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Urodilatin (URO) is a natriuretic peptide isolated from human urine which is thought to be produced by distal tubular cells. We measured urinary URO excretion in 50 healthy children and 23 children with acute (ARF), chronic renal failure (CRF), or hereditary tubular disorders, using a specific radioimmunoassay. The mean URO excreted in these four groups was 56, 45, 94, and 121 fmol/min per 1.73 m2, respectively (differences between first three groups not significant). The variation in URO excretion was larger in patients with kidney disease than in controls. There were significant correlations between urinary URO and sodium excretion in controls and CRF, but not in ARF. URO excretion also correlated with urine flow rate in CRF. Although no correlation was found between URO excretion and creatinine clearance, urinary URO was increased in some patients with advanced CRF, which suggests stimulated tubular production to compensate for reduced sodium excretion. In view of the therapeutic potential of URO in renal insufficiency, further study of the renal handling of URO is warranted.

In early infancy, complex disorders of acid base metabolism are more frequent than in any other age group, with a predisposition to metabolic acidosis due to an age-related low renal capacity for acid excretion and an unphysiologically high actual renal acid load in nutrition with common formulas. Recently in preterm and small-for-gestational-age infants, persistent maximum renal net acid excretion (NAE) with subnormal or normal blood acid base status, impaired weight gain, and adaptive hormonal reactions have been observed. Incipient late metabolic acidosis is one example of a mixed disorder of acid base metabolism with maximum renal NAE in early infancy. Alkali therapy is highly effective and can be realized both on an individual basis, using urine pH screening as a diagnostic criterium for maximum renal acid stimulation, or on a general preventive level using modified standard formula with a reduced actual renal NAE similar to that seen on alimentation with human milk. From an integrated point of view, the low glomerular filtration rate and renal capacity for acid excretion beyond the developmental age of more than 44 weeks, may well be interpreted as the result of a specific adaptation to breast feeding sparing energy, and thus an evolutionary advantage for the survival of mother and child.

To study the effect of a moderate increase in insulin secretion produced by an increased daily protein intake on dehydroepiandrosterone sulfate (DHEAS), a balanced randomized crossover trial consisting of three strictly controlled dietary regimens was performed in six healthy male volunteers. The basic diet (B) contained 50 g protein/d; diets P and M (also basic diets) were enriched with either 32 g protein/d (P) or 10 mmol L-methionine/d (M). Methionine was given (as a specific nonprotein source of endogenously derived sulfate) to control for possible confounding effects on DHEAS due to an increased sulfate supply. At the end of each 4-day diet period, blood and 24-hour urine samples were collected. Fasting plasma levels of testosterone, cortisol, insulin-like growth factor-I (IGF-I), and insulin, as well as urinary output of total (hot acid-cleaved) testosterone conjugates and 3alpha-androstanediol glucuronide, did not show significant changes in response to dietary manipulations. Endogenous sulfate availability (as reflected by renal sulfate output per 24 hours) approximately doubled with diets P and M. However, plasma levels (6.3 +/- 1.5, 6.8 +/- 1.8, and 6.9 +/- 2.1 micromol/L for B, P, and M, respectively) and urinary excretion (8.8 +/- 9.8, 9.4 +/- 11.2, 8.0 +/- 8.3 micromol/d) of DHEAS remained unaffected. Considering the clear increments (P < .01) in urinary C-peptide excretion with diet P (20.4 +/- 10.3 nmol/d) versus diets B and M (12.6 +/- 5.1 and 13.2 +/- 3.6 nmol/d), respectively, our results suggest that a moderately strong diet-induced increase in daily insulin secretion does not alter urinary and plasma levels of DHEAS.

