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Biomedical subjects

O Mehls

Publications and source records attributed to O Mehls.

At least 73 records · Page 4Linked to original sources
PubMed1998

Inappropriate elevation of serum leptin levels in children with chronic renal failure. European Study Group for Nutritional Treatment of Chronic Renal Failure in Childhood.

Decreased spontaneous nutrient intake is a frequent clinical problem in patients with chronic renal failure (CRF). Leptin, the recently characterized gene product of the obese gene, is produced by adipocytes and is thought to act as an afferent satiety signal on the appetite and satiety centers of the brain. Serum leptin levels were investigated in 134 pediatric patients in different stages of CRF to evaluate a possible relationship between leptin, GFR, and spontaneous energy intake. Serum leptin levels, measured by a specific RIA, were elevated above the 50th percentile of the normal range in 78% of CRF patients and above the 95th percentile in 45% of patients. Gel chromatography of CRF sera yielded only one single immunoreactive peak at 16 kD, indicating that the increase of immunoreactive leptin levels in CRF serum was not due to accumulation of leptin degradation products. Multiple stepwise regression analysis revealed the percentage of body fat as assessed from skinfold measurements (r = 0.79, P < 0.0001) and GFR (r = -0.17, P < 0.005) as independent predictors of serum leptin levels, accounting for 66% of total statistical variability. There was an inverse linear correlation between standardized leptin levels (leptin z-score) and the spontaneous energy intake quantified from written dietary diaries (r = -0.36, P < 0.001). These data suggest that the percentage of body fat remains the main determinant of serum leptin in CRF patients, but their levels increase with declining GFR, presumably by reduced renal clearance. Leptin levels in CRF serum that are inappropriately elevated in relation to the percentage of body fat might lead to a dysregulation of the normal peripheral-central leptin feedback loop, thereby contributing to decreased nutrient intake in uremia.

Adolescent↗
PubMed1998

Pharmacokinetics of mycophenolic acid (MPA) and determinants of MPA free fraction in pediatric and adult renal transplant recipients. German Study group on Mycophenolate Mofetil Therapy in Pediatric Renal Transplant Recipients.

Dosage guidelines for mycophenolate mofetil (MMF), an ester prodrug of the immunosuppressant mycophenolic acid (MPA), are still preliminary in children. This study compares the pharmacokinetics of MPA and its major metabolite MPA glucuronide (MPAG) in pediatric renal transplant recipients receiving 600 mg MMF/m2 body surface area twice a day to those of adults on the currently recommended oral dose of 1 g of MMF twice a day. Concentration-time profiles of 18 children (age, 10.7+/-0.72 yr; range, 5.9 to 15.3 yr) and 10 adults were investigated 1 and 3 wk after transplantation. Plasma concentrations of MPA and MPAG were measured by reverse-phase HPLC. Because MPA is extensively bound to serum albumin and only the free fraction is presumed to be pharmacologically active, the MPA free fraction was also analyzed by HPLC after separation through ultrafiltration. The areas under the concentration-time curves (AUC0-12) of total and free MPA throughout the 12-h dosing interval in children were, in general, comparable to the corresponding data in adult patients. The mean AUC0-12 of MPA and free MPA did not change significantly over the first 3 wk after transplantation, but there was substantial intra- and interindividual variation. MPAG-AUC0-12 values in children with primary renal transplant dysfunction were threefold higher than in those with functioning transplants. Renal impairment had no consistent effect on total MPA-AUC0-12 values, but the MPA free fraction in children (median, 1.65%; range, 0.40 to 13.8%) was significantly (r2=0.46) modulated by renal transplant function and serum albumin levels. In conclusion, concentration-time profiles of pediatric renal transplant recipients administered 600 mg MMF/m2 body surface area twice a day are comparable to those in adults on 1 g MMF twice a day in the first 3 wk after transplantation. Renal impairment and decreased serum albumin levels led to an increase in the free fraction of MPA and the free MPA-AUC0-12 values. Because the pharmacologic activity of MPA is a function of unbound drug concentration, these findings might be relevant for the pharmacodynamic effects of MPA.

