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PubMed1998

Urinary excretion of oestrone sulphate and cortisol in early pregnant gilts treated with glucocorticoids.

The aim of this study was to determine rates of urinary excretion of oestrone sulphate and cortisol in early pregnant gilts that were untreated or treated with either dexamethasone, corn oil or hydrocortisone. Twenty Polish Landrace gilts were used. They were grouped immediately after mating as follows: Experiment I--Group 1 (5 gilts), control animals and Group 2 (5 gilts), injected i.m. with dexamethasone (30 micrograms/kg) at 12-h intervals from day 13 to day 22 of pregnancy; Experiment II--Group 3 (5 gilts), injected i.m. with corn oil at 12-h intervals from day 13 to day 22 of pregnancy and Group 4 (5 gilts), injected i.m. with hydrocortisone acetate (250 mg) at 12-h intervals from day 11 to day 20 of pregnancy. Gilts were placed in metabolic cages, and 24-h urine aliquots were collected from day 6 to day 32 of pregnancy. On days 34-36 of pregnancy gilts were slaughtered and clinical data were collected. Rates of urinary excretion of oestrone sulphate and cortisol were determined by enhanced chemiluminescence immunoassays. The urinary excretion of oestrone sulphate expressed in nmol/24 h and mumol/mol creatinine were significantly correlated. There was no correlation between cortisol expressed in nmol/24 h and mumol/mol creatinine (p > 0.5). A first significant increase of urinary oestrone sulphate excretion, expressed in nmol/24 h, on days 13-14 and a second one on days 19-20 of gestation occurred in control untreated and oil-treated gilts. The urinary excretion of oestrone sulphate reached maximum values between days 25 and 32 of gestation. In dexamethasone-treated gilts cortisol excretion significantly decreased on day 16, i.e. 3 days after injections of dexamethasone had commenced. The treatment with hydrocortisone resulted in a significantly increased cortisol excretion after the last injection of hydrocortisone. There were no relations between levels of urinary oestrone sulphate excretion expressed in nmol/24 h and the number of foetuses. When the urinary excretion of oestrone sulphate was expressed in mol/mol creatinine we found a positive relation between concentrations on day 20 of pregnancy and the number of foetuses. In one untreated gilt with a relatively high urinary excretion of cortisol (more than 200 nmol/24 h) a lower number of foetuses was found at autopsy. In conclusion, both dexamethasone and hydrocortisone treatment seemed to delay the first observed peak in oestrone sulphate in gilts without affecting the embryonic survival and the number of viable foetuses.

Animals↗
PubMed1997

Iodine intake and urinary excretion among adults in the Netherlands.

OBJECTIVE: To assess the prevalence of low and marginal iodine intake and urinary iodine excretion among adults in the Netherlands and to investigate determinants of urinary iodine excretion. DESIGN AND SUBJECTS: The study population consisted of 444 people aged 20-79 y, balanced for sex and 10 y age classes with an over-representation of people with a low habitual intake of vitamin B6. Food consumption was measured by three day food records and 24 h urine was sampled twice. RESULTS AND CONCLUSIONS: On average, iodine intake (mean of three days) in men was in the recommended range of 150-300 microg/d, but average intake in women was not. Mean 24 h urinary excretion values confirmed this observation. Estimation of the prevalence of low iodine excretion depended on the parameter chosen (absolute per 24 h, per kg body weight per 24 h, as concentration or per creatinin). The prevalence of low iodine supply, based on intake <100 microg/d (mean of three days) and intake or excretion parameters per creatinin excretion or per kg body weight, varied from 4-14% among adult women and from 5-17% among adult men. The prevalence of marginal iodine intake (<50 microg/d) and excretion was less than 5% in all adult age-sex groups. Urinary iodine excretion was most strongly associated with intake of iodine as such or as bread in combination with urinary excretion of sodium or potassium, confirming the importance of iodized salt (in bread) for iodine status. Age and total energy intake had a relatively minor impact on urinary iodine excretion.

Adult↗
PubMed1990

Effects of inducers and inhibitors of mixed-function oxidases on the biliary excretion of pentacaine metabolites.

