Publications by authors named "Karlien Cransberg"

64 Publications

Body mass index is associated with hyperparathyroidism in pediatric kidney transplant recipients.

Pediatr Nephrol 2021 Apr 9;36(4):977-986. Epub 2020 Oct 9.

Department of Pediatric Nephrology and Rheumatology, Ghent University Hospital, Corneel Heymanslaan 10, 9000, Ghent, Belgium.

Background: Hyperparathyroidism persists in up to 50% of pediatric kidney transplant recipients. The aims of this study were to describe the evolution of parathyroid hormone (PTH) in the first year after transplantation and to identify factors associated with hyperparathyroidism.

Methods: This retrospective study included children who underwent kidney transplantation at the University Hospitals of Ghent, Leuven, Rotterdam, or Amsterdam. Data from 149 patients were collected before and up to 12 months after transplantation. Severe hyperparathyroidism was defined as PTH 2-fold above the reference value. Factors associated with hyperparathyroidism and severe hyperparathyroidism were identified using multivariate logistic regression analysis.

Results: Before transplantation, 97 out of 137 patients (71%) had hyperparathyroidism. The probability of hyperparathyroidism and severe hyperparathyroidism declined from 0.49 and 0.17 to 0.29 and 0.09 at 3 and 12 months after transplantation, respectively. BMI SDS (β: 0.509; p = 0.011; 95% CI: 1.122-2.468), eGFR (β: - 0.227; p = 0.030; 95% CI: 0.649-0.978), and pre-transplant hyperparathyroidism (β: 1.149; p = 0.039; 95% CI: 1.062-9.369) were associated with hyperparathyroidism 12 months after transplantation. Pre-transplant hyperparathyroidism (β: 2.115; p = 0.044; 95% CI: 1.055-65.084), defined as intact parathormone (iPTH) levels > 65 ng/l (6.9 pmol/l) or 1-84 PTH > 58 ng/l (6.2 pmol/l), was associated with severe hyperparathyroidism at 3 months. Only eGFR (β: - 0.488; p = 0.010; 95% CI: 0.425-0.888) was inversely associated with severe hyperparathyroidism at 9 months after transplantation.

Conclusions: Allograft function remains the main determinant of severe hyperparathyroidism after transplantation. Our findings emphasize the importance of BMI and pre-transplant PTH control.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00467-020-04796-wDOI Listing
April 2021

Use of amlodipine oral solution for the treatment of hypertension in children.

Int J Clin Pharm 2020 Jun 6;42(3):848-852. Epub 2020 May 6.

Department of Hospital Pharmacy, Erasmus MC-Sophia Children's Hospital, University Medical Center Rotterdam, PO Box 2040, 3000 CA, Rotterdam, The Netherlands.

Background Amlodipine is a widely used antihypertensive agent for the treatment of paediatric hypertension, but the commercially available tablets are not suitable to treat young patients, who need lower, flexible dosages and a liquid formulation. Objective To determine the pharmacokinetic properties of amlodipine and the acceptability of a standardised, extemporaneous oral solution. Method A newly developed liquid formulation of amlodipine was administered to hypertensive children between the age of 6 months and 11 years. Using a limited sampling strategy, population PK analysis was performed using nonlinear mixed effects modelling. Results Nine children, with a median age of 2.9 years (IQR 1.8-8.4), receiving stable amlodipine therapy in a median dose of 0.15 mg kg day (IQR 0.11-0.18), were switched to study medication. The population pharmacokinetic model was able to accurately predict the clearance of amlodipine in the study population. Based on the final model, clearance was reduced by 31.2% (RSE: 10%) in females. Patient reported outcomes on taste from a five-point hedonic scale were available for five patients, who scored the taste from positive to slightly negative. Conclusion The results from the PK study and the acceptability assessment show that the amlodipine oral solution presented in this study offers an appropriate treatment option for young children.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11096-020-01000-9DOI Listing
June 2020

A Population Pharmacokinetic Model Does Not Predict the Optimal Starting Dose of Tacrolimus in Pediatric Renal Transplant Recipients in a Prospective Study: Lessons Learned and Model Improvement.

Clin Pharmacokinet 2020 05;59(5):591-603

Department of Pediatric Nephrology, Erasmus MC-Sophia Children's Hospital, Rotterdam, The Netherlands.

Background And Objective: Bodyweight-based dosing of tacrolimus is considered standard care. Currently, at first steady state, a third of pediatric kidney transplant recipients has a tacrolimus pre-dose concentration within the target range. We investigated whether adaptation of the starting dose according to a validated dosing algorithm could increase this proportion.

Methods: This was a multi-center, single-arm, prospective trial with a planned interim analysis after 16 patients, in which the tacrolimus starting dose was based on bodyweight, cytochrome P450 3A5 genotype, and donor status (living vs. deceased donor).

Results: At the interim analysis, 31% of children had a tacrolimus pre-dose concentration within the target range. As the original dosing algorithm was poorly predictive of tacrolimus exposure, the clinical trial was terminated prematurely. Next, the original model was improved by including the data of the children included in this trial, thereby doubling the number of children in the model building cohort. Data were best described with a two-compartment model with inter-individual variability, allometric scaling, and inter-occasion variability on clearance. Cytochrome P450 3A5 genotype, hematocrit, and creatinine influenced the tacrolimus clearance. A new starting dose model was developed in which the cytochrome P450 3A5 genotype was incorporated. Both models were successfully internally and externally validated.

Conclusions: The weight-normalized starting dose of tacrolimus should be higher in patients with a lower bodyweight and in those who are cytochrome P450 3A5 expressers.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s40262-019-00831-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7217818PMC
May 2020

Epidemiology and Outcome of Critically Ill Pediatric Cancer and Hematopoietic Stem Cell Transplant Patients Requiring Continuous Renal Replacement Therapy: A Retrospective Nationwide Cohort Study.

Crit Care Med 2019 11;47(11):e893-e901

Department of Pediatric Intensive Care, Wilhelmina Children's Hospital/University Medical Center Utrecht, Utrecht, The Netherlands.

Objective: Acute kidney injury requiring continuous renal replacement therapy is a serious treatment-related complication in pediatric cancer and hematopoietic stem cell transplant patients. The purpose of this study was to assess epidemiology and outcome of these patients requiring continuous renal replacement therapy in the PICU.

Design: A nationwide, multicenter, retrospective, observational study.

Setting: Eight PICUs of a tertiary care hospitals in the Netherlands.

Patients: Pediatric cancer and hematopoietic stem cell transplant patients (cancer and noncancer) who received continuous renal replacement therapy from January 2006 to July 2017 in the Netherlands.

Interventions: None.

