The DOQI pediatric nutritional guidelines--critical remarks.
Explore the source record for details and available documents.
Anthropometry↗
Biomedical subjects
G Filler
Publications and source records attributed to G Filler.
Treatment of FSGS with plasma exchange and immunadsorption.
In primary focal and segmental glomerulosclerosis (FSGS) renal prognosis is poor if no remission of proteinuria can be achieved with treatment. Currently, most children with FSGS are treated with cyclosporine and steroids after establishing steroid resistance, and approximately 60% of patients benefit from this therapy. For the remaining 40%, no generally approved therapeutic recommendations exist for children. We treated nine children with cyclosporine-resistant primary FSGS with plasma exchange (PE), two with relapsing FSGS after renal transplantation and seven with FSGS in their native kidneys. Three patients did not respond to PE, but five came into complete remission and one patient achieved partial remission. Three patients relapsed between 6 weeks and 2 years following cessation of PE, and were subsequently treated with plasma immunadsorption (PIA), which also reliably reduced proteinuria. The patients without response to PE tended to have a longer duration of the disease. We conclude that PE and PIA are a useful option for treatment of steroid- and cyclosporine-resistant FSGS, particularly if applied early in the course of the disease. Although more demanding on supportive resources, PIA seems preferable to PE, since there is no necessity for additional albumin or fresh-frozen plasma, as with PE.
Adolescent↗
Effect of adding Mycophenolate mofetil in paediatric renal transplant recipients with chronical cyclosporine nephrotoxicity.
Cyclosporine (CyA) has made a great impact on 1-year allograft survival, however, after years, renal function deteriorates, possibly due to chronic toxicity. Recently, Mycophenolate mofetil (MMF) was introduced as a non-nephrotoxic immunosuppressant that might be effective in chronical transplant arteriolopathy. We therefore started MMF at a dose of 600 mg/m2 b. i. d. in 18 pediatric renal transplant recipients (10.8 +/- 3.9 (SD) years of age at transplantation, 11/18 with a history of rejections) with biopsy-proven chronic arteriolopathy and other signs of CyA toxicity at a mean follow up time of 6.2 +/- 2.7 (range 2.3-11.8) years after transplantation. One month prior to conversion, mean serum creatinine was 171 +/- 96 micromol/l, lower than at the time of conversion (188 +/- 100 micromol/l, P = 0.003, paired t-test). At last follow-up (median 13.7 months, range 5.0 to 25.0 months) after conversion, mean serum creatinine decreased significantly to 127 +/- 69 micromol/l (P = 0,0003, paired t-test). The CyA dosage was reduced from a mean of 150 +/- 39 mg/ m2 per day to 59 +/- 13 mg/m2 per day in 7 patients, and CyA was discontinued in 11 patients after a median period of nine months (range 1-18 months). After a median period of 21 days, a pharmacokinetic profile was performed in all patients. The mean MMF dose was 1117 +/- 319 mg/m2 per day (range 675-1774 mg/m2 per day). The mean Mycophenolic acid (MPA) trough concentration was 4.0 +/- 2.0 microg/ml, range 1.4-7.9 microg/ml. Mean 12 h MPA AUC was 70.6 +/- 28.1 (range 31.9-127) microg x h/ml. Except for one patient with diarrhea associated with a high AUC, and for one patient with a steroid-sensitive rejection episode after 566 days, no other patient experienced side effects or a rejection episode. Prednisolone was left unaltered at 2-4 mg/m2 per day. We conclude that MMF allows safe reduction of CyA with markedly better graft function, suggesting that chronical CyA-toxicity partially accounts for deteriorating allograft function.
Adolescent↗
Bioimpedance and inferior vena cava diameter for assessment of dialysis dry weight.
