C H Schröder

University Medical Center Utrecht, Utrecht, Utrecht, Netherlands

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Publications (133)192.8 Total impact

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    ABSTRACT: Reduced serum IgG and subclass levels have been demonstrated in children with chronic renal failure. To study possible causes of this reduction, we analysed B cell subset composition, T helper cell frequencies and immunoglobulin (Ig) production capacity in vitro in children with chronic renal failure, with or without dialysis treatment. B cell subsets were characterized by determining CD27, IgM, IgD and CD5 expression within the CD19(+) population. Intracellular expression of interferon (IFN)-gamma, interleukin (IL)-2 and IL-4 in PMA/ionomycin-stimulated peripheral blood mononuclear cells (PBMC) was used to evaluate T helper frequencies. The capacity of B cells to secrete Ig in vitro was determined by measuring IgG(1), IgG(2) and IgM in culture supernatants of anti-CD2/CD28 monoclonal antibody (MoAb)- or SAC/IL-2-stimulated PBMC. Memory B cell numbers (identified as percentage or absolute number of CD19(+) IgM-IgD- or CD19(+)CD27(+) lymphocytes) were lower in children treated with haemodialysis (HD), peritoneal dialysis (PD) and children with chronic renal failure before starting dialysis treatment (CRF) compared to healthy controls (HC) (P < 0.05). Compared with HC, CD5(+) (naive) B cells were reduced in HD-treated patients but not for PD or for children with chronic renal failure before starting dialysis treatment (CRF). No significant differences in CD4(+) T helper cell subsets were found between the groups. However, CRF children had a higher percentage of IFN-gamma producing CD8(+) T lymphocytes compared to HC (P = 0.02). Finally, IgG(1), IgG(2) and IgM production in vitro was similar in the four groups. In conclusion, significantly lower numbers of memory type B cells were found in children with chronic renal failure compared to healthy controls. This reduction may contribute to the low Ig levels found in these children.
    Clinical & Experimental Immunology 09/2004; 137(3):589-94. DOI:10.1111/j.1365-2249.2004.02571.x · 3.04 Impact Factor
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    ABSTRACT: The present studywas designed to retrospectively evaluate the use of renal biopsies prior to cyclophosphamide therapy. The aim of the study was to determine in how many cases histological outcome of the biopsies had subsequently changed the decision to treat or refrain from treatment. Between January 1980 and September 2001, 85 children with steroid-sensitive nephrotic syndrome (SSNS) underwent a renal biopsy in the University Hospitals of Utrecht and Nijmegen before the start of an 8-week cyclophosphamide treatment. MCNS was suspected in all children because of the following criteria: edema, proteinuria, hypoalbuminemia, absence of macroscopic hematuria and in rare cases microscopic hematuria, no permanent hypertension, normal C3 serum level, a normal glomerular filtration rate as determined by creatinine clearance and age > 1 year. Cyclophosphamide therapy was indicated because of a frequently relapsing (FR) course of illness in 8 children, because of steroid dependence (SD) in 22 children and because of combined FR and SD in 55 children. Steroid-resistant children were excluded from this study. Histology confirmed the diagnosis MCNS in 84 out of 85 children. In addition to MCNS, IgA deposits were observed in renal specimens of 2 children. In 1 SD child, the initial diagnosis MCNS was changed 3 years later when a repeated biopsy showed progression into focal segmental glomerulosclerosis (FSGS). In summary, no renal biopsy is required prior to cytotoxic therapy in children with uncomplicated steroid-sensitive nephrotic syndrome.
