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Biomedical subjects

F Schaefer

Publications and source records attributed to F Schaefer.

At least 91 records · Page 5Linked to original sources
PubMed1994

Less acidic forms of luteinizing hormone are associated with lower testosterone secretion in men on haemodialysis treatment.

OBJECTIVE: Men with chronic renal failure treated by haemodialysis have raised levels of bioactive LH (B-LH) and immunoreactive LH (I-LH) but reduced B-LH:I-LH (B:I) ratio and testosterone (T) secretion. This study investigated the LH isoform distribution in serum from normal adult males and males on regular haemodialysis treatment. DESIGN: Four blood samples (2 ml) were obtained at 15-minute intervals from a group of men on regular haemodialysis treatment. These samples were part of a larger pulse profile series and showed no evidence of LH pulsatility. The serum was pooled for each individual patient. Blood (10 ml) was also drawn randomly from healthy male volunteers. The sera were chromatofocused on a 4-ml mono-P column attached to a fast performance liquid chromatography system. This procedure separates the LH isoforms according to their isoelectric point. The pH gradient was between pH 7 and pH 4. PATIENTS: The five men with chronic renal failure were aged between 18 and 40 years and had been on haemodialysis for a mean of 10 months (5-20). They were sampled the night prior to a dialysis session. The five normal healthy volunteers had never had any endocrine disorder diagnosed. MEASUREMENTS: An immunoradiometric assay and a commercially available (Delfia) immunofluorimetric assay were employed for detection of LH in the sera and in chromatofocusing fractions. B-LH and testosterone were also measured in the sera. RESULTS: Hormone data (mean +/- SEM for normal and renal subjects respectively) were 15.5 IU/l +/- 1.2 and 26.9 +/- 7.2 (B-LH), 6.0 IU/l +/- 0.3 and 16.5 +/- 4.8 (irmaLH), 5.7 +/- 0.5 and 13.6 +/- 4.8 (fluorLH), 25.2nmol/l +/- 2.0 and 12.1 +/- 1.2 (T). The serum B:I ratios were 2.6 +/- 0.1 and 2.6 +/- 0.2 (controls, irmaLH and fluorLH respectively) and 1.7 +/- 0.1 and 2.1 +/- 0.1 (chronic renal failure group). Recovery of LH from the column was 111 +/- 12% (mean +/- SEM) by IRMA and 104 +/- 7% by IFMA for the ten FPLC runs. The median pI for the LH distribution measured by both assays was in the region 6.54-6.40 for subjects with chronic renal failure and 6.09-5.95 for controls. Median pI was negatively correlated to the B-LH:irmaLH (P < 0.0001) and B-LH:fluorLH ratios (P = 0.002) in the serum. Furthermore, the proportion of isoforms recovered in the pH region 6.25-5.50 increased with increasing T levels in the serum (P < 0.004). CONCLUSION: The distribution of LH in serum of men on haemodialysis is more basic than in normal men. The greater the proportion of more acidic LH species, particularly those with a pI of between 5.50-6.25, the higher the ratio of LH bioactivity to immunoactivity and consequently testosterone levels.

Adolescent↗
PubMed1994

Growth and skeletal maturation in children with phenylketonuria.