The biliary excretion of 3H-pentacaine and its metabolites was studied in rats pretreated with an inducer or inhibitor of mixed-function oxidases. Over one-fourth (25.8 per cent) of a 2 mg kg-1 intraportal dose of 3H-pentacaine was excreted in bile in urethaneanaesthetized control rats within 3 h. The radioactivity appeared in the form of the parent drug, basic metabolites, and metabolite conjugates, 3.1, 86.5, and 10.4 per cent of the total radioactivity excreted, respectively. Pretreatment of rats with phenobarbital enhanced only slightly the biliary excretion of basic metabolites, and pretreatment with 3-methylcholanthrene had no effect. Phenobarbital also increased the initial rate of excretion of conjugates, but this effect was not sustained. 3-Methylcholanthrene had a tendency to impair excretion of conjugates by bile. Pretreatment of rats with SKF 525-A decreased the biliary excretion of both basic metabolites and conjugates while cimetidine did not alter significantly the biliary excretion of pentacaine metabolites. These results suggest that the canalicular transport of metabolites may be the most important factor in controlling pentacaine metabolite excretion in bile.

Animals↗
PubMedDate not supplied

Biliary and urinary excretion of sulfated, glucuronidated and tetrahydroxylated bile acids in cirrhotic patients.

In patients with hepatobiliary diseases, considerable amounts of sulfated and glucuronidated bile acids are excreted in urine. Information on the biliary excretion of these compounds is lacking. We used an intestinal perfusion method to determine the biliary excretion of sulfated and glucuronidated bile acids in eight patients with alcoholic cirrhosis and moderately severe cholestasis and compared results with urinary excretion rates. In bile, the patients excreted 508.7 mumoles per hr (mean) nonsulfated, nonglucuronidated bile acids, 8.1 mumoles per hr sulfated bile acids and 4.0 mumoles per hr glucuronidated bile acids. In urine, these patients excreted 0.27 mumoles per hr nonsulfated, nonglucuronidated bile acids, 0.88 mumoles per hr sulfated bile acids and 0.02 mumoles per hr glucuronidated bile acids. Sulfates and glucuronides of mono-, di- and trihydroxy bile acids were detected in urine and bile. In urine, tetrahydroxy bile acids were only excreted as nonsulfated and nonglucuronidated forms. The bile:urine excretion ratio of sulfated bile acids was 9:1 and of glucuronidated bile acids was 226:1. In alcoholic cirrhosis with cholestasis, biliary excretion is an important excretory route of sulfated and glucuronidated bile acids.

Adult↗
PubMed1995

Biliary excretion of copper, metallothionein, and glutathione into Long-Evans Cinnamon rats: a convincing animal model for Wilson disease.

Long-Evans Cinnamon (LEC) rats, characterized by a gross accumulation of hepatic Cu and the spontaneous onset of hepatitis, have been established to be an animal model for Wilson disease. They were used to estimate the relationships among copper (Cu), metallothionein (MT), and reduced glutathione (GSH) in biliary excretion in this study. Even though a huge amount of MT existed in the LEC rat liver (5016 micrograms/g liver) compared to that (63 micrograms/g liver) of controls (Fischer rats), the biliary excretion of MT (65 ng/ml bile) did not reflect the accumulated MT level in LEC rats. It seems likely that MT does not excrete intrinsically into the bile. Biliary excretion of Cu (0.17 microgram/ml) in LEC rats was significantly lower than that (0.57 microgram/ml) in Fischer rats. The difference in biliary excretion of GSH between the two groups was significant but slight. The reduced excretion of GSH into bile in LEC rats may be due to increased hepatic gamma-glutamyltransferase but not to hepatic GSH levels. There were no differences in biliary potassium and inorganic phosphorous between the two groups. On the other hand, excretion of lysosomal enzymes such as beta-N-acetylglucosaminidase into bile was much lower in LEC rats (15.6 units/liter) than in controls (42.5 units/liter). The defective biliary excretion of Cu may be due to impaired lysosomal exocytosis, rather than canalicular membrane impairment. The LEC rat is very useful for research into the dynamics of metal excretion via the hepatobiliary system.

Acetylglucosaminidase↗
PubMed1994

Biliary excretion of lysosomal enzymes, iron, and oxidized protein in Fischer-344 and Sprague-Dawley rats and the effects of diquat and acetaminophen.