It is essential to carry out a clinical assessment of dry body weight in dialysis-dependent children in order to develop a suitable dialysis prescription. Bioimpedance analysis and inferior vena cava diameter (IVCD) have been evaluated and utilized in adults as noninvasive parameters for the assessment of dry weight and extracellular volume. Since there are no data available for normal children, we performed a prospective study to establish reference standards for a pediatric population (111 females and 95 males, aged 6.8-16 years). We found strong correlations of both resistance and IVCD with age, height, weight, and, in particular, with body surface area. IVCD and resistance also correlated with each other. We also investigated 28 pediatric dialysis patients who showed growth retardation and delayed puberty. Applying age-related reference intervals to pediatric dialysis patients resulted in an underestimation of overhydration. The combination of both methods using body surface area-related reference limits with the clinical features of deviation of dry weight will serve as an adjunct to the assessment of post-dialysis dry weight.
Adolescent↗
Does growth hormone therapy harmonize distorted morphology and body composition in chronic renal failure?
Recombinant human growth hormone (rhGH) therapy of growth retardation in chronic renal failure (CRF) has become well established. While there are ample data about its effectiveness in restoring longitudinal growth delay, data on complex anthropometry are scarce. Twenty-three children with CRF (6 after renal transplantation) were investigated using 24 different parameters. The analysis revealed disproportionate growth in CRF. While parameters of the trunk and transverse dimension of the head were preserved, the extremities were affected more severely. Bone dimensions of the legs and arms as well as muscle mass were affected the most. RhGH therapy was effective in restoring impaired longitudinal dimensions of the body in CRF. The restoration of growth retardation occurred predominantly in the extremities. This was accompanied by an increase in transversal dimensions, circumferences and soft tissue of the extremities, as well as an increase in bone and muscle volume, indicating harmonization of the total body shape. The dimensions of trunk, forehead diameter and morphological face height remained within the normal range. There was no evidence of acromegaly in children with CRF and rhGH therapy. We conclude that rhGH therapy at a dose of 28 iU/m2/week is effective in restoring previously disproportional body structure and shape in children with CRF.
Anthropometry↗
Pharmacokinetics of mycophenolate mofetil are influenced by concomitant immunosuppression.
The recommended dosage for mycophenolate mofetil (MMF) in combination with cyclosporin (CyA) for pediatric kidney transplant recipients is 600 mg/m(2) twice daily (b.i.d.). We recently published pharmacokinetic (PK) profiles of MMF in combination with tacrolimus (FK506): in order to keep the mycophenolic acid (MPA) pre-dose trough concentration between 2 and 5 microg/ml and to avoid side effects, mean MMF doses were reduced to 300 mg/m(2) b.i.d. In order to investigate whether this striking difference was due to alterations of MPA clearance by CyA or FK506, we analyzed PK profiles from 13 patients who received MMF without CyA or FK506, and compared these data with 14 patients who received a combination of MMF and FK506 and 15 patients who received MMF and CyA. Mean area under the curve (AUC) in all PK profiles was 61.9+/-23.8 microgxh/ml. Although the AUCs did not differ between the groups, the dose per square meter was significantly lower in patients receiving concomitant FK506 compared with CyA, and the dose-normalized AUC was significantly higher. The MMF doses were 1,158+/-301 mg/m(2) per day in the CyA group, 555+/-289 mg/m(2) per day in the tacrolimus group, and 866+/-401 mg/m(2) per day in the group without concomitant calcineurin inhibitor treatment. The apparent clearance of MPA is reduced in combination with tacrolimus. The reason for this remains unknown. There was a trend towards lower dose-normalized AUCs in the CyA group compared with the group without calcineurin inhibitor treatment. We conclude that concomitant medication alters the clearance of MPA. It is noteworthy that there was substantial interindividual variation, despite the rather marked differences between the groups, and therefore we recommend starting MMF in combination with CyA at a dose of 600 mg/m(2) b.i.d., in combination with tacrolimus at a dose of 300 mg/m(2) b.i.d., and without a calcineurin inhibitor at a dose of 500 mg/m(2) b.i.d., and adjusting doses using therapeutic drug monitoring of MPA.