Measurement And Main Results: Of 1,927 PICU admissions of pediatric cancer and hematopoietic stem cell transplant patients, 68 of 70 evaluable patients who received continuous renal replacement therapy were included. Raw PICU mortality was 11.2% (216/1,972 admissions). PICU mortality of patients requiring continuous renal replacement therapy was 54.4% (37/68 patients). Fluid overload (odds ratio, 1.08; 95% CI, 1.01-1.17) and need for inotropic support (odds ratio, 6.53; 95% CI, 1.86-23.08) at the start of continuous renal replacement therapy were associated with PICU mortality. Serum creatinine levels increased above 150% of baseline 3 days before the start of continuous renal replacement therapy. Urine production did not reach the critical limit of oliguria. In contrast, body weight (fluid overload) increased already 5 days prior to continuous renal replacement therapy initiation.

Conclusions: PICU mortality of pediatric cancer and hematopoietic stem cell transplant patients requiring continuous renal replacement therapy is sadly high. Fluid overload at the initiation of continuous renal replacement therapy is the most important and earliest predictor of PICU mortality. Our results suggest that the most commonly used criteria of acute kidney injury, that is, serum creatinine and urine production, are not useful as a trigger to initiate continuous renal replacement therapy. This highlights the urgent need for prospective studies to generate recommendations for effective therapeutic interventions at an early phase in this specific patient population.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/CCM.0000000000003973DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6798750PMC
November 2019

Growth Patterns After Kidney Transplantation in European Children Over the Past 25 Years: An ESPN/ERA-EDTA Registry Study.

Transplantation 2020 01;104(1):137-144

Pediatric Nephrology Unit, Bordeaux University Hospital, Bordeaux, France.

Background: Improved management of growth impairment might have resulted in less growth retardation after pediatric kidney transplantation (KT) over time. We aimed to analyze recent longitudinal growth data after KT in comparison to previous eras, its determinants, and the association with transplant outcome in a large cohort of transplanted children using data from the European Society for Paediatric Nephrology/European Renal Association and European Dialysis and Transplant Association Registry.

Methods: A total of 3492 patients transplanted before 18 years from 1990 to 2012 were included. Height SD scores (SDS) were calculated using recent national or European growth charts. We used generalized equation models to estimate the prevalence of growth deficit and linear mixed models to calculate adjusted mean height SDS.

Results: Mean adjusted height post-KT was -1.77 SDS. Height SDS was within normal range in 55%, whereas 28% showed moderate, and 17% severe growth deficit. Girls were significantly shorter than boys, but catch-up growth by 5 years post-KT was observed in both boys and girls. Children <6 years were shortest at KT and showed the greatest increase in height, whereas there was no catch-up growth in children transplanted >12.

Conclusions: Catch-up growth post-KT remains limited, height SDS did not improve over time, resulting in short stature in nearly half of transplanted children in Europe.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/TP.0000000000002726DOI Listing
January 2020

Recovery of Kidney Function in Children Treated with Maintenance Dialysis.

Clin J Am Soc Nephrol 2018 10 20;13(10):1510-1516. Epub 2018 Sep 20.

European Society for Pediatric Nephrology/ European Renal Association-European Dialysis and Transplant Association Registry, Department of Medical Informatics, Academic Medical Center, University of Amsterdam, Amsterdam Public Health Research Institute, Amsterdam, The Netherlands.

Background And Objectives: Data on recovery of kidney function in pediatric patients with presumed ESKD are scarce. We examined the occurrence of recovery of kidney function and its determinants in a large cohort of pediatric patients on maintenance dialysis in Europe.

Design, Setting, Participants, & Measurements: Data for 6574 patients from 36 European countries commencing dialysis at an age below 15 years, between 1990 and 2014 were extracted from the European Society for Pediatric Nephrology/European Renal Association-European Dialysis and Transplant Association Registry. Recovery of kidney function was defined as discontinuation of dialysis for at least 30 days. Time to recovery was studied using a cumulative incidence competing risk approach and adjusted Cox proportional hazard models.

Results: Two years after dialysis initiation, 130 patients (2%) experienced recovery of their kidney function after a median of 5.0 (interquartile range, 2.0-9.6) months on dialysis. Compared with patients with congenital anomalies of the kidney and urinary tract, recovery more often occurred in patients with vasculitis (11% at 2 years; adjusted hazard ratio [HR], 20.4; 95% confidence interval [95% CI], 9.7 to 42.8), ischemic kidney failure (12%; adjusted HR, 11.4; 95% CI, 5.6 to 23.1), and hemolytic uremic syndrome (13%; adjusted HR, 15.6; 95% CI, 8.9 to 27.3). Younger age and initiation on hemodialysis instead of peritoneal dialysis were also associated with recovery. For 42 patients (32%), recovery was transient as they returned to kidney replacement therapy after a median recovery period of 19.7 (interquartile range, 9.0-41.3) months.

Conclusions: We demonstrate a recovery rate of 2% within 2 years after dialysis initiation in a large cohort of pediatric patients on maintenance dialysis. There is a clinically important chance of recovery in patients on dialysis with vasculitis, ischemic kidney failure, and hemolytic uremic syndrome, which should be considered when planning kidney transplantation in these children.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2215/CJN.01500218DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6218837PMC
October 2018

Diagnosing Alport Syndrome: Lessons from the Pediatric Ward.

Nephron 2018 13;140(3):203-210. Epub 2018 Sep 13.

Department of Pediatric Nephrology, Erasmus University Medical Center Rotterdam, Rotterdam, the Netherlands.

Background: Alport syndrome is a rare inheritable kidney disease frequently leading to end-stage kidney disease in young adults. Patients could benefit from early recognition of the disease. In several children with Alport syndrome, a parent was noticed to have renal symptoms attributed to another renal disease.

Aim: To review the renal history of the closest family members of a cohort of pediatric patients with genetically proven Alport syndrome.

Methods: The medical records of all children with genetically proven Alport syndrome identified at our pediatric nephrology department in the last 20 years were reviewed, with focus on the medical history of affected parents.

Results: Twenty-three children with Alport syndrome from 21 different families were identified. Eight of 21 probands had family member(s) with renal symptoms attributed to other diseases. In these, a type IV collagen mutation was determined only after the manifestation of Alport syndrome in their child. One proband presented atypically with acute membrano-proliferative glomerulo-nephritis. Only 3 out of 8 probands with a known family history of Alport syndrome had been intentionally screened for this disease. A COL4A5 mutation was found in 18 probands, COL4A3 in 2, and COL4A4 in 1. Each family showed private mutations; 17 out of 21 mutations were novel.

Conclusions: Atypical presentation of Alport syndrome was quite common in mothers of our pediatric patients. To enable earlier diagnosis of Alport syndrome, nephrologists should look for a positive diagnosis in any patient with persistent renal symptoms, especially if there is a positive family history of (any) renal disease.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1159/000492438DOI Listing
October 2019

Drug-metabolizing enzymes CYP3A as a link between tacrolimus and vitamin D in renal transplant recipients: is it relevant in clinical practice?

