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Biomedical subjects

O Mehls

Publications and source records attributed to O Mehls.

At least 19 recordsLinked to original sources
PubMed2004

Pediatric renal transplantation and the dysfunctional bladder.

We retrospectively reviewed our long-term experience with pediatric renal transplantation into a dysfunctional lower urinary tract to evaluate graft survival, function, and special urological complications. Between 1967 and March 2000, a total of 349 renal transplantations were performed in children younger than 18 years. Malformations of the lower urinary tract were the reasons for end-stage renal failure in 66 children (18.6%). The cause of urinary tract disorders included: meningomyelocele connected with neuropathic bladder (n = 4 transplantations); prune belly syndrome (n = 5 transplantations); VATER association (n = 2 transplantations); posterior urethral valves (n = 27 transplantations); and vesico-uretero-renal reflux (n = 28 transplantations). The majority of the patients underwent surgical interventions to preserve renal function or to prepare renal transplantation. The 1- and 5-year graft survival rate was evaluated with special reference to the underlying disease. The 1-year graft survival rate in all children with lower urinary tract malformations was 83.3%, compared with 88% for all children. In those children with vesico-ureteral reflux, it was 92.8% and in the children with Vater association and prune belly syndrome, it was 85.7%. One graft was lost in the children who had neurogenic bladder, so the 1-year graft survival rate was 75%. The worst 1-year graft survival rate was obtained for boys who had posterior urethral valves (1-year graft survival rate: 74%; 5-year graft survival rate: 62.9%). Concerning the 5-year graft survival rate, it was 70% for all children with malformations of the urinary tract. The best rate was obtained for children with reflux in the native kidneys (78.5%), followed by those with VATER association and prune belly syndrome. As an additional child with neurogenic bladder lost his graft, the 5-year graft survival rate was 50%. Pediatric renal transplantation into a dysfunctional bladder can be connected with high urological complication rates which may contribute to worse graft survival. The 1- and 5-year graft survival rate in children with malformations of the lower urinary tract is worse than in children without bladder dysfunction. We regarded a striking difference between graft survival and the urological disorders which led to renal insufficiency. We obtained the worst graft survival rates in children with posterior urethral valves which are usually connected with bladder emptying problems and dysfunctional voiding. Potential pediatric transplant recipients must be classified according to pathophysiological as well as anatomical abnormalities of the urinary tract and all urological problems have to be solved prior to transplantation. At our center, living donors are favored to plan transplantation of these children properly.

Adolescent↗
PubMed2004

Survival in nephroblastoma treated according to the trial and study SIOP-9/GPOH with respect to relapse and morbidity.

BACKGROUND: Recent Wilms' tumor (WT) trials and studies have tried to determine the minimal therapy needed for cure. The goal was survival without morbidity. PATIENTS AND METHODS: From January 1989 to March 1994 the German Society of Pediatric Oncology and Hematology registered 440 patients (median age 2.9 years; 231 male, 209 female) with WTs (preoperative chemotherapy 362) for therapy according to the International Society of Pediatric Oncology Trial and Study 9. Therapy for relapse depended on site of relapse and therapy already received. Follow-up included inquiries for morbidity. Prognostic factors for relapse and death were evaluated. RESULTS: Five-year survival of WTs was 89.5%; 98.2% (385 of 392) of survivors had a follow-up of 5 years (range 0.8-12.6; median 8). In non-anaplastic WTs, young age (<2 years) was of significance (P = 0.026) for a better survival. Non-anaplastic WTs (407 patients) had a 5-year survival of 92.3%, versus 48.5% in anaplastic WTs (33 patients), and a 5-year relapse-free survival of 87.6% versus 42.4%. Survival after relapse was significantly worse for anaplastic than for non-anaplastic WTs (residual 3-year survival 11.8% versus 54.3%; P <0.0001). In preoperatively treated WTs, anaplasia was a strong prognostic factor for death [relative risk (RR) 4.7], followed by poor response to preoperative therapy (RR 3.6), stage IV (RR 3.2) and abdominal stage III (RR 2.2). Low abdominal stages (<III) dominated (280 versus 82). In the 334 unilateral stage I-IV WTs (median age 3.2 years), diffuse anaplasia (21 patients) had a 5-year relapse-free survival of 38.1%, versus 58.4% in blastemal WTs (25 patients); survival was 42.9% in diffuse anaplasia versus 84% in blastemal WTs. None of 46 patients (median age 1.9 years; 91.3% stages I or II) with differentiated WTs (nine epithelial, 37 stromal) relapsed despite their non-response; two died (one therapy related, one due to bilaterization). In the 25 non-anaplastic bilateral WTs, differentiated cases (one epithelial, eight stromal, 33.3% abdominal stage III) were more frequent (P = 0.048) than in unilateral WTs (one stromal, abdominal stage III relapsed). In all, 52.9% of the 5-year survivors had received adriamycin (250-400 mg/m(2)), 25.7% radiation, 6.4% ifosfamide (24-30 g/m(2)) and 6.7% carboplatin plus etoposide. Abnormal parameters according to the National Cancer Institute score were seen in 18.9% during follow-up, but only 6.4% were treated for morbidity at the end of follow-up. Three WTs developed renal failure due to Drash syndrome, but none due to tumor therapy. After adriamycin 1.9% of WTs (9% of those receiving 400 mg/m(2)) required therapy for cardiac toxicity. CONCLUSIONS: Initial therapy should be more individualized, taking the above risk groups (age in non-anaplastic WTs, poor response, anaplasia, etc.) into account, as morbidity even after relapse therapy with ifosfamide, carboplatin and etoposide was not high. Milder therapy in low stages of differentiated and of well responding WTs should be tested.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2003