Studies specifically investigating the effects of single dietary components on plasma levels of dehydroepiandrosterone (DHEA) and its sulfate ester (DHEAS) are rare. Especially no data is available with regard to specific dietary fibers. Therefore, the impact of pectin (a representative fiber that affects the enterohepatic recirculation of bile acids) was studied in a randomized crossover trial consisting of three diet periods characterized by the same food supply and daily doses of 0 g, 15 g or 30 g pectin. Blood and 24-h-urine samples were collected at the end of each 4-day diet period from 6 healthy male volunteers. Plasma levels of DHEA, cortisol and the major binding protein of DHEAS albumin remained unchanged with the varying pectin supplements. Also, no changes were observed for several urinary analytes including urinary DHEAS. However, effects of pectin intake (30, 15 versus 0 g/d) were seen for plasma DHEAS (9.3 +/- 2.8, 9.2 +/- 2.6, 8.0 +/- 3.1 mumol/L, p < 0.01) and total plasma cholesterol (4.4 +/- 0.7, 4.5 +/- 0.7, 4.7 +/- 0.8 mmol/L, p = 0.1). Obviously, the altered intake of fiber in the form of pectin affects plasma concentrations of DHEAS and cholesterol in an opposite direction. The reason for this is not known but a dietetically induced modulation of the binding properties of plasma albumin for DHEAS appears possible. Our findings suggest that the target tissue-available, not protein-bound fraction of circulating DHEAS (as reflected by the renal DHEAS output) is not necessarily altered when total plasma concentrations of DHEAS vary.

Low serum levels of vitamin D metabolites have been associated with an increased risk for colon cancer. To investigate the effects of vitamin D deficiency on the colon, 4-week-old mice were fed a diet either containing (100,000 IU/kg diet) or lacking this vitamin for 3 weeks. Food consumption and body weight gain were similar in both groups. Following injection with 3H-thymidine to label dividing cells, cellular proliferation and migration up the colonic crypt were determined autoradiographically. Although overall crypt lengths were similar in both groups, there was hyperplasia and hyperproliferation in crypts of the deficient animals. Also, their epithelial cells migrated up the crypt at a significantly slower rate (maximum 0.78 micron/h) than did those from control mice (1.42 microns/h). There was no difference in cellularity, proliferation or migration in duodenal epithelium. These results indicate that vitamin D deficiency significantly alters colonic but not duodenal epithelial cells.

The purpose of this study was to calculate the potential renal acid load (PRAL) of selected, frequently consumed foods. A physiologically based calculation model was recently validated to yield an appropriate estimate of renal net acid excretion (NAE); the model depends primarily on nutrient intake data. When nutrient data from actual food composition tables were used, the calculation model yielded PRAL values that ranged from an average maximum of 23.6 mEq/100 g for certain hard cheeses over 0 mEq/100 g for fats and oils to an average minimum of approximately -3 mEq/100 g for fruits and fruit juices and vegetables. By means of these PRAL data (summed according to the amounts of foods and beverages consumed daily and by an estimate of excretion of organic acids [based on body size]), the daily NAE can be calculated. This calculation methodology, primarily based on PRAL, allows an appropriate prediction of the effects of diet on the acidity of urine. For practical applicability in dietetic prevention of recurrent urolithiasis or in other fields of dietetics, the additionally determined correlation (r = .83; P < .001) between NAE and urine pH can be used to ascertain NAE target values for a desired urine pH modification.

Galactosyl-hydroxylysine (Gal-Hyl) is the predominant product of the posttranslational glycosylation of skeletal collagen. Urinary Gal-Hyl excretion is regarded as a marker of bone resorption in adults, but little information is available on the validity of this parameter in pediatric age groups. Using 24-h urine samples from 88 healthy children and adolescents ages 4-18 yr, reference ranges were established for this age group, and values were compared with measurements in children with overt GH deficiency (n = 14) or Ullrich-Turner syndrome (n = 21). When expressed relative to body weight (Gal-Hyl/wt), urinary Gal-Hyl excretion was 3.2 to 4.7 times higher in subjects 4-16 yr of age than in adults. Highest values were observed in very young children and during the pubertal growth spurt. In the total population, urinary Gal-Hyl/wt was closely related to growth velocity (r = 0.72) and significantly correlated with the urinary excretion of both hydroxyproline (r = 0.74) and deoxypyridinoline (r = 0.88; P < 0.001 each). Urinary Gal-Hyl/wt was significantly lower in children with GH deficiency or Ullrich-Turner syndrome than in healthy children (P < 0.001 each). The urinary excretion of Gal-Hyl was significantly correlated with growth velocity in GH-deficient children (r = 0.69; P = 0.004) but not in patients with Ullrich-Turner syndrome. In the latter, the increase in urinary Gal-Hyl excretion after 3 months of treatment with recombinant human GH correlated significantly with the increase in growth velocity after 12 months of treatment (r = 0.76; P = 0.002). We conclude that the urinary excretion of Gal-Hyl is a valid and potentially useful index of skeletal growth in children.