Pediatr Nephrol 2019 07 30;34(7):1201-1210. Epub 2018 Jul 30.

Paediatric Nephrology and Rheumatology Department, Ghent University Hospital, C Heymanslaan 10, 9000, Ghent, Belgium.

CYP3A enzymes are involved in the metabolism of calcineurin inhibitor tacrolimus as well as vitamin D. In this review, we summarize the clinical aspects of CYP3A-mediated metabolism of tacrolimus and vitamin D with emphasis on the influence of single-nucleotide polymorphisms on tacrolimus disposition. We describe the utility of 4β hydroxycholesterol as a marker of CYP3A activity. Then, we discuss the possible interaction between calcineurin inhibitors and vitamin D in solid organ transplant recipients. Also, we review other mechanisms which may contribute to side effects of calcineurin inhibitors on bone. Lastly, suggestions for future research and clinical perspectives are discussed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00467-018-4030-3DOI Listing
July 2019

Children on dialysis as well as renal transplanted children report severely impaired health-related quality of life.

Qual Life Res 2018 06 27;27(6):1445-1454. Epub 2018 Jan 27.

Department of Pediatric Nephrology, Emma Children's Hospital, Amsterdam, The Netherlands.

Objectives: To assess health-related quality of life (HRQoL) across three renal replacement therapy modalities (preemptive transplant, non-preemptive transplant, and dialysis) in comparison with the healthy norm and other chronic health conditions, and to explore related patient factors.

Study Design: All prevalent end-stage renal disease (ESRD) patients aged 8-18 years who spent at least 6 months on their current treatment modality in the Netherlands, Belgium, and part of Germany were approached to complete the Pediatric Quality of Life Inventory 4.0 (PedsQL™) questionnaire. We determined the differences between groups on PedsQL™ mean scores, the proportion of children with an impaired HRQoL (≥ 1 SD lower than the healthy norm), the proportion of problems on individual items of the PedsQL™, and the effect of time on current treatment. Linear regression models were used to explore determinants of HRQoL.

Results: 192 out of 278 patients (20% preemptive transplant, 58% non-preemptive transplant, 22% dialysis) filled in the PedsQL™ (response rate 69%). Independent of treatment modality, patients had significantly lower mean scores and consequently higher proportions of impaired HRQoL on almost all domains compared to the healthy norm and other chronic health conditions. Patients with a preemptive transplant only reported higher scores on physical health compared to the other treatment modalities. Having comorbidities was the most important determinant associated with lower HRQoL scores.

Conclusion: Dialysis and renal transplantation both have a severe impact on the HRQoL of children with ESRD. Physicians should be aware of this continuous burden. Furthermore, to develop tailored interventions for children with ESRD, qualitative studies are needed to gain more insight in the determinants of HRQoL in the different treatment modalities.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11136-018-1789-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5951873PMC
June 2018

How to stent the ureter after kidney transplantation in children?-A comparison of two methods of urinary drainage.

Pediatr Transplant 2018 02 27;22(1). Epub 2017 Oct 27.

Department of Pediatric Nephrology, Erasmus MC-Sophia Children's Hospital, Rotterdam, The Netherlands.

Ureteral stenting after pediatric renal transplantation serves to prevent obstruction and urinary leakage, but can also cause complications. This study compares the complication rates of both methods. Data were retrospectively collected at Erasmus MC, Rotterdam, the Netherlands (splint group, n = 61) and Hospital for Sick Children, Toronto, Canada (JJ catheter group, n = 50). Outcome measures included urological interventions and incidence of UTIs during the first 3 months post-transplantation. The splint was removed after a median of 9 (IQR 8-12), the JJ catheter after 42 (IQR 36-50) days. Seven (11.5%) children in the splint group needed at least one urological re-intervention versus two in the JJ catheter group (P-value .20). UTIs developed in 19 children (31.1%) in the splint group and in twenty-five (50.0%) children in the JJ catheter group (P-value .04), with a total number of 27 vs. 57 UTIs (P-value .02). Nine (33.3%) vs. 35 (61.4%) of these, respectively, occurred during the presence of the splint (P-value <.001). Children with a JJ catheter developed more UTIs than children with a splint; the latter, however, tended to require more re-interventions. Modification of either method is needed to find the best way to stent the ureter.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/petr.13065DOI Listing
February 2018

A Population Pharmacokinetic Model to Predict the Individual Starting Dose of Tacrolimus Following Pediatric Renal Transplantation.

Clin Pharmacokinet 2018 04;57(4):475-489

Department of Hospital Pharmacy, Erasmus Medical Center, University Medical Center Rotterdam, P. O. Box 2040, 3000 CA, Rotterdam, The Netherlands.

Background: Multiple clinical, demographic, and genetic factors affect the pharmacokinetics of tacrolimus in children, yet in daily practice, a uniform body-weight based starting dose is used. It can take weeks to reach the target tacrolimus pre-dose concentration.

Objectives: The objectives of this study were to determine the pharmacokinetics of tacrolimus immediately after kidney transplantation and to find relevant parameters for dose individualization using a population pharmacokinetic analysis.

Methods: A total of 722 blood samples were collected from 46 children treated with tacrolimus over the first 6 weeks after renal transplantation. Non-linear mixed-effects modeling (NONMEM) was used to develop a population pharmacokinetic model and perform a covariate analysis. Simulations were performed to determine the optimal starting dose and to develop dosing guidelines.

Results: The data were accurately described by a two-compartment model with allometric scaling for bodyweight. Mean tacrolimus apparent clearance was 50.5 L/h, with an inter-patient variability of 25%. Higher bodyweight, lower estimated glomerular filtration rate, and higher hematocrit levels resulted in lower total tacrolimus clearance. Cytochrome P450 3A5 expressers and recipients who received a kidney from a deceased donor had a significantly higher tacrolimus clearance. The model was successfully externally validated. In total, these covariates explained 41% of the variability in clearance. From the significant covariates, the cytochrome P450 3A5 genotype, bodyweight, and donor type were useful to adjust the starting dose to reach the target pre-dose concentration. Dosing guidelines range from 0.27 to 1.33 mg/kg/day.

Conclusion: During the first 6 weeks after transplantation, the tacrolimus weight-normalized starting dose should be higher in pediatric kidney transplant recipients with a lower bodyweight, those who express the cytochrome P450 3A5 genotype, and those who receive a kidney from a deceased donor.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s40262-017-0567-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5856873PMC
April 2018

Clinical and Histopathologic Characteristics Associated with Renal Outcomes in Lupus Nephritis.

Clin J Am Soc Nephrol 2017 May 4;12(5):734-743. Epub 2017 May 4.

Departments of Pathology.

Background And Objectives: The prognostic significance of histopathologic (sub)classes in the current classification of lupus nephritis (LN) is controversial. We analyzed clinical and histopathologic predictors of renal outcome in LN outside the framework of the classification.