Growth and skeletal maturation was evaluated in 82 children participating in the German Collaborative Study of Children Treated for Phenylketonuria (PKU). Height, weight, head circumference and bone age were recorded at regular intervals for the first 6 years of life. The mean SD score (SDS) for height was not significantly different from zero at study entry, but decreased mainly during the second year of life to a nadir of -0.78 in boys and -0.54 in girls at 2.5 years. During the subsequent years, a significant trend towards a regain of height SDS was noted in both sexes. Weight-for-height SDS was close to zero in both sexes, with a significant continuous increasing trend throughout the observation period. Head circumference SDS decreased in boys during the first year of life from -0.28 to -0.68, whereas girls showed only a minor change. During the further follow-up period, head circumference SDS remained at approximately -0.3 in boys and 0.0 in girls. While the mean verbal and performance IQ of the total study population at 5 and 6 years of age did not differ from a group of 212 healthy non-PKU children, patients with a head circumference SDS less than the population median at 2 years of age exhibited poorer cognitive abilities at school age than those patients with a relative head size greater than the population median. The children with a head circumference less than the median at 2 years had smaller head sizes already at birth; in addition, the change in relative head size during the first 2 years was correlated significantly with cognitive abilities at school age in boys. Mean bone age was identical to chronological age at each time point of observation. The rate of maturation was one year of bone age per year of chronological age. No correlation between phenylalanine intake or phenylalanine concentrations and the rates of body or head growth or skeletal maturation could be established. We conclude that despite adequate weight gain, moderate growth retardation occurred during the first 2 years of life in this group of children treated for PKU. Growth was more compromised in boys than in girls and tended to be compensated during later follow-up. Early infantile head circumference and growth appear to be predictors of cognitive development.

Age Determination by Skeleton↗
PubMed1994

In vivo alterations in the gonadotropin-releasing hormone pulse generator and the secretion and clearance of luteinizing hormone in the uremic castrate rat.

To investigate the mechanisms subserving the reported alterations in the pulsatile release of LH in uremia, we simultaneously studied endogenous accumulation of GnRH in the pituitary gland and the secretion and clearance of LH in vivo in experimentally uremic, orchidectomized rats. The temporal pattern of GnRH secretion was assessed by intrapituitary microdialysis, the dynamics of plasma LH by continuous exchange transfusion. Studies were performed in rats rendered uremic by subtotal nephrectomy (n = 8) and control rats which were either fed ad libitum (n = 8) or pair-fed with the uremic animals (n = 8). Blood samples were obtained at 5-min and microdialysate samples at 10-min intervals over a period of 270 min. The pulsatile secretory characteristics of GnRH and LH and the half-life of plasma LH were estimated by multiple-parameter deconvolution analysis. The temporal relationship between the hormone concentrations and between the secretory events of GnRH and LH was assessed by cross-correlation analysis and hypergeometric coincidence analysis. We observed that: (1) the estimated half-life of plasma LH was prolonged in uremic (59 +/- 10 min) rats compared to ad libitum-fed (17 +/- 3 min, p = 0.014) and pair-fed controls (19 +/- 3 min, p = 0.025); (2) the LH production rate was decreased in uremic animals (18 +/- 5 ng/ml.270 min) compared to ad libitum-fed (37 +/- 4 ng/ml.270 min, p = 0.002) and pair-fed controls (48 +/- 9 ng/ml.270 min, p = 0.0006); (3) the reduction of LH secretion rate in the uremic animals was accounted for by a decrease in detectable LH pulse frequency (2.1 +/- 0.2 peaks/h) compared to ad libitum-fed (3.1 +/- 0.1 peaks/h, p = 0.01) and pair-fed controls (2.8 +/- 0.2 peaks/h, p = 0.06) and a diminished mass of hormone released per burst (uremic 1.8 +/- 0.2 ng/ml, ad libitum-fed 2.6 +/- 0.3 ng/ml, p = 0.05, pair-fed 3.8 +/- 0.8 ng/ml, p = 0.025); (4) the secretion rate of GnRH was reduced to a similar degree in uremic rats (180 +/- 15 pg/tube.270 min, p = 0.04) and pair-fed controls (170 +/- 26 pg/tube.270 min, p = 0.04) compared to ad libitum-fed controls (270 +/- 36 pg/tube.270 min). In contrast to the reduced number of detectable LH secretory events, the frequency of GnRH secretory peaks in uremic rats was not different from ad libitum-fed and pair-fed controls.(ABSTRACT TRUNCATED AT 400 WORDS)

Animal Nutritional Physiological Phenomena↗
PubMed1994

Metabolic clearance of recombinant human growth hormone in health and chronic renal failure.