Administration of hepatotoxic doses of diquat to male Fischer-344 rats increases biliary excretion of nonheme iron, whereas comparably hepatotoxic doses of acetaminophen decrease biliary export of iron. The effects of acetaminophen and diquat on the activities in bile of representative lysosomal enzymes, beta-N-acetylglucosaminidase (beta-NAG) and beta-glucuronidase (beta-GLUC) were examined as a means of assessing the possible role of lysosomal exocytosis in the effects of these hepatotoxins on biliary excretion of iron. In pentobarbital-anesthetized male Fischer-344 rats, diquat at 0.1 mmol/kg increased the biliary export of biliary beta-NAG and beta-GLUC, in conjunction with similar increases in iron. Sprague-Dawley rats, which are resistant to diquat-induced hepatic necrosis despite showing marked oxidant stress responses, showed no increases in biliary efflux of iron, beta-NAG, or beta-GLUC in response to diquat. Conversely, acetaminophen at doses of 400 or 1500 mg/kg markedly decreased biliary concentrations and efflux rates of beta-NAG and beta-GLUC in Fischer-344 rats in parallel with decreases in biliary iron, suggesting that the hepatotoxin-induced effects on biliary iron excretion may be mediated through effects on lysosomal exocytosis. Both acetaminophen and diquat increased total protein content of bile in both strains of rats; however, the proteins excreted after administration of diquat to Fischer-344 rats showed marked increases in contents of protein carbonyls, as assayed with 2,4-dinitrophenylhydrazine, whereas biliary proteins in acetaminophen-treated animals were not more oxidized than in controls. Sprague-Dawley rats given diquat showed no increase in the biliary excretion of protein carbonyls, despite the increased excretion of glutathione disulfide observed in these animals. The significant increases in biliary excretion of protein carbonyls by the diquat-treated Fischer-344 rats suggest oxidation of cellular proteins catalyzed by chemically reactive iron chelates and the excretion of at least some of the oxidized proteins to the bile, possibly through lysosomal exocytosis. The effects of acetaminophen on biliary protein excretion do not appear to involve oxidation.

Acetaminophen↗
PubMed1998

Biotransformation of perchloroethene: dose-dependent excretion of trichloroacetic acid, dichloroacetic acid, and N-acetyl-S-(trichlorovinyl)-L-cysteine in rats and humans after inhalation.

Chronic exposure of rodents to perchloroethene (PER) increased the incidence of liver tumors in male mice and resulted in a small but significant increase in the incidence of renal tumors in male rats. The tumorigenicity of PER is mediated by metabolic activation reactions. PER is metabolized by cytochrome P450 and by conjugation with glutathione. Cytochrome P450 oxidation of PER results in trichloroacetyl chloride which reacts with water to trichloroacetic acid (TCA) which is excreted. The formation of S-(trichlorovinyl)glutathione (TCVG) from PER results in nephrotoxic metabolites. TCVG is cleaved to S-(trichlorovinyl)-L-cysteine (TCVC) and acetylated to N-acetyl-S-(trichlorovinyl)-L-cysteine (N-ac-TCVC), which is excreted with urine. TCVC is also cleaved in the kidney by cysteine conjugate beta-lyase to dichlorothioketene which may react with water to dichloroacetic acid (DCA) or with cellular macromolecules. The object of this study was to comparatively quantify the dose-dependent excretion of PER metabolites in urine of humans and rats after inhalation exposure. Three female and three male human volunteers and three female and three male rats were exposed to 10, 20, and 40 ppm PER for 6 h, and three female and three male rats to 400 ppm. A dose-dependent increase in the excretion of TCA and N-ac-TCVC after exposure to PER was found both in humans and in rats. A total of 20.4 +/- 7.77 mumol of TCA and 0.21 +/- 0.05 mumol of N-ac-TCVC were excreted in urine of human over 78 h after the start of exposure to 40 ppm PER; only traces of DCA were present. After identical exposure conditions, rats excreted 1.64 +/- 0.42 mumol of TCA, 0.006 +/- 0.002 mumol of N-ac-TCVC and 0.18 +/- 0.04 mumol of DCA. Excretion of N-ac-TCVC in male rats exposed to 400 ppm PER (103.7 nmol) was significantly higher, compared to female rats (31.5 nmol) exposed under identical conditions. N-ac-TCVC was rapidly eliminated with urine both in humans (t1/2 = 14.1 h) and in rats (t1/2 = 7.5 h). When comparing the urinary excretion of N-ac-TCVC, a potential marker for the formation of reactive intermediates in the kidney, humans received a significantly lower dose (3 nmol/kg at 40 ppm) compared to rats (23.0 nmol/kg) after identical exposure conditions. In addition, rats excreted large amounts of DCA which likely is a product of the beta-lyase-dependent metabolism of TCVC in the kidney. The obtained data suggest that glutathione conjugate formation and beta-lyase-dependent bioactivation of TCVC in PER metabolism is significantly higher in rats than in humans. Thus, using rat tumorigenicity data for human risk assessment of PER exposure may overestimate human tumor risks.