1,25(OH)2D3 and dihydrotestosterone interact to regulate proliferation and differentiation of epiphyseal chondrocytes.

Growth plate chondrocytes are affected by 1,25(OH)2D3 and androgens, which may critically interact to regulate proliferation and differentiation during the male pubertal growth spurt. We investigated possible interactions of 1,25(OH)2D3 and the non-aromatizable androgen dihydrotestosterone (DHT) in primary chondrocyte cultures from young male rats. DHT and 1,25(OH)2D3 independently stimulated DNA synthesis and cell proliferation in a dose-dependent manner with maximally effective doses of [10(-8) M] and [10(-12) M], respectively. Both DHT and 1,25(OH)2D3 stimulated the expression and release of IGF-I, and the proliferative effects of each hormone were prevented by an IGF-I antibody. DHT and 1,25(OH)2D3 increased messenger RNAs (mRNAs) of their cognate receptors and of IGF-I receptor mRNA (IGF-I-R). 1,25(OH)2D3 also stimulated mRNA of the androgen receptor (AR), whereas DHT did not affect mRNA of the vitamin-D receptor (VDR). Coincubation with both steroid hormones did not stimulate receptor mRNAs more than either hormone alone. The proliferative effects of DHT and 1,25(OH)2D3 were completely inhibited by simultaneous incubation with both hormones, despite potentiation of IGF-I synthesis. In contrast, both hormones synergistically stimulated cell differentiation as judged by alkaline phosphatase activity, collagen X mRNA, and matrix calcification in long-term experiments. We conclude that DHT and 1,25(OH)2D3 interact with respect to chondrocyte proliferation and cell differentiation. The proliferative effects of both hormones are mediated by local IGF-I synthesis. Simultaneous coincubation with both hormones blunts the proliferative effect exerted by either hormone alone, in favor of a more marked stimulation of cell differentiation.

Androgens↗
PubMed2003

Vitamin D and dexamethasone inversely regulate parathyroid hormone-induced regulator of G protein signaling-2 expression in osteoblast-like cells.