    Clinical nephrology 11/2003; 60(5):315-7. · 1.13 Impact Factor
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    ABSTRACT: The majority of hemodialysis (HD) treatments incorporate a prescription for fluid removal targeted to a patients “dry” weight. Hypotension, cramps or headache often complicates fluid removal in children. The purpose of this study was to evaluate whether non-invasive blood volume monitoring by hematocrit could be used for the determination of dry weight and prevention of intra-dialytic complaints in children on chronic HD.Patients and methods: 128 dialysis sessions in 16 patients, aged 3–17 years, were evaluated. Non-invasive monitoring of hematocrit (NIMH) (Crit-lineTM, HemaMetrics) was performed during the whole HD session and expressed as % Δ of blood volume (%BVΔ).Results: Changes in blood volume significantly correlated with the changes of patient's weight during hemodialysis treatments (p = 0.001). Thirty HD sessions were complicated by symptomatic hypotension in 12 patients.Conclusion: Changes in blood volume measured by Crit-line correlate with the changes of patient's weight during hemodialysis treatments. Complicated HD sessions were associated with lower halfway %BVΔ. This indicates that NIMH might be useful for the determination of dry weight and for prevention of intra-dialytic morbidity in children by remodeling of the ultrafiltration profile.
    Hemodialysis International 02/2003; 7(1). DOI:10.1046/j.1492-7535.2003.01282.x · 1.24 Impact Factor
  • Clinical nephrology 01/2003; DOI:10.5414/CNP60315 · 1.13 Impact Factor
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    Peritoneal dialysis international: journal of the International Society for Peritoneal Dialysis 01/2001; 21(1):88-90. · 1.53 Impact Factor
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    ABSTRACT: Icodextrin use in adults provides sustained ultrafiltration (UF) in long-term dwells. No information is available on UF and metabolism in children. In 11 children, a volume of 1,049+/-138 ml/m2 of the study fluid (1.36% glucose, 7.5% icodextrin, 3.86% glucose) was administered for 12 h. Net UF with icodextrin (339+/-147 ml/1.73 m2) did not differ from UF with 3.86% glucose (450+/-306 ml/1.73 m2, P=0.53) and was higher than UF with 1.36% glucose (-87+/-239 ml/1.73 m2, P=0.003). Icodextrin added 0.52+/-0.07 to the weekly Kt/V. Over 6 weeks, icodextrin was used for 12-h daytime dwell. Total icodextrin reached a steady-state level of 2.91+/-1.22 g/l at 2 weeks. The main icodextrin metabolites were maltose, maltotriose, and maltotetraose. After 2 weeks, steady state levels were 2.02+/-0.66 mmol/l, 1.46+/-0.35 mmol/l, and 0.45+/-0.12 mmol/l. No icodextrin or metabolites were detectable 4 weeks after the study. We conclude that 7.5% icodextrin is capable of maintaining UF during 12-h dwell in children and is comparable to UF obtained with 3.86% glucose. Steady-state levels of icodextrin and metabolites were reached at 2 weeks and disappeared after the study.
    Pediatric Nephrology 12/2000; 15(1-2):21-4. DOI:10.1007/s004670000406 · 2.86 Impact Factor
  • M R Lilien · M Duran · J. M. E. Quak · J J Frankhuisen · C H Schröder
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    ABSTRACT: The use of recombinant human erythropoietin (rhEPO) has greatly facilitated the treatment of anemia in children with chronic renal failure, but is expensive. Several reports on adult patients have shown that supplementation with L-carnitine can decrease the requirement for rhEPO. The objective of this study was to investigate the effect of oral supplementation with L-carnitine on the rhEPO requirement in children on dialysis. We investigated 16 children on dialysis (11 hemodialysis, 5 peritoneal dialysis) with a median age of 10.2 years. All children were stable on rhEPO treatment at least 3 months before study entrance. After obtaining baseline data, all children were supplemented with L-carnitine 20 mg/kg/day. Data were collected for 26 weeks. Follow-up was completed for 12 patients (8 hemodialysis, 4 peritoneal dialysis). At baseline free carnitine (32+/-18 micromol/l) and total carnitine levels (54+/-37 micromol/l) were normal. At the end of the study free carnitine levels had increased to 97+/-56 micromol/l (P<0.05) and total carnitine levels to 163+/-90 micromol/l (P<0.05). There was no significant change in rhEPO requirement. Hemoglobin level or hematocrit did not change significantly during the study. In conclusion we could not demonstrate a beneficial effect of supplementation with L-carnitine on rhEPO requirement in children on dialysis.