Design, Setting, Participants, & Measurements: Variables (50 histopathologic and ten clinical) were tested in mixed, linear, and Cox regression models for their association with renal flare, ESRD, and eGFR during follow-up (1, 5, and 10 years) in 105 patients with LN who underwent biopsy from 1987 to 2011. The Cockcroft-Gault (normalized to a body surface area of 1.73 m) and Schwartz formulas were used to calculate eGFR for adults and children, respectively.

Results: During median follow-up of 9.9 years (25th-75th percentile, 5.9-13.8), 47 patients experienced a renal flare and 21 progressed to ESRD. Renal flare was predicted by fibrinoid necrosis (hazard ratio [HR], 1.04 per %; 95% confidence interval [95% CI], 1.00 to 1.07) and nonwhite race (HR, 2.23; 95% CI, 1.23 to 4.04). ESRD was predicted by fibrinoid necrosis (HR, 1.08 per %; 95% CI, 1.02 to 1.13), fibrous crescents (HR, 1.09 per %; 95% CI, 1.02 to 1.17), interstitial fibrosis/tubular atrophy (IF/TA) ≥25% (HR, 3.89; 95% CI, 1.25 to 12.14), eGFR at baseline (HR, 0.98 per ml/min per 1.73 m; 95% CI, 0.97 to 1.00), and nonwhite race (HR, 7.16; 95% CI, 2.34 to 21.91). A higher mean eGFR during follow-up was associated with normal glomeruli (+0.2 ml/min per 1.73 m per %; 95% CI, 0.1 to 0.4). Like ESRD, a lower eGFR during follow-up was associated with fibrous crescents, IF/TA≥25%, and nonwhite race, as well as with cellular/fibrocellular crescents (-0.4 ml/min per 1.73 m per %; 95% CI, -0.6 to -0.2) and age (-0.8 ml/min per 1.73 m per year; 95% CI, -1.2 to -0.4).

Conclusion: The LN classification should include an index of evidence-based prognosticators. Awaiting validation of a formal index, we suggest that at least fibrinoid necrosis, fibrous crescents, and IF/TA warrant explicit independent scoring to assess the risk of progressive renal dysfunction in conjunction with clinical findings.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2215/CJN.10601016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5477219PMC
May 2017

Childhood Estimates of Glomerular Filtration Rate Based on Creatinine and Cystatin C: Importance of Body Composition.

Am J Nephrol 2017 1;45(4):320-326. Epub 2017 Mar 1.

The Generation R Study Group, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.

Background: Creatinine and cystatin C concentrations are commonly used to estimate glomerular filtration rate (eGFR) in clinical practice and epidemiological studies. To estimate the influence of different body composition measures on eGFR from creatinine and cystatin C blood concentrations, we compared the associations of different anthropometric and body composition measures with eGFR derived from creatinine (eGFRcreat) and cystatin C (eGFRcystC) blood concentrations.

Methods: In a population-based cohort study among 4,305 children aged 6.0 years (95% range 5.7-8.0), we measured weight and height and calculated body mass index (BMI) and body surface area (BSA), and lean and fat mass using dual-energy X-ray absorptiometry. At the same age, we measured creatinine and cystatin C blood concentrations and estimated the GFR.

Results: Correlation between eGFR based on creatinine and cystatin C concentrations was r = 0.40 (p value <0.01). Higher BMI was associated with lower eGFRcystC but not with eGFRcreat. Higher BSA was associated with higher eGFRcreat and lower eGFRcystC (p value <0.05). Lean and fat mass percentages were associated with eGFRcreat but not with eGFRcystC.

Conclusion: Our findings suggest that both eGFRcreat and eGFRcystC are influenced by BMI and BSA. eGFRcreat is more strongly influenced by body composition than eGFRcystC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1159/000463395DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5408927PMC
January 2018

Epidemiology and management of hypertension in paediatric and young adult kidney transplant recipients in The Netherlands.

Nephrol Dial Transplant 2016 11 10;31(11):1947-1956. Epub 2016 Jun 10.

Department of Pediatric Nephrology, Emma Children's Hospital, Academic Medical Center at the University of Amsterdam, Room H7-232 Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands.

Introduction: Hypertension in kidney transplant recipients (KTRs) is a risk factor for cardiovascular mortality and graft loss. Data on the prevalence of hypertension and uncontrolled hypertension (uHT) in paediatric and young adult KTRs are scarce. Also, it is unknown whether 'transition' (the transfer from paediatric to adult care) influences control of hypertension. We assessed the prevalence of hypertension and uHT among Dutch paediatric and young adult KTRs and analysed the effects of transition. Additionally, we made an inventory of variations in treatment policies in Dutch transplant centres.

Methods: Cross-sectional and longitudinal national data from living KTRs ≤30 years of age (≥1-year post-transplant, eGFR >20 mL/min) were extracted from the 'RICH Q' database, which comprises information about all Dutch KTRs <19 years of age, and the Netherlands Organ Transplant Registry database for adult KTRs (≥18-30 years of age). We used both upper-limit blood pressure (BP) thresholds for treatment according to Kidney Disease: Improving Global Outcomes (KDIGO) guidelines. uHT was defined as a BP above the threshold. A questionnaire on treatment policies was sent to paediatric and adult nephrologists at eight Dutch transplant centres.

Results: Hypertension and uHT were more prevalent in young adult KTRs (86.4 and 75.8%) than in paediatric KTRs (62.7 and 38.3%) according to the KDIGO definition. Time after transplantation was comparable between these groups. Longitudinal analysis showed no evidence of effect of transition on systolic BP or prevalence of uHT. Policies vary considerably between and within centres on the definition of hypertension, BP measurement and antihypertensive treatment.

Conclusion: Average BP in KTRs increases continuously with age between 6 and 30 years. Young adult KTRs have significantly more uHT than paediatric KTRs according to KDIGO guidelines. Transition does not influence the prevalence of uHT.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/ndt/gfw225DOI Listing
November 2016

The Effect of Weight and CYP3A5 Genotype on the Population Pharmacokinetics of Tacrolimus in Stable Paediatric Renal Transplant Recipients.

Clin Pharmacokinet 2016 09;55(9):1129-43

Department of Hospital Pharmacy-Clinical Pharmacology Unit, Academic Medical Center, Amsterdam, The Netherlands.

Background: The aim of this study was to develop a population pharmacokinetic model of tacrolimus in paediatric patients at least 1 year after renal transplantation and simulate individualised dosage regimens.

