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Biomedical subjects

G Klaus

Publications and source records attributed to G Klaus.

At least 19 recordsLinked to original sources
PubMed2005

Prevention and treatment of renal osteodystrophy in children on chronic renal failure: European guidelines.

Childhood renal osteodystrophy (ROD) is the consequence of disturbances of the calcium-regulating hormones vitamin D and parathyroid hormone (PTH) as well as of the somatotroph hormone axis associated with local modulation of bone and growth cartilage function. The resulting growth retardation and the potentially rapid onset of ROD in children are different from ROD in adults. The biochemical changes of ROD as well as its prevention and treatment affect calcium and phosphorus homeostasis and are directly associated with the development of cardiovascular disease in pediatric renal patients. The aims of the clinical and biochemical surveillance of pediatric patients with CRF or on dialysis are prevention of hyperphosphatemia, avoidance of hypercalcemia and keeping the calcium phosphorus product below 5 mmol(2)/l(2). The PTH levels should be within the normal range in chronic renal failure (CRF) and up to 2-3 times the upper limit of normal levels in dialysed children. Prevention of ROD is expected to result in improved growth and less vascular calcification.

Algorithms↗
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↗
PubMed2002

Stimulated cortisol secretion is not correlated with prednisone dose or with steroid side-effects in children after renal transplantation.

Impairment of adrenocortical function and other adverse effects have to be considered whenever corticosteroids are applied for a prolonged period of time. We hypothesized that the assessment of adrenal function with adrenocortiocotropin (ACTH) stimulation reflects the sensitivity to corticosteroids and would predict the development of side-effects in pediatric patients on triple immunosuppression after renal transplantation.

Adolescent↗
PubMed2001

Evaluation of long-term treatment with indomethacin in hereditary hypokalemic salt-losing tubulopathies.

OBJECTIVE: Evaluation of the benefit/risk ratio of long-term treatment with indomethacin in salt-losing tubulopathies with special attention to renal function. STUDY DESIGN: Twelve patients (median age, 14.9 years) had received indomethacin for a median of 13 years (median cumulative dose, 10.7 g/kg). Creatinine clearance, serum electrolyte levels, endocrine status, and excretion of prostaglandins and electrolytes were examined during indomethacin therapy and after its withdrawal. All patients underwent ultrasound-guided renal biopsy. For statistical evaluation, the Wilcoxon test and Pearson correlation coefficient were used. RESULTS: After indomethacin withdrawal, the biochemical features of the tubulopathy reappeared. The median creatinine clearance rose from 67.4 to 96.5 mL/min/1.73 m(2) (P <.05) but remained subnormal in 4 patients. Ultrasonography elucidated medullary nephrocalcinosis in 8 patients. Renal tissue showed slight/moderate focal tubular atrophy and interstitial fibrosis in 8 patients. Comparison with biopsy specimens, obtained 11 to 14 years before study participation from 5 patients, revealed no progression. A correlation between fractional sodium and magnesium excretion and percentage of altered tubulointerstitial compartment was found (P <.001). The 4 patients with mutations in the gene of the inwardly rectifying adenosine triphosphate-regulated potassium channel (ROMK) had almost normal renal histologic findings and normal renal function. CONCLUSION: Renal function and histology are unaffected by long-term indomethacin treatment.

Adolescent↗
PubMed2001

Hypokalemic salt-losing tubulopathy with chronic renal failure and sensorineural deafness.

OBJECTIVE: To characterize a rare inherited hypokalemic salt-losing tubulopathy with linkage to chromosome 1p31. METHODS: We conducted a retrospective analysis of the clinical data for 7 patients in whom cosegregation of the disease with chromosome 1p31 had been demonstrated. In addition, in 1 kindred, prenatal diagnosis in the second child was established, allowing a prospective clinical evaluation. RESULTS: Clinical presentation of the patients was homogeneous and included premature birth attributable to polyhydramnios, severe renal salt loss, normotensive hyperreninemia, hypokalemic alkalosis, and excessive hyperprostaglandin E-uria, which suggested the diagnosis of hyperprostaglandin E syndrome/antenatal Bartter syndrome. However, the response to indomethacin was only poor, accounting for a more severe variant of the disease. The patients invariably developed chronic renal failure. The majority had extreme growth retardation, and motor development was markedly delayed. In addition, all patients turned out to be deaf. CONCLUSION: The hypokalemic salt-losing tubulopathy with chronic renal failure and sensorineural deafness represents not only genetically but also clinically a disease entity distinct from hyperprostaglandin E syndrome/antenatal Bartter syndrome. A pleiotropic effect of a single gene defect is most likely causative for syndromic hearing loss.