Despite the increasing therapeutic use of recombinant human growth hormone (rhGH), its metabolic clearance has not been investigated in detail. To evaluate the kinetics of rhGH as a possible function of GH plasma concentration and glomerular filtration rate (GFR), we investigated the steady state metabolic clearance rate (MCR), disappearance half-life, and apparent volume of distribution of rhGH at low and high physiological as well as supraphysiological plasma GH levels during pharmacological suppression of endogenous GH secretion in human subjects with normal and reduced renal function. GH in plasma and urine was determined by an immunoradiometric assay, and GFR by inulin clearance. In all subjects MCR decreased and plasma half-life increased with increasing plasma GH concentrations (P < 0.001). MCR of rhGH was approximately half in patients with chronic renal failure at each GH level and plasma half-life was increased by 25-50%. Allowing for the linear dependence of MCR on GFR and assuming single-compartment distribution, the estimated renal fraction of total MCR was 25-53 and 4-15% in controls and patients, respectively. Saturation of extrarenal disposal of GH was suggested by an inverse hyperbolic relationship between extrarenal MCR and plasma GH concentrations in all subjects. Fractional GH excretion was up to 1,000-fold higher in patients than in controls. We conclude that MCR of hGH is a function of plasma GH concentrations and GFR. Extrarenal elimination is saturable in the upper physiological range of GH concentrations, whereas renal MCR is independent of plasma GH levels. The kidney handles GH like a microprotein involving glomerular filtration, tubular reabsorption, and urinary excretion.

Adolescent↗
PubMed1994

Alterations in growth hormone secretion and clearance in peripubertal boys with chronic renal failure and after renal transplantation. Cooperative Study Group of Pubertal development in Chronic Renal Failure.

To elucidate the endocrine mechanisms underlying the pubertal growth failure observed in patients with chronic renal failure (CRF), we used deconvolution analysis to estimate the rates of GH secretion and elimination in nighttime plasma GH profiles of peripubertal boys with CRF and after renal transplantation (Tx). Forty-three boys with advanced CRF (conservative treatment with glomerular filtration rate < 25 mL/min.1.73 m2 or dialysis; CT/D group), 38 boys after Tx, and 40 healthy control boys were studied. The estimated plasma GH half-life (mean +/- SEM) was significantly higher (P < 0.05) in CRF (25 +/- 1.8 min) than in Tx patients (21 +/- 1.6 min) and controls (20 +/- 0.5 min). In the pre- and early pubertal CT/D boys, the calculated GH secretion rate was low normal or reduced when expressed in absolute numbers or normalized per unit distribution volume or body surface. In late puberty, whereas body surface-corrected GH secretion was double the prepubertal value in normal boys (389 +/- 56 vs. 868 +/- 113 micrograms/m2.11 h; P < 0.01), it did not differ significantly from the prepubertal rate in CT/D boys (281 +/- 59 vs. 389 +/- 56 micrograms/m2.11 h). GH hyposecretion resulted from a decrease in the mass of GH released within each burst, whereas burst frequency was unchanged. In the Tx group, GH secretion rates were significantly reduced in the prepubertal (221 +/- 39 micrograms/m2.11 h; P < 0.05) and late pubertal period (266 +/- 64 micrograms/m2.11 h; P < 0.01). The mass of hormone secreted per burst was significantly reduced at each pubertal stage, whereas GH secretory burst frequency tended to be increased (significant in prepubertal group, P < 0.05). The GH secretion rate was positively correlated with plasma testosterone levels (r = 0.58; P < 0.0001) in controls, but not in CT/D or Tx patients. GH secretion rates were lower than expected at each level of plasma testosterone in both patient groups except CT/D boys with plasma testosterone below 0.9 nmol/L. In the Tx group, GH secretion rate was positively correlated with relative height (r = 0.31; P < 0.05). The dosage of corticosteroids administered for immunosuppression was negatively correlated with GH burst mass (r = -0.42; P < 0.01) and GH secretion rate (r = -0.29; P = 0.08) and positively correlated with GH burst frequency (r = 0.49; P < 0.01). We conclude that in peripubertal boys with CRF, a state of GH hyposecretion is associated with an increase in the apparent plasma half-life of GH.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗
PubMed1994

Changes in the kinetics and biopotency of luteinizing hormone in hemodialyzed men during treatment with recombinant human erythropoietin.