Adolescent↗
Glucose metabolism in children with renal failure: oral or intravenous glucose tolerance.
There is debate about the most suitable test for investigation of glucose tolerance in children with chronic renal failure. We therefore studied the agreement between the two most commonly used glucose tolerance tests in 33 children with chronic renal failure (mean age 10.9+/-5.3 years, median GFR was 24 ml/min/1.73 m2). All children underwent an oral glucose tolerance test (OGTT) with blood sampling up to 180 minutes and after an oral load of 1.75 g/kg and a standard intravenous glucose tolerance test (IVGTT) using 0.5 g/kg i.v. The two tests were performed at an interval of 23+/-5 days, with 9 patients having the OGTT before and 24 after the IVGTT. In order to account for the differing glucose load, a subgroup of 19 patients also received a glucose infusion test (GIT) using a total of 1.75 g/kg i.v. On IVGTT, 27 patients had a normal and 6 had a pathological glucose decay constant (k-value). On OGTT, 12 patients had an impaired glucose tolerance (IGT) and 3 patients were diabetic according to WHO standard, and only 18 patients had a normal glucose tolerance. While there was good correlation between both glucose and insulin concentrations between IVGTT and OGTT, only when reapplying the WHO criteria of a glucose concentration below 6.7 mmol/l to the concentration measured 180 minutes instead of 120 minutes after oral glucose load, the agreement between the two tests improved. The proportion of normal findings on GIT when compared to OGTT was identical. When using the appropriate definitions for normal and abnormal carbohydrate tolerance, interestingly the insulin (IRI) concentrations on OGTT were not discriminative between the normal and the pathological group, whereas IRI first phase secretion on IVGTT and IRI 0-180 AUC on GIT did discriminate. We conclude that the standard WHO OGTT criteria may have to be reconsidered in children with chronic renal failure and that OGTT should be extended to 180 minutes. The IVGTT, particularly when insulin early phase secretion (at 0, 1, 3 and 5 minutes) is also monitored, provides a reliable test for assessing glucose tolerance in children with chronic renal failure.
Adolescent↗
Tacrolimus reversibly reduces insulin secretion in paediatric renal transplant recipients.
BACKGROUND: Conflicting reports exist about the mechanism of tacrolimus-induced post-transplant diabetes mellitus. METHODS: We analysed intravenous glucose tolerance tests (IVGTT) of 14 paediatric renal transplant recipients on cyclosporin (CsA) microemulsion and 15 patients on tacrolimus (FK506). The groups were similar in age (13.2+/-4.2 vs 13.0+/-3.7 years), body mass index, serum creatinine concentrations (96+/-60 vs 97+/-44 micromol/l), time after renal transplantation, and cumulative steroid dose over 12 weeks prior to the test (3.4 vs 3.5 mg/m(2)/day, NS, Mann-Whitney). Parameters of glucose tolerance included glucose, insulin, C-peptide concentrations, and HbA1c. The mean concentrations of the primary immunosuppressant were similar to treatments employed in other centres (CsA 165+/-59 ng ml and FK506 7. 5+/-2.2 ng ml). RESULTS: Baseline glucose concentrations were significantly higher on FK506 therapy compared with CsA microemulsion therapy. Baseline insulin concentrations and C-peptide concentrations were identical in both treatment groups. FK506 trough levels correlated negatively with k values (glucose constant decay) in the FK506 group. There was a significant reduction of the insulin first-phase concentrations, both after 1 min and after 3 min in the FK506 group compared with the CsA group (112+/-17 vs 237+/-57 microU/ml, P=0.034). In patients with repetitive IVGTTs, glucose constant decay and insulin production improved after lowering FK506 whole-blood trough levels. CONCLUSIONS: We conclude that post-transplant glucose intolerance could be due to a dose-dependent, direct effect of FK506 on the pancreatic beta cell function, which can be controlled by dose reduction.
Adolescent↗
Limited sampling strategy for mycophenolic acid area under the curve.