Acetylcysteine↗
PubMed1994

The effect of endogenous parathyroid hormone, exogenous calcitonin, and dibutyryl cyclic AMP on urinary excretion of N-acetyl-beta-D-glucosaminidase.

Urinary excretion of N-acetyl-beta-D-glucosaminidase (NAG) transiently increases after PTH(1-34) infusion in idiopathic hypoparathyroidism (IHP) but this response is impaired in pseudohypoparathyroidism (PHP) type I. We investigated the effects of endogenous PTH, exogenous calcitonin (CT), and dibutyryl cAMP (DBcAMP) on urinary excretion of NAG. Urinary NAG excretion in 14 patients with primary hyperparathyroidism (1 degree HPT) was more than in normal subjects (P < 0.001) and decreased after parathyroidectomy (P < 0.01). Urinary NAG excretion increased after the infusion of 1.5 MRC/kg of eel CT in eight normal subjects (P < 0.001), two patients with IHP, and a patient with PHP type Ib but not in a patient with PHP type Ia. The increases of urinary NAG excretion by CT and by PTH(1-34) were positively correlated with the increases of urinary cAMP excretion (r = 0.752; P < 0.001 and r = 0.534; P < 0.002, respectively). Urinary NAG excretion increased after DB-cAMP infusion in five normal subjects (P < 0.01), two patients with IHP, and two with PHP type I. The increase of urinary NAG by 6.0 mg/kg of DBcAMP was more than by 2.5 mg/kg of DBcAMP in normal subjects (P < 0.01). The increase of urinary NAG by 2.5 mg/kg of DBcAMP in PHP type I was comparable with that by 6.0 mg/kg in normal subjects, suggesting a hyperresponsiveness to DBcAMP in PHP type I. Urinary excretion of NAG is a useful indicator of renal tubular responsiveness to PTH and CT. Cyclic AMP-dependent mechanism is probably involved in PTH and CT-induced increase in urinary excretion of NAG.

Acetylglucosaminidase↗
PubMed1994

Smoking and dietary intake of polycyclic aromatic hydrocarbons as sources of interindividual variability in the baseline excretion of 1-hydroxypyrene in urine.

Seventy-six male volunteers, who were not occupationally exposed to polycyclic aromatic hydrocarbons (PAHs), participated in a study on the effect of tobacco smoking, alcohol consumption, dietary PAH intake, age, and body fat content on the baseline excretion of 1-hydroxypyrene in urine. Major determinants of urinary 1-hydroxypyrene excretion were smoking, dietary PAH intake, and age. The mean 1-hydroxypyrene concentrations in the urine of the volunteers in this study ranged between 0.05 and 0.79 mumol/mol creatinine. Smokers excreted on average 0.25 mumol/mol creatinine (range: 0.10-0.79 mumol/mol creatinine), and nonsmokers on average 0.12 mumol/mol creatinine (range: 0.04-0.29 mumol/mol creatinine). The average number of cigarettes smoked per day correlated well with urinary 1-hydroxypyrene concentrations (rs = 0.67, P < 0.001). The consumption of PAH-containing food products and active smoking account for 99% of total pyrene intake. The effect of age on 1-hydroxypyrene excretion is probably caused by a lower creatinine excretion in the elderly. Passive smoking and fat content had a statistically significant, but negligible effect on urinary 1-hydroxypyrene excretion. Passive smoking and the inhalation of ambient air are relatively in important for total pyrene intake (both account for less than 1%). Neither the consumption of alcohol nor the inhalation of ambient air significantly affected urinary 1-hydroxypyrene excretion. It is concluded that when urinary 1-OH-pyrene excretion is used in the assessment of PAH exposure, one should particularly be aware of the interindividual variability of the baseline excretion of PAH metabolites due to tobacco smoking and dietary PAH intake.