    Pediatric Nephrology 12/2000; 15(1-2):17-20. DOI:10.1007/s004670000423 · 2.86 Impact Factor
  • K.J.M. Van Hoeck · M R Lilien · D C Brinkman · C H Schroeder
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    ABSTRACT: The use of the online urea monitor has not been validated in children on hemodialysis. We compared online measured Kt/V(urea) and protein catabolic rate (PCR) with single- and double-pool Daugirdas formula (DF and eDF) based Kt/V(urea) and with protein intake derived from dietary records (DPI). In 8 children aged 8-18 years, 26 measurements were performed with the online urea monitor (UM 1000) with double-needle access. In 7 children, aged 4-14 years, 12 additional measurements were performed using single-needle dialysis. Pre-dialysis serum urea was determined by the monitor in equilibrated ultrafiltrate, obtained with ultrafiltration rates (UF) of 0.5 or 1.0 l/h, in 10 and 23 experiments respectively, and compared with the laboratory results. Urea determination in ultrafiltrate correlated well with blood sample urea: r=0.945 and 0.88 for UF rates of 0.5 l/h and 1.0 l/h, respectively. The correlation of online Kt/V with DF and eDF was 0.79 for double-needle and 0.21 for single-needle access. Bland-Altmann analysis showed a mean bias of 0.02 and 0.001, but levels of agreement of +0.3 and -0.3 for double-needle and +0.77 and -0.77 for single-needle dialysis respectively with DF. Maximum percentage error for double-needle access was 18% and 59% for single-needle access. The correlation of DPI with PCR was 0.5. A Bland-Altmann plot showed a mean bias of =0.22 with upper and lower limits of agreement of +0.55 and -0.1, respectively. Online urea kinetic modelling is feasible in children with double-needle hemodialysis only. Even with small dialyzers, an accurate serum urea measurement is obtained. PCR underestimates dietary protein intake.
    Pediatric Nephrology 05/2000; 14(4):280-3. DOI:10.1007/s004670050759 · 2.86 Impact Factor
  • C H Schröder · E Rusthoven · L A Monnens
    Pediatric Nephrology 02/2000; 14(1):84-5. · 2.86 Impact Factor
  • E. Rusthoven · J L Willems · L.A.H. Monnens · C H Schröder
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    ABSTRACT: Adult patients with renal failure have a high total homocysteine concentration in plasma. Hyperhomocysteinemia is an independent risk factor for cardiovascular diseases. Folic acid lowers the homocysteine concentrations in plasma in hyperhomocysteinemia. Whether this results in a reduced risk for cardiovascular diseases remains to be proven by intervention studies. In the present study we investigated: (1) if homocysteine concentrations are elevated in the plasma of children with renal failure and (2) the influence of folic acid administration on the plasma homocysteine concentration. The plasma homocysteine concentration was measured in 21 children, 9 on hemodialysis and 12 on peritoneal dialysis, before and 4 weeks after treatment with 2.5 mg folic acid daily. Healthy children (234) constituted the control group. In controls the median homocysteine concentration was 9.1 micromol/l (range 4.3-20.0 micromol/l). The median plasma homocysteine concentration in patients before folic acid treatment was 20.0 micromol/l (Q1-Q3 13.7-26.0; Q, quartile). After 4 weeks of folic acid treatment the median plasma homocysteine concentration was 12.0 micromol/l [Q1-Q3 9.8-14.3 (P<0.0001 Wilcoxon signed rank test)]. There was no significant difference between hemodialysis and peritoneal dialysis patients. Children with renal failure treated with hemodialysis or peritoneal dialysis have elevated plasma homocysteine concentrations, but this is significantly reduced after administration of 2.5 mg folic acid daily for 4 weeks. It is suggested that folic acid be added to the treatment of children with renal failure, although a beneficial effect still has to be proven. The required dose needs further study.