Adolescent↗
PubMed1997

Randomised multicentre study of a low-protein diet on the progression of chronic renal failure in children. European Study Group of Nutritional Treatment of Chronic Renal Failure in Childhood.

BACKGROUND: Some studies have suggested that a low-protein diet slows the deterioration of renal function in patients with chronic renal failure (CRF). The effects of a low-protein diet on renal function and growth, have not been assessed in a large, prospective randomised trial in children with CRF. METHODS: A 2-year prospective, stratified, and randomised multicentre study recruited 191 patients aged 2-18 years. After a run-in period of at least 6 months, patients were stratified into either a progressive or non-progressive category based on the change in creatinine clearance in this period. The patients were also stratified into three renal-disease categories and then randomly assigned to a control or diet group. In the diet group, the protein intake was the lowest, safe WHO recommendation--i.e., 0.8-1.1 g/kg daily adjusted for age. All patients were advised to have a calorie intake of at least 70% of the WHO recommendations. Glomerular filtration rate (GFR) was measured every 2 months by creatinine clearance; dietary compliance was checked by urinary urea-nitrogen excretion and dietary diaries (weighing method). 112 patients completed an optional third year of the study. FINDINGS: The low-protein diet did not affect growth. However, there was no effect of diet on the mean decline in creatinine clearance over 2 years (diet vs control: progressive group -9.7 [SD 8.0] vs -10.7 [11.8] mL/min per 1.73 m2; non-progressive group -2.5 [7.5] vs -4.3 [10.0] mL/min per 1.73 m2). Patients classified as having progressive disease were older and had a lower creatinine clearance and a higher blood pressure at randomisation, and had a greater decrease in creatinine clearance than non-progressive patients. On multivariate regression analysis proteinuria (partial R2 = 0.259) and systolic blood pressure (partial R2 = 0.087) were independent predictors of the change in GFR. Similar results were found after the study was extended for a third year. INTERPRETATION: A low-protein diet for 3 years did not affect the decrease in renal function in children with CRF. Proteinuria and blood pressure explain a large part of the variability of, and may be causally related to the decline in the GFR.

Adolescent↗
PubMed1997

Body growth in primary de Toni-Debré-Fanconi syndrome.

Body growth in nine children with primary de Toni-Debré-Fanconi syndrome was followed from birth to adolescence or adult life. At the time of diagnosis, corresponding to the start of treatment, the median age was 2.3 (range 0.4-13.9) years and height standard deviation score (SDS) was always decreased (median -3.5, range -6.8 to -2.1). Despite continuous electrolyte and bicarbonate supplementation only four patients showed a slight improvement in growth. At the time of the last observation at the age of 17.2 (4.5-20.1) years median height was -4.7 (-5.9 to -1.8) SDS. The median difference between height at last observation and target height was -4.5 SDS. Final height (n = 5) ranged between -1.8 and -5.5 (median -4.3) SDS. The pubertal growth spurt was absent in two children. Metabolic acidosis was identified as a significant growth-retarding factor. Mean serial blood bicarbonate levels and height SDS at the last observation were correlated (r = -0.87, P < 0.01). No correlation was observed between last height SDS and the degree of hypokalemia, hypophosphatemia, or hypercalciuria. In conclusion, patients with primary de Toni-Debré-Fanconi-syndrome present severe growth failure at the time of diagnosis which persists into adult life. Supportive therapy is frequently unable to prevent further loss of relative height.

Adolescent↗
PubMed1997

Parathyroid hormone prevents 1,25 (OH)2D3 induced down-regulation of the vitamin D receptor in growth plate chondrocytes in vitro.

