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Biomedical subjects

T Remer

Publications and source records attributed to T Remer.

At least 19 recordsLinked to original sources

Muscularity and adiposity in addition to net acid excretion as predictors of 24-h urinary pH in young adults and elderly.

OBJECTIVE: In patients with nephrolithiasis, an inverse relationship between 24-h urinary pH (24h-UpH) and body weight has been reported. Whether body composition indices and 24h-UpH are similarly associated in healthy subjects needs investigation. DESIGN: Cross-sectional, retrospective analysis. SETTING: Dortmund, Germany and Gothenburg, Sweden. SUBJECTS: Healthy young adults (18-23 years; n=117) and elderly (55-75 years; n=85) having a mean body mass index (BMI) of 22.80+/-3.4 and 25.3+/-3.9 kg/m2, respectively. METHODS: Anthropometric data, 24h-UpH, and 24-h urinary excretion rates of net acid (NAE), creatinine, and urea were determined. After adjusting for urea (reflecting protein intake), renal creatinine output was used as a biochemical marker for muscularity. The BMI served as a marker of adiposity. RESULTS: NAE, body weight, and BMI were significantly (P<0.05) higher, and height and creatinine significantly lower in the elderly, whereas body-surface area (BSA) was not different. Step-wise multiple regression analysis using BSA-corrected urinary variables revealed NAE as the primary predictor of 24h-UpH (with R2 values of 0.64 and 0.68 in young adults and elderly, respectively, P<0.0001), followed by urea (P<0.0001), creatinine (P<0.05), and BMI (P<0.05 for the young adults and P=0.12 for the elderly). These associations were negative for NAE and BMI, and positive for urea and creatinine. CONCLUSIONS: Muscularity (i.e. creatinine adjusted for urea) and particularly in the group of young adults, adiposity (i.e. BMI) proved to be modest, but significant predictors of 24h-UpH. Future research should focus on more obese subjects in whom insulin resistance and particular kidney functions should also be examined to further substantiate the role of obesity in low-urine pH-associated conditions, for example, nephrolithiasis.

Adipose Tissue↗

The bone mass concept: problems in short stature.

Bone densitometry is currently one of the mainstays in the evaluation of systemic bone diseases in adults and is also increasingly used to assess primary or secondary bone disorders in children and adolescents. The purpose of carrying out densitometric studies in such circumstances is to measure the densitometric indicators of bone stability. Following procedures which were established for diagnosing adult osteoporosis, a decrease in densitometric surrogates of bone stability is usually interpreted as indicating increased fracture risk. The most basic densitometric parameter is bone mineral content (BMC), which can be measured with most densitometric techniques. BMC is either defined as the mass of mineral contained in an entire bone or as the mass of mineral per unit bone length. While mineral mass can be expected to be a good surrogate for bone stability, BMC is obviously a size-dependent parameter, since small bones weigh less than big bones. This is a drawback in paediatric use, since many children and adolescents who are examined by densitometry suffer from chronic disorders and are small-for-age. Short children will have a lower BMC than their healthy age-matched peers, even if their (smaller) bones are otherwise completely normal.

Adolescent↗

Influence of nutrition on acid-base balance--metabolic aspects.

BACKGROUND: Nutrition has long been known to strongly influence acid-base balance. Recently, we have shown that it is possible to appropriately estimate the renal net acid excretion (NAE) of healthy subjects from the composition of their diets. AIM OF THE STUDY: 1) To briefly present a physiologically based calculation model that allows a reasonable estimation of the analytically determined urinary NAE, 2) to summarize the underlying metabolic mechanisms and 3) to study the specific effect of protein on ammoniagenesis which may counteract, to a small degree, the primary acid load-increasing potential of protein. METHODS: The calculation model and the algorithm for predicting the dietary acid load are summarized, major metabolic (and intestinal) pathways of acid and base equivalents are explained, and urinary excretion rates of ammonium and NAE were specifically examined with special regard to the respective protein intake levels. For the latter examinations, data from diet experiments in adults and epidemiological data from children (protein intake; NAE, pH, and ammonium excretion in 24-h urine samples) were analyzed. RESULTS: The paper shows that the diet-induced generation of acidity and alkalinity is not only determined by the metabolism (oxidation) of sulfur-containing amino acids and organic acid anions of alkali salts, respectively. The intestine is also directly involved in the generation of food-derived acid or alkali loads which is due to the considerably different intestinal absorption rates of relevant food components, i. e., protein and minerals. Further analyses of the interrelation between diet and acid-base status revealed that increasing protein intake (despite its potential to increase NAE) also significantly improves the capacity for renal net acid excretion by stimulating urinary ammonium excretion. CONCLUSION: An adequate concept to estimate renal NAE and potential renal acid loads from dietary intakes must consider the specific bioavailability of the individual nutrients. Furthermore, an increased protein intake does not necessarily result in an accordingly increased use of endogenous acid excretion capacity for two reasons: 1) additional alkali loads in an appropriately composed diet can compensate for the protein-related raised acid production and 2) protein itself moderately improves the renal capacity to excrete net acid by increasing the endogenous supply of ammonia which is the major urinary hydrogen ion acceptor.