To investigate the effect of recombinant human erythropoietin (rh-EPO) on the hypothalamo-pituitary-gonadal axis in end-stage renal failure, plasma luteinizing hormone (LH) concentration release was assessed by frequent blood sampling (every 10 min), both during an 8-h baseline period and after stimulation with an iv bolus of gonadotropin-releasing hormone (GnRH). Seven adult hemodialyzed men were studied before and after partial correction of anemia by rh-EPO treatment. LH was determined by an in vitro Leydig cell bioassay (bio-LH) and a highly sensitive immunoradiometric assay. Pulsatile bio-LH secretion and clearance characteristics were assessed by multiple-parameter deconvolution analysis. Although the rh-EPO treatment did not lead to a change in average concentrations of plasma bio-LH, the mass of hormone released per secretory burst more than doubled, and the estimated bio-LH production rate increased from 8.8 +/- 2.3 to 15.6 +/- 5.2 IU/L per hour (P = 0.05). The lack of change in mean plasma bio-LH is explained by a simultaneous decrease in plasma half-life from 106 +/- 27 to 67 +/- 19 min (P < 0.02). The decrease in the plasma half-life of bio-LH was closely associated with the rise in hematocrit, suggesting an effect of the increased red blood cell mass on LH distribution space and elimination kinetics. As a consequence of the changes in hormone kinetics, the incremental amplitudes of the plasma concentration pulses of bio-LH increased from 112 to 121% of nadir levels (P < 0.05), resulting in a more distinctly pulsatile pattern of hormone signals.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Higher KT/V urea associated with greater protein catabolic rate and dietary protein intake in children treated with CCPD compared to CAPD. Mid-European Pediatric CPD Study Group (MPCS).

Being more suitable to children's lifestyle habits, continuous cycling peritoneal dialysis (CCPD) is becoming the treatment modality of first choice in the pediatric CPD population. In order to establish whether these regimens, prescribed on an empirical basis, provide an equally effective dialysis as does standard continuous ambulatory peritoneal dialysis (CAPD), we performed a cross-sectional analysis of dialysate and residual renal small molecule clearances in 85 children aged 3 months to 20 years, who were treated in 16 pediatric dialysis centers. Forty-three children were on CAPD and 42 were on CCPD. The two patient groups did not differ in age, body size, duration of dialysis, underlying disease distribution, or residual renal function. The CAPD patients achieved an average daily drain volume of 159 +/- 40 mL/kg body weight, as compared to 208 +/- 95 mL/kg in the CCPD group (p < 0.005). Average serum creatinine and BUN values were similar in both groups. While the (total) creatinine clearance did not differ, the KT/V urea was significantly higher in the patients treated with CCPD (0.35 +/- 0.12 vs 0.28 +/- 0.13, p < 0.05). The estimated protein catabolic rate (PCR) was significantly higher in the CCPD group (1.39 +/- 0.6 g/kg d) than in the CAPD patients (1.08 +/- 0.48 g/kg d, p < 0.05). Three-day dietary histories, available in 20 patients, showed a similar difference in dietary protein intake between CCPD and CAPD patients. We conclude that CCPD treatment regimens, at the dose currently prescribed in Mid-European pediatric dialysis centers, provide a higher clearance of urea and, possibly, other small molecules.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

Stimulation of growth by recombinant human growth hormone in children undergoing peritoneal or hemodialysis treatment. German Study Group for Growth Hormone Treatment in Chronic Renal Failure.