1,25(OH)2D3 has an antiproliferative effect on growth plate chondrocytes when given in high doses, whereas low doses stimulate chondrocyte proliferation. In the present in vitro study we investigated the effects of parathyroid hormone (PTH) when given concomitantly with 1,25(OH)2D3 on cell proliferation and vitamin D receptor (VDR) regulation. Freshly isolated rat tibial chondrocytes were grown in monolayer cultures or in agarose stabilized suspension cultures (10% charcoal-treated FCS). VDR expression was determined by RT-PCR generating a 297 bp fragment and by binding assays (Scatchard analysis) with [3H]-1,25(OH)2D3. Cell proliferation was measured by [3H]-thymidine incorporation, growth curves in monolayer cultures and by colony formation in agarose-stabilized suspension cultures. Optimal concentration of 1,25(OH)2D3 (10(-12) M) and of PTH fragments [bPTH(1-34) or hPTH(28-48), 10(-10)M] showed additive effects on DNA synthesis of and colony formation by growth plate chondrocytes. This may be explained in part by an up-regulation of VDR by PTH: PTH increased both mRNA expression of VDR and binding capacity. 1,25(OH)2D3 (10(-12) M) induced an up-regulation of the VDR within 24 hours followed by a down-regulation after incubation for more than 24 hours. PTH fragments added concomitantly prevented the down-regulation seen with 1,25(OH)2D3. These findings provide evidence that PTH is a growth promoting hormone that also modulates the effects of 1,25(OH)2D3 by regulating the VDR status of 1,25(OH)2D3 target cells.

Animals↗
PubMed1997

Insulin-like growth factors (IGFs) and IGF binding proteins, serum acid-labile subunit and growth hormone binding protein in nephrotic children.

We hypothesized that the increased glomerular permeability to serum proteins in the nephrotic syndrome might lead to alterations of the somatotropic hormone axis, thereby contributing to growth failure and catabolism in the nephrotic state. The insulin-like growth factors (IGF)-I and -II and the IGF binding proteins (IGFBP)-1, -2 and -3 were analyzed in serum and urine of 21 children with the nephrotic syndrome and normal glomerular filtration rate. Mean age-related serum IGF-I levels by RIA (-0.53 +/- 0.34 SD) were slightly, but significantly (P < 0.05) decreased compared with the reference population, whereas mean age-related serum IGF-II levels (0.68 +/- 0.21 SD) were slightly, but significantly (P < 0.005) increased. The urinary excretion rate of both peptides was enhanced fivefold. By RIA, mean age-related serum IGFBP-1 (2.05 +/- 0.19 SD) and, even more pronounced, IGFBP-2 (5.97 +/- 0.65 SD) were clearly elevated despite a 12-fold and 2-fold increase of the respective urinary excretion rate. There was a tight and specific correlation between age-related serum IGFBP-2 levels and the degree of the nephrotic syndrome, as estimated by serum albumin levels (r = -0.78, P < 0.0001). Serum immunoreactive IGFBP-3 levels were also elevated (1.79 +/- 0.33 SD) in nephrotic serum, due to an increase of low-molecular weight IGFBP-3 fragments. By FPLC analysis, there was a decrease of the 150 kDa IGFBP ternary complex in nephrotic serum, which in the presence of normal concentrations of the acid-labile subunit by RIA appears to be due to a reduction of intact IGFBP-3. Serum levels of the high-affinity GH binding protein that presumably reflects GH receptor status in tissues were normal. In summary, total serum IGFs in children with the nephrotic syndrome are normal, but the binding of IGFs to IGFBPs in the circulation is altered with a shift from the 150 kDa IGFBP complex to an excess of low molecular weight IGFBPs. Because increased unsaturated high-affinity IGFBPs in nephrotic serum have the ability to inhibit IGF action on target tissues by competing with the type 1 IGF receptor for IGF binding, this alteration is likely to contribute to growth failure and tissue catabolism in the nephrotic state.

Carrier Proteins↗
PubMed1997

Reduced concentration of serum growth hormone (GH)-binding protein in children with chronic renal failure: correlation with GH insensitivity. The European Study Group for Nutritional Treatment of Chronic Renal Failure in Childhood. The German Study Group for Growth Hormone Treatment in Chronic Renal Failure.

