in USE (684%) in INF3W. A similar response was also observed in INF16W. In INF3WDX, VO produced an immediate and large increase (P < 0.01) in UFR (547%) and USE (1211%). Similarly, in INF3W VO increased (P < 0.01) UFR (394%) and USE (894%). Compared with INF3W, VO induced a higher (P < 0.01) USE in INF3WDX, whose values were similar to those for CON3W. These results suggest that renal sympathetic activity may be involved in sodium retention induced by congestive heart failure. This premise is supported by the observation that in bilaterally renal denervated INF3WDX rats myocardial infarction was unable to reduce volume expansion-induced natriuresis. However, the mechanism involved in urinary volume regulation seems to be insensitive to the factors that alter natriuresis.

Effect of strenuous maternal exercise before and during pregnancy on rat progeny renal function

The effects of strenuous exercise before and during pregnancy on the renal function and morphological alterations of the progeny were determined in a study on female Wistar rats. This research was done based on a previous study carried out in our laboratory, which showed morphological alterations in rats submitted to this kind of exercise. As the form is related to the function, the physiological relevance of submitting a pregnant female to a high-intensity exercise training regimen could be explained by the fact that morphological alterations can influence kidney function. The animals were assigned to one of two groups: control animals that did not exercise during pregnancy and trained animals that swam for 120 min 5 days a week for 8 weeks before pregnancy and daily for 60 min over a period of 8 weeks starting on the second day of pregnancy. Seven rats of each group were analyzed for morphological alterations and for renal function. The progeny of the rats used for morphological evaluation were born by cesarean section and the progeny of the animals used to evaluate renal function were born normally. The progeny were two months old when renal function was evaluated. Fertility and morbidity were the same for both groups. Strenuous maternal exercise had no significant influence on glomerular filtration rate (GFR) but renal plasma flow was lower in the progeny of the trained group (mean ± SD, 16.65 ± 3.77 ml min-1 kg-1) compared to the progeny of the control group (33.42 ± 2.56 ml min-1 kg-1). Antidiuretic and antinatriuretic effects on the progeny of the trained group were observed, since urine flow as percentage of GFR and the fraction of urinary sodium excretion were lower in this group (1.38 ± 0.10 and 0.60 ± 0.04%, respectively) compared to the progeny of the control group (2.36 ± 0.11 and 1.55 ± 0.20%, respectively). Moreover, in this exercise program, fetuses from trained animals were small-sized (2.45 ± 0.19 vs 4.66 ± 2.45 g for control animals) and showed lower differentiation compared to fetuses from the control group. These effects were probably caused by caloric restriction, hypoxia and reduction of umbilical cord length.

Effect of chronic fish oil supplementation on renal function of normal and cachectic rats

In the present study we determined the effect of chronic diet supplementation with n-3 PUFA on renal function of healthy and cachectic subjects by providing fish oil (1 g/kg body weight) to female rats throughout pregnancy and lactation and then to their offspring post-weaning and examined its effect on renal function parameters during their adulthood. The animals were divided into four groups of 5-10 rats in each group: control, control supplemented with fish oil (P), cachectic Walker 256 tumor-bearing (W), and W supplemented with fish oil (WP). Food intake was significantly lower in the W group compared to control (12.66 ± 4.24 vs 25.30 ± 1.07 g/day). Treatment with fish oil significantly reversed this reduction (22.70 ± 2.94 g/day). Tumor growth rate was markedly reduced in the P group (16.41 ± 2.09 for WP vs 24.06 ± 2.64 g for W). WP group showed a significant increase in mean glomerular filtration rate compared to P and control (1.520 ± 0.214 ml min-1 kg body weight-1; P < 0.05). Tumor-bearing groups had low urine osmolality compared to control rats. The fractional sodium excretion decreased in the W group compared to control (0.43 ± 0.16 vs 2.99 ± 0.87%; P < 0.05), and partially recovered in the WP group (0.90 ± 0.20%). In summary, the chronic supplementation with fish oil used in this study increased the amount of fat in the diet by only 0.1%, but caused remarkable changes in tumor growth rate and cachexia, also showing a renoprotective function.