Fourteen patients on hemodialysis (HD) and 17 patients on continuous peritoneal dialysis (CPD) were treated with 28-30 IU/m2/week of recombinant human growth hormone (rhGH) for at least 12 months. The HD and CPD patient groups were comparable with regard to age, bone age, height standard deviation scores (SDS), and height velocity at start of treatment. During the first year of rhGH treatment, height velocity increased from 2.9 +/- 1.9 to 5.5 +/- 1.7 cm/year in the HD group and from 3.0 +/- 2.2 to 7.2 +/- 3.2 cm/year in the CPD group. The increase in growth rate was significant in both groups (p < 0.001), and tended to be significantly greater in the CPD than in the HD group (p = 0.09). The marked acceleration of growth under rhGH treatment resulted in an increase in relative height by 0.37 +/- 0.38 SDS in the HD group and by 0.47 +/- 0.69 SDS in the CPD group during the first treatment year. Seven HD and 7 CPD patients completed a second year of rhGH treatment. In these patients, height velocity dropped to 3.6 +/- 2.7 cm/year (HD) and 3.6 +/- 2.3 cm/year (CPD), respectively during the second treatment year. We conclude that rhGH treatment accelerates growth in children both on HD and CPD. The treatment response tends to be greater in CPD compared to HD patients. The efficacy of treatment decreases considerably during the second treatment year.

Adolescent↗
PubMed1994

Usefulness of bioelectric impedance and skinfold measurements in predicting fat-free mass derived from total body potassium in children.

Despite the increasing use of tetrapolar whole-body bioelectric impedance (BI) analysis in the assessment of body composition, its usefulness in estimating fat-free mass (FFM) has not been evaluated in comparison with conventional skinfold anthropometry in children. We therefore compared 1) the intraobserver and interobserver reproducibility of BI and skinfold measurements and the derived FFM estimates, and 2) the predictability of FFM as calculated from measurements of total body potassium (TBK) using 40K spectrometry by equations based on either BI or skinfold measurements in 112 healthy children, adolescents, and young adults aged 3.9 to 19.3 y. A best-fitting equation to predict TBK-derived FFM from BI and other potential independent predictors was developed and cross validated in two randomly selected subgroups of the study population by stepwise multiple regression analysis. Although the technical error associated with BI measurements was much smaller than that of skinfold measurements, the reproducibility of BI-derived FFM estimates (intraobserver coefficient of variation [CV], 0.39%; interobserver CV, 1.23%) was only slightly better than that of FFM estimates obtained by use of weight and two skinfold measurements (0.62% and 1.39%, respectively). The cross validation procedure yielded the following best-fitting prediction equation: FFM = 0.65 x (height2/impedance) + 0.68 x age + 0.15 (R2 = 0.975, root mean square error = 1.98 kg, CV = 5.8%, 95% limits of agreement = -11.1% to +12.4%). Conventional anthropometry, using published equations to estimate FFM from skinfolds, slightly over-estimated TBK-derived FFM, but predicted FFM with precision similar to the best-fitting equation involving BI. Previously published FFM equations incorporating BI predicted TBK-drived FFM with variable predictive precision and accuracy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1993

Body growth in urinary tract malformations.

Body height and height velocity were analysed in 54 children with obstructive urinary tract malformations over a mean period of 8.7 years, using new auxological methods. At the time of diagnosis, 9% of patients had a height of more than 2 standard deviations below the normal mean. Mean relative height changed significantly from the first to the last observation, the standard deviation score (SDS) increasing from -0.16 to +0.36 in patients with hydronephrosis compared with normal children (P < 0.05) and from -0.63 to +0.02 SDS in those without hydronephrosis (P < 0.005). The pathogenesis of the described growth disturbance is not clear. Stepwise multiple regression analysis pointed to a possible link between the duration of antibiotic treatment and the recovery of growth capacity, but improved growth could not clearly be attributed to any medical or surgical treatment. The synchronized average growth velocity curve was similar to that of healthy children and showed a normal pubertal spurt. Final height and target height calculated from parents' height differed only slightly from that of the normal population.