Adolescent↗
PubMed2001

Risk of steroid withdrawal in pediatric renal transplant patients with suspected steroid toxicity.

BACKGROUND: Glucocorticoids are still a cornerstone in immunosuppressive regimens in pediatric patients after renal transplantation (Tx). Due to the side effects, steroid withdrawal may significantly improve the appearance and growth of children with renal grafts, but bears a substantial risk for late rejections. AIM OF THE STUDY: To investigate whether exclusion of subclinical acute rejection by renal histology in combination with a prolonged steroid withdrawal period is predictive of a successful outcome. PATIENTS AND METHODS: Ten children (5 females) with a median age of 12.3 (range 7.9-20.9) years and 1.8 (0.7-7.5) years after Tx with a stable graft function and a median calculated creatinine clearance (C(Cr)) of 71 (60.5-99.7) ml/min/1.73 m2 were included. All patients showed steroid toxicity signs. Immunosuppressive regimen included low-dose steroids (median 2.72 mg/m2) in all patients, in addition to cyclosporin A (CsA) and azathioprine in 8, CsA on its own and CsA combined with mycophenolate mofetil in one patient each. A graft biopsy was performed in 8 patients prior to the start of steroid withdrawal, which was done over a median period of 6 months. Renal function was calculated as creatinine clearance using the Schwartz formula. RESULTS: None of the biopsied grafts showed histologic signs of rejection. Cyclosporin A dosage and trough levels were not significantly different before and after steroid withdrawal. While steroid side effects improved in most of the patients after withdrawal, C(Cr) decreased significantly within a median observation time of 42 (11.4-49.3) months. This decrease was due to loss of renal function in 4 patients who had biopsy-proven rejection episodes at 21.6 (8.1-29.9) months after the start of steroid withdrawal. CONCLUSION: Slow steroid withdrawal in pediatric Tx patients using conventional immunosuppression reduces side effects, but bears a high risk of late rejection. A pre-withdrawal renal biopsy was not useful for the prediction of successful steroid withdrawal.

Acute Disease↗
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

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

Experience with deflazacort in children and adolescents after renal transplantation.

Deflazacort (DFZ) has been proposed as an alternative drug for immunosuppression after renal transplantation (TX), with fewer side effects than conventional glucocorticoids. We investigated renal function, body growth, body fat, and bone mineral density (BMD) after switching from oral methylprednisolone (MPR) to equivalent doses of DFZ 1-9 years after TX in 20 patients aged 5-20 years, selected because of severe adverse effects from previous steroid therapy. At conversion the patients received a mean dose of 7.4 +/- 2.4 mg DFZ/m2 per day. The drug was continued for a mean of 3.7 (1.2-5.5) years. Under DFZ, the glomerular filtration rate dropped slightly (NS). A single rejection episode occurred. Growth velocity significantly improved in the 1st year on DFZ treatment and height standard deviation score (SDS) increased steadily after introduction of DFZ (from -2.64 to -1.96 after 4 years, P = 0.06). However, in 10 prepubertal children the height gain (+0.20 SDS in 2 years on DFZ) was not significant and the overall mean annual growth rate after TX was similar to that in 10 matched prepubertal TX children on continued MPR treatment. Relative obesity, estimated from mean body mass index corrected for height, was reduced from +1.11 SDS at the start of DFZ to +0.71 SDS after 2 years (P = 0.03) and to +0.39 SDS after 4 years (NS). BMD-SDS of the lumbar spine (L2-4) increased after 1 year on DFZ (P = 0.005). In conclusion, DFZ is well tolerated and safe in pediatric patients after TX. It improves relative obesity and bone mineralization. However, body growth is not significantly influenced pre puberty.