    Pediatric Nephrology 09/1999; 13(7):583-5. DOI:10.1007/s004670050748 · 2.86 Impact Factor
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    ABSTRACT: An increased rate of obstruction of peritoneal dialysis catheters is observed during peritonitis. Hypercoagulation and hypofibrinolysis may explain this increased occurrence. We studied plasminogen activator inhibitor type 1 antigen (PAI-1), tissue-type plasminogen activator antigen (t-PA), D-dimer (DD), plasmin-alpha2-antiplasmin complexes (PAP), and thrombin-antithrombin III complexes (TAT) in 7 children with peritonitis (group A) and 12 children during stable peritoneal dialysis (group B). Albumin, beta2-microglobulin, IgG, and alpha2-macroglobulin were measured for baseline transperitoneal protein transport. After a dwell of 6 h with 1.36% Dianeal, dialysate and serum samples were collected. Dialysate to plasma ratios of all proteins were calculated. During peritonitis (group A) TAT was higher: 34.7 versus 22.0 (P=0.01). PAI-1 was increased in group A: 76.5 versus 22.9 (P=0.004). PAP was decreased during peritonitis (group A): 24.9 versus 39.3 (P=0.01). In group A, DD were decreased. 10.8 versus 26.7 (P=0.002). t-PA was similar in both groups (23.7 in group A vs. 27.7 in group B; P=0.26). In both groups TAT, PAI-1, t-PA, PAP, and DD were significantly higher than in baseline transperitoneal transport, suggesting intraperitoneal production. Hypercoagulability and hypofibrinolysis were present during peritonitis compared with the control situation.
    Pediatric Nephrology 06/1999; 13(4):284-7. DOI:10.1007/s004670050609 · 2.86 Impact Factor
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    ABSTRACT: The COL4A3-COL4A4-COL4A5 network in the glomerular basement membrane is affected in the inherited renal disorder Alport's syndrome (AS). Approximately 85% of the AS patients are expected to carry a mutation in the X-chromosomal COL4A5 gene and 15% in the autosomal COL4A3 and COL4A4 genes. The COL4A5 chain is also present in the epidermal basement membrane (EBM). It is predicted that approximately 70% of the COL4A5 mutations prevent incorporation of this chain in basement membranes. We investigated whether or not COL4A5 defects could be detected by immunohistochemical analysis of the EBM. Punch skin biopsies were obtained from 22 patients out of 17 families and two biopsy specimens from healthy males were used as controls. In four cases with the COL4A5 frameshift or missense mutations, the COL4A5 chain was either lacking from the EBM (male) or showed a focally negative pattern (female). In three other patients with a COL4A5 missense mutation, a COL4A3 and a COL4A4 mutation, respectively, the COL4A5 staining was normal. A (focally) negative EBM-COL4A5 staining was found in three patients of six families with a diagnosis of AS and in one family of a group of four families with possible AS. The (focal) absence of COL4A5 in the EBM of skin biopsy specimens can be used for fast identification of COL4A5 defects. Combined with polymorphic COL4A5 markers, both postnatal and prenatal DNA diagnosis are possible in the family of the patient.