Patients And Methods: We included 54 children with median age of 11.1 years (range 3.8-18.4 years) with 120 pharmacokinetic profiles performed over 2 to 4 h. The pharmacokinetic analysis was performed using the non-linear mixed-effects modelling software (NONMEM(®)). The impact of covariates including concomitant medications, age, the cytochrome P450 (CYP) CYP3A5*3 gene and the adenosine triphosphate binding cassette protein B1 (ABCB1) 3435 C→T gene polymorphism on tacrolimus pharmacokinetics was analysed. The final model was externally validated on an independent dataset and dosing regimens were simulated.

Results: A two-compartment model adequately described tacrolimus pharmacokinetics. Apparent oral clearance (CL/F) was associated with weight (allometric scaling) but not age. Children with lower weight and CYP3A5 expressers required higher weight-normalised tacrolimus doses. CL/F was inversely associated with haematocrit (P < 0.05) and γ-glutamyl transpeptidase (γGT) (P < 0.001) and was increased by 45 % in carriers of the CYP3A5*1 allele (P < 0.001). CL/F was not associated with concomitant medications. Dose simulations show that a daily tacrolimus dose of 0.2 mg/kg generates a pre-dose concentration (C 0) ranging from 5 to 10 µg/L depending on the weight and CYP3A5 polymorphism. The median area under the plasma concentration-time curve (AUC) corresponding with a tacrolimus C 0 of 4-8 µg/L was 97 h·µg/L (interquartile range 80-120).

Conclusions: In patients beyond the first year after transplantation, there is a cumulative effect of CYP3A5*1 polymorphism and weight on the tacrolimus C 0. Children with lower weight and carriers of the CYP3A5*1 allele have higher weight-normalised tacrolimus dose requirements.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s40262-016-0390-7DOI Listing
September 2016

The impact of estimated glomerular filtration rate equations on chronic kidney disease staging in pediatric renal or heart transplant recipients.

Pediatr Nephrol 2016 07 9;31(7):1145-55. Epub 2016 Feb 9.

Department of Clinical Chemistry, Erasmus University Medical Center, Rotterdam, The Netherlands.

Background: The aim of this study was to evaluate the performance of selected pediatric estimated glomerular filtration rate (eGFR) equations in relation to the clinical management of children after renal or heart transplantation or post-chemotherapy treatment.

Methods: This study was a retrospective cross-sectional analysis of 61 children whose glomerular function (GFR) had been determined using a single-dose inulin clearance (iGFR) method. Eight equations for estimating the GFR were evaluated for bias, agreement, accuracy, and clinical stratification.

Results: The outcome of all eight eGFR equations differed from the value determined using the iGFR method, with the mean bias ranging from -3.4 to 20.7 ml/min/1.73 m(2) and 90 % accuracy ranging from 16 to 26 %. All eGFR equations overestimated renal function in patients with decreased kidney function as determined by the iGFR method and underestimated renal function in patients with normal kidney function. Consequently, based on the eGFR values, patients with low GFR values according to the iGFR method were staged in a less severe chronic kidney disease (CKD) category, and patients with normal GFR values according to the iGFR method were staged in a more severe CKD category. The percentage of correctly classified patients ranged from 32.6 to 41.6 %.

Conclusions: In our cohort we found the CKiDIII equation to be the best alternative to calculating the GFR using the inulin clearance method, closely followed by the Hoste and the revised Grubb equations. The performances of all eight eGFR equations assessed were moderate at best and only slightly better than the easy-to-do bedside Schwartz equation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00467-016-3312-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4880629PMC
July 2016

Urinary Neutrophil Gelatinase-Associated Lipocalin Predicts Renal Injury Following Extracorporeal Membrane Oxygenation.

Pediatr Crit Care Med 2015 Sep;16(7):663-70

1Intensive Care and Department of Pediatric Surgery, Erasmus Medical Center-Sophia Children's Hospital, Rotterdam, The Netherlands. 2Department of Pediatric Nephrology, Erasmus Medical Center-Sophia Children's Hospital, Rotterdam, The Netherlands. 3Department of Clinical Chemistry, Erasmus Medical Center, Rotterdam, The Netherlands. 4Department of Biostatistics, Erasmus Medical Center, Rotterdam, The Netherlands.

Objective: To evaluate the course of urinary neutrophil gelatinase-associated lipocalin and urinary kidney injury molecule-1 levels in young children during extracorporeal membrane oxygenation and concomitant continuous hemofiltration. Furthermore, to evaluate whether these levels predict outcome.

Design: Prospective observational cohort study from July 2010 to July 2013.

Setting: ICU of a level III university children's hospital.

Patients: Thirty-one extracorporeal membrane oxygenation-treated children up to 1 year were included.

Interventions: None.

Measurements And Main Results: Patients were weaned from extracorporeal membrane oxygenation after a median of 162 hours (interquartile range, 83-304). Throughout the study, 58% of the patients met the criteria for acute kidney injury (i.e., Risk Injury Failure Loss End-Stage Renal Disease-Risk or higher defined as an increase in serum creatinine corresponding to ≥ 150% when compared with age-specific reference values). Levels of both biomarker patterns changed significantly throughout extracorporeal membrane oxygenation (urinary neutrophil gelatinase-associated lipocalin, p < 0.001 and urinary kidney injury molecule-1, p = 0.005, linear mixed model analyses). Urinary neutrophil gelatinase-associated lipocalin levels were already high before extracorporeal membrane oxygenation, whereas urinary kidney injury molecule-1 levels increased throughout the first extracorporeal membrane oxygenation day and peaked at 12-24 hours. Also, urinary neutrophil gelatinase-associated lipocalin levels at 12-24 hours of extracorporeal membrane oxygenation therapy were higher among patients with acute kidney injury post extracorporeal membrane oxygenation (p = 0.002, Mann-Whitney U test). Biomarker levels did not differ between survivors and nonsurvivors.

Conclusions: The increased urinary neutrophil gelatinase-associated lipocalin and urinary kidney injury molecule-1 levels confirm that renal tubular damage occurs in critically ill infants in need of extracorporeal membrane oxygenation. The fact that the maximal urinary neutrophil gelatinase-associated lipocalin levels were measured 24 hours earlier than urinary kidney injury molecule-1 supports the use of biomarker combinations rather than a single biomarker to identify patients at risk of acute kidney injury. Finally, since urinary neutrophil gelatinase-associated lipocalin levels at 12-24 hours of extracorporeal membrane oxygenation therapy were associated with acute kidney injury post extracorporeal membrane oxygenation, this marker may facilitate more timely adjustment of therapeutic interventions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/PCC.0000000000000476DOI Listing
September 2015

Pharmacokinetics of rituximab in a pediatric patient with therapy-resistant nephrotic syndrome.

Pediatr Nephrol 2015 Aug 9;30(8):1367-70. Epub 2015 Jun 9.

Department of Pediatrics, Leiden University Medical Center (LUMC), Albinusdreef 2, 2333 ZA, Leiden, The Netherlands.

Background: Rituximab (RTX) has recently been introduced as a second-line therapy for nephrotic syndrome in children. Studies show that RTX given during the nephrotic state may be less effective than treatment during a non-nephrotic state, possibly due to loss of RTX in the urine.