Acid-Base Equilibrium↗

Measurements of urinary leptin and capillary leptin: alternative tools for the assessment of the leptin status?

OBJECTIVES: The aim of this study was to check whether leptin is reliably measurable in urine samples of children, adolescents, and adults and to examine whether capillary leptin measurements can be utilized as an alternative tool to assess the leptin status. METHODS: Two studies were performed. In both studies, leptin was quantified by an ultrasensitive and highly specific enzyme immunoassay (ELISA; R & D Systems). Anthropometric measures were taken from all study subjects, and body fat was calculated using skinfold thickness measurements. In study 1, leptin was analyzed in 24-hour urine samples of 155 healthy children and adolescents and 26 healthy adults after a methodological modification of the assay necessary for urine analysis. In study 2, venous and capillary blood samples were collected in 26 healthy adults within 10 min on the same day. RESULTS: After adapting the assay system to urine matrix, the detection range was 20-160 pg/ml. Only in 2 of 181 urine samples reproducibly measurable urinary leptin concentrations in the lowest detection range were found. In study 2, a close correlation was found between log capillary and log venous leptin concentrations (r = 0.98, p < 0.001) and between log capillary as well as log venous leptin levels and percent body fat (r = 0.86, p < 0.001). CONCLUSIONS: Our results based on one of the most specific and sensitive ELISAs currently available show that leptin is generally undetectable in the urine from healthy children, adolescents and adults. Thus, urinary leptin excretion cannot be used as a noninvasive marker of the leptin status. Our findings in healthy adults show that the merely moderately invasive determination of capillary leptin allows a reliable assessment of the individual leptin status and may be used instead of venous leptin as a biochemical indicator of body fatness.

Adolescent↗

The midgrowth spurt in healthy children is not caused by adrenarche.

A small transient increase in growth, the midgrowth spurt, has been observed in several growth studies in healthy children around the age of 7 yr. During this time adrenarche (the physiological increase in adrenal androgen secretion) also occurs. Although it is now well established that estrogen, not androgen, has a critical role in the male (and female) pubertal growth spurt, a direct effect of androgens on growth cannot be excluded. In accordance with published observations that growth is frequently accelerated in infants and young children with late-diagnosed 21-hydroxylase deficiency (before adequate androgen suppression), it has been speculated that the adrenarchal increase in adrenal androgen secretion in healthy children could be responsible for the midgrowth spurt. To test this hypothesis we studied long-term serial changes in urinary 24-h excretion rates of dehydroepiandrosterone sulfate and total 17-ketosteroid sulfates in a group of healthy children (n = 12) in which yearly auxological measurements allowed the identification of a midgrowth spurt. Annual measurements of standing height were performed over periods of 6-9 yr before the onset of puberty. All children collected five to seven serial 24-h urine samples (1-yr intervals) each at the time of anthropometric examination. The peak of the midgrowth spurt was found to occur at a mean age of 6.8 +/- 1.0 yr. The average height of the midgrowth peak, i.e. average maximum gain in height velocity, was 0.9 cm/yr. In a peak-centered examination of individual 24-h excretion rates of dehydroepiandrosterone sulfate and 17-ketosteroid sulfates, primarily weak 1-yr changes in adrenal androgens were observed until the peak was attained. Only after the peak did increments in urinary adrenal androgen output become more pronounced. ANOVA performed on the peak-centered dehydroepiandrosterone sulfate and 17-ketosteroid sulfate excretion rates revealed a highly significant overall increase in adrenal androgen secretion from 2 yr before to 2 yr after the midgrowth spurt. After multiple testing, however, significant increments, when compared with the respective preceding androgen excretion levels, were for the first time seen 1 yr after the midgrowth spurt (dehydroepiandrosterone sulfate) or 2 yr later (17-ketosteroid sulfates). In conclusion, our longitudinal analysis of prepubertal growth and urinary adrenal androgen excretion in healthy children disproves the speculation that the midgrowth spurt is primarily caused by the adrenarchal increase in adrenal androgen secretion. However, the present results do not rule out a growth-accelerating effect of clearly higher androgen levels, as in premature adrenarche.