The PTH/PTHrP receptor stimulates both adenylate cyclase- and phospholipase C-dependent signaling pathways via different G proteins. The biological actions of PTH on bone are modified by steroid hormones. PTH induces expression of regulator of G protein signaling (RGS)-2, a putative preferential inhibitor of G(q)-mediated phospholipase C activation. We investigated whether steroid hormones interfere with PTH signaling by modulating PTH-induced RGS-2 expression in osteoblast-like UMR 106-01 cells. PTH (1-34) rapidly and transiently induced expression of RGS-2 mRNA and protein via the cAMP/protein kinase A pathway within 30 min, with maximal protein abundance after 2 h. PTH-induced RGS-2 preferentially bound to Galpha(q), compared with Galpha(s) protein. 1,25-(OH)(2)D(3) pretreatment enhanced PTH-induced RGS-2 mRNA and protein accumulation, whereas dexamethasone preincubation had an attenuating effect. These effects were due to modulation of the RGS-2 gene transcription rate, which increased by 35% with 1,25-(OH)(2)D(3) and decreased by 63% with dexamethasone pretreatment. RGS-2 mRNA half-life was not affected by either steroid. The transcriptional effects of dexamethasone and 1,25-(OH)(2)D(3) were independent of PTH/PTHrP receptor activation and were not explained by effects on cAMP accumulation, cAMP response element-binding protein expression or phosphorylation, or the abundance of the osteoblast-specific transcription factor core-binding factor alpha (CBFa1/Runx2), a known activator of RGS-2 expression. In conclusion, glucocorticoids and 1,25-(OH)(2)D(3) inversely modulate PTH-induced RGS-2 gene transcription. Regulation of RGS-2 may constitute a novel mechanism by which steroids modulate signaling via the PTH/PTHrP receptor and other G protein-coupled receptors in bone.

Animals↗
PubMed2003

Mycophenolate mofetil in pediatric renal transplantation.

Since mycophenolate mofetil (MMF), an ester prodrug of the immunosuppressant mycophenolic acid (MPA), has been approved for maintenance immunosuppressive therapy also in children after renal transplantation it has become an important part of immunosuppressive protocols. By inhibiting inosine monophosphate dehydrogenase, the key enzyme in the de novo purine biosynthesis of proliferating T and B lymphocytes, MMF acts as a relatively specific inhibitor of human lymphocyte proliferation. MMF is more effective than azathioprine in combination with cyclosporin A (CsA) and corticosteroids and distinctly reduces the incidence of acute rejection episodes in the 1st year post-transplant in adults as well as in children. Beneficial effects on steroid-resistant rejection and chronic allograft dysfunction have been shown. In general, MMF is well tolerated. Major adverse events in pediatric renal transplant recipients include leukopenia, infections and gastrointestinal problems. Pharmacokinetic monitoring of MPA can help to optimise MMF therapy after renal transplantation, as associations between the risk of acute rejection episodes and MPA-AUC values and MPA predose levels have been demonstrated. The incidence of MMF-related side effects such as leukopenia and/or infections, however, is associated with pharmacokinetic parameters of free MPA. Reference data of relevant pharmacokinetic parameters are available. The possible steroid-sparing potential of MMF is an important issue in pediatric renal transplantation. Preliminary data demonstrate improved longitudinal growth, less cushingoid habitus and lower blood pressure after steroid-withdrawal in pediatric renal transplant recipients under MMF and CsA therapy.

Adrenal Cortex Hormones↗
PubMed2002

Adult height after GH therapy in 188 Ullrich-Turner syndrome patients: results of the German IGLU Follow-up Study 2001.

OBJECTIVES: We aimed to evaluate the factors influencing true adult height (HT) after long-term (from 1987 to 2000) GH treatment in Ullrich-Turner syndrome (UTS) based on modalities conceived in the 1980s. DESIGN: Out of 347 near-adult (>16 Years) patients from 96 German centres, whose longitudinal growth was documented within KIGS (Pharmacia International Growth Database), 188 (45, X=59%; bone age >15 Years) were available for further anthropometric measurements. RESULTS: At a median GH dose of 0.88 (10th/90th percentiles: 0.47/1.06) IU/kg per week, a gain of 6.0 (-1.3/+13) cm above the projected adult height was recorded. Variables were recorded at GH start, after 1 Year GH, puberty onset, and last visit on GH therapy. At these visits, the median ages were 11.7, 12.7, 14.2, 16.6 and 18.7 Years; and median heights, 0.4, 1.1, 1.7, 1.7 and 1.3 SDS (UTS) respectively. Height gain (DeltaHT) after GH discontinuation was 1.5 cm. Total DeltaHT correlated (P<0.001) negatively with bone age and HT SDS at GH start, but positively with DeltaHT after the first Year, DeltaHT at puberty onset, and GH duration. Final HT correlated (P<0.001) positively with HT at GH start, first-Year DeltaHT, and HT at puberty onset. Body mass index increased slightly (P<0.05), with values at start and adult follow-up correlating highly (R=0.70, P<0.001). No major side effects of GH occurred. CONCLUSIONS: GH dosages conceived in the 1980s are safe but too low for most UTS patients. HT gain and height are determined by age and HT at GH start. Height gain during the first Year on GH is indicative of overall height gain. After spontaneous or induced puberty, little gain in height occurs.