Adult↗
PubMed1995

Albumin excretion and vascular deaths in NIDDM.

Non-insulin-dependent diabetes mellitus (NIDDM) is associated with premature mortality, generally thought to be exaggerated in patients with microalbuminuria. This prospective 8-year follow-up study aimed to determine outcome, mortality and cause of death in NIDDM patients with abnormal urinary albumin excretion compared to those with normal albumin excretion. We recruited 153 NIDDM patients with abnormal urinary albumin excretion and 153 control subjects with albumin excretion within the normal non-diabetic range, matched for age, sex and duration of diabetes, from three University hospital diabetic clinics in Newcastle upon Tyne. The outcome measures were status at follow-up, mortality and cause of death. Subjects with abnormal albumin excretion had a significantly higher 8-year mortality than matched control subjects (Odds Ratio 1.47, p = 0.02; 108 vs 66 per 1000 person years follow-up, p < 0.001). This difference was seen at all levels of abnormal albumin excretion, from just outside the normal range (10.6-29.9 microgram/min: 104 vs 61 per 1000 person years follow-up, p < 0.001) to more conventional definitions of microalbuminuria (> or = 30 micrograms/min: 111 vs 71 per 1000 person years follow-up, p < 0.01). Those with abnormal albumin excretion had an excess of vascular deaths compared to matched control subjects (Odds Ratio 1.70, p = 0.009), again at different levels of albumin excretion (10.6-29.9 micrograms/min p < 0.01, 30-150 micrograms/min p < 0.05). On multivariate analysis, age, initial ischaemic heart disease and initial albumin excretion rates were independent predictors of death from all causes.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1996

Evidence for early and persistent impairment of salivary gland excretion after irradiation of head and neck tumours.

Salivary gland scintigraphy with technetium-99m pertechnetate was used to follow changes in the excretion and uptake function of the major salivary glands until 1 year after irradiation. Twenty-five patients who received radiotherapy for head and neck tumours were included in the study. Seventy-nine salivary glands (39 parotid and 40 submandibular) were evaluated in relation to the average received radiation dose. Salivary gland scintigraphy was performed before and 1, 6 and 12 months after radiotherapy. For each gland the excretion response to carbachol, evaluated by calculation of the salivary excretion fraction (SEF), the cumulative gland uptake (CGU) and the absolute excreted activity (AEA) at various intervals after radiotherapy were compared with the baseline values. The excretion response decreased in 20 of 25 patients at 1 month after radiotherapy. One month after radiotherapy both SEF and AEA decreased significantly in relation to the radiation dose. These decreases in excretion parameters persisted during the follow-up period. Parotid excretion was affected significantly more than submandibular excretion. CGU values did not change significantly until 6 months after radiotherapy, but at 12 months a significant decrease related to radiation dose was observed. Xerostomia was assessed during radiotherapy and on the days of the scintigraphic tests. The incidence of xerostomia did not correspond to the effects observed in the scintigraphic studies. It is concluded that radiotherapy induces early and persistent impairment of salivary gland excretion, related to the radiation dose. This impairment is stronger in parotid glands than in submandibular glands.

Dose-Response Relationship, Radiation↗
PubMed1994

Dose dependency of fermentation and the extent of renal excretion of palatinit (isomalt) in rats with respect to its energy value.