17-Ketosteroids↗

Long-Term stability of 6-hydroxymelatonin sulfate in 24-h urine samples stored at -20 degrees C.

The purpose of the present feasibility study was to determine whether the concentration of 6-hydroxymelatonin sulfate (6-OHMS) remains stable in urine samples stored over at least 15 yr. To test this, 117 twenty-four-hour urine samples were analyzed, which were obtained from healthy children ages 8 to 9 yr within the periods of 1985-1987,1991-1993, and 1997-1999. 6-OHMS concentrations were determined by enzyme-linked immunosorbent assay. The statistical analyses clearly indicate that the concentration of 6-OHMS remains stable for at least 15 yr if the urine is stored at -20 degrees C.

Child↗

Adrenarche and nutritional status.

The prepubertal fat spurt seen in mid-childhood coincides with the beginning of adrenarche and is associated with rising serum levels of insulin and insulin-like growth factor-I. As the adrenal cortex expresses receptors for these anabolic peptides, implying that the nutritional status is communicated to the adrenal gland, we hypothesized that nutritional status may be causally involved in the regulation of adrenal androgen secretion. To test this hypothesis, anthropometric indices of the nutritional status and 24-h urinary excretion rates of dehydroepiandrosterone sulfate (DHEAS) were studied longitudinally (during observation periods of at least 4 years) in healthy normal-weight prepubertal and pubertal children. Increases in urinary DHEAS excretion proved to be significantly elevated during periods of individual highest rises in body mass index. These findings provide the first in vivo evidence that a change in nutritional status is an important physiological regulator of adrenarche.

Anthropometry↗

Increased risk of iodine deficiency with vegetarian nutrition.

Observational studies primarily based on diet questionnaires or food records have reported that vegetarians can have a very low I intake. However, analytically ascertained data on the possible degree of I deficiency with this form of diet is lacking. Six healthy adult volunteers participated in the present controlled experimental diet study carried out in four separate 5 d diet periods. The study diets, normal, protein-rich, lactovegetarian, and repeat of the initial normal diet, were almost isoenergetic and contained no fish, sea food, iodized salt or processed foods fortified with I. During the last 48 h of each diet period two 24 h urine samples were obtained from each subject. I analyses were performed in the urine samples and in representative samples taken from all ingested diets. Urinary I excretion was significantly lower with the lactovegetarian diet (36.6 (SD 8.8) micrograms/d) than with the normal and the protein-rich diets (50.2 (SD 14.0) and 61.0 (SD 8.0) micrograms/d respectively). Accordingly, a markedly reduced I intake was confirmed analytically for the lactovegetarian diet (15.6 micrograms/d v. 35.2 and 44.5 micrograms/d respectively). Our results provide experimental confirmation of literature findings indicating that I supply is higher with non-vegetarian than with vegetarian diets. Specifically, the extremely low intake and urinary output of I as analytically determined for one exemplary vegetarian diet, demonstrate that dietary I may be limiting when strict forms of vegetarian dietary practices (no iodized salt, no I supplements) are followed. The present study is, therefore, the first diet-experiment-based pointer to the potential danger of I deficiency disorders due to strict forms of vegetarian nutrition, especially when fruits and vegetables grown in soils with low I levels are ingested.

Adult↗

Role of nutritional status in the regulation of adrenarche.