Thalidomide and pentoxifylline block the renal effects of supernatants of macrophages activated with Crotalus durissus cascavella venom

Because thalidomide and pentoxifylline inhibit the synthesis and release of tumor necrosis factor-alpha (TNF-alpha), we determined the effect of these drugs on the renal damage induced by supernatants of macrophages activated with Crotalus durissus cascavella venom in order to identify the role of TNF-alpha in the process. Rat peritoneal macrophages were collected with RPMI medium and stimulated in vitro with C.d. cascavella venom (10 µg/ml) in the absence and presence of thalidomide (15 µM) or pentoxifylline (500 µM) for 1 h and washed and kept in culture for 2 h. Supernatant (1 ml) was tested on an isolated perfused rat kidney (N = 6 for each group). The first 30 min of each experiment were used as control. The supernatant was added to the perfusion system. All experiments lasted 120 min. The toxic effect of the preparation of venom-stimulated macrophages on renal parameters was determined. At 120 min, thalidomide (Thalid) and pentoxifylline (Ptx) inhibited (P < 0.05) the increase in perfusion pressure caused by the venom (control = 114.0 ± 1.3; venom = 137.1 ± 1.5; Thalid = 121.0 ± 2.5; Ptx = 121.4 ± 4.0 mmHg), renal vascular resistance (control = 4.5 ± 0.2; venom = 7.3 ± 0.6; Thalid = 4.5 ± 0.9; Ptx = 4.8 ± 0.6 mmHg/ml g-1 min-1), urinary flow (control = 0.23 ± 0.001; venom = 0.44 ± 0.01; Thalid = 0.22 ± 0.007; Ptx = 0.21 ± 0.009 ml g-1 min-1), glomerular filtration rate (control = 0.72 ± 0.06; venom = 1.91 ± 0.11; Thalid = 0.75 ± 0.04; Ptx = 0.77 ± 0.05 ml g-1 min-1) and the decrease in percent tubular sodium transport (control = 77.0 ± 0.9; venom = 73.9 ± 0.66; Thalid = 76.6 ± 1.1; Ptx = 81.8 ± 2.0%), percent tubular chloride transport (control = 77.1 ± 1.2; venom = 71.4 ± 1.1; Thalid = 77.6 ± 1.7; Ptx = 76.8 ± 1.2%), and percent tubular potassium transport (control = 72.7 ± 1.1; venom = 63.0 ± 1.1; Thalid = 72.6 ± 1.0; Ptx = 74.8 ± 1.0%), 30 min before and during the stimulation of macrophages with C.d. cascavella venom. These data suggest the participation of TNF-alpha in the renal effects induced by supernatant of macrophages activated with C.d. cascavella venom.

Acute effect of amiodarone on cardiovascular reflexes of normotensive and renal hypertensive rats

The aim of the present study was to evaluate the effect of amiodarone on mean arterial pressure (MAP), heart rate (HR), baroreflex, Bezold-Jarisch, and peripheral chemoreflex in normotensive and chronic one-kidney, one-clip (1K1C) hypertensive rats (N = 9 to 11 rats in each group). Amiodarone (50 mg/kg, iv) elicited hypotension and bradycardia in normotensive (-10 ± 1 mmHg, -57 ± 6 bpm) and hypertensive rats (-37 ± 7 mmHg, -39 ± 19 bpm). The baroreflex index (deltaHR/deltaMAP) was significantly attenuated by amiodarone in both normotensive (-0.61 ± 0.12 vs -1.47 ± 0.14 bpm/mmHg for reflex bradycardia and -1.15 ± 0.19 vs -2.63 ± 0.26 bpm/mmHg for reflex tachycardia) and hypertensive rats (-0.26 ± 0.05 vs -0.72 ± 0.16 bpm/mmHg for reflex bradycardia and -0.92 ± 0.19 vs -1.51 ± 0.19 bpm/mmHg for reflex tachycardia). The slope of linear regression from deltapulse interval/deltaMAP was attenuated for both reflex bradycardia and tachycardia in normotensive rats (-0.47 ± 0.13 vs -0.94 ± 0.19 ms/mmHg and -0.80 ± 0.13 vs -1.11 ± 0.13 ms/mmHg), but only for reflex bradycardia in hypertensive rats (-0.15 ± 0.02 vs -0.23 ± 0.3 ms/mmHg). In addition, the MAP and HR responses to the Bezold-Jarisch reflex were 20-30% smaller in amiodarone-treated normotensive or hypertensive rats. The bradycardic response to peripheral chemoreflex activation with intravenous potassium cyanide was also attenuated by amiodarone in both normotensive (-30 ± 6 vs -49 ± 8 bpm) and hypertensive rats (-34 ± 13 vs -42 ± 10 bpm). On the basis of the well-known electrophysiological effects of amiodarone, the sinus node might be the responsible for the attenuation of the cardiovascular reflexes found in the present study.