Adolescent↗
PubMed2001

Impact of ACE I/D gene polymorphism on congenital renal malformations.

To investigate the role of the angiotensin converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism on prevalence and progression of disease in children with chronic renal failure (CRF), we determined the ACE I/D genotype in 95 children with CRF due to renal malformations (hypo-/dysplasia, obstructive uropathy, reflux nephropathy; n = 59), other congenital or hereditary diseases (n = 23), or acquired glomerular disorders (n = 13), who had been followed prospectively over a 2-year period. CRF progression rate was followed in each individual by linear regression analysis of estimates of glomerular filtration rate (GFR) obtained every 2 months. Actuarial renal 'survival' analysis was performed, using a GFR loss of 10 ml/min per 1.73 m2 as a cutoff point. The distribution of the ACE genotype did not differ among the disease groups. There was also no difference in ACE genotype distribution between the patients and a control group of healthy Caucasian children (n = 163). Among the children with renal malformations, the 2-year renal survival was significantly lower in those with the DD genotype (61%) than in patients with ID or II genotype (89%, P < 0.01). In the other disease groups, the ACE I/D genotype was not predictive of CRF progression. In a multivariate analysis of risk factors, the adverse effect of the DD genotype (risk ratio 10.2, P < 0.05) was independent of and additive to those of arterial hypertension (RR 13.2, P < 0.001) and gross proteinuria (RR 4.7, P < 0.05). We conclude that the ACE DD genotype is a significant risk factor for children with congenital renal malformations to develop progressive CRF. The effect of the ACE polymorphism in this patient group is independent of hypertension and proteinuria.

Adolescent↗
PubMed2001

Long-term treatment with growth hormone in short children with nephropathic cystinosis.

OBJECTIVE: The objective was to assess the efficacy and safety of growth hormone (GH) treatment in severely growth retarded children with nephropathic cystinosis during conservative treatment and during renal replacement therapy. STUDY DESIGN: The design was an open-labeled prospective trial with a run-in period of 1 year. RESULTS: A total of 74 children with cystinosis (age 3.0 to 18 years) were treated with GH over a mean period of 3.1 years (range 1 to 10 years); 52 patients were receiving conservative treatment (mean age 7.1 years), 7 were receiving dialysis (12.5 years), and 15 had received a renal transplant (14.8 years). The mean standardized height (SD score) was -4.0 in the conservative treatment group, -4.4 in the dialysis group, and -4.9 in the renal transplant group. During the first treatment year, height velocity doubled in the conservative treatment group, increased by 80% in the dialysis group, and increased by 45% in renal transplant group. Within 3 years the height SD score increased by +1.6 (P <.001) in prepubertal patients receiving conservative treatment, and percentile parallel growth was maintained thereafter. These effects of GH were less expressed in peripubertal patients receiving renal replacement therapy. No major side effects were observed. CONCLUSION: Long-term GH treatment is safe and effective in young children with nephropathic cystinosis. GH treatment should be started early in the course of the disease if adequate nutrition and cysteamine treatment do not prevent growth retardation.

Adolescent↗
PubMed2001

Renal transplantation in small children--a comparison between surgical procedures.

OBJECTIVES: Renal transplantation is the therapy of choice for patients with end-stage renal failure. From the surgical point of view, small children remain a challenging patient group. METHODS: We report our experience with 61 consecutive kidney transplantations in small children aged < or =6 years. Outcome and graft survival rates were presented with special reference to the surgical procedure used to perform the renal transplantation. RESULTS: Of the 31 renal grafts, placed into the fossa iliaca (group 1), 8 grafts were lost shortly after transplantation due to a vascular complication (5 venous thromboses and 3 arterial thromboses). Six allografts were lost because of acute rejection. All in all, the 1- and 5-year graft survival rate in this group was 55.8% (p = 0.0106)/51.6% (p = 0.0134), respectively. Thirty grafts were placed retroperitoneally, using the aorta and the distal caval vein to perform end-to-side anastomoses (group 2). One graft was lost because of a venous thrombosis 6 weeks following transplantation, 3 further grafts were lost during the 1st year after transplantation due to acute rejection. The 1- and 5-year graft survival rate in that group was 86.6% (p = 0.0106)/83.3% (p = 0.0134), respectively. Comparing the 1-year graft survival rates of the two patient groups with special reference to vascular complications, we observed a 1-year graft survival rate of 74.2% (group 1) versus 96.6% (group 2; p = 0.026). CONCLUSIONS: Our results on kidney transplantation in small children have considerably improved with the consistent use of the aorta and the distal caval vein to perform vascular anastomoses. The number of vascular complications following renal transplantation decreased, and especially for very small children the retroperitoneal placement of the graft is a safe, feasible surgical procedure that should be performed whenever possible.

