Linda Koster-Kamphuis

Important differences in management policies for children with end-stage renal disease in the Netherlands and Belgium--report from the RICH-Q study.

BACKGROUND The low prevalence of childhood end-stage renal disease and the small centre sizes have been a barrier for clinical studies and the development of evidence-based guidelines for chronic renal replacement therapy (cRRT) in children. Few data exist on the quality of care for these patients and the applicability of existing guidelines. The aim of this study is to quantify variation in treatment policies and actually delivered care in nine centres that deliver cRRT for children. METHODS We surveyed treatment policies in all nine centres in the Netherlands and Belgium and compared them with the actually provided therapies and with recommendations from available guidelines. Data on treatment policies were gathered by questionnaires; actually provided care and outcomes were registered prospectively from 2007 to 2010. RESULTS Data on policies and actual patient care were obtained from all nine centres. We found relevant differences between centres in treatment policies on various topics, e.g. estimated glomerular filtration rate threshold as an indication for initiation of cRRT, preferred initial mode of cRRT, peritoneal dialysis catheter care, haemodialysis frequency and vascular access. Discrepancies were seen between stated treatment policies and actual performed therapies. For the majority of policies, no evidence-based guidelines are available. CONCLUSIONS Health care disparities exist due to large and unwanted variation in treatment policies between hospitals providing cRRT for children. Delivered care does not live up to stated policies, for which clear and internationally accepted guidelines are lacking.

Fewer pre-emptive renal transplantations and more rejections in immigrant children compared to native Dutch and Belgian children

BACKGROUND In the Netherlands and Belgium, an increasing number of children who have end-stage renal disease (ESRD) are of non-Western origin. We analysed renal transplantation practices and outcome for immigrant ESRD children as compared to native children in both countries. METHODS All Dutch and Belgian children aged <19 years who received their first renal transplantation between 1 September 2007 and 1 January 2011 were included. Therapy characteristics and outcomes were registered prospectively on a 3-monthly basis. Immigrants were defined as children of whom one or both parents had been born outside Western European countries. Multivariable Cox regression analysis was used to quantify the hazard ratio for acute rejection. RESULTS One hundred and nineteen first renal transplant recipients were included, of which 41 (34%) were immigrants. Median [range] follow-up time of transplantation was 18 [2-28] months. Compared to native children, immigrants had pre-emptive transplantations (15 versus 32%, P = 0.040) and transplantations with a kidney from a living donor less often (24 versus 59%, P < 0.001). Survival analysis in 96 children with at least 3 months of follow-up showed an increased risk for acute rejection in immigrants adjusted for donor source, duration of dialysis and number of HLA mismatches on the DR locus [hazard ratio (95% confidence interval) 2.5 (1.1-5.9)]. CONCLUSIONS Immigrant children receive fewer pre-emptive and living donor transplantations compared to native children. After transplantation, immigrant children are at higher risk for acute rejection irrespective of the mode of transplantation.

Tubular Injury Biomarkers to Detect Gentamicin-Induced Acute Kidney Injury in the Neonatal Intensive Care Unit.

OBJECTIVE We evaluated whether urinary excretion of tubular injury markers could be useful for early detection of gentamicin (GM)-induced renal damage in neonates. STUDY DESIGN We conducted a prospective, observational trial in neonates admitted to the neonatal intensive care unit (26 GM treated, 20 control). Kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), N-acetyl-β-D-glucosaminidase (NAG), and π- and α-glutathione-S-transferase (GSTP1-1 and GSTA1-1) were measured every 2 hours during admission and compared with serum creatinine (sCr) and urine output. RESULTS Nine neonates developed AKI during the course of the study. The peak in excretion of urinary biomarkers preceded the peak in sCr (p < 0.0001). GM administration resulted in a more pronounced increase of sCr compared with control (13 [12-28] vs. 10 µmol/L [8.5-17]; p < 0.05). The urinary excretion of NAG (178 [104-698] vs. 32 ng/mol Cr [9-82]; p < 0.001) and NGAL (569 [168-1,681] vs. 222 ng/mol Cr [90-497]; p < 0.05) was higher in the GM group compared with control and preceded the peak of sCr and urine output decrease. CONCLUSION GM administration to neonates is associated with renal damage reflected by a more pronounced increase in sCr preceded by urinary excretion of biomarkers. Urinary biomarkers may be useful for earlier identification of renal injury in neonates.

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

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.

Lessons learned from efforts to improve the quality of care in children with end-stage renal disease in the Netherlands and Belgium

Quality improvement research strives to bridge the gap between ideal and actual care.1 Many paediatric diseases are rare, and thus there is insufficient evidence to define ‘ideal care’. Low prevalences and generally small patient numbers in centres in which children with rare diseases are treated create considerable barriers for clinical studies and for the development of evidence based guidelines. As a consequence, most existing guidelines are derived from studies in adults and lack any paediatric evidence.2 Here we focus on paediatric end-stage renal disease (ESRD) as an example of a clinical field in which these challenges are encountered.