Case-diagnosis/treatment: We describe a 10-year-old boy with steroid-resistant nephrotic syndrome (SRNS) treated with RTX during a phase of active non-selective proteinuria. The serum half-life of RTX in this patient was less than 1 day compared to 20 days in patients without protein losses. Urinary clearance was at least 25 %, compared to approximately 0 % in control patients. However, RTX loss in the urine, as well as in pleural effusion and ascites, only partly explains the rapid drop in the serum RTX concentration of this patient.

Conclusions: Serum half-life of RTX can be extremely short, partly due to excessive urinary losses in therapy-resistant nephrotic syndrome with non-selective proteinuria, as seen in our patient. These findings may help to explain the poor results of RTX treatment in patients with active proteinuria.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00467-015-3120-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4483248PMC
August 2015

Cardiac Arrest in Children: Long-Term Health Status and Health-Related Quality of Life.

Pediatr Crit Care Med 2015 Oct;16(8):693-702

1Intensive Care and Department of Pediatric Surgery, Erasmus MC-Sophia Children's Hospital, Rotterdam, The Netherlands. 2Department of Child and Adolescent Psychiatry/Psychology, Erasmus MC-Sophia Children's Hospital, Rotterdam, The Netherlands. 3Department of Pediatrics, Subdivision of Pediatric Nephrology, Erasmus MC-Sophia Children's Hospital, Rotterdam, The Netherlands. 4Department of Pediatric Gastroenterology, Erasmus MC-Sophia Children's Hospital, Rotterdam, The Netherlands.

Objective: To assess long-term health status and health-related quality of life in survivors of cardiac arrest in childhood and their parents. In addition, to identify predictors of health status and health-related quality of life.

Design: This medical follow-up study involved consecutive children surviving cardiac arrest between January 2002 and December 2011, who had been admitted to the ICU. Health status was assessed with a medical interview, physical examination, and the Health Utilities Index. Health-related quality of life was assessed with the Child Health Questionnaires and Short-Form 36.

Setting: A tertiary care university children's hospital.

Patients: Of the eligible 107 children, 57 (53%) filled out online questionnaires and 47 visited the outpatient clinic (median age, 8.7 yr; median follow-up interval, 5.6 yr).

Interventions: None.

Measurements And Main Results: Of the participants, 60% had an in-hospital cardiac arrest, 90% a nonshockable rhythm, and 50% a respiratory etiology of arrest. Mortality rate after hospital discharge was 10%. On health status, we found that 13% had long-term neurologic deficits, 34% chronic symptoms (e.g., fatigue, headache), 19% at least one sign suggestive of chronic kidney injury, and 15% needed special education. Health Utilities Index scores were significantly decreased on most utility scores and the overall Health Utilities Index mark 3 score. Compared with Dutch normative data, parent-reported health-related quality of life of cardiac arrest survivors was significantly worse on general health perception, physical role functioning, parental impact, and overall physical summary. On patient reports, no significant differences with normative data were found. Parents reported better family cohesion and better health-related quality of life for themselves on most scales. Patients' health status, general health perceptions, and physical summary scores were significantly associated with cardiac arrest-related preexisting condition.

Conclusions: Considering the impact of cardiac arrest, the overall outcome after cardiac arrest in childhood is reasonably good. Prospective long-term outcome research in large homogeneous groups is needed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/PCC.0000000000000452DOI Listing
October 2015

Urinary neutrophil gelatinase-associated lipocalin identifies critically ill young children with acute kidney injury following intensive care admission: a prospective cohort study.

Crit Care 2015 Apr 21;19:181. Epub 2015 Apr 21.

Department of Pediatric Nephrology, Erasmus Medical Center-Sophia Children's Hospital, Wytemaweg 80, 3015 CN, Rotterdam, the Netherlands.

Introduction: Children admitted to a pediatric intensive care unit (ICU) are at high risk of developing acute kidney injury (AKI). Although serum creatinine (SCr) levels are used in clinical practice, they are insensitive for early diagnosis of AKI. Urinary neutrophil gelatinase-associated lipocalin (uNGAL) and kidney injury molecule-1 (KIM-1) are novel AKI biomarkers whose performance in pediatric ICU patients is largely unknown. In this study, we aimed to characterize uNGAL and KIM-1 patterns in children following ICU admission and to assess their properties in relation to identifying children at risk for AKI development.

Methods: From June 2010 until January 2014, we conducted a prospective observational cohort study of term-born children ages 1 day to 1 year on mechanical ventilation. Blood and urine samples were obtained every 6 to 12 hours up to 72 hours post-admission. Blood samples were assayed for SCr, and urine samples were assayed for uNGAL and KIM-1. The RIFLE (risk, injury, failure, loss, end-stage renal disease) classification as 150%, 200% or 300% of median SCr reference values was used to define AKI.

Results: A total of 100 children were included (80 survived). Their median age at admission was 27.7 days (interquartile range (IQR), 1.5 to 85.5). The median duration of mechanical ventilation was 5.8 days (IQR, 3.1 to 11.4). Thirty-five patients had evidence of AKI within the first 48 hours post-admission, of whom 24 (69%) already had AKI when they entered the ICU. uNGAL and KIM-1 concentrations in AKI peaked between 6 to 12 hours and between 12 to 24 hours post-admission, respectively. The maximal area under the receiver operating characteristic curve (AUC) for uNGAL was 0.815 (95% confidence interval (CI), 0.685 to 0.945, P < 0.001) at 0 to 6 hours post-admission. The discriminative ability of KIM-1 was moderate, with a largest AUC of 0.737 (95% CI, 0.628 to 0.847; P < 0.001) at 12 to 24 hours post-admission. At the optimal cutoff point (126 ng/ml), uNGAL concentration predicted AKI development correctly in 16 (84%) of 19 children, up to 24 hours before a rise in SCr became apparent.

Conclusions: Levels of uNGAL and KIM-1 increase in patients with AKI following ICU admission and peak at 6 to 12 hours and 12 to 24 hours post-admission, respectively. uNGAL seems to be a reliable marker for identifying children who will develop AKI 24 hours later.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13054-015-0910-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4422047PMC
April 2015

Dosing algorithms for initiation of immunosuppressive drugs in solid organ transplant recipients.

Expert Opin Drug Metab Toxicol 2015 Jun 12;11(6):921-36. Epub 2015 Apr 12.

Erasmus MC, University Medical Center Rotterdam, Department of Hospital Pharmacy , Room Na-206, P.O. Box 2040, 3000 CA, Rotterdam , The Netherlands +31 10 703 3202 ; +31 10 703 2400 ;

Introduction: Starting doses of tacrolimus and ciclosporin are typically chosen on a calculated mg/kg bodyweight basis. After initiation of treatment, doses are adjusted with therapeutic drug monitoring (TDM). This trial-and-error approach has been accepted by most physicians and pharmacists involved in the care of transplanted patients.

