Abnormalities of calcium, phosphorous and vitamin D metabolism with proximal renal tubular dysfunction in subjects environmentally exposed to cadmium

Calcium, phosphorus and vitamin D metabolism were examined in 21 male and 13 female subjects with renal tubular dysfunction in the cadmium-polluted Jinzu River basin in Toyama prefecture, Japan. Multiple proximal renal tubular dysfunction was detected in all subjects showing increased FE beta 2-m and FFua, generalized aminoaciduria and renal glucosuria. Reduced ability of tubular reabsorption of phosphate resulted in hypophosphatemia in 31% of the women. Despite decreased tubular reabsorption of calcium, the level of serum calcium remained normal in all subjects. Serum 1,25-dihydroxyvitamin-D [1,25(OH)2D], which is produced in the proximal tubules through 1 alpha-hydroxylation from 25-hydroxyvitamin-D [25OHD], was normal or increased to more than 60pg/ml. The serum level of 1,25(OH)2D was inversely related to creatinine clearance in both the men (p < 0.05) and women (p < 0.01). Serum iPTH was slightly increased to more than 0.9 mg/ml, whereas the levels of other hormones, including 25OHD, calcitonin, thyroxine (T4) and triiodothyronine (T3) were normal. The serum alkaline phosphatase activity and serum osteocalcin concentration were significantly increased compared to those of controls in both sexes. Bone loss detected by the measurement of bone density was prominent in female subjects. These results support the hypothesis that the serum phosphate concentration is more important than the serum concentration of 1,25(OH)2D for abnormalities of bone metabolism in cadmium-induced renal tubular dysfunction.     

Exercise activates renal dysfunction in hypertension

A bilateral, exercise-mediated renal functional abnormality was first described more than a decade ago. The disturbance is specific for hypertension, is seen in different forms of hypertension, and has been studied most extensively in hypertensives with renovascular disease. The bilateral-abnormal exercise renogram identifies the disturbance. Hypertensives with unilateral renovascular disease were studied in the continuing evaluation of the bilateral function disturbance. We examined 31 hypertensives with documented unilateral renovascular disease, all of whom had renography at rest and during 60 to 80 W ergometric exercise. An additional seven normotensives and 17 essential hypertensives served as controls, and had the same sequence of studies. All patients reported upon continued on to an infusion clearance with 131I-hippurate and 111In-diethylenetriamine pentaacetic acid to determine glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) at rest, and during 25 W ergometric exercise. Eighteen of 31 hypertensives with unilateral renovascular disease were found to have a bilateral-abnormal exercise renogram. Clearance examinations in these identified a prominent reduction of the GFR and a lesser decrease in the ERPF during exercise. Hypertensives with normal exercise renograms did not have the exercise mediated abnormal clearance pattern. Similar results were observed in the control population of essential hypertensives, 65% of whom developed the functional disturbance. The seven normotensives controls did not exhibit the exercise mediated function changes. We conclude that an exercise-mediated bilaterally occurring functional disturbance exists in certain hypertensives, who then have a bilateral-abnormal exercise renogram. Associated with this is a distinctly abnormal clearance during exercise which is characterized by a low filtration fraction.     

Pathophysiology of female lower urinary tract dysfunction

Urinary incontinence is a disorder with widely varying severity, patient symptoms, and etiologies. Urine loss can be because of reversible or irreversible systemic disease, abnormalities of urine storage, or voiding phase disorders. The optimal work up of an individual incontinence may include evaluation of neurologic, muscular, and urogenital systems, as well as medical, pharmaceutical, environmental, and psychosocial issues.     

Early biochemical indicators of renal damage in arterial hypertension

The demonstration that stains reduce the risk of cardiovascular diseases, in both secondary and primary prevention trials, led to the recent publication of sophisticated pharmaco-economical studies. A lot of factors may influence the cost-effectiveness ratio of the pharmacological intervention, especially the mode of calculation of various costs, the initial level of cardiovascular risk of the patients and the medico-economical particularities of each country. What so ever, available studies appear to justify the use of statins in secondary prevention, i.e. in coronary patients, even those with only a moderate hypercholesterolaemia, and, in primary prevention, i.e in hypercholesterolaemia individuals with obvious high risk of cardiovascular disease.     