Bodybuilders often prefer a high protein diet to achieve maximum skeletal muscle hypertrophy. In this study the effect of a high protein diet on renal acid load and renal handling of proton excretion was studied comparing dietary intake and urinary ionograms in 37 male bodybuilders and 20 young male adults. Energy intake (+ 7%), protein intake (128 vs 88 g/d/1.73 m2), and renal net acid excretion (95 vs 64 mmol/d/1.73 m2) were higher in the bodybuilders than in the controls, however, urine-pH was only slightly lower (5.83 vs 6.12). In the bodybuilders renal ammonium excretion was higher at any given value of urine pH than in the controls. In a regression analysis protein intake proved to be an independent factor modulating the ratio between urine-pH and renal ammonium excretion. The concomitant increase of renal net acid excretion and maximum renal acid excretion capacity in periods of high protein intake appears to be a highly effective response of the kidney to a specific food intake leaving a large renal surplus capacity for an additional renal acid load.

To reinvestigate the effect of hCG on circulating and urinary dehydroepiandrosterone sulfate (DHEAS), a hCG stimulation test (5000 IU administered i.m. at 8.30 h on 3 consecutive days) was performed in 6 healthy males (aged 24 to 35 years). Blood specimens and 24-h urine samples were collected immediately before the first and directly after the last hCG administration. Contrary to previous findings in normal men, the present study revealed significant DHEAS responses after testicular stimulation with hCG: plasma DHEAS increased from 7.9 +/- 2.3 to 9.6 +/- 2.2 mumol/L (P < 0.05) and urinary DHEAS from 5.7 +/- 3.6 to 9.3 +/- 5.2 mumol/day (P < 0.05). There was also a marked rise (P < 0.05) in the urinary excretion of total 17-ketosteroid sulfates. Clear increases of unconjugated plasma dehydroepiandrosterone as well as of circulating and renally excreted androstenedione and testosterone definitely confirmed an adequate Leydig cell stimulation. Significant post-hCG changes were additionally observed for plasma and urinary 3 alpha-androstanediol glucuronide (149% and 79% increases, respectively) and for urinary cortisol (21% decrease). Significant correlations were found for the post-hCG percent increases of plasma androstenedione versus plasma DHEAS (r = 0.86) and for the percent increases of plasma testosterone versus urinary DHEAS (r = 0.98), indicating that the extent of gonadal androgen elevations in the circulation of normal men is a determinant of DHEAS increases in blood or urine. These findings provide an explanation for the frequently observed sex differences for DHEAS in adults.(ABSTRACT TRUNCATED AT 250 WORDS)

The object of this study was to determine whether it is possible to reliably estimate the renal net acid excretion (NAE) produced by adults consuming different amounts of dietary protein. A physiologically based calculation model that corrects for intestinal absorption of minerals and sulfur-containing protein and assumes a rate of urinary excretion of organic acids proportional to body surface area was used to estimate NAE. Urinary excretion of different minerals and NAE was measured during the last 48 h of each of four separate 5-d diet periods in six healthy adults. On the basis of food tables, the four nearly isoenergetic diets (one lacto-vegetarian and one high- and two moderate-protein diets) were estimated to yield the following NAE values: 3.7, 117.5, 62.2, and 102.2 mEq/d, respectively. The analytically determined urinary NAE (24.1 +/- 10.7, 135.5 +/- 16.4, 69.7 +/- 21.4, and 112.6 +/- 10.9 mEq/d) corresponded reasonably well to these estimates, suggesting that the calculation model is appropriate to predict the renal NAE from nutrient intake and anthropometric data.