Areas Covered: Dosing algorithms have only fairly recently been proposed to better individualize the starting dose. This review provides an overview of all the currently available dosing algorithms in adult and children for the starting dose of ciclosporin, tacrolimus and mycophenolic acid. In these algorithms, multiple other covariates influencing the starting dose, such as age, hematocrit, comedication and genotype are taken into account. After selecting the starting dose with an algorithm and after initiation of treatment, TDM will, however, remain necessary. Whether or not implementation of such algorithms will improve clinical outcome remains to be demonstrated.

Expert Opinion: First of all an algorithm needs to be validated, against an independent dataset. Second, in a prospective study the algorithm should prove to reduce the time to reach the target concentration, and to reduce the number of patients with drug concentrations (far) outside the therapeutic window. Finally, a clinical trial demonstrating a benefit on clinical outcome will be crucial in achieving broad acceptance of calculating starting dose using individualized dosing algorithms.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1517/17425255.2015.1033397DOI Listing
June 2015

Reference intervals for renal injury biomarkers neutrophil gelatinase-associated lipocalin and kidney injury molecule-1 in young infants.

Clin Chem Lab Med 2015 Jul;53(8):1279-89

Background: Reliable reference intervals for two novel urinary biomarkers of renal injury, neutrophil gelatinase-associated lipocalin (uNGAL) and kidney injury molecule-1 (uKIM-1) are lacking for infants. Therefore, the aim of our study was to establish reference intervals for urinary NGAL and KIM-1 absolute concentrations as well as normalized to urinary creatinine in young infants categorized in small age intervals.

Methods: From June 2010 to March 2014, serum and urine samples of 106 basically healthy infants (born between 37 and 42 weeks of gestation) aged 1 day to 1 year were collected. Blood samples were assayed for serum creatinine levels to confirm a healthy renal status. Urine samples were assayed for creatinine, uNGAL (ng/mL) and uKIM-1 (ng/mL).

Results: Two thirds of the study cohort were boys. uNGAL concentrations declined with increasing age (likelihood ratio test, p=0.001). Also, uNGAL concentrations were higher in girls (50th centile uNGAL was 27.1 ng/mL) than boys (50th centile uNGAL was 14.3 ng/mL) (two tailed Wald test, p<0.001) NGAL concentrations were not related to ethnicity. uKIM-1 concentrations were extremely low in almost all 106 subjects [median uKIM-1 was 0.08 (IQR 0.08-0.08) ng/mL] and not related with age, gender or ethnicity (all p>0.05).

Conclusions: Our data uniquely provide uNGAL and uKIM-1 reference intervals for the first year of life. Notably, only uNGAL levels decreased with increasing age and were higher in girls. These reference intervals enable future studies to evaluate the performance of both biomarkers in detecting early kidney tubular injury, particularly in the setting of critical care.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1515/cclm-2014-1020DOI Listing
July 2015

Young Adult Kidney Transplant Recipients: Nonadherent and Happy.

Transplantation 2015 Aug;99(8):e89-96

1 Department of Internal Medicine, Section Nephrology & Kidney Transplant, Erasmus MC, Rotterdam, the Netherlands. 2 Department of Paediatric Nephrology, Erasmus MC Sophia Children's Hospital, Rotterdam, the Netherlands.

Background: The aim of this study was to investigate (a) the extent to which age at first renal replacement therapy, achievement of developmental milestones, satisfaction of psychological needs, and coping were related to subjective well-being and medication adherence among young adult kidney transplant recipients; and (b) the relationship between subjective well-being and immunosuppressive medication adherence.

Methods: A cross-sectional, interview study was conducted among renal transplant patients aged 20 to 30 years. In addition to sociodemographic and medical characteristics, concepts measured were: subjective well-being (Positive And Negative Affect Schedule; Satisfaction With Life Scale), medication adherence (Basel Assessment of Adherence to Immunosuppressive Medication Scale), dispositional coping (Brief COPE), achievement of developmental milestones (Course of Life Questionnaire), and satisfaction of psychological needs (Basic Psychological Needs Scale).

Results: Sixty-two patients participated (66% men; mean age, 26 years). Sixty-five percent were classified as nonadherent in the past month. In contrast, subjective self-rated overall adherence was high. None of the variables measured were related to nonadherence. Higher feelings of competence and autonomy, and timely achievement of social and psychosexual developmental milestones were related to higher subjective well-being. Well-being and adherence did not differ according to age at diagnosis or first renal replacement therapy.

Conclusions: Two thirds of participants were classified as nonadherent which conflicts with participants' own high rating of medication adherence. This emphasizes the need for continued adherence support among young adult transplant recipients; however, no targets for interventions were found in this study. Potential targets for interventions aimed at improving well-being include competence and autonomy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/TP.0000000000000639DOI Listing
August 2015

CKD and hypertension during long-term follow-up in children and adolescents previously treated with extracorporeal membrane oxygenation.

Clin J Am Soc Nephrol 2014 Dec 2;9(12):2070-8. Epub 2014 Oct 2.

Department of Pediatric Nephrology, Erasmus Medical Center-Sophia Children's Hospital, Rotterdam, The Netherlands; and

Background And Objectives: Many children receiving extracorporeal membrane oxygenation develop AKI. If AKI leads to permanent nephron loss, it may increase the risk of developing CKD. The prevalence of CKD and hypertension and its predictive factors during long-term follow-up of children and adolescents previously treated with neonatal extracorporeal membrane oxygenation were determined.

Design, Setting, Participants, & Measurements: Between November of 2010 and February of 2014, neonatal survivors of extracorporeal membrane oxygenation who visited the prospective follow-up program at 1, 2, 5, 8, 12, and 18 years of age were screened for CKD and hypertension (BP≥95th percentile of reference values). CKD was suspected in children with either an eGFR<90 ml/min per 1.73 m(2) or proteinuria (urinary protein-to-creatinine ratio >0.50 for children ages ≤24 months and >0.20 at >24 months). The RIFLE classification (risk, injury, or failure as 150%, 200%, or 300% of serum creatinine reference values) was used to define AKI during extracorporeal membrane oxygenation without preemptive hemofiltration.

Results: Median follow-up of 169 screened participants was 8.2 years (interquartile range=5.2-12.1 years). Nine children had a lower eGFR, but all rates were >60 ml/min per 1.73 m(2). Proteinuria was observed in 20 children (median=0.26 mg protein/mg creatinine; interquartile range=0.23-0.32 mg protein/mg creatinine), and 32 children had hypertension. Only history of AKI was associated with CKD (P=0.004). Children with RIFLE scores injury and failure had 4.3 times higher odds of CKD signs or hypertension than those without AKI (95% confidence interval, 1.6 to 12.1; P=0.004).