The impact of dose-dependent caloric salvage by microbial fermentation processes in the lower gut and the extent of renal excretion for the overall energetic availability of the alternative bulk sweetener Palatinit were investigated in rats. To evaluate the extent of dose-dependent fermentation a conventional and a germ-free rat model were used and fecal excretions of Palatinit after intragastric application were compared. Because of the lack of bacterial colonization in the gastrointestinal tract in germ-free rat the difference in fecal excretion of Palatinit between germ-free and conventional rat is mainly due to bacterial fermentation. To determine the amount of renal excretion of Palatinit the urine was collected. The experiments were conducted using different amounts of Palatinit (300 and 1,200 mg/kg body weight = mg/kg b.w.). Fecal excretions of Palatinit and its monomers (sorbitol and mannitol) were measured by high-performance liquid chromatography (HPLC) and for the determination of renal excretions a gas chromatography system was used. After the application of 300 mg/kg b.w. Palatinit only the breakdown product sorbitol could be recovered in the feces of germ-free rats (29% of the applied dose). No intact Palatinit could be found. In contrast, neither Palatinit nor the breakdown products sorbitol or mannitol could be detected in the feces of conventional rats after application of the same dose. After the application of the higher dose only small amounts of intact Palatinit were found in the feces of germ-free rats (average 12%). There was no intact measurable Palatinit in the feces of conventional rats. The fecal excretions of sorbitol and mannitol in the feces of the germ-free rats were 55% and 39%; in conventional rats only 21% sorbitol was excreted. Only traces of Palatinit, sorbitol or mannitol were found in the urine of conventional and germ-free rats after application of the low as well as the high dose. In conclusion, this study clearly shows the dose dependency of fermentation and therefore the dose dependency of the energetic (i.e., caloric) availability of this disaccharide sugar alcohol. In the calculation of the energy value of Palatinit the renal excretion of Palatinit and its monomers can be neglected.

Animals↗
PubMedDate not supplied

Endogenous excretion and true absorption of cobalt as affected by the oral supply of cobalt.

At the end of a 49-d experiment with 32 growing male rats, a period of 8 d was used to determine endogenous excretion and true absorption as well as apparent absorption and retention of cobalt with the aid of the isotope dilution technique. For this purpose, a single im dose of 58Co was applied at d 35 of the experiment. After that, urine and feces were collected separately from d 8 to 15 after injection of the isotope. The specific cobalt activity of the liver was used as an endogenous reference source. The basal diet provided 5.9 ppb cobalt, the different treatment groups were obtained by supplementing the diet with 0, 10, 50, 250, or 1250 ppb cobalt. The different diets were offered from the beginning of the experiment. In the balance period, apparent and true absorption as well as fecal excretion behaved similar to cobalt intake, whereas urinary excretion increased more rapidly with increasing cobalt supply. Endogenous fecal excretion accounted for 3.5 ng Co/d in the groups fed the diets without and with 10 ppb cobalt. An increase was not observed until supplementing the diet with 50 ppb cobalt. This increase between 250 and 1250 ppb cobalt was higher than the corresponding increase in the dietary cobalt supply. This indicates that endogenous fecal excretion might be more important for homeostatic regulation at a higher dietary cobalt concentration. Endogenous renal excretion as calculated from the results of the isotope dilution technique showed a similar kind of response to increasing cobalt supply as endogenous fecal loss. Nevertheless, the elimination of excessive cobalt mainly took place by adjusting urinary excretion, whereas the variations in true absorption and endogenous fecal excretion had no quantitative importance. Apparent and true absorption were on average 28.0 and 29.8%, respectively, of the cobalt intake. In the case of retention, a marked decline was observed from 19% in the depletion group to 3% with 1250 ppb cobalt, again demonstrating the importance of urinary excretion for controlling the cobalt content of the organism.

Administration, Oral↗
PubMed1999

Heritability of albumin excretion rate in families of patients with Type II diabetes.

AIMS/HYPOTHESIS: To study whether albumin excretion rate is an inherited trait in families of patients with Type II (non-insulin-dependent) diabetes mellitus. METHODS: We used three different approaches. Heritability of albumin excretion rate was studied in 267 nuclear families from the Botnia Study in Western Finland using parent-offspring regression. Albumin excretion rate was also measured in 206 non-diabetic offspring of 119 Type II diabetic parents with or without albuminuria (albumin excretion rate > 20 microg/min). Finally, albumin excretion rate was measured in altogether 652 siblings of 74 microalbuminuric and 320 normoalbuminuric probands. To study the potential confounding effect of blood pressure, the heritability of blood pressure was estimated in 718 nuclear families. RESULTS: Using parent-offspring regression, the heritability of albumin excretion rate was about 30 %, being the strongest from mothers to sons (35-39 % resemblance). The heritability for systolic blood pressure ranged from 10 to 20 % and for diastolic blood pressure from 10 to 27 %. Offspring of albuminuric Type II diabetic parents had higher albumin excretion rates (median 5.4 [range 1.0-195] vs 4.0 [1.0-23] microg/min, p = 0. 0001) and a higher frequency of microalbuminuria (11 vs 2 %, p = 0. 012) than offspring of normoalbuminuric parents. Further, siblings of microalbuminuric probands had higher albumin excretion rates than siblings of normoalbuminuric probands (4.1 [0.6-14.5] vs 3.6 [0.2-14. 4] microg/min, p < 0.01). CONCLUSION/INTERPRETATION: The data suggest that albumin excretion rate is an inherited trait in families of patients with Type II diabetes. [Diabetologia (1999) 42: 1359-1366]