Adipose Tissue↗
PubMed2000

Nasal carriage of Staphylococcus aureus in families of children on peritoneal dialysis. European Pediatric Peritoneal Dialysis Study Group (EPPS).

Nasal carriage of Staphylococcus aureus is a risk factor for catheter-related infections with S. aureus in patients on chronic peritoneal dialysis (CPD). In children, S. aureus may transmitted to the catheter either from the patients' nares, or from the nares of caregiving carriers. As part of a prospective trial on the efficacy of mupirocin prophylaxis in children on CPD and their caregivers, we evaluated the prevalence of S. aureus carriage in 92 families of pediatric CPD patients. Patients and their caregivers (usually both parents) were screened by three nasal cultures obtained within four weeks. In 62% of the families, neither the patients nor any caregiver carried S. aureus. In 23%, the patient or at least one caregiver (sometimes both) was identified as a carrier. In 15%, at least one caregiver, but not the patient, was colonized with S. aureus. During further follow-up by once-monthly nasal cultures, 5 of the 57 initially negative patients developed S. aureus colonization, and in two families, at least one caregiver turned positive. Including these "occasional" carriers, the cumulative likelihood of one or several family members carrying S. aureus gradually increased to a plateau of about 55% after 6 observation months. Susceptibility rates of cultured S. aureus were 100% for vancomycin, 99% for aminoglycosides, 95% for piperacillin/tazobactam, 94% for cephalosporins, and 15% for ampicillin. In two patients and two caregivers (four different families), methicillin-resistant S. aureus was found. Three isolates from three different families were resistant to mupirocin. We conclude that S. aureus colonization is common in families of children on CPD. While 85% of carrier families are detected by 3 sequential nose cultures in patient and caregivers, up to 9 cultures may be required in "occasional" carriers.

Adolescent↗
PubMed1999

Antagonistic effects of vitamin D and parathyroid hormone on lipoprotein lipase in cultured adipocytes.

The effects of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) (calcitriol) and parathyroid hormone (PTH) on synthesis and secretion of lipoprotein lipase (LPL) were studied in 3T3-L1 adipocytes. Expression of the vitamin D receptor was demonstrated by saturation kinetics with radiolabeled calcitriol. Incubation with calcitriol (10(-8) M) for up to 4 d resulted in a time-dependent significant increase in heparin-releasable LPL activity (LPLa) accompanied by a significant increase in LPL mRNA. In contrast, incubation with intact (1-84) PTH (10(-6) to 10(-9) M) produced a time- and dose-dependent significant decrease in LPLa, but no change in LPL mRNA. The effect of PTH (24-h incubation, 10(-8) M) could be prevented by the calcium channel blocker verapamil. Coincubation with both calcitriol and PTH at equimolar concentration (10(-8) M) resulted in an increase in LPLa and LPL mRNA. These data indicate an antagonistic role for calcitriol and PTH in the regulation of LPL, possibly mediated by intracellular calcium, which may contribute to the alterations in lipoprotein metabolism occurring in uremia.

Adipocytes↗
PubMed1999

Intermittent versus continuous intraperitoneal glycopeptide/ceftazidime treatment in children with peritoneal dialysis-associated peritonitis. The Mid-European Pediatric Peritoneal Dialysis Study Group (MEPPS).