Efficacy of amphipathic dithiocarbamates in intracellular cadmium mobilization and in modulation of hepatic and renal metallothionein in cadmium pre-exposed rat

Forty-eight hours after an intraperitoneal injection of cadmium chloride (1.5 mg Cd/kg) to female albino rats, Cd was mainly localized in the hepatic and renal supernatant cytosolic fraction (SCF). Seventy-two hours later, the total hepatic burden remained unchanged but the total renal burden was enhanced, showing its tendency to accumulate in the kidney. A single dose (0.4 mmol/kg, i.p.) of sodium N-benzyl-D-glucamine dithiocarbamate (BG.DTC) or sodium N-(4-methoxybenzyl)-D-glucamine dithiocarbamate (MeO.BG.DTC), 24 h after Cd injection, efficiently mobilized Cd from hepatic SCF, apparently from cadmium-metallothionein (Cd-MT); MeO.BG.DTC also removed Cd from hepatic nuclear mitochondrial fraction. This treatment, however, increased the renal burden of Cd, indicating that the chelating agents, at least partly, transport Cd from the liver and possibly from other sites into the kidney. Three doses of the chelators further enhanced mobilization of Cd from hepatic as well as renal SCF, as corroborated by its enhanced urinary and, to a greater extent, fecal excretion. Hepatic and renal MT were induced several-fold above normal after a single dose of Cd as well as single or repeated doses of BG.DTC or MeO.BG.DTC. Seventy-two hours after a Cd injection, the hepatic MT declined to half of the induced level while the renal MT remained elevated. Administration of BG.DTC or MeO.BG.DTC in Cd pre-treated rats produced an additive response in hepatic MT, but the response in renal MT was less than additive at one dose and slightly declined after three doses. Hepatic Zn and Cu and renal Zn increased on treatment with Cd but were depleted after a single or repeated injection of BG.DTC or MeO.BG.DTC in normal as well as in Cd pre-exposed animals. The results indicate that intracellular access of amphipathic dithiocarbamates effectively mobilizes MT-bound Cd, which is preferentially excreted in the feces, and helps avoid further burden on the kidney and consequent nephrotoxicity. Additionally, MeO.BG.DTC was a better inducer of hepatic MT to help increased capture of toxic metal from the initial circulation and consequent toxicity.     

Vagal dysfunction and impaired urinary sodium and water excretion in cirrhosis

OBJECTIVE: To evaluate the possible role of vagal impairment in the disturbances of urinary sodium and water excretion observed in cirrhosis. METHODS: Standard cardiovascular reflex tests were used to assess Autonomic function in 11 cirrhotic patients, and the response to an acute intravenous water load was determined. Changes in plasma noradrenaline, antidiuretic hormone, renin, and atrial natriuretic peptide also were evaluated. RESULTS: Patients with vagal dysfunction were shown to have significantly impaired urinary sodium and water excretion, compared with those whose cardiovascular tests were normal (5-h urinary sodium excretion, 32.3 +/- 9.0 vs. 69.4 +/- 12.7 mmol, p < 0.05; % water load excreted at 5 h, 67.8 +/- 10.5 vs. 109.2 +/- 3.67%, p < 0.008). This was associated with higher circulating noradrenaline, renin, and antidiuretic hormone levels after the water load in the vagal dysfunction group. Urinary sodium excretion correlated with the heart rate variation on deep breathing (r = 0.74, p < 0.013) and the heart rate response to atropine (r = 0.75, p < 0.020); the % water load excreted correlated with the number of abnormal cardiovascular tests in each patient (rS = 0.67, p < 0.02). Although patients with vagal abnormalities had worse liver function, urinary sodium and water excretion correlated better with parasympathetic tests than with standard parameters of hepatic function. CONCLUSIONS: The presence of vagal impairment in cirrhosis appears to be associated with impaired urinary sodium and water excretion, as well as disturbances in circulating vasoactive hormones. These findings could be due to an afferent defect resulting in diminished inhibitory input from intrathoracic volume and arterial baroreceptors, although a confounding effect of worse hepatic function in patients with vagal impairment cannot be excluded.     