Conclusions: Altogether, 54 participants (32%) had at least one sign of CKD and/or hypertension. However, most values were marginally abnormal, with no immediate consequences for clinical care. Nevertheless, a prevalence of 32% clearly indicates that survivors of neonatal extracorporeal membrane oxygenation, especially those with AKI, are at risk of a more rapid decline of kidney function with increasing age. Therefore, screening for CKD development in adulthood is recommended.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2215/CJN.02890314DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4255400PMC
December 2014

Rotterdam: main port for organ transplantation research in the Netherlands.

Transpl Immunol 2014 Oct 18;31(4):200-6. Epub 2014 Sep 18.

Department of Internal Medicine, Erasmus MC-University Medical Centre, Rotterdam, The Netherlands.

This overview describes the full spectrum of current pre-clinical and clinical kidney-, liver-, heart- and lung transplantation research performed in Erasmus MC - University Medical Centre in Rotterdam, The Netherlands. An update is provided on the development of a large living donor kidney transplantation program and on optimization of kidney allocation, including the implementation of a domino kidney-donation program. Our current research efforts to optimize immunosuppressive regimens and find novel targets for immunosuppressive therapy, our recent studies on prevention of ischemia-reperfusion-induced graft injury, our newest findings on stimulation of tissue regeneration, our novel approaches to prevent rejection and viral infection, and our latest insights in the regulation of allograft rejection, are summarized.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.trim.2014.09.005DOI Listing
October 2014

[Chronic renal insufficiency following childhood cancer].

Ned Tijdschr Geneeskd 2014 ;158:A6692

Erasmus Medisch Centrum - Sophia Kinderziekenhuis, Rotterdam.

Modern intensive treatment modalities have led to an increasing number of survivors of childhood cancer, who are at risk for developing long-term sequelae. Since decline of renal function can develop subclinically, adequate surveillance is required for survivors previously treated with nephrotoxic treatment modalities. We describe a 34-year-old man, who had been treated for nephroblastoma (stage I) at the age of 5 years and who regularly visited the adult late-effects clinic for survivors of childhood cancer. Twenty years after his treatment for nephroblastoma glomerular function started to decline and progressive chronic kidney disease (CKD) stage 3 developed. It is important to recognise that survivors of childhood cancer can be at risk of developing long-term effects, including impaired renal function. Apart from regular surveillance by expert medical specialists dedicated to childhood cancer survivor care, more intensive communication with primary health care physicians is necessary to improve awareness of these issues in the growing cohort of childhood cancer survivors.
View Article and Find Full Text PDF

Download full-text PDF

Source
April 2015

Reference ranges for serum β-trace protein in neonates and children younger than 1 year of age.

Clin Chem Lab Med 2014 Dec;52(12):1815-21

Background: β-Trace protein (BTP) has been proposed as an alternative endogenous marker of glomerular filtration rate. Data on BTP reference ranges in young children are scarce. We therefore aim to establish reference ranges and examine the developmental course of serum BTP in basically healthy children younger than 1 year of age.

Methods: Single blood samples were taken from healthy children (born at gestational age ≥37 weeks) <12 months of age. Serum BTP was measured using the N latex B-trace protein assay (Siemens Diagnostics, Deerfield, IL, USA) on an Immage® 800 Rate Nephelometer (Beckman Coulter Inc. Brea, CA, USA). Serum creatinine and cystatin C were additionally determined and compared to reference values to confirm a normal renal function.

Results: From June 2010 to January 2014, 95 blood samples were collected from 95 children {67.4% male; median age 120 days [inter quartile range 57-166]}. BTP was normally distributed (mean concentration 0.84±standard deviation 0.35 mg/L). Considering all children, the 50th centile BTP reference concentration was 0.82 mg/L (5th-95th centiles; 0.27-1.38). BTP concentrations were the highest in neonates and steadily declined with increasing age (Spearman's rank correlation was -0.415, p=0.002). No gender differences were found.

Conclusions: Our data provide a BTP reference range for the first year of life. Seeing the biological pattern of BTP, with only a limited postnatal decline, this marker might offer a promising alternative to serum creatinine-based methods for estimating glomerular filtration rate in newborns.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1515/cclm-2014-0371DOI Listing
December 2014

Loop diuretics are an independent risk factor for acute kidney injury in children on extracorporeal membrane oxygenation with pre-emptive continuous hemofiltration.

Intensive Care Med 2014 Apr 11;40(4):627-8. Epub 2014 Feb 11.

Intensive Care and Department of Paediatric Surgery, Erasmus Medical Centre-Sophia Children's Hospital, Dr. Molewaterplein 60, 3015 GJ, Rotterdam, The Netherlands,

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00134-014-3221-zDOI Listing
April 2014

Children of non-Western origin with end-stage renal disease in the Netherlands, Belgium and a part of Germany have impaired health-related quality of life compared with Western children.

Nephrol Dial Transplant 2014 Feb 13;29(2):448-57. Epub 2013 Nov 13.

Department of Paediatric Nephrology, Emma Children's Hospital Academic Medical Centre, Amsterdam, The Netherlands.

Background: Many children with end-stage renal disease (ESRD) living in Western Europe are of non-Western European origin. They have unfavourable somatic outcomes compared with ESRD children of Western origin. In this study, we compared the Health-related Quality of Life (HRQoL) of both groups.

Methods: All children (5-18 years) with ESRD included in the RICH-Q project (Renal Insufficiency therapy in Children-Quality assessment and improvement) or their parents were asked to complete the generic version of the Paediatric Quality-of-Life Inventory 4.0 (PedsQL). RICH-Q comprises the Netherlands, Belgium and a part of Germany. Children were considered to be of non-Western origin if they or at least one parent was born outside Western-European countries. Impaired HRQoL for children with ESRD of Western or non-Western origin was defined as a PedsQL score less than fifth percentile for healthy Dutch children of Western or non-Western origin, respectively.

Results: Of the 259 eligible children, 230 agreed to participate. One hundred and seventy-four children responded (response rate 67%) and 55 (32%) were of non-Western origin. Overall, 31 (56%) of the ESRD children of non-Western origin, and 58 (49%) of Western origin had an impaired total HRQoL score. Total HRQoL scores of children with ESRD of Western origin and non-Western origin were comparable, but scores on emotional functioning and school functioning were lower in non-Western origin (P=0.004 and 0.01, respectively). The adjusted odds ratios (95% confidence interval) for ESRD children of non-Western origin to have impaired emotional functioning and school functioning, compared with Western origin, were 3.3(1.5-7.1) and 2.2(1.1-4.2), respectively.

Conclusion: Children with ESRD of non-Western origin in three Western countries were found to be at risk for impaired HRQoL on emotional and school functioning. These children warrant special attention.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/ndt/gft436DOI Listing
February 2014