    Kidney International 05/1999; 55(4):1217-24. DOI:10.1046/j.1523-1755.1999.00357.x · 8.56 Impact Factor
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    M Lilien · M Duran · K Van Hoeck · B T Poll-The · C Schröder
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    ABSTRACT: Hyperhomocyst(e)inaemia has been identified as a significant risk factor for the occurrence of atherosclerosis in adults with chronic renal failure. Because of its presumed direct toxic effect on the vascular wall, long-standing hyperhomocyst(e)inaemia in children with chronic renal failure might have an important influence on their risk of future development of atherosclerosis. Hitherto no data on hyperhomocyst(e)inaemia in children with renal failure have been published. We investigated 16 children with chronic renal failure on conservative management, 12 children on haemodialysis and 17 children with a renal transplant. Age-matched controls were used for comparison. Plasma homocyst(e)ine levels after an overnight fast were determined by HPLC. Glomerular filtration rate was estimated by the Schwartz formula. Mean plasma homocyst(e)ine levels were 12.6 +/- 5.2 micromol/l in the conservatively managed group, 22.2 +/- 13.5 micromol/l in the haemodialysed group, 14.2 +/- 2.1 micromol/l in transplanted children with an estimated GFR > 60 ml/min/1.73 m2 and 17.5 +/- 5.1 micromol/l in transplanted children with a lower estimated GFR. In all groups homocyst(e)ine levels were significantly elevated as compared to controls. Homocyst(e)ine levels were significantly correlated with age and negatively correlated with estimated GFR and serum folate levels. Hyperhomocyst(e)inaemia is a feature of chronic renal failure in children as well as in adults. Elevated homocyst(e)ine levels can already be demonstrated in children with renal failure before end-stage renal disease has developed and persist after renal transplantation. Whether treatment of hyperhomocyst(e)inaemia in children with renal failure decreases the risk for future atherosclerosis remains to be proven.
    Nephrology Dialysis Transplantation 02/1999; 14(2):366-8. DOI:10.1093/ndt/14.2.366 · 3.58 Impact Factor
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    Nephrology Dialysis Transplantation 02/1999; 14(1):257-8. DOI:10.1093/ndt/14.1.257 · 3.58 Impact Factor
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    ABSTRACT: The passage of proteins across the glomerular filtration barrier is mainly determined by the size of the protein. In nephrotic syndrome (NS) the glomerular permselectivity is affected, causing proteinuria. Some authors suggest the existence of a generalized basement membrane defect. The permeability characteristics of the peritoneal basement membrane in children with NS are not known. The transperitoneal transport of proteins with a different molecular weight (beta2-microglobulin MW 11800 D, albumin MW 69000 D, IgG MW 160000 D, and alpha2-macroglobulin MW 820000 D) was studied in a study group (group A) consisting of six stable nephrotic children (three with glomerulosclerosis and three with congenital nephrotic syndrome, one of them with mesangial sclerosis) and compared to a control group (group B) consisting of eight stable children on peritoneal dialysis. After a dwell of 6 h with Dianeal 1.36% dialysate and serum samples were collected. For each patient the dialysate to plasma (D/P) ratios of the four proteins were calculated. The D/P ratios of the nephrotic patients in group A were compared to the D/P ratios of the patients in the control group B. Data were expressed as mean +/- SD. The values for the D/P ratios (in percentage) of beta2-microglobulin, albumin, IgG and alpha2-macroglobulin in group A were 19.6+/-9.9, 2.7+/-1.7, 1.6+/-0.9, and 0.5+/-0.4, compared to 24.9+/-10.2, 4.0+/-2.3, 2.2 +/- 1.2, and 0.7 +/- 0.3 in the control group B. The ratios were plotted against MW on a double logarithmic scale. In all patients a linear relationship between molecular weight and D/P ratio of the proteins was obtained. The D/P ratios of the study group did not differ significantly from the control group. We conclude that the size selectivity of the capillary permeability is not affected in the peritoneal membrane in children with NS due to glomerulosclerosis and congenital nephrotic syndrome.