Growth retardation in children with chronic renal failure (CRF) despite normal or elevated GH levels indicates a peripheral insensitivity to the action of GH. One possible molecular mechanism is a reduced density of GH receptors in GH target organs. In humans, the circulating high affinity GH binding protein (GHBP) is thought to reflect GH receptor expression, because it is derived from the extra-cellular domain of the GH receptor by proteolytic cleavage. We, therefore, analyzed serum GHBP levels by ligand-mediated immunofunctional assay in 126 children with CRF compared to reference values obtained by analysis of 773 healthy children. In 77% of CRF patients, serum GHBP concentrations were below the mean for age- and gender-matched controls. The decrease in serum GHBP levels was related to the degree of renal dysfunction. In advanced CRF (glomerular filtration rate, < 35 mL/min.1.73 m2), mean age- and gender-adjusted GHBP levels were -1.40 +/- 0.18 SD score; 36% of patients had GHBP levels below the normal range (< -2 SD score). Children with end-stage renal disease (n = 26) had the lowest GHBP levels (-2.25 +/- 0.22 SD score). Multiple linear regression analysis revealed that body mass index, rather than glomerular filtration rate, is the prevailing determinant of serum GHBP levels in CRF. GHBP levels correlated with both the spontaneous growth rate ( r = 0.44; P < 0.0001) and the growth response to GH therapy (r = 0.48; P < 0.005), indicating decreased sensitivity to both endogenous and exogenous GH. Subcutaneous GH therapy did not consistently affect serum GHBP levels after 3 months of treatment. It is suggested that low GHBP levels in children with CRF represent a quantitative tissue GH receptor deficiency as one of the molecular mechanisms of GH insensitivity.

Adolescent↗
PubMed1997

Insulin-like growth factor-binding protein-6 levels are elevated in serum of children with chronic renal failure: a report of the Southwest Pediatric Nephrology Study Group.

Previous studies suggest that growth retardation in children with chronic renal failure (CRF) results in part from inhibition of insulin-like growth factor (IGF) action by excess serum IGF-binding proteins (IGFBPs). Excess IGFBPs in CRF serum include IGFBP-1, -2, and -3 and a diffuse approximately 24- to 28-kDa IGFBP band identified by [125I]IGF ligand blot. The present studies characterized this diffuse approximately 24- to 28-kDa band. Initial studies identified this band as IGFBP-6, because it was immunoprecipitated by antiserum raised against a synthetic peptide of human IGFBP-6 (hIGFBP-6). Additional [125I]IGF ligand blots found that the immunoprecipitated band was 1) recognized by [125I]IGF-II but not [125I]IGF-1, 2) more abundant in CRF than in normal serum, and 3) more abundant in serum from dialyzed than nondialyzed prepubertal CRF children. Using the hIGFBP-6 antiserum in a specific and sensitive RIA, we found that serum IGFBP-6 levels were 4.7 +/- 1.7 nmol/L in 10 normal prepubertal children, 21.4 +/- 6.1 nmol/L in 44 nondialyzed prepubertal CRF children, 73.5 +/- 14.4 nmol/L in 7 dialyzed prepubertal CRF children, and 94.6 +/- 26.2 nmol/L in 14 dialyzed pubertal CRF children. IGFBP-6 levels were also elevated in 71 nondialyzed European children with CRF. In nondialyzed CRF children, serum IGFBP-6 levels 1) correlated inversely with the glomerular filtration rate, 2) did not correlate with height SD score, and 3) were not altered by 12 months of daily recombinant hGH treatment. In summary, a specific antiserum and RIA were used to demonstrate elevated levels of intact IGF-II-binding IGFBP-6 in serum of CRF children. We postulate that the excess IGFBP-6 may modulate the action of IGF-II on target tissues.

Adolescent↗
PubMed1997

Impaired postprandial regulation of insulin-like growth factor binding protein-1 in children with chronic renal failure.