The immunosuppressive potential of mycophenolate mofetil (MMF), a prodrug for mycophenolic acid, is related to the area under the time-concentration curve (AUC). Full pharmacokinetic (PK) profiles are expensive and cumbersome, and therefore a limited sampling technique would be favorable. The authors retrospectively analyzed 114 full 10-point PK profiles from 61 pediatric patients receiving MMF. Stepwise multiple regression analysis was used to calculate limited sampling approaches. Correlation between AUC and predose trough concentration was r2 = 0.29 (p < 0.0001), and between AUC and postdose trough concentration was r2 = 0.48 (p < 0.0001). The best correlations were with the 2 hours (C2, r2 = 0.59, p < 0.0001), three hours (C3, r2 = 0.52, p < 0.0001), 1.5 hours (C1.5, r2 = 0.50, p < 0.0001), and six hours (C6 r2 = 0.43, p < 0.0001). No combination of any two sampling points resulted in significantly better correlation with AUC, but three-point estimates at C1, C2, and C6 resulted in excellent correlation between predicted AUC and AUC from the full profile when using the formula AUC = 10.75 + (0.98 x C1) + (2.38 x C2) + (4.86 x C6), Pearson r = 0.93, 95% confidence interval 0.89 to 0.95. Bland and Altman analysis revealed good agreement between predicted AUC and AUC from the full profile. The AUC of mycophenolic acid can be predicted by limited sampling including C1, C2, and C6.
Adolescent↗
Acute renal failure in an infant associated with cytotoxic Aeromonas sobria isolated from patient's stool and from aquarium water as suspected source of infection.
Explore the source record for details and available documents.
Acute Kidney Injury↗
Functional characterization of the molecular defects causing nephrogenic diabetes insipidus in eight families.
X-Linked nephrogenic diabetes insipidus (NDI) is a rare inherited disorder characterized by the excretion of abnormal large volumes of diluted urine mainly caused by mutations in the V2 vasopressin receptor (AVPR2) gene. By screening NDI patients for mutations within the AVPR2 gene we have identified three novel (I46K, F105V, I130F) and four recurrent (D85N, R106C, R113W, Q225X) mutations. In addition, a recurrent missense mutation (A147T) within the aquaporin-2 gene was identified in a female patient with autosomal recessive NDI associated with sensorineural deafness. Selected clinical data of the NDI patients were compared with the results from the in vitro studies. Functional analysis of I46K and I130F revealed reduced maximum agonist-induced cAMP responses as a result of an improper cell surface targeting. In contrast, the F105V mutation is delivered to the cell surface and displayed an unchanged maximum cAMP response, but impaired ligand binding abilities of F105V were reflected in a shifted concentration-response curve toward higher vasopressin concentrations. As the extracellularly located F105 is highly conserved among the vasopressin/oxytocin receptor family, functional analysis of this residue implicates an important role in high affinity agonist binding.
Amino Acid Sequence↗
Compound deletion of the rhoGAP C1 and V2 vasopressin receptor genes in a patient with nephrogenic diabetes insipidus.
The function of small GTPases is fine-tuned by a complex network of regulatory proteins such as GTPase-activating proteins. The C1 gene at Xq28 encodes a protein assumed to function as a Rho GTPase-activating protein (rhoGAP). Characterization of the molecular defect causing X-linked nephrogenic diabetes insipidus (NDI) in a patient revealed a submicroscopic deletion of a 21.5-kb genomic fragment encompassing the entire arginine-vasopressin V2 receptor gene (AVPR2) and most of the C1 gene locus. In the absence of detailed information about the physiological relevance and specific functions of rhoGAP C1, a thorough clinical and laboratory investigation of the patient was performed. Besides clearly defined NDI symptoms caused by deletion of the AVPR2 gene, no major morphological abnormalities as determined by physical examination, radiography, ultrasound, and computed tomographic scan were detected. Extensive analysis of blood chemical, enzyme, and hormone values over a period of 16 years showed no deviations from normal ranges. On the basis of our observations, the rhoGAP C1 protein is not essential for normal development in the human. Because of a predominant expression pattern of the C1 gene in hematopoietic cells, we focused on immunologic and hematologic laboratory parameters of the affected boy and the mother who was found to be heterozygous. Differential white cell counts, including lymphocyte typing, determination of lymphokines, cytokines, and immunoglobulins, as well as numerous leukocyte function tests, showed no pathological findings. Therefore, we postulate that the loss of rhoGAP C1 function is most likely compensated by other members of the GAP family.