Urodynamic risk factors for renal dysfunction in men with obstructive and nonobstructive voiding dysfunction

BACKGROUND AND PURPOSE: Adrenomedullin is a recently discovered vasoactive peptide that is structurally related to calcitonin gene-related peptide (CGRP). Adrenomedullin is produced by vascular endothelium and smooth muscle and is present in the brain. The goals of this study were to determine (1) whether adrenomedullin produces dilatation of cerebral arterioles and whether this effect is mediated by activation of CGRP receptors and (2) whether vasodilatation to adrenomedullin was mediated by K+ channels. METHODS: Diameter of cerebral arterioles (mean +/- SE baseline, 46 +/- 1 microns) was measured using a closed cranial window in anesthetized rats. RESULTS: Application of rat adrenomedullin (10(-7) and 10(-6) mol/L) increased vessel diameter by 16 +/- 3% and 45 +/- 8% (n = 5), respectively. Vasodilator responses to repeated application of adrenomedullin were reproducible. Pretreatment of cerebral arterioles with the specific CGRP1 receptor antagonist CGRP-(8-37) (5 x 10(-7) mol/L) selectively inhibited the vasodilator responses to adrenomedullin without inhibiting responses to ADP (10(-5) to 10(-3) mol/L). Responses to adrenomedullin (10(-7) and 10(-6) mol/L) were 14 +/- 1% and 40 +/- 3% before and 2 +/- 2% and 6 +/- 1% after CGRP-(8-37), respectively (P < .01). Glibenclamide (10(-6) mol/L), an inhibitor of ATP-sensitive K+ channels, reduced the responses to adrenomedullin without attenuating responses to ADP. Responses to adrenomedullin were 19 +/- 4% and 35 +/- 6% before and 6 +/- 3% and 19 +/- 5% after glibenclamide, respectively (P < .05). Iberiotoxin (10(-7) mol/L), an inhibitor of calcium-dependent K+ channels, also significantly attenuated responses to adrenomedullin and did not inhibit vasodilatation to papaverine. Responses to adrenomedullin were 16 +/- 2% and 55 +/- 8% before and 12 +/- 4% and 26 +/- 3% after iberiotoxin, respectively (P < .01 for 10(-6) mol/L adrenomedullin). CONCLUSIONS: Adrenomedullin produces substantial dilatation of cerebral arterioles in vivo, and the response is mediated in large part by activation of CGRP1 receptors. Cerebral vasodilatation to adrenomedullin appears to be dependent on activation of K+ channels.     

Variants of dysfunction of the upper urinary tract in urolithiasis

Registration of contractility of the upper urinary tracts (UUT) at multichannel impedance ureterography was conducted in 30 patients with concrements in the kidneys and ureters before extracorporeal lithotripsy. By defects in urodynamics, the patients were divided into 4 groups. The most severe affection of urodynamics (low amplitude of the peristalsis, high tonicity of UUT wall) occurred in group 4. From group 1 to 4 contraction arrhythmia, deformity of contraction complexes, retrograde contraction waves were increasing. The index has been calculated for estimation of UUT performance in transporting urine.     

Sexual dysfunction in men with lower urinary tract symptoms

The conventional view that sexual function is not adversely affected by lower urinary tract symptoms (LUTS), assumed to be caused by enlargement secondary to benign prostatic hyperplasia (BPH), was investigated in this study of 423 men aged 40 years and over in a community population in the UK and 1271 urology clinic attenders aged 45 years and over in 12 countries, using the ICSmale and ICSsex questionnaires. Sexual dysfunction was found to be common: in the community, age standardized prevalences of reduced rigidity of erections were 53%, reduced ejaculation 47%, and pain on ejaculation 5%; in clinic men, age standardized prevalences of reduced rigidity of erections were 60%, reduced ejaculation 62%, and pain on ejaculation 17%. Sex lives were reported to be spoiled by LUTS in 8% of community men and 46% in the clinic. There were negative trends for age in the extent to which clinic men were bothered by these symptoms, although older men were still very concerned. Significantly raised odds ratios of sexual dysfunction were found in those with LUTS, especially storage symptoms associated with incontinence. Urinary flow rates were not associated with sexual symptoms. Sexual dysfunction is, therefore, strongly associated with LUTS, is a matter of concern to the men affected, and should be taken into account when managing patients with LUTS.     