Adult↗
PubMed1998

Increased urinary excretion of carnitine in patients treated with cisplatin.

OBJECTIVE: To study the effect of cisplatin on plasma concentrations and urinary excretion of carnitine in ten patients with different malignancies treated with chemotherapy. METHODS: Carnitine concentrations were determined using a radioenzymatic assay and other metabolites by routine methods of clinical chemistry. Renal clearances were calculated by dividing urinary excretions by the respective plasma concentrations. RESULTS: Before treatment, all patients had a normal plasma carnitine concentration. During treatment with cisplatin, the plasma total carnitine concentration increased by approximately 30% and normalized 7 days after stopping therapy. Urinary excretion of total carnitine increased by a factor of 10 during cisplatin administration and also normalized 7 days after cessation of chemotherapy. This increase was due to excretion of both free carnitine and acylcarnitine and averaged approximately 1 mmol carnitine per day. Similarly, urinary clearance of total carnitine was increased during therapy with cisplatin by a factor of approximately 8 and returned to normal 7 days after chemotherapy. In comparison, patients with similar malignancies treated with radiotherapy showed no significant increase in renal carnitine excretion. Similar to urinary excretion of carnitine, excretion of glucose and phosphate, two metabolites also reabsorbed by the proximal tubule of the nephron, was increased during therapy with cisplatin. There was a strong linear correlation between urinary excretion of free carnitine and acylcarnitines. CONCLUSIONS: Treatment with cisplatin is associated with a tenfold increase in renal carnitine excretion, most likely due to inhibition of carnitine reabsorption by the proximal tubule of the nephron. Well-nourished patients support this loss of carnitine even after repeated cycles of chemotherapy without developing hypocarnitinaemia. However, cachectic patients with decreased dietary carnitine uptake may develop carnitine deficiency when treated repeatedly with chemotherapies including cisplatin.

Adult↗
PubMed2004

Urinary alpha1-microglobulin excretion as biomarker of renal toxicity in trichloroethylene-exposed persons.

OBJECTIVES: Concern on human renal toxicity and carcinogenicity of trichloroethylene is based on findings of increased incidences of renal cell cancers in persons with long-lasting and high occupational exposures to this solvent. The full tumour development is likely to require promotional stimuli, by repetitive episodes of high peak exposures to trichloroethylene, leading to nephrotoxicity. This process is visualised by the excretion of tubular marker proteins in the urine of exposed persons. For this purpose, surveillance of alpha1-microglobulin excretion is being suggested by the Deutsche Forschungsgemeinschaft. METHODS: The present study assessed the applicability of alpha1-microglobulin as a biomarker of proximal tubule damage in the prevention of nephrotoxicity by trichloroethylene exposures. For this purpose, alpha1-microglobulin excretions were assessed in trichloroethylene-exposed and non-exposed subgroups of both cases (diseased with renal cancer) and controls (not diseased with renal cancer) of a recent case-control study. RESULTS: The median of alpha1-microglobulin excretions in non-exposed persons was below the detection limit, but it was clearly elevated in exposed persons. The Wilcoxon rank sum test showed a significant difference ( P=0.0090). Consistent with the underlying concept, renal cell cancer cases who had been exposed to trichloroethylene had higher alpha1-microglobulin excretions than non-exposed cases ( P=0.0005) and also had higher alpha1-microglobulin excretions than exposed controls ( P=0.0004). Of 20 trichloroethylene-exposed renal cell cancer cases only three (15%) displayed a normal alpha1-microglobulin excretion of <5 mg/l. By contrast, 41 (52%) out of 79 non-exposed renal cancer cases showed normal excretions of the biomarker. CONCLUSION: The present data are in agreement with the concept of pathogenesis of renal cell cancers developing under high (suggested: >500 ppm peak exposures) and long-term (several years) exposure to trichloroethylene. They also visualise the potential value of alpha1-microglobulin excretion as a routine biomarker of renal toxicity that may be used in the medical surveillance of trichloroethylene-exposed persons.