Adolescent↗
Abbreviated cyclosporine AUCs on Neoral--the search continues!
Cyclosporine is a powerful immunosuppressant with a narrow therapeutic window and considerable inter- and intrapatient variability. The pre-dose trough concentration (C(min)) is commonly used for therapeutic drug monitoring. With the new microemulsion (Neoral), intrapatient variability was reduced. However, the usefulness of Neoral C(min) was questioned. Firstly, because of the improved and more-rapid absorption, accidental intake before blood sampling has a greater impact on C(min) than with classic cyclosporine. Secondly, C(min) may be low despite high drug exposure, due to rapid clearance in children. A full pharmacokinetic (PK) profile with determination of the area under the curve (AUC) is expensive and cumbersome, and therefore a search for an abbreviated AUC began. Here, we present a retrospective analysis of 84 PK profiles from 78 pediatric renal transplant recipients. By analysis of rejection episodes and toxicity, we estimated a target AUC above 5,000 ng x h/ml in the early post-transplant period and 3,900 ng x h/ml beyond 100 days. The abbreviated AUC using the 2- and 6-h concentrations (C2 and C6) and a simple estimate derived from the 3-h concentration (C3) were equally well correlated with the AUC. From our data, we recommend a target C3 at approximately 800 ng/ml early after transplantation and 450-550 ng/ml beyond 100 days.
Adolescent↗
Diagnostic sensitivity of serum cystatin for impaired glomerular filtration rate.
Recently, the reciprocal of cystatin C (Cys-C), a non-glycosylated 13-kilodalton protein that is produced by all investigated nucleated cells, was found to correlate closely with glomerular filtration rate (GFR). In order to determine the diagnostic validity in children for the detection of impaired GFR, venous blood samples from 381 children (aged 1.7-18 years) with various renal pathology referred for 51Cr-EDTA clearance investigations were obtained for measurement of Cys-C as well as beta2-microglobulin (beta2-MG) and serum creatinine. Two hundred and sixteen children with clearance values >90 ml/min per 1.73 m2 constituted a control group, with a normal GFR. In the control group, Cys-C values were normally distributed with a mean of 0.94+/-0.27 mg/l and an upper reference limit (97.5th percentile) of 1.47 mg/l. In all children, there was a positive correlation between 51Cr-EDTA clearance and the reciprocal of Cys-C (r=0.64, P<0.0001), beta2-MG (r=0.59, P<0.0001), creatinine (r=0.55, P<0.0001), and the height/creatinine ratio (r=0.73, P<0.0001). Receiver-operating characteristics analysis showed that there were no significant differences between these three parameters for discriminating between patients with normal and reduced GFR, although there was a tendency towards the best diagnostic sensitivity of the GFR estimate according to the Schwartz formula. We conclude that for the detection of mildly impaired GFR, a full clearance study cannot be replaced by measurement of serum Cys-C or beta2-MG concentrations.
Adolescent↗
Long-term prognosis of hemolytic uremic syndrome and effective renal plasma flow.