Adolescent↗
PubMed1993

Opposite effects of intranigral ibotenic acid and 6-hydroxydopamine on motor behavior and on striatal neuropeptide Y neurons.

Unilateral lesions of the basal ganglia circuit induce a disequilibrium of motor processing, most obviously expressed by the resulting circling behavior. Compensatory events, which reduce the motor asymmetry, could be accompanied by changes in neurotransmitter/modulator parameters in the involved brain regions. In the present investigation, the effects of an interruption of the striato-nigro-thalamic loop by ibotenic acid (IBO)-induced lesions of total substantia nigra (SN) on circling behavior and on striatal neuropeptide Y (NPY) neurons were compared with those after the selective destruction of the dopaminergic nigrostriatal projection with 6-hydroxydopamine (6-OHDA). Directly after the operation, IBO-lesioned rats showed a high circling rate to the side contralateral to the lesion, whereas 6-OHDA-lesioned rats showed ipsiversive circling. With the lesion-induced development of dopamine receptor supersensitivity, 6-OHDA-treated rats, when stimulated with the dopaminergic agonist apomorphine, change their circling direction to the contralateral side. Complete IBO lesions of the SN abolished this effect: rats continued to circle to the contralateral side. These observations suggest that not only the dopaminergic denervation of the striatum but also the imbalance in the activity of the thalamo-cortical projection (reduced after 6-OHDA, augmented after IBO) are instrumental in determining the degree and direction of circling. Quantification of NPY-immunoreactive neurons in striatum revealed a decrease in 6-OHDA lesioned rats after 3 days on the side contralateral to the lesion, an effect even more pronounced after 4 month's survival time. IBO-induced lesions of the SN had an opposite effect on NPY-immunoreactivity in the striatum: neuron counts were lower on the ipsi- than on the contralateral side. In addition, a time-dependent variation in total number of NPY-neurons was noted: during the early postoperative periods an increase, followed by a prolonged decrease to values below 50% of the controls after 4 months. Taken together, these results provide evidence that a dopaminergic deafferentation and its consequences on the nigro-thalamo-cortical loop will determine NPY expression in the striatal interneurons. In particular, it is suggested that the number of striatal NPY-neurons and the imbalance in cortical activity are tightly coupled in terms of a negative correlation.

Animals↗
PubMed1993

Elevated serum immunoreactive inhibin levels in peripubertal boys with chronic renal failure. Cooperative Study Group on Pubertal Development in Chronic Renal Failure (CSPCRF).