    Nephrology Dialysis Transplantation 10/1998; 13(9):2348-50. · 3.58 Impact Factor
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    ABSTRACT: Chronic renal failure (CRF) is associated, especially in young children, with delayed cognitive development of unknown origin. As cerebrospinal fluid (CSF) reflects the composition of the extracellular fluid of the brain, not only plasma but also CSF amino acids concentrations were determined in 8 infants (age 2-8 months) and 3 children (age 26, 32 and 56 months) with CRF (creatinine clearance 13 +/- 9 ml/min/ 1.73 m2). In three of these children investigations were repeated after six weeks of CAPD treatment. In the infants, a significant decrease was found in CSF of alpha-aminobutyric acid, valine, isoleucine, leucine, tyrosine, tryptophane, histidine and n-zeta-methyl-1-lysine, whereas there was a significant increase of 3-methylhistidine. In plasma serine, valine, leucine, tyrosine and histidine were significantly decreased, whereas there was a significant increase of aspartic acid, citrulline, and 3-methylhistidine. These abnormalities remained constant after the start of CAPD except for the normalization in CSF and plasma of 3-methylhistidine. These data indicate a generalized disturbance of amino acids in young children with CRF. An abnormal substrate is offered to the neurons and astroglia in children with CRF.
    Neuropediatrics 02/1998; 29(1):35-9. DOI:10.1055/s-2007-973531 · 1.24 Impact Factor
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    ABSTRACT: To establish the effectivity of administration of erythropoietin intraperitoneally in a small amount of fluid in children with renal anemia on continuous ambulatory peritoneal dialysis (CAPD). Prospective study in which children with renal anemia on CAPD were treated with erythropoietin intraperitoneally, administered in a specially designed bag containing 50 mL NaCl 0.9%. University hospital. The patient population consisted of 9 children treated with CAPD and 1 treated with nightly intermittent peritoneal dialysis. The median age was 7.8 years (range 4.1-15.2). Four of these children had not been treated with erythropoietin before (group A), and 6 had been treated with erythropoietin administered intraperitoneally in 250 mL of dialysis fluid (group B). Patients in group A started on a dose of approximately 300 units/kg per week (group A). Patients in group B received their previous dose. Dosage was adjusted to achieve a target hemoglobin level of 6.5-7.0 mmol/L (104-112 g/L). Serum ferritin levels and transferrin saturation were monitored and iron supplementation was prescribed in the case of iron deficiency. Weekly erythropoietin dose in relation to hemoglobin level. In group A, median hemoglobin level rose from 5.3 mmol/L (85 g/L) to 6.6 mmol/L (106 g/L) after 6 months of therapy, whereas the median erythropoietin dose decreased from 266 to 234 U/kg/week. In group B, hemoglobin levels remained stable and median erythropoietin dose decreased from 262 to 194 U/kg/week. One patient in this group, for unknown reasons, never responded to erythropoietin treatment. He was excluded from further analysis. In the remaining 5 patients the median cumulative erythropoietin dose was 3250 U/kg in the 3-month period prior to the start of the study and 2713 in the 3-month period starting 6 months after the beginning of the study. This difference of 17% was statistically significant using a Wilcoxon test (p < 0.05). Intraperitoneal administration of erythropoietin in a small amount of dialysis fluid leads to a decrease in the required dose.
    Peritoneal dialysis international: journal of the International Society for Peritoneal Dialysis 09/1997; 17(5):467-70. · 1.53 Impact Factor
  • Immunology Letters 05/1997; 56:333. DOI:10.1016/S0165-2478(97)86348-1 · 2.51 Impact Factor

Publication Stats

984 Citations
192.80 Total Impact Points


  • 2000–2004
    • University Medical Center Utrecht
      • Wilhelmina Children´s Hospital
      Utrecht, Utrecht, Netherlands
    • Utrecht University
      Utrecht, Utrecht, Netherlands
  • 1999–2003
    • Canisius-Wilhelmina Ziekenhuis
      Nymegen, Gelderland, Netherlands
    • Leiden University
      Leyden, South Holland, Netherlands
  • 1986–1995
    • Radboud University Nijmegen
      • • Department of Pediatrics
      • • Department of Biochemistry
      Nijmegen, Provincie Gelderland, Netherlands