Effect of intraperitoneally administered hydrolyzed whey protein on blood pressure and renal sodium handling in awake spontaneously hypertensive rats

The present study evaluated the acute effect of the intraperitoneal (ip) administration of a whey protein hydrolysate (WPH) on systolic arterial blood pressure (SBP) and renal sodium handling by conscious spontaneously hypertensive rats (SHR). The ip administration of WPH in a volume of 1 ml dose-dependently lowered the SBP in SHR 2 h after administration at doses of 0.5 g/kg (0.15 M NaCl: 188.5 ± 9.3 mmHg vs WPH: 176.6 ± 4.9 mmHg, N = 8, P = 0.001) and 1.0 g/kg (0.15 M NaCl: 188.5 ± 9.3 mmHg vs WPH: 163.8 ± 5.9 mmHg, N = 8, P = 0.0018). Creatinine clearance decreased significantly (P = 0.0084) in the WPH-treated group (326 ± 67 µL min-1 100 g body weight-1) compared to 0.15 M NaCl-treated (890 ± 26 µL min-1 100 g body weight-1) and captopril-treated (903 ± 72 µL min-1 100 g body weight-1) rats. The ip administration of 1.0 g WPH/kg also decreased fractional sodium excretion to 0.021 ± 0.019% compared to 0.126 ± 0.041 and 0.66 ± 0.015% in 0.15 M NaCl and captopril-treated rats, respectively (P = 0.033). Similarly, the fractional potassium excretion in WPH-treated rats (0.25 ± 0.05%) was significantly lower (P = 0.0063) than in control (0.91 ± 0.15%) and captopril-treated rats (1.24 ± 0.30%), respectively. The present study shows a decreased SBP in SHR after the administration of WPH associated with a rise in tubule sodium reabsorption despite an angiotensin I-converting enzyme (ACE)-inhibiting in vitro activity (IC50 = 0.68 mg/mL). The present findings suggest a pathway involving ACE inhibition but measurements of plasma ACE activity and angiotensin II levels are needed to support this suggestion.

Improvement of adynamic bone disease after renal transplantation

Low bone remodeling and relatively low serum parathyroid hormone (PTH) levels characterize adynamic bone disease (ABD). The impact of renal transplantation (RT) on the course of ABD is unknown. We studied prospectively 13 patients with biopsy-proven ABD after RT. Bone histomorphometry and bone mineral density (BMD) measurements were performed in the 1st and 12th months after RT. Serum PTH, 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, and osteocalcin were measured regularly throughout the study. Serum PTH levels were slightly elevated at transplantation, normalized at the end of the third month and remained stable thereafter. Bone biopsies performed in the first month after RT revealed low bone turnover in all patients, with positive bone aluminum staining in 5. In the 12th month, second biopsies were performed on 12 patients. Bone histomorphometric dynamic parameters improved in 9 and were completely normalized in 6, whereas no bone mineralization was detected in 3 of these 12 patients. At 12 months post-RT, no bone aluminum was detected in any patient. We also found a decrease in lumbar BMD and an increase in femoral BMD. Patients suffering from ABD, even those with a reduction in PTH levels, may present partial or complete recovery of bone turnover after successful renal transplantation. However, it is not possible to positively identify the mechanisms responsible for the improvement. Identifying these mechanisms should lead to a better understanding of the physiopathology of ABD and to the development of more effective treatments.

Prevalence of low trauma fractures in long-term kidney transplant patients with preserved renal function