The long-term prognosis of diarrhea-associated hemolytic uremic syndrome (D+ HUS) was evaluated in a cohort of 127 of 149 children who had survived the acute phase. Glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were estimated by serial (51)Cr-EDTA and (123)iodine-hippurate clearances. All children had acute renal failure during the initial phase and 74% of patients were dialyzed. During the 1st year, mean GFR and ERPF increased continuously until a plateau was reached. In the 2nd year after the diagnosis of HUS, GFR was below 80 and ERPF below 515 ml/min per 1. 73 m(2) in 16% and 47% of patients, respectively. At the end of a median follow-up of 5.0 (range 2.0-13.2) years, the proportion of children with renal sequelae such as proteinuria >/=300 mg/l, hypertension, or a GFR <80 ml/min per 1.73 m(2) was 23%. Anuria of more than 7 days' duration and hypertension during the acute phase were statistically significant risk factors for an unfavorable outcome. A reduced ERPF in the 2nd year was found in 93% of patients with sequelae. Mean filtration fraction (SD) in these patients was 0. 26 (+/-0.07) versus 0.19 (+/-0.05) in patients without sequelae (P<0. 0001). These data suggest that loss of nephrons during the acute phase may implicate hyperfiltration in the residual functioning kidney mass leading to progressive renal disease. ERPF in the 2nd year after D+ HUS may serve as an excellent parameter to detect patients with a high risk of an unfavorable long-term outcome.
Child↗
Evaluation of pediatric nephropathies by a computerized Urine Protein Expert System (UPES).
A computerized Urine Protein Expert System (UPES) measuring creatinine, total protein, albumin, IgG, alpha(1)-microglobulin, alpha(2)-macroglobulin, and N-acetyl-beta-D-glucosaminidase, together with urine dipstick testing for granulocyte esterase and hemoglobin pseudoperoxidase, and measurement of serum creatinine had been found to be useful in adults for differentiating between renal disorders. The objective of this study was to investigate UPES for identifying the different types of proteinuria and their underlying prerenal, glomerular, tubular, and postrenal causes in 146 children characterized by routine and invasive nephrological investigations. UPES proved to be a useful tool in pediatric renal patients after refinements were implemented in the program. Comparing UPES with the pediatric nephrologist's interpretation of all available clinical and laboratory data, UPES diagnosed glomerulopathies in 46 (75%) of 61 patients. In a further 23% it suggested glomerular involvement by indicating either a disturbed glomerular permeability or increased excretion of albumin. Tubular proteinuria was correctly described by UPES in 23 (100%) patients with different tubulopathies. UPES revealed normal kidney function in all healthy children and all children with remission of renal disorders. Therefore, UPES can be regarded as a useful tool in the automated differentiation of renal diseases in children.
Adolescent↗
Non-random distribution of mutations in the PHEX gene, and under-detected missense mutations at non-conserved residues.
Thirty newly detected mutations in the PHEX gene are reported, and pooled with all the previously published mutations. The spectrum of mutations displayed 16% deletions, 8% insertions, 34% missense, 27% nonsense, and 15% splice site mutations, with two peaks in exon 15, and 17. Since 32.8% of PHEX amino acids were conserved in the endopeptidases family, the number of missense mutations detected at non-conserved residues was smaller than expected, whereas the number of nonsense mutations observed at non-conserved residues was very close to the expected number. Compared with conserved amino acids, the changes in non-conserved amino acids may result in benign polymorphisms or possibly mild disease that may go undiagnosed.
Exons↗
Sonomorphologic evaluation of goiter in an iodine deficiency area in the Ivory Coast.
OBJECTIVES: This study evaluated the extent of thyroid abnormalities in a remote iodine-deficient area of the Ivory Coast. METHODS: Ultrasonography was used in detecting the presence of goiter. RESULTS: The overall prevalence rates of goiter were 64.7% among females and 53.3% among males. In children aged 6 to 15 years (n = 314), the prevalence of goiter was 62% regardless of sex. Thyroid volume increased steadily with age, with significantly larger goiters in women 25 years and older. Frequency of cysts and calcifications did not correlate with sex. CONCLUSIONS: Especially in developing countries, prophylaxis of iodine deficiency disorders must be improved in iodine-deficient areas to prevent substantial morbidity, which is more severe in women and elderly persons.
Adolescent↗