Patients with chronic renal failure (CRF) have elevated plasma levels of insulin-like growth factor-1 (IGFBP-1). We sought to determine the dynamics of plasma IGFBP-1 in response to an endogenous insulin pulse during an oral glucose tolerance test (oGTT) in 12 prepubertal children with advanced CRF [glomerular filtration rate (GFR) 12.5 +/- 4 mL/min/1.73 m2] and in 9 age-, gender-, and body size-matched controls with normal renal function. Glucose and insulin responses to oGTT were significantly elevated in CRF (P < 0.01), indicating decreased sensitivity to the hypoglycemic action of insulin. Fasting plasma IGFBP-1 levels in CRF (235 +/- 40 ng/mL) were 2.5-fold increased compared with controls (94 +/- 11.6 ng/mL, P < 0.0001). In controls, plasma IGFBP-1 levels rapidly decreased with time by 52%, to a level of 45 +/- 6.7 ng/mL 180 min after the oral glucose load. In contrast, plasma IGFBP-1 levels in CRF patients slowly decreased with time by 25%, to a level of 176 +/- 28 ng/mL (P < 0.001 vs. controls) 180 min after the oral glucose load. For the group as a whole, the percent decrease in IGFBP-1 at 180 min was positively correlated with GFR (r = 0.85, P < 0.0001). Plasma GH concentrations were not statistically different at baseline, but showed a paradoxical increase in CRF patients thereafter. Plasma IGF-I concentrations at baseline were comparable in CRF patients and controls and similarly decreased by about 10% (P < 0.01) after the oral glucose load. In summary, our study shows that the decline of plasma IGFBP-1 in response to an oral glucose load is impaired in children with CRF despite increased insulin levels. This impaired postprandial decline of plasma IGFBP-1 might interfere with glucose homeostasis by blocking insulin-like activity of free IGFs in vivo and thereby contribute to glucose intolerance in uremia.

Administration, Oral↗
PubMed1997

Factors affecting growth and strategies for treatment in children after renal transplantation.

Growth failure is a frequent side effect of long-term high-dose glucocorticoid therapy in children. Pharmacological doses of glucocorticoids interfere at different levels with the integrity of the somatotropic hormone axis. The majority of patients on chronic corticosteroid medication present with overt GH hyposecretion, apparently due to enhancement of hypothalamic somatostatin release. Glucocorticoids also inhibit IGF bioactivity by the induction of IGF inhibitors and stimulate the production of certain IGFBPs. In addition, glucocorticoids inhibit growth directly at the tissue level by suppressing local growth factors and skeletal tissue matrix production. In children post renal transplantation, concomitant treatment with cyclosporin A for immunosuppression allows low-dose glucocorticoid medication. Reduction of glucocorticoids, in particular when given as alternate-day therapy, improves growth in some but not all children. The new glucocorticoid deflazacort appears to have fewer side effects regarding steroid-induced osteopenia and cushingoid appearance. A beneficial effect on longitudinal growth has not been clearly established. Recent experimental and clinical data indicate that the catabolic and growth-depressing effects of glucocorticoids can be counterbalanced by concomitant anabolic treatment with rhGH. The potential role of rhIGF-I is less well investigated. Treatment with rhGH is able to antagonize several side effects of long-term glucocorticoid administration, such as growth failure, protein-wasting and osteoporosis. If catch-up growth cannot be achieved by an alternate-day steroid regimen and discontinuation of glucocorticoids appears to be an intolerable risk for graft survival, rhGH therapy may be initiated. However, rhGH therapy in this setting must still be considered experimental, because the possible interference of rhGH with the immunosuppressive action of glucocorticoids in children after organ transplantation is still incompletely defined.

Anti-Inflammatory Agents↗
PubMed1997

Interactions between glucocorticoids and the growth hormone-insulin-like growth factor axis.

Glucocorticoids in pharmacological doses interfere with the integrity of the somatotropics hormone axis. However, the apparent discrepancies between the in vitro and in vivo studies, short-term vs. long-term exposure, and species-specific changes complicate a clear assessment of these interactions. The growth-depressing effects of glucocorticoids are multifactorial and involve suppression of pituitary GH release by stimulating hypothalamic somatostatin tone, down-regulation of hepatic GH receptors, inhibition of GH bioactivity by the induction of IGF inhibitors, complex alteration of the IGFBP serum profile, and a direct suppressive effect on tissue matrix production and synthesis of local growth factors.

Glucocorticoids↗
PubMed1997

Derangements of the somatotropic hormone axis in chronic renal failure.