OBJECTIVE: Boys with chronic renal failure have delayed progress through puberty and have raised gonadotrophin and low testosterone levels indicative of disturbed hypothalamo-pituitary-testicular function. Most studies into the mechanisms underlying the dysfunction have concentrated on the LH-Leydig cell interaction. However, it is now possible to probe the FSH-Sertoli cell axis by measuring plasma immunoreactive inhibin, which is a marker of Sertoli cell function. This study investigated the FSH-Sertoli cell (immunoreactive inhibin) axis in boys with chronic renal failure on conservative and dialysis treatment as they progressed through puberty. The effect of renal transplantation in chronic renal failure was also investigated. DESIGN: Blood was drawn at 15-minute intervals between 2000 and 0700 h from 51 boys with chronic renal failure at various stages of puberty. The samples were divided into two pools, corresponding to the hormone secretion in the first and second part of the night. Single blood samples were drawn from a group of normal boys between 0800 and 1000 h. PATIENTS: A total of 37 normal boys and 51 boys with chronic renal failure were examined immediately before and during puberty. Of a total of 80 pulse profiles taken in chronic renal failure, 36 were from transplanted and 44 from non-transplanted uraemic subjects. MEASUREMENTS: Immunoreactive inhibin, FSH and testosterone were measured using standard radioimmunoassays. The subjects were pooled into pubertal stages I, II/III and IV/V for analysis of hormone data. RESULTS: Early morning levels of immunoreactive inhibin like molecules (i-Inh) rose steadily with pubertal progression for all subject groups, those for boys with chronic renal failure being significantly elevated over normal boys from pubertal stage II/III onwards. Uraemic boys had higher levels than those who had been transplanted at all pubertal stages (P < 0.05). Early morning levels of FSH were significantly higher in uraemic patients with pubertal stages IV/V compared to our normal boys. There were no differences in i-Inh levels in plasma pooled from the samples taken between 2000 and 0115 h and 0130 and 0700 h for either treatment group at any stage of puberty. Testosterone levels rose in the second part of the profile from pubertal stages II/III onwards for both treatment groups. The proportional increase of testosterone was lower by mid puberty in uraemic than in transplanted children (percentage increases of 92 +/- 29 and 569 +/- 190 respectively, mean +/- SEM). i-Inh failed to correlate with FSH at any Tanner stage or for any subject group. CONCLUSION: Peripubertal boys with chronic renal failure have highly elevated serum immunoreactive inhibin and FSH levels which are partially reduced by renal transplantation. There was no evidence of any relationship between i-Inh and FSH secretion in either normal boys or in uraemic or transplanted boys with the exception of a positive correlation in late pubertal patients after transplantation. Finally, despite problems associated with the current immunoassay for inhibin, this assay may still prove to be a useful marker of Sertoli cell function in testicular pathology.

Adolescent↗
PubMed1992

Growth failure in renal disease.

Children with congenital CRF lose height potential mainly during two distinct growth periods; infancy and puberty. The onset of puberty is late, the pubertal growth spurt starts from a very low rate of growth velocity, and peak height velocity is lower than normal although the absolute increment of height velocity is comparable to the increment in normal children. Furthermore, the duration of pubertal growth spurt is reduced in CRF. During infancy and early childhood, malnutrition, electrolyte disturbances and metabolic acidosis are the main contributing factors for reduced growth, whereas hormonal disturbances are responsible for growth impairment during puberty. There is evidence for resistance to growth hormone in CRF, which starts in early childhood and persists until the end of puberty. Growth hormone secretion is normal in CRF, but GH half-life is prolonged. The binding activity of the stable growth hormone binding protein is reduced, which points to a low receptor expression in the liver. Hepatic IGF-I production is diminished. However, the serum concentration of IGF binding proteins (IGFBP) is increased due to reduced renal filtration of low molecular weight subunits of IGFBP. Mainly, the accumulation of IGFBP-3 leads to increased IGF-binding capacity of the uraemic serum. Both, reduced IGF-I production and increased binding of IGF to IGFBP-3 result in decreased IGF bioactivity. During infancy, loss of growth potential can be prevented by adequate nutrition. Later in life, catch-up growth cannot be induced by nutritional intervention or dialysis. Renal transplantation allows catch-up growth in only a small percentage of patients. Treatment with one IU rhGH/kg/week improves growth velocity and growth in all stages of renal disease. The mean increment of height in prepubertal children is +1.5 SDS within two treatment years. The effect of rhGH during puberty as well as the effect on final height remain to be determined.

Adolescent↗
PubMed1992

Evaluation of peritoneal solute transfer by the peritoneal equilibration test in children.