Child↗
PubMed2001

The interaction of glucocorticoids with the growth hormone-insulin-like growth factor axis and its effects on growth plate chondrocytes and bone cells.

Glucocorticosteroids interfere with the growth hormone (GH)-insulin-like growth factor-I (IGF-I) axis at different levels, and while low-dose corticosteroids may have permissive effects, high-dose, long-term treatment with corticosteroids may lead to growth disturbance. The mechanism involved is not clearly understood. The Janus kinase (JAK)-2/signal transducers and activators of transcription (STAT)-5 pathway is the means by which the corticosteroid interacts with the target-cell GH receptors. The production of local IGF-I is lowered by the corticosteroid via IGF-I transcription inhibition, and the rate of apoptosis is also increased, both in growth plate chondrocytes and osteoblast cell lines. GH in vitro and in vivo can partly counterbalance the negative effects of glucocorticoids on growth. GH has been seen to normalize growth rates in corticosteroid-treated rats as well as in children receiving glucocorticoids for immunosuppression following kidney transplantation.

Animals↗
PubMed2000

Effect of growth hormone treatment on the adult height of children with chronic renal failure. German Study Group for Growth Hormone Treatment in Chronic Renal Failure.

BACKGROUND: Growth hormone treatment stimulates growth in short children with chronic renal failure. However, the extent to which this therapy increases final adult height is not known. METHODS: We followed 38 initially prepubertal children with chronic renal failure treated with growth hormone for a mean of 5.3 years until they reached their final adult height. The mean (+/-SD) age at the start of treatment was 10.4+/-2.2 years, the mean bone age was 7.1+/-2.3 years, and the mean height was 3.1+/-1.2 SD below normal. Fifty matched children with chronic renal failure who were not treated with growth hormone served as controls. RESULTS: The children treated with growth hormone had sustained catch-up growth, whereas the control children had progressive growth failure. The mean final height of the growth hormone-treated children was 165 cm for boys and 156 cm for girls. The mean final adult height of the growth hormone-treated children was 1.6+/-1.2 SD below normal, which was 1.4 SD above their standardized height at base line (P< 0.001). In contrast, the final height of the untreated children (2.1+/-1.2 SD below normal) was 0.6 SD below their standardized height at base line (P<0.001). Although prepubertal bone maturation was accelerated in growth hormone-treated children, treatment was not associated with a shortening of the pubertal growth spurt. The total height gain was positively associated with the initial target-height deficit and the duration of growth hormone therapy and was negatively associated with the percentage of the observation period spent receiving dialysis treatment. CONCLUSIONS: Long-term growth hormone treatment of children with chronic renal failure induces persistent catch-up growth, and the majority of patients achieve normal adult height.

Adolescent↗
PubMed2000

Suppression of growth plate chondrocyte proliferation by corticosteroids.

Growth depression is a side effect of high-dose glucocorticoid therapy in childhood. It is partially mediated by alterations of the somatotropic hormone axis and partially by direct local effects on growth plate chondrocytes. The mechanisms of interaction of corticosteroids and somatotropic and calciotropic hormones at the cellular level were recently investigated in more detail, using experimental models of primary cultures of growth plate chondrocytes. In proliferative chondrocytes, growth hormone (GH) and the calciotropic hormones parathyroid hormone (PTH) and 1,25-dihydroxyvitamin D [1alpha,25(OH)2D3] increase cell proliferation via stimulation of paracrine insulin-like growth factor-I (IGF-I) secretion. Corticosteroids decreased GH, and PTH or 1alpha,25(OH)2D3 stimulated cell growth in a dose-dependent manner. Corticosteroids in high doses reduced the expression of the GH receptor and type 1 IGF receptor. But the main antiproliferative molecular effect of corticosteroid was the reduction in basal and hormone-stimulated IGF-I secretion. The in vitro results are in accordance with the observation in animal experiments and in children treated with corticosteroids, demonstrating that the growth-depressing effect of corticosteroids can be compensated for by supraphysiological doses of GH or IGF-I.