Intermittent intraperitoneal antibiotic administration appears as a practical and economical therapeutic concept in continuous peritoneal dialysis (CPD)-related peritonitis, but the equivalence of this principle with standard continuous treatment awaits confirmation by prospective, randomized clinical trials. This study evaluates the efficacy, safety, and clinical acceptance of an initial combination treatment including a glycopeptide (vancomycin or teicoplanin) and ceftazidime, each applied either intermittently or continuously, in a cohort of pediatric patients with CPD-related peritonitis. Patients randomized for continuous treatment received an intraperitoneal loading dose of glycopeptide and ceftazidime followed by maintenance doses added to each dialysate bag. In the intermittent treatment groups, the glycopeptide was administered in two loading doses 7 d apart, and ceftazidime during one dialysis cycle per day. Initial treatment response was evaluated after 60 h by the change in a Disease Severity Score and by the clinical decision to continue initial treatment. Of 152 patients observed for a total of 234 patient years, 90 patients developed 195 episodes of peritonitis (including 27 relapses within 4 wk after end of treatment). Dialysate cultures were positive in 83% of the episodes. In gram-positive peritonitis (79% of culture-positive cases), the primary success (overall 95%) and relapse rates (21%) were not different between continuous and intermittent, or between vancomycin and teicoplanin treatment. Oversensitivity reactions occurred in three and ototoxicity in one vancomycin-treated patient, whereas no such side effects were observed with teicoplanin. Residual renal function declined during peritonitis episodes regardless of treatment modality. In gram-negative peritonitis (18% of cases), intermittent ceftazidime treatment was less successful than continuous treatment according to clinical judgment (3 of 11 versus 10 of 14, P < 0.05), but not when rated by Disease Severity Score (8 of 11 versus 12 of 14). In conclusion, intermittent and continuous intraperitoneal treatment of CPD-related peritonitis with glycopeptides and ceftazidime is equally efficacious and safe when measured by objective clinical criteria. This contrasts with a strong tendency of clinicians to move from intermittent to continuous treatment in severe peritonitis.

Adolescent↗
PubMed1999

Peritoneal transport properties and dialysis dose affect growth and nutritional status in children on chronic peritoneal dialysis. Mid-European Pediatric Peritoneal Dialysis Study Group.

To evaluate a possible effect of peritoneal transport properties and dialysis dose on the physical development of children on chronic peritoneal dialysis, a cohort of 51 children was prospectively followed for 18 mo. Peritoneal transport characteristics were assessed by serial peritoneal equilibration tests (PET), dialysis efficacy by dialysate and residual renal clearance measurements, and growth and nutritional status by the longitudinal changes (delta) of height SD score (SDS), body mass index (BMI) SDS, and serum albumin. delta height SDS was negatively correlated with the creatinine equilibration rate observed in the initial PET (r = -0.31, P < 0.05). Multiple regression analysis confirmed the negative effect of the high transporter state (partial r2 = 0.07), and disclosed an additional positive effect of dialytic C(Cr) (partial r2 = 0.11) and a weak negative effect of daily dialysate volume (partial r2 = 0.04) on delta height SDS. delta BMI SDS was strongly age-dependent (r = -0.48, P < 0.001); while relative body mass gradually increased below 4 yr of age, it remained stable in older children. Positive changes in BMI SDS were associated with rapid PET creatinine equilibration rates (univariate r = 0.35, P < 0.05) and/or large dialysate volumes (multivariate partial r2 = 0.11), suggesting a role of dialytic glucose uptake in the development of obesity. The change in serum albumin concentrations was positively correlated with dialysate volume (partial r2 = 0.14), and negatively affected by dialytic protein losses (partial r2 = 0.06). In conclusion, the peritoneal transporter state is a weak but significant determinant of growth and body mass gain in children on chronic peritoneal dialysis. Rapid small solute equilibration contributes to impaired growth but enhanced acquisition of body mass. Dialytic small solute clearance has a weak positive effect on statural growth independent of the transporter state, but does not affect body mass gain.

Adolescent↗
PubMed1999

Current practice of peritoneal dialysis in children: results of a longitudinal survey. Mid European Pediatric Peritoneal Dialysis Study Group (MEPPS).