Alpha-Globulins↗
PubMed1997

Low molecular weight protein excretion in glomerular disease: a comparative analysis.

We studied 23 children with steroid-sensitive nephrotic syndrome (SSNS), 21 children with steroid-resistant types of nephrotic syndrome and 32 children with other types of nephritis. Our controls were 43 apparently healthy children. We measured the urinary excretion of N-acetyl-beta-D-glucosaminidase (NAG) and the low molecular weight (LMW) protein beta 2-microglobulin (B2M), retinol-binding protein (RBP), alpha 1-microglobulin (A1M) and urine protein 1 (UP1). Results for B2M were considered only for a urine pH greater than 6.0. Comparisons were made with urine albumin excretion, glomerular filtration rate (GFR) and tubular abnormalities in selected renal biopsy samples. We found that abnormalities of LMW protein excretion occurred in between 50% (B2M) and 88% (UP1) of all subjects. In children with SSNS, A1M (r = 0.73), UP1 (r = 0.65) and NAG (r = 0.54) excretion were significantly correlated with albumin excretion, but not RBP or B2M excretion. Increased fractional excretion of A1M, B2M and UP1 and increased plasma A1M were demonstrated in 9 children with SSNS, suggesting competition for tubular reabsorption with albumin, most marked for UP1. In the steroid-resistant nephrotic and nephritic syndromes, correlation with albumin was found for all proteins. In these subjects, RBP (r = 0.37), B2M (r = 0.42) and A1M (r = 0.28) were inversely correlated with GFR, but not UP1, NAG or albumin. We found that RBP excretion was significantly greater in the presence of severe tubular abnormalities in 11 children with recent renal biopsies, but not A1M, UP1 or NAG. We conclude that LMW proteinuria is common in children with glomerular disease, and does not necessarily imply a poor prognosis. Factors other than histologically proven tubular abnormality may account for elevated LMW protein excretion. RBP is the LMW protein most closely associated with structural abnormality and least affected by increasing albuminuria.

Albuminuria↗
PubMed2002

One-week losartan administration increases sodium excretion in cirrhotic patients with and without ascites.

BACKGROUND: Losartan, a highly selective angiotensin II type 1 receptor antagonist, has been reported to have a significant portal hypotensive effect in cirrhotic patients. A recent study also showed that losartan exerted a dramatic natriuretic effect in preascitic cirrhosis. The influence of losartan on renal hemodynamics and sodium homeostasis in cirrhotic patients with ascites is unclear. This study was undertaken to evaluate the renal effects of 1-week losartan treatment in cirrhotic patients with and without ascites. METHODS: All 12 patients in the study received a daily oral dose of 25 mg losartan for 7 consecutive days. Effective renal plasma flow, urine volume, creatinine clearance, 24h urine sodium excretion and fractional excretion of sodium, blood urea nitrogen, and serum creatinine were measured before and after treatment. RESULTS: In cirrhotic patients without ascites, creatinine clearance, 24-h urinary sodium excretion, and fractional excretion of sodium were significantly increased after losartan administration. Effective renal plasma flow and serum creatinine showed almost no change after treatment. In cirrhotic patients with ascites, creatinine clearance, 24-h urinary sodium excretion, fractional excretion of sodium, and effective renal plasma flow were significantly increased after losartan administration. In addition, the magnitudes of the increases in the fractional excretion of sodium and in the 24-h urinary sodium excretion were greater in cirrhotic patients with ascites than in those without ascites. CONCLUSIONS: One-week treatment with losartan increases sodium excretion in association with an improvement of renal function in cirrhotic patients with and without ascites. The natriuretic effect was more profound in cirrhotic patients with ascites than in those without ascites.

Aged↗