Adrenal Cortex Hormones↗
PubMed2000

Daily but not pulse calcitriol therapy improves growth in experimental uremia.

Calcitriol (C) pulse therapy is widely used to suppress secondary renal hyperparathyroidism. However, high C serum concentrations may have an antiproliferative effect on growth cartilage cells and may suppress growth rate. The study was designed to evaluate whether daily C and pulse C therapy have differential effects on growth in uremic rats. Female Sprague-Dawley rats (150 g, n=5-10 per group) underwent two-stage subtotal nephrectomy (U). The duration of uremia was 14-18 days. The animals were fed a standard diet or a diet with a low-calcium content. Rats on a low-calcium diet were randomized for recombinant human growth hormone (rhGH) treatment (2.5 IU/kg per day) or solvent. C was injected subcutaneous twice daily (15 pmol/day) or intraperitoneal (105 pmol) twice per week. Weight gain and length gain was determined weekly. After sacrifice, total body calcium was determined by total body neutron activation analysis. Bone micromorphometric analysis of third lumbar vertebra and double staining with tetracycline for determination of mineralization rate were performed. Whereas daily C significantly increased total body length gain within 2 weeks, pulse C did not (U solvent 4.0+/-0.3 cm, UC bolus 4.3+/-0.4 cm, UC daily 5.3+/-0.3 cm, P<0.05). A low-calcium diet reduced and rhGH increased basal length gain and weight gain; regardless of these preconditions, daily but not bolus C increased length gain significantly. C both daily and in bolus form reduced bone osteoid content, but daily C improved mineral apposition rate more than C bolus. Total body calcium corrected for body weight decreased with a low-calcium diet, was lowest with concomitant rhGH treatment, and was not improved by C. In conclusion, daily but not bolus C treatment improves growth in uremic rats.

Animals↗
PubMed2000

Assessment of body composition in children with chronic renal failure.

In children with chronic renal failure treated conservatively by dialysis or by transplantation, various alterations of the nutritional, metabolic and fluid homeostasis may occur that may critically affect the patients' acute and chronic well-being. In the past, the assessment of body composition in children was hampered by insufficient precision, standardization and/or availability of appropriate anthropometric tools. Recently, there have been several methodological advances that may facilitate close and precise monitoring of body composition in this population. Specifically, the use of body mass index (BMI) data in children has become possible by the introduction of pediatric reference values processed for the calculation of standard deviation scores accounting for the skewed distribution of BMI. Skewness-adapted reference data have also been provided for percentage fat mass as assessed by multisite skinfold measurements. In addition, bioelectrical impedance analysis has been validated in healthy children as well as in pediatric dialysis and renal transplant populations. This novel auxological technique provides a highly reproducible, non-invasive and inexpensive way of assessing changes in total body water content in dialysed patients, as well as changes in fat and fat-free mass prior to dialysis and after renal transplantation.

Body Composition↗
PubMed2000

Serum insulin-like growth factor binding protein (IGFBP)-4 and IGFBP-5 in children with chronic renal failure: relationship to growth and glomerular filtration rate. The European Study Group for Nutritional Treatment of Chronic Renal Failure in Childhood. German Study Group for Growth Hormone Treatment in Chronic Renal Failure.