Two new markers of bone resorption, the collagen cross-linking amino acids pyridinoline (PYD) and deoxypyridinoline (DPD), were measured in 24-h urine collections from 88 healthy children (45 females, 43 males; age 4 to 18 years) and 17 adults. Normal values for pediatric use were established for these parameters. Related to daily excretion of creatinine PYD and DPD were about 3 to 6 fold higher in the pediatric groups than in adults. The collagen cross-links showed a highly significant correlation to the urinary excretion of hydroxyproline (OHP): r = 0.65 for PYD and r = 0.60 for DPD (p < 0.001). Both collagen cross-links and OHP excretion related to creatinine were significantly correlated to growth velocity (r = 0.67, 0.62 and 0.51 for PYD, DPD and OHP respectively; p < 0.001 in each case). PYD and DPD may be useful for the monitoring of growth in children.

A commercial 125I radioimmunoassay designed for the quantification of dehydroepiandrosterone sulfate (DHEAS) in blood samples was tested for its direct applicability to 24-hour urine samples from children and adults. Average recoveries in parallelism and spiking experiments were found to be near 100%. Intra- and inter-assay coefficients of variation were below 10%. Urinary DHEAS concentrations determined directly by the radioimmunoassay (x) differed only slightly from corresponding radioimmunoassay values (y) obtained after C18 reversed-phase extraction and LH-20 chromatography (y = 0.85x + 0.12; r = 0.99). Cross-reactivity data from related steroids suggested only a small contribution to the DHEAS titer by other steroids. In 8-year-old children compared to preadrenarchal children (4 years old) a clearly increased median daily urinary DHEAS output could be observed both for absolute excretion data (0.163 versus 0.05 mumol/d, P < 0.01) and for excretion values related to body surface area (0.181 versus 0.071 mumol/d/1.73 m2, P < 0.05). However, this "onset of adrenarche" was no longer statistically significant when urinary creatinine was taken as adjustment parameter for renal androgen sulfate output. After correction with the individual body surface area, rises of urinary DHEAS from childhood to adulthood were nearly in the order of the literature data on age-corresponding serum increases of DHEAS. In conclusion, the direct radioimmunological quantification of DHEAS in 24-hour urine samples with subsequent correction for individual body surface area appears to present a physiologically meaningful way to assess the adrenal gland's secretory activity for this androgen sulfate.

According to published data the group of urinary total 17-ketosteroid sulfates appears to represent an index of overall adrenal androgen production, at least before the onset of puberty. To quantify total 17-ketosteroid sulfates a modified colorimetric assay based on the Zimmermann reaction was validated. 17-ketosteroid sulfates were measured without previous hydrolysis (as conjugated Zimmermann chromogens against authentic dehydroepiandrosterone sulfate (DHEAS) as assay standard) after C18 reversed-phase extraction and LH-20 chromatography. Intra- and inter-assay coefficients of variation were 8.4% (15.0%) and 5.9% (17.6%), respectively, at urinary 17-ketosteroid sulfate concentrations of 10.8 (1.9) nmol/ml. Recoveries observed in spiking and parallelism experiments varied between 88 and 102%. In a group of 4-year-old children showing a renal DHEAS output of less than 0.1 mumol/d/1.73 m2 (measured by radioimmunoassay) a relatively high median 17-ketosteroid sulfate excretion of 1.29 mumol/d/1.73 m2 was found. Older children aged 8 years as well as a group aged 12-14 years demonstrated only moderately higher urinary 17-ketosteroid sulfates whereas excretion of DHEAS/d/1.73 m2 more than tripled from age group to age group. For children from 8 years onwards, adolescents, and adults, linear regression analysis indicated that urinary DHEAS elevations seem to contribute with a constant proportion of approximately 70% to the increments of total urinary 17-ketosteroid sulfates. These findings suggest that the attainment of such a constant relationship (between the total 17-ketosteroid sulfates and their major component) from about 8 years of age onwards could represent the hormonal correlate of the completion of the continuous zona reticularis in the adrenal gland (developing around this age from a focal reticularis zone).