We evaluated the prevalence of low bone mineral density (BMD) and osteoporotic fractures in kidney transplantation (KT) patients and determined risk factors associated with osteoporotic fractures. The study was conducted on 191 patients (94 men and 97 women) with first KT for 3 years or more presenting stable and preserved renal function (serum creatinine levels lower than 2.5 mg/dl). KT patients were on immunosuppressive therapy and the cumulative doses of these drugs were also evaluated. BMD was determined by dual-energy X-ray absorptiometry at multiple sites (spine, femur and total body). Quantitative ultrasound of the calcaneus (broadband ultrasound attenuation, speed of sound, and stiffness index, SI) was also performed. Twenty-four percent (46) of all patients had either vertebral (29/46) or appendicular (17/46) fractures. We found osteoporosis and osteopenia in 8.5-13.4 and 30.9-35.1% of KT patients, respectively. Women had more fractures than men. In women, prevalent fractures were associated with diabetes mellitus [OR = 11.5, 95% CI (2.4-55.7)], time since menopause [OR = 3.7, 95% CI (1.2-11.9)], femoral neck BMD [OR = 1.99, 95% CI (1.4-2.8)], cumulative dose of steroids [OR = 1.1, 95% CI (1.02-1.12)] and low SI [OR = 1.1, 95% CI (1.0-1.2)]. In men, fractures were associated with lower lumbar spine BMD [OR = 1.75, 95% CI (1.1-2.7)], lower SI [OR = 1.1, 95% CI (1.03-1.13)], duration of dialysis [OR = 1.3, 95% CI (1.13-2.7)], and lower body mass index [OR = 1.24, 95% CI (1.1-1.4). Our results demonstrate high prevalence of low BMD and osteoporotic fractures in patients receiving a successful kidney transplant and indicate the need for specific intervention to prevent osteoporosis in this population.

Renal and extrarenal manifestations of autosomal dominant polycystic kidney disease

The objective of the present study was to determine the frequency of the most common clinical features in patients with autosomal dominant polycystic kidney disease in a sample of the Brazilian population. The medical records of 92 patients with autosomal dominant polycystic kidney disease attended during the period from 1985 to 2003 were reviewed. The following data were recorded: age at diagnosis, gender, associated clinical manifestations, occurrence of stroke, age at loss of renal function (beginning of dialysis), and presence of a family history. The involvement of abdominal viscera was investigated by ultrasonography. Intracranial alterations were prospectively investigated by magnetic resonance angiography in 42 asymptomatic patients, and complemented with digital subtraction arteriography when indicated. Mean age at diagnosis was 35.1 ± 14.9 years, and mean serum creatinine at referral was 2.4 ± 2.8 mg/dL. The most frequent clinical manifestations during the disease were arterial hypertension (63.3%), lumbar pain (55.4%), an abdominal mass (47.8%), and urinary infection (35.8%). Loss of renal function occurred in 27 patients (mean age: 45.4 ± 9.5 years). The liver was the second organ most frequently affected (39.1%). Stroke occurred in 7.6% of the patients. Asymptomatic intracranial aneurysm was detected in 3 patients and arachnoid cysts in 3 other patients. In conclusion, the most common clinical features were lumbar pain, arterial hypertension, abdominal mass, and urinary infection, and the most serious complications were chronic renal failure and stroke. Both intracranial aneurysms and arachnoid cysts occurred in asymptomatic patients at a frequency of 7.14%.

Increased expression of p38 mitogen- activated protein kinase is related to the acute renal lesions induced by gentamicin

Mitogen-activated protein kinases (MAPK) may be involved in the pathogenesis of acute renal failure. This study investigated the expression of p-p38 MAPK and nuclear factor kappa B (NF-kappaB) in the renal cortex of rats treated with gentamicin. Twenty rats were injected with gentamicin, 40 mg/kg, im, twice a day for 9 days, 20 with gentamicin + pyrrolidine dithiocarbamate (PDTC, an NF-kappaB inhibitor), 14 with 0.15 M NaCl, im, twice a day for 9 days, and 14 with 0.15 M NaCl , im, twice a day for 9 days and PDTC, 50 mg kg-1 day-1, ip, twice a day for 15 days. The animals were killed 5 and 30 days after the last of the injections and the kidneys were removed for histological, immunohistochemical and Western blot analysis and for nitrate determination. The results of the immunohistochemical study were evaluated by counting the p-p38 MAPK-positive cells per area of renal cortex measuring 0.05 mm². Creatinine was measured by the Jaffé method in blood samples collected 5 and 30 days after the end of the treatments. Gentamicin-treated rats presented a transitory increase in plasma creatinine levels. In addition, animals killed 5 days after the end of gentamicin treatment presented acute tubular necrosis and increased nitrate levels in the renal cortex. Increased expression of p-p38 MAPK and NF-kappaB was also observed in the kidneys from these animals. The animals killed 30 days after gentamicin treatment showed residual areas of interstitial fibrosis in the renal cortex, although the expression of p-p38 MAPK in their kidneys did not differ from control. Treatment with PDTC reduced the functional and structural changes induced by gentamicin as well as the expression of p-p38 MAPK and NF-kappaB. The increased expression of p-p38 MAPK and NF-kappaB observed in these rats suggests that these signaling molecules may be involved in the pathogenesis of tubulointerstitial nephritis induced by gentamicin.