Growth retardation in children with chronic renal failure (CRF) is partly due to an inhibition of insulin-like growth factor (IGF) activity by an excess of high-affinity IGF-binding proteins (IGFBPs). The aim of this study was to analyze the serum levels and forms of IGFBP-4 and IGFBP-5 in CRF patients using specific, recently developed radioimmunoassays (RIAs) and immunoblot analysis. We examined 89 children [age 11.5 (2.8-19.0) years] with CRF [glomerular filtration rate 26.6 (7.0-67.4) ml/min per 1.73 m2], nine of them with end-stage renal disease undergoing peritoneal dialysis. Serum-immunoreactive IGFBP-4 levels were fourfold increased in CRF (prepubertal 1080+/-268 ng/ml; pubertal 989+/-299 ng/ml) compared to healthy prepubertal controls (265+/-73 ng/ml). In contrast, serum IGFBP-5 levels were not significantly increased neither in prepubertal (361+/-120 ng/ml vs 282+/-75 ng/ml in controls) nor pubertal CRF children (478+/-165 ng/ml vs 491+/-80 ng/ml in controls). Immunoblot analysis showed the presence of intact as well as fragmented IGFBP-4 and IGFBP-5. Serum IGFBP-4, but not IGFBP-5, levels were inversely correlated with GFR (r=-0.39, P<0.001). In prepubertal children, IGFBP-4 levels were inversely correlated with standardized height (r=-0.40; P<0.005). In contrast, IGFBP-5 levels were positively correlated both with standardized height (r=0.32, P<0.02) and baseline height velocity (r=0.45, P<0.005). A 3-month therapy with rhGH stimulated serum IGFBP-5 levels by 43% (P<0.01); there was no consistent effect on IGFBP-4 levels. There was a positive correlation between IGFBP-4 and IGFBP-2 (r=0.46, P<0.001); IGFBP-5 was positively correlated with IGF-I (r=0.59, P<0.001), IGF-II(r=0.42, P<0.001)and IGFBP-3 (r=0.47, P<0.001) and inversely correlated with IGFBP-1 (r=-0.41, P<0.001). In summary, serum IGFBP-4 is fourfold elevated in children with CRF in relation to the degree of renal dysfunction and contributes to the marked increase in IGF-binding capacity in CRF serum. The inverse correlation of serum IGFBP-4 with standardized height is consistent with its role as another inhibitor of the biological action of the IGFs on growth plate cartilage. In contrast, serum IGFBP-5 is not elevated in CRF serum and circulates mainly as proteolysed fragments. The positive correlation of serum IGFBP-5 with growth and its increase during GH therapy indicate that IGFBP-5 is a stimulatory IGFBP in patients with CRF, either by enhancing IGF activity through better presentation of TGF to its receptor or by an IGF-independent effect through activation of a specific, recently described putative IGFBP-5-receptor.

Adolescent↗
PubMed2000

Calcitriol pulse therapy is not more effective than daily calcitriol therapy in controlling secondary hyperparathyroidism in children with chronic renal failure. European Study Group on Vitamin D in Children with Renal Failure.

Calcitriol oral pulse therapy has been suggested as the treatment of choice for secondary hyperparathyroidism, but its efficacy and safety are still under discussion. The present randomized multicenter study compares the effect of an 8-week course of daily versus intermittent (twice weekly) calcitriol therapy on parathyroid hormone (PTH) suppression in 59 children (mean age 8.4+/-4.7 years) with chronic renal insufficiency (mean Ccr 22.4+/-11.6 ml/min per 1.73 m2) and secondary hyperparathyroidism. After a 3-week washout period, the patients were randomly assigned to treatment with daily oral calcitriol (10 ng/kg per day) or intermittent oral calcitriol (35 ng/kg given twice a week). The calcitriol dose was not changed throughout the study period of 8 weeks. At start of the study, the median intact PTH (iPTH) level was 485 pg/ml (range 83-2032) in the daily group (n=29) and 315 pg/ml (range 93-1638) in the intermittent group (n=30). After 8 weeks, the respective median iPTH concentrations were 232 pg/ml (range 63-1614) and 218 pg/ml (range 2-1785) (ns). The mean iPTH decrease from baseline was 19.2+/-57.8% and 13.7+/-46.7% respectively (not significant). Calcitriol reduced the iPTH concentration in 23/29 patients in the daily group and in 21/30 in the intermittent group. One episode of hypercalcemia (>11.5 mg/dl) was observed in both groups and a single episode of hyperphosphatemia (>7.5 mg/dl) was observed in the daily group. It is concluded that oral calcitriol pulse therapy does not control secondary hyperparathyroidism more effectively than the daily administration of calcitriol in children with chronic renal failure prior to dialysis.

Acute Kidney Injury↗