To evaluate the characteristics of peritoneal kinetics in the young, we investigated solute and water transfer rates by a modified Peritoneal Equilibration Test (PET) in 20 pediatric patients aged 1.9 to 19.8 years. 1000 ml/m2 body surface area of a 2.3% glucose PD solution were instilled in the peritoneal cavity. Glucose, creatinine, urea, sodium, potassium and phosphate were measured in the dialysate (D), 7 times during 4 hours and in plasma (P) after 2 hours dwell time. At 4 hours, the mean (+/- SD) D/P ratio was 1.06 +/- 0.16 for urea, 0.79 +/- 0.14 for creatinine, 0.82 +/- 0.21 for potassium, 0.92 +/- 0.04 for sodium and 0.79 +/- 0.30 for phosphate. Mean D/D0 of glucose was 0.36 +/- 0.13. The 4-hour solute equilibration curves were analytically best approximated by logarithmic functions for urea (mean R2 = 0.983), creatinine (R2 = 0.973) and potassium (R2 = 0.979), by a linear function for phosphate (R2 = 0.964), and by an exponential model for glucose (R2 = 0.969). The linear or exponential regression coefficients were used to express the peritoneal solute transfer rates. Although the transfer rates of most solutes were correlated with each other, the individual variation of peritoneal permeability for different solutes was high. Close associations were observed between the glucose and creatinine transfer rates (r = 0.91, p < 0.0001) and between ultrafiltration rate and glucose (r = -0.90, p < 0.0005) and creatinine (r = -0.88, p < 0.005). Peritoneal permeability for all solutes tended to be inversely correlated with body size (urea transfer rate vs. height: r = 0.49, p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1992

New insights into endocrine disturbances of chronic renal failure.

Secondary hyperparathyroidism occurs in the very early stages of renal failure. In the past, there has been considerable controversy concerning the signal triggering secondary hyperparathyroidism. Recently, it has become clear that secondary hyperparathyroidism is, at least to a major extent, the consequence of the deranged endocrine feedback between calcitriol, the secretory product of renal 1-alpha-hydroxylase, and parathyroid hormone. Another recent insight concerns disturbances of the secretion of hypophyseal hormones. These hormones, e.g. GH, gonadotropins and TSH, are secreted in a pulsatile fashion. For all three hormones, reversible abnormalities of secretory rhythmicity have been demonstrated in renal failure. Disturbed oscillatory patterns of hormone secretion provide a new dimension to our understanding of the genesis of endocrine disturbances.

Feedback↗
PubMed1991

The application of knemometry in renal disease: preliminary observations.

Short-term lower leg length was measured longitudinally using a high-precision device called a knemometer in 11 children with chronic renal failure and 12 normal children. The method has a high accuracy (mean standard error 0.13 mm) and may prove useful for prediction of long-term total body growth. Its application in renal patients undergoing corticosteroid, growth hormone (GH) and erythropoietin (EPO) therapy is documented. GH was shown to improve lower leg growth in an adolescent who already had passed the maximum of his pubertal spurt. EPO treatment produced no consistent increase of short-term growth.

Adolescent↗
PubMed1991

Recombinant human growth hormone overcomes the growth-suppressive effect of methylprednisolone in uraemic rats.

Paediatric renal allograft recipients frequently manifest growth retardation because of suboptimal graft function and/or concomitant corticosteroid treatment. To determine if the growth-suppressive effects of methylprednisolone (MP) could be counterbalanced by concomitant treatment with recombinant human growth hormone (rhGH) under conditions of normal and reduced renal function, the following animal model was set up. Female uraemic Sprague-Dawley rats (140 g) together with pair-fed and ad libitum-fed control animals were treated with 6 mg/kg per day MP with or without 10 IU/kg per day rhGH. MP suppressed linear growth and weight gain by 43% and 63%, respectively in ad libitum-fed normal control animals; the suppression was more pronounced in uraemic animals (57% and 107%, respectively). The suppressive effects were independent of food intake. The food conversion ratio (weight gain/food intake) was diminished to one-third in control and to more than one-tenth in uraemic animals. Concomitant treatment with rhGH completely reversed the suppression of length gain and weight gain (total body and muscle) and normalized the food conversion ratio. We concluded that rhGH can completely reverse the catabolic effects of corticosteroids under conditions of normal or reduced renal function. The data provide a reasonable rationale for prospective controlled studies on the use of rhGH treatment in paediatric kidney transplant recipients with growth failure.

Animals↗