Recent evidence indicates that disturbances of the somatotropic hormone axis play an important pathogenic role for growth retardation and catabolism in children with chronic renal failure (CRF). Whereas the growth hormone (GH) secretion rate in CRF is variable between patients and studies, a prolonged half-life of GH as a result of a reduced renal metabolic clearance rate is a consistent finding. Accordingly, the serum GH levels in children with CRF are normal or elevated depending on the extent of renal failure. The apparent discrepancy between normal or elevated GH levels and diminished longitudinal growth in CRF has led to the concept of GH insensitivity, which is caused by multiple alterations in the distal components of the somatotropic hormone axis. Serum insulin-like growth factor (IGF)-I and IGF-II levels are normal in preterminal CRF, while in end-stage renal disease (ESRD) IGF-I levels are slightly decreased and IGF-II levels slightly increased. In view of the prevailing elevated growth hormone levels in ESRD, these serum IGF-I levels appear as inadequately low. Indeed, there is both clinical and experimental evidence for a decreased hepatic IGF-I production rate in CRF. This hepatic insensitivity to the action of GH may be partially the consequence of a reduced GH receptor expression in liver tissue. The action and metabolism of IGFs are modulated by specific high-affinity IGF binding proteins (IGFBPs), which bind approximately 99% of circulating IGF. IGFBP-1, IGFBP-2, and low molecular weight IGFBP-3 fragments are increased in CRF serum in relation to the degree of renal dysfunction. Both decreased renal filtration, in particular of low molecular weight IGFBP-3 fragments, and increased hepatic production of IGFBP-1 and -2 contribute to high IGFBP serum levels. Experimental and clinical evidence suggests that these excessive high-affinity IGFBPs in CRF serum inhibit IGF action on target tissues by competition with the type 1 IGF receptor for IGF binding.

Adolescent↗
PubMed1996

Serum insulin-like growth factors and their binding proteins in children with end-stage renal disease.

Serum levels of insulin-like growth factor-I (IGF-I), IGF-II, and IGF binding protein-1 (IGFBP-1), IGFBP-2, and IGFBP-3 were measured in 54 children with end-stage renal disease (ESRD). The results were compared with their respective age-dependent normal ranges. IGFs and IGFBPs were quantified by specific radioimmunoassay. Serum IGF-I in children with ESRD tended to cluster in the low-normal range. Mean age-related serum IGF-I levels were slightly, but significantly decreased (-1.08 +/- 0.17 SDS). In view of the prevailing elevated growth hormone levels in ESRD, these serum IGF-I levels must be interpreted as inadequately low. In contrast to IGF-I, individual serum IGF-II levels were either in the upper-normal range or clearly elevated. Mean age-related IGF-II (1.09 +/- 0.15 SDS) was slightly, but significantly elevated. Mean age-related IGFBP-1 serum levels (2.20 +/- 0.10 SDS) were moderately increased, while mean age-related serum IGFBP-2 (5.65 +/- 0.36) and IGFBP-3 levels (3.60 +/- 0.19) were markedly elevated. Affinity cross-linking of 125iodine-IGF-II to sera from patients with ESRD and immunoprecipitation with a specific antiserum showed that low molecular weight IGFBP-3 fragments in ESRD serum are capable of binding IGF. In patients with ESRD, a rapid and persistent decline of immunoreactive IGFBP-3 in response to restoration of renal function by renal transplantation was observed. This finding indicates that renal dysfunction contributes to high immunoreactive IGFBP-3 levels in ESRD. In conclusion, the imbalance between normal total IGF levels and the excess of IGFBPs in ESRD is likely to play a role in growth failure in these children.

Adolescent↗
PubMed1996

Early age-dependent growth impairment in chronic renal failure. European Study Group for Nutritional Treatment of Chronic Renal Failure in Childhood.