The factors regulating adrenarche are unknown. Recent in vitro studies have demonstrated that insulin and insulin-like growth factor I induce major adrenal steroidogenic enzyme genes and increase the production of adrenal androgens. Literature findings strongly suggest that changes in body mass index (BMI) reflect an integrated nonhormonal index of changes in serum levels and/or bioactivities of insulin and insulin-like growth factor I. We therefore longitudinally investigated individual changes in BMI and urinary 24-h excretion rates of dehydroepiandrosterone sulfate (DHEAS) in a prepuberty (PreC; n = 22, 11 boys and 11 girls) and a puberty (PubC; n = 20, 10 boys and 10 girls) cohort of healthy children. Twenty-four-hour urine samples were collected at yearly intervals during observation periods that lasted at least 4 yr (comprising > or = 5 consecutive 24-h urine collections). For 4-yr intervals highly significant tracking coefficients (P < 0.001) of 0.73 (PreC) and 0.93 (PubC) were observed for DHEAS, emphasizing the importance of individual (and genetic) influences on adrenal androgen excretion. In both cohorts almost 3-fold higher median increases in urinary DHEAS excretion rates (P < 0.05) were observed during the 1-yr period of the individually highest rises in BMI compared with the 1-yr period of significantly lower rises in BMI (P < 0.01) in the same children after the factor age was controlled for. However, no consistently significant associations were found between urinary DHEAS output and BMI from simple cross-sectional correlations at defined age points. These findings provide the first in vivo evidence that a change in the nutritional status, measurable in the form of delta-BMI (but not BMI alone), is an important physiological regulator of adrenarche regardless of individual adrenal androgen excretion level, age, and developmental stage.

Adolescent↗

Urinary excretion of urodilatin in healthy children and children with renal disease.

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.

Acute Kidney Injury↗

The impact of dietary protein intake on urinary creatinine excretion in a healthy pediatric population.

OBJECTIVE: The aim of the study was to investigate the effect of daily protein intake on urinary creatinine (CR) excretion in healthy children. METHODS: In a cross-sectional study, 24-hour urinary CR excretion rates were measured in 350 children aged 4 to 13 years. Body composition was assessed according to anthropometric measurements, and intake of protein was estimated from dietary records. RESULTS: CR excretion adjusted for fat-free mass (FFM) showed a strong age dependency and correlated clearly with total protein intake and animal protein intake. Stepwise regression analyses revealed that age was the main predictor; however, animal protein intake improved the proportion of explained variance in FFM-related CR excretion. Comparisons of urinary CR output in subgroups of children with low (1st tertile) or high (3rd tertile) animal protein intake showed that on average, a difference of about 9% in CR excretion corresponded to a difference of 1.1 g/kg of body weight per day of animal protein intake. CONCLUSIONS: Animal protein intake must be taken into account when urinary CR output is used for evaluating body composition in children. Additionally, the finding of a clearly stronger increase in urinary CR than in FFM with age offers an explanation for the commonly observed phenomenon of a decreasing ratio of numerous urinary analytes related to CR during childhood.

Adolescent↗

Short-term impact of a lactovegetarian diet on adrenocortical activity and adrenal androgens.

The aim of this study was to determine whether definite diet changes affect adrenocortical activity and/or adrenal androgen metabolism. A controlled experimental diet study with four consecutive diet periods (repeated measure design) was carried out in six healthy adult volunteers. Four nearly isoenergetic diets, two normal (N) moderately protein-rich, one protein-rich (P), and one low protein lactovegetarian (L), were fed. At the end of each 5-day diet period a blood sample and two 24-h urine specimens were obtained from each subject. Plasma levels of dehydroepiandrosterone sulfate (DHEAS) were elevated with diet L (6.5 +/- 1.4 vs. 5.3 +/- 1.1 mumol/L; P < 0.05) compared to diet N, whereas other plasma hormones, including cortisol and insulin-like growth factor I did not vary markedly. A marked increase of 60% was seen in the urinary 24-h output of 3 alpha-androstanediol glucuronide with diet P. Urinary 24-h excretion rates for C peptide, free cortisol, DHEAS, and total 17-ketosteroid sulfates were clearly reduced with diet L compared to those with diet N or P. Our results show that a lactovegetarian diet can reduce adrenocortical activity (at least after a short term diet change). In addition, this vegetarian nutrition leads to a particular metabolic situation (elevated plasma DHEAS and reduced urinary DHEAS output) that usually is characteristic of fasting. Peripheral androgen metabolism as reflected by urinary 3 alpha-androstanediol glucuronide appears to be influenced only by high protein intake (diet P). Further research (controlled dietary long term investigation) is required 1) to validate whether the effects of diet on adrenocortical activity represent sustained endocrine changes and 2) to elucidate the underlying mechanism.

17-Ketosteroids↗

Renal acid excretion in early infancy.

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.

Acid-Base Equilibrium↗