Treatment of urinary infections in chronic renal insufficiency

The author describes some differences in the course of treatment of urinary pathway infections in prolonged reduced renal function. He emphasizes changes from the aspect of the clinical course of urinary infections and changes in the pharmacokinetics and pharmacodynamics of antibiotics and principles for selection of therapy are outlined.     

Levels of cadmium in serum of patients with chronic renal failure

The aim of the study was obtain answers the following questions: 1. Are serum cadmium concentrations in patients with chronic renal failure (CRF) different from levels in healthy subjects? 2. Are serum concentrations of above mentioned metal different between haemodialysed and non-haemodialysed patients. 3. Are serum cadmium concentrations changing during haemodialysis? 66 patients with chronic renal failure (42 patients treated with haemodialysis and 24 non-haemodialysed patients) and 16 healthy subjects were observed. The blood samples in non-haemodialysed patients and healthy subjects were withdrawn only after cannula had been inserted into the antebrachial vein. The blood samples in haemodialysed patients were withdrawn four times: just before dialysis, during haemodialysis (in one hour of dialysis just in front of dialyser and just behind one) and after haemodialysis. Cadmium concentrations in serum in all examined group and cadmium concentrations in dialysis fluid and in demineralised water were measured by flame atomic absorption spectrophotometry. No significant changes were observed in serum cadmium concentration between patients with CRF and healthy subjects. Cadmium-concentration in non-haemodialysed patients was significantly higher than in haemodialysed patients. During haemodialysis a significant increase of serum cadmium level was observed. Conclusions: 1. Serum cadmium concentration in patients with CRF and in healthy subjects are not statistically different; 2. No significant changes in cadmium concentration between uraemic group patients were found; 3. Haemodialysis influences significantly on cadmium concentration.     

Medical management of urinary calculi in a stallion with breeding dysfunction

A 9-year-old Thoroughbred stallion was examined because of breeding dysfunction and possible urethritis. The stallion had good libido and readily obtained an erection, mounted, and intromitted but did not thrust and ejaculate. After mounting the mare, the stallion would squeal and dismount. Endoscopic examination of the urethra and bladder revealed irregular, spiculate yellow crystals (< 1 cm in size) and sabulous deposits; numerous calculi were embedded in the mucosa of the bladder. Because the horse was at the start of a breeding season, the owner would not give permission for general anesthesia. Medical management was attempted, because postoperative convalescence after surgical removal of calculi might have curtailed breeding activities, and the calculi were small. Every 1 to 3 days, the bladder was lavaged with saline solution containing acetic acid, and anti-inflammatory and antimicrobial drugs were administered. The stallion was able to return to breeding mares, and sperm numbers and semen quality were good. However, urine contamination of the ejaculate was detected, suggesting that the stallion may have had a primary neurologic deficit affecting bladder control and function that was causing calculi to form secondarily because of delay in movement of urine through the urinary tract.     

Pretransplant renal dysfunction predicts poorer outcome in liver transplantation

BACKGROUND: Numerous clinicians and researchers have expressed concern about the necessity and potential adverse consequences of many cesarean births in the United States. The purpose of this study was to explore college students' attitudes and beliefs about cesarean section. METHODS: One hundred two college students (66% women) completed a 20-item questionnaire that asked if they viewed cesarean delivery as a potentially negative experience, as a normal or acceptable method of childbirth, and as medically necessary, and asked about their beliefs concerning risk and prevention of cesarean birth. RESULTS: The number of "undecided" responses in the study was striking (7.8% to 69.6% across the 20 items). In general, women and men responded similarly, although women were significantly more likely than men to say they would be profoundly disappointed if their babies had to be delivered by cesarean section. Despite expressing cynicism about the cesarean birth rate (40% agreed that many unnecessary cesarean births occurred) and not viewing the procedure as a normal way of giving birth (47%), most respondents (over 70%) disagreed that giving birth by cesarean would be a negative experience or would make a woman feel like a failure. CONCLUSION: A high level of uncertainty exists about certain aspects of cesarean birth among young women and men, highlighting the need for information for prospective parents. Most college students did not view the cesarean birth experience as either potentially negative or normal. Future research should explore coverage of cesarean birth in childbirth education classes and the roles physicians, nurses, and midwives play in preparing expectant parents for the possibility of cesarean delivery.