Since 1993, the Mid European Pediatric Peritoneal Dialysis Study Group (MEPPS) has been accumulating epidemiological data regarding the practice of peritoneal dialysis (PD) in children. More than 200 children have been evaluated to date. While treatment modalities were evenly distributed in 1993, automated peritoneal dialysis (APD) has emerged as the preferred mode of therapy during the last few years. Technique survival was 95% at 2 years, but decreased to 65% after 4 years of treatment, the main reasons for treatment failure being recurrent peritonitis, ultrafiltration failure, or both. Most centers use double-cuff curled Tenckhoff catheters with an upward pointing exit site. The first catheter was still functioning in 82% of patients after 1 year, and in 57% of patients after 4 years of treatment. While the overall peritonitis incidence between 1993 and 1997 was 1 episode per 17 months, it was much higher in children below 6 years of age. Empirical PD prescription resulted in a mean total weekly creatinine clearance of 57 L/1.73 m2/week in both continuous ambulatory peritoneal dialysis (CAPD) and APD patients, while average total weekly Kt/V urea was higher in APD-treated (2.45) than in CAPD-treated children (1.96). Antihypertensive treatment was required in 40%-50% of patients; oral phosphate binders in 75%-80%; bicarbonate substitution in 30%; potassium binders in 7%-14%; and NaCl supplementation in 9%-21% of patients. While growth retardation had a prevalence of 57%, body mass relative to height was in the normal range. After one year of dialysis, 20% of patients received growth hormone treatment. In conclusion, peritoneal dialysis in children, preferably performed as APD, achieves technique survival rates similar to those reported for adults. Young children are at increased risk for peritonitis. The current empirical PD prescription is of limited efficacy in terms of small-solute and fluid removal.

Body Constitution↗
PubMed1999

Residual peritoneal volume and body size in children on peritoneal dialysis. [Members of the Mid European Pediatric Peritoneal Dialysis Study Group (MEPPS)].

Residual peritoneal volume may play an important role in dialysis efficacy and abdominal compliance in patients on chronic peritoneal dialysis (CPD). In children on CPD, the relationship between residual peritoneal volume and different measures of body size, as well as the day-to-day variability of residual volume, have not been established. We therefore investigated, on two consecutive days, residual peritoneal volume in 25 children on CPD, using the dextran dilution technique. Residual volume was linearly correlated with body size. Residual volume was independent of body size when normalized to body surface area, but decreased with increasing body size when normalized to body weight (r = -0.62, p < 0.001). Mean residual volume was 79 +/- 25 mL/m2, with an intra-individual day-to-day coefficient of variation of 21% +/- 15%. Residual volume was not correlated with the duration of PD, frequency of peritonitis, or peritoneal permeability as estimated by D/P creatinine or D/D0 glucose. In conclusion, residual peritoneal volume is constant across the pediatric age range when normalized to body surface area. It accounts for approximately 8% of the usual fill volume in patients on CPD. Residual volume is not a major confounder of the transport status estimation obtained by peritoneal equilibration test.

Adolescent↗
PubMed1998

Weight-/height-related bone mineral density is not reduced after renal transplantation.

Growth retardation is a frequent finding in patients after renal transplantation (Tx). Areal bone mineral density (BMD) in these patients has usually been reported to be low for age. We investigated the possible influence of height and weight retardation on the measurement of BMD in lumbar spine (BMD(L2-4)) and total body (BMDbody) using dual-energy X-ray absorptiometry in 44 (13 female) pediatric Tx patients with a median age of 13.1 (range 3.3-23.1) years. Patients were studied at 2.9 (range 1-10) years after Tx. Median body height in female and male patients was -2.10 (-3.6 to -0.3) and -2.35 (-5.3 to +1.0) standard deviation score (SDS), respectively. BMD expressed as grams per square centimeter bone area according to age was below the 5th percentile in 10 of 44 patients, but only 1 patient had low values for BMD(L2-4), and none for BMDbody, when the data were corrected for height or weight. BMDbody was closely correlated with height, weight, and body surface area (r=0.88), whereas the correlation for BMD(L2-4) was less (r=0.76). In 6 patients who achieved final height, height SDS was -2.27 (-4.3-0.4). Z-scores for BMDbody related to age, height, and weight were -1.0 (-2.6 to -2.3), 1.25 (0.1-3.4), and 0.81 (0.0-2.4), respectively. There was no age-dependent change when areal BMD values (g/cm2) were corrected for vertebral size to obtain bone volumetric density (BMDvol, g/cm3). Independent of height, cumulative methylprednisolone dose correlated negatively with BMD(L2-4) only in patients who had received a total dose of more than 6 g/m2 of the drug (r = -0.54, P= 0.045). In conclusion, BMD in pediatric patients after Tx is no longer diminished when the data are corrected for height or weight rather than age, or when the data are expressed as bone volumetric density.

Adolescent↗