We report early linear growth in 73 children (51 boys, 22 girls) with early onset of chronic renal failure (CRF). The inclusion criteria was onset of CRF before 6 months of age, two or more height measurements during the 1st year of life, follow-up for at least 3 years and continuously impaired renal function with a glomerular filtration rate below 50 ml/min per 1.73 m2 at 1 year or later. Only height measurements taken during conservative treatment or dialysis were included. The data were analysed in terms of the infancy-childhood-puberty growth model. There was an age-dependent growth failure in early life leading to an attained height of -3 standard deviation score (SDS) at 3 years of age. Approximately one-third of the reduction in height occurred during fetal life and one-third during the first postnatal months. Between 0.75 and 1.5 years of age height also decreased by 1 SD as a consequence of a delayed onset of the second, the 'childhood', phase of growth in 36% of the patients and by an 'offset childhood' growth pattern--i.e. a return to the infancy phase pattern after onset of the childhood phase--in 60% of the patients. Growth between 0.25-0.75 and 1.5-5 years of age was generally percentile parallel and thus less likely to be affected in CRF with early disease onset. The glomerular filtration rate was not related to the height gain in early life. We speculate that the growth failure during fetal life and the first postnatal months reflects metabolic and/or nutritional influences and the impaired growth at 0.75-1.5 years of age is related to a partial insensitivity to growth hormone.

Aging↗
PubMed1996

Growth charts for prepubertal children with chronic renal failure due to congenital renal disorders. European Study Group for Nutritional Treatment of Chronic Renal Failure in Childhood.

Despite the high prevalence of and therapeutic attention to growth failure in children with chronic renal failure (CRF), systematic evaluations of spontaneous growth in CRF are lacking. Therefore, we collected retrospectively longitudinal growth and biochemical data in 321 prepubertal patients treated for CRF due to congenital renal disorders. Data were recorded at 3-month intervals during the first 2 years of life and 6-monthly thereafter, up to the age of 10 years. Around 100 measurements were available per age interval. Mixed-longitudinal percentile curves of height and height velocity were constructed. Moreover, a statistical comparison with the heights and height velocities of healthy children and an evaluation of the effect of biochemical parameters on growth was performed. The CRF children had normal heights at birth but dropped below the 3rd normal percentile during the first 15 months of life. Thereafter, growth patterns usually were percentile parallel, with a mean height standard deviation score (SDS) of -2.37 +/- 1.6. Height velocities were consistently lower in patients with glomerular filtration rates (GFRs) below one-third of the lower normal limit (25 ml/min per 1.73 m2 for patients > 1 year) than in patients with better renal function. This difference in growth rates resulted in a mean height SDS of -1.65 +/- 1.5 SDS and -2.79 +/- 1.4 SDS (age 1-10 years) in the subgroups with relatively better and worse GFR, respectively. Regression analysis confirmed that GFR was a weak but significant predictor of height velocity SDS in most age groups.

Child↗
PubMed1996

Short dialyzed children respond less to growth hormone than patients prior to dialysis. German Study Group for Growth Hormone Treatment in Chronic Renal Failure.

Recombinant human growth hormone (rhGH) is a new treatment modality for short children with chronic renal failure (CRF) prior to and during dialysis. It is difficult to analyze whether dialysis patients respond less to rhGH than children with CRF on conservative treatment because they are older and often in a pubertal age range. One hundred and eight patients were treated with 28-30 IU rhGH/kg per week for at least 1 year. We analyzed the growth response to rhGH in 56 prepubertal patients aged less than 10 years at the start of rhGH treatment; 38 children with a mean age of 6.5 +/- 2.4 years were on conservative treatment (CT) and 18 patients with a mean age of 6.5 +/- 2 years on dialysis treatment (D). Mean height velocity was 4.9 +/- 2.3 cm/year in children on CT and 4.6 +/- 1.8 cm/year in children on D. During the 1st treatment year, height velocity was 9.5 +/- 3.8 cm/year in CT patients and 7.3 +/- 1.3 cm/year in D patients (P < 0.05). The change in height was +1.1 +/- 0.8 standard deviation (SD) in CT patients and +0.5 +/- 0.4 SD in D patients (P < 0.005). During the 2nd treatment year, the change in height was again greater in CT patients (0.5 +/- 0.4 SD vs. 0.2 +/- 0.4 SD; P < 0.05). The difference in height velocity and change in height standard deviation score was also significant when a subgroup of patients was matched for sex, age, height. Height velocity and the change in height velocity during rhGH treatment were not correlated with residual renal function, the degree of anemia, or metabolic acidosis. We conclude that short children on D respond less to rhGH than short children on CT, indicating a greater insensitivity to rhGH during D treatment.

Acidosis↗