The chronic effect of daily i. m. administration of ACTH (1 U/kg bodyweight (BW), group A) and of insulin (15/kg BW, group B) on circulating dehydroepiandrosterone sulfate (DHEA-S) and testosterone was investigated in postpubertal male Wistar rats. NaCl-injected animals served as controls (group C). After at least 8 days under the respective hormone or NaCl treatment "basally" circulating testosterone levels were slightly suppressed in insulin- (1.56 +/- 0.86 ng/ml) and markedly reduced (0.54 +/- 0.21 ng/ml) in ACTH-treated rats vs. controls (2.33 +/- 0.69 ng/ml). DHEA-S levels, however, nearly doubled under chronic insulin administration (0.4 +/- 0.18 ng/ml) in comparison to the groups A (0.22 +/- 0.11 ng/ml) and C (0.23 +/- 0.09 ng/ml). Food intake and weight gain were also elevated (vs. groups A and C) as were the basal plasma corticosterone levels (vs. group C) in insulin treated rats. Following an acute ACTH stimulation test (12 U/kg BW i.m.) performed in all three treatment groups, plasma DHEA-S showed a further increase in the animals receiving insulin (0.75 +/- 0.32 ng/ml), whereas no response was detectable in rats from group A (0.27 +/- 0.13 ng/ml) or C (0.24 +/- 0.11 ng/ml). Further measurements of corticosterone or testosterone responses following endocrinological stimulation tests with supraphysiological doses of either ACTH or human chorionic gonadotropin (hCG) indicated that a lowering in the catabolism (metabolic clearance) of corticosteroids or androgens could not be the cause for the elevated DHEA-S levels seen after daily insulin injections.(ABSTRACT TRUNCATED AT 250 WORDS)

In 22 healthy toddlers (age: 2.5 +/- 0.06 years; from families living in Dortmund, FRG) measurements of iodine and creatinine concentrations were carried out in spontaneous urine samples collected in the afternoon (U1), as well as during the night (U2). Median iodine-creatinine ratios found in the "afternoon specimens" U1 were significantly elevated (p < 0.05) compared to U2 (181.3 vs. 119.5 micrograms/g). Higher values in U1 than in U2 were also obtained when total daily iodine excretion (under the assumption of an average creatinine excretion of 15 mg/kg/d for infants) was calculated and the corresponding data were related to body surface area (BSA). The results of the specimens collected during the night were (after expressing as iodine-creatinine ratio as well as after correcting for BSA) comparable with the excretion data of accurately timed 24-h urine collections obtained in a separate group of toddlers (n = 23) of nearly the same age. When the iodine-creatinine ratios established by the WHO--after standardizing with BSA--were taken as criteria for iodine deficiency, then in both study groups (spontaneous urine samples at night (U2) and timed 24-h urine collections) about half of the infants would fall in the deficiency state II with an elevated risk for iodine-deficiency goiter. It is suggested that the nutritional status of iodine can be reliably monitored (in infants) by determining iodine and creatinine concentrations in overnight urine samples and relating the data to BSA.

The mineral contents of Na, K, Ca, Mg, Cl and P was determined in different batches of 5 preterm formulas. The purpose of this study was 1st to investigate whether the analytical data are in agreement with the specifications of the manufactures and 2nd whether there are large variations between different batches of the same formula. For each analyzed mineral we found marked differences between the specifications and our measurements in at least one of the formulas. In these cases the differences between the labels and the medians of the analytical data were larger than half of the range of all determinations of the respective formula. Without exception the mean values for K were all clearly lower than the specifications of the producers. In 4 of the 5 premature formulas variation coefficients greater than 10% were observed for at least one mineral. The results show that coincidental variations of mineral contents in different batches can result in a disadvantageous mineral composition because of synergistic effects on metabolism. In this context the importance of the sum of Na and K over Cl in premature formulas is stressed with regard to renal acid excretion. The introduction of more stringent quality standards is proposed.

Bioavailability studies of micronutrients (vitamins, minerals) from different food stuffs, as well as from pharmaceutical preparations are of great importance for the calculation of nutrient intake and/or the evaluation of the therapeutic value. In practice, bioavailability studies are not generally performed on a standardized level. For this reason basic criterions are presented and discussed. Finally, the investigation of the bioavailability of folate is demonstrated by an example. The parameters investigated are: the maximal concentration (cmax), the time to reach this maximum (tmax), and especially the bioavailability ratio determined from the area under the curve (AUC) after administration of the folic acid containing test and reference preparation. The results indicate that 5-formyl-tetrahydrofolic acid given in the tested form has nearly the same bioavailability (ratio: 1.02) as folic acid (pteroylmonoglutamic acid) in aqueous solution.