Breakthrough VZV infection after immunization, presenting as herpes zoster

An immunocompromized, VZV-vaccinated child had a breakthrough infection with VZV, acquired at a day-care centre during a chickenpox outbreak. Interestingly, the infection manifested as herpes zoster of 1 dermatome. Typing showed wild-type virus, which suggests that exogenous reinfection with a new strain may present as herpes zoster.

Genetic and clinical characterization of Pakistani families with Bardet-Biedl syndrome extends the genetic and phenotypic spectrum

Bardet-Biedl syndrome (BBS) is an autosomal recessive disorder that is both genetically and clinically heterogeneous. To date 19 genes have been associated with BBS, which encode proteins active at the primary cilium, an antenna-like organelle that acts as the cell’s signaling hub. In the current study, a combination of mutation screening, targeted sequencing of ciliopathy genes associated with BBS, and whole-exome sequencing was used for the genetic characterization of five families including four with classic BBS symptoms and one BBS-like syndrome. This resulted in the identification of novel mutations in BBS genes ARL6 and BBS5, and recurrent mutations in BBS9 and CEP164. In the case of CEP164, this is the first report of two siblings with a BBS-like syndrome with mutations in this gene. Mutations in this gene were previously associated with nephronophthisis 15, thus the current results expand the CEP164-associated phenotypic spectrum. The clinical and genetic spectrum of BBS and BBS-like phenotypes is not fully defined in Pakistan. Therefore, genetic studies are needed to gain insights into genotype-phenotype correlations, which will in turn improve the clinician’s ability to make an early and accurate diagnosis, and facilitate genetic counseling, leading to directly benefiting families with affected individuals.

Poiseuille’s law in polyuria

Dear Sir,In their recent paper, Caletti et al. describe urinary tract find-ings in children with nephrogenic diabetes insipidus (NDI)and show that seven out of ten patients have renal pelvicdilatation that improved or even normalized during follow-up[1].Treatmentwithalowosmolardietincombinationwithdiuretics and indomethacin reduced the urine output from10.5 to 4.4 ml/kg/h.This transition in urine production is similar to the physi-ologicalchangesaroundbirth.Inthe lastweeksofpregnancy,a fetus produces on average 10–15 ml/kg/h of urine. Indeed,fetal renal pelvic dilatation is regularly found, making it themostfrequentlyfoundabnormalityduringprenatalultrasoundscreening[2].Inapproximately50–70%ofcasesofantenatalhydronephrosis, postnatal follow-up shows no significant uri-nary tract abnormalities and are therefore labeled as transientorphysiologic.Postnatalrenalultrasoundwillevenbewithoutany abnormalities in about 21–28 % of cases, generally asso-ciatedwithonlymildantenatalhydronephrosis[2].Inanalogywith NDI during treatment, urine production after birth isgreatly reduced to around 4 ml/kg/h, which will further de-crease with increasing age.A likely explanation for the reduction in renal pelvic dila-tation with a reduction in urine volume, the common denom-inator, can be found in Poiseuille’s law stating that a higherflow through a tube will increase the pressure. When appliedto the urinary tract, polyuria will lead to a higher pressure intherenalpelvis,whichgenerallyresultsindilatation.Withtheuse of the Whitaker test, a higher flow rate was indeed foundto lead to an increase in renal pelvic pressure, and somepatientsonlyshowedsignsofobstructionathigherurineflowrates [3]. Dilatation of the upper urinary tract can be exacer-batedbysuboptimalemptyingofthebladder,aswasrightfullystated by Caletti et al. [1].Whether the genetic mutation leading to NDI has an addi-tional influence on the development of the urinary tract, andtherefore directly results in hydronephrosis, remains to bedetermined.Theabsenceofdevelopmentaldefectsofperistal-sis in the renal pelvis of animal models of NDI, such as micewith an aquaporin-2 mutation [4], seems to suggest that thisdoes not play a role.Normal fluid physiology provides a perfect explana-tion for the urinary tract findings in NDI, and thereforereducing urine volume and optimizing voiding habitsremains the cornerstone of treatment for hydronephrosis inNDI patients.References

Unexplained hypothermia and bradycardia in two pediatric patients with Wegener’s granulomatosis

Sirs,We report remarkable symptoms of Wegener’s granuloma-tosis (WG), which might occur more often than reported sofar. Two patients (13 and 16 years old) with acute renalfailure due to WG developed simultaneous hypothermia(<36.5˚C) and bradycardia (<60 bpm) duringthefirst weeksof treatment with intravenous pulse methylprednisolone(IPM), cyclophosphamide (CYC), hemodialysis (HD), andtherapeutic plasma exchange (TPE). In both patients, rapidlyprogressivepauci-immuneglomerulonephritiswasconfirmedby renal biopsy, and antineutrophil cytoplasmic antibody(ANCA)-serology was positive. They received 3-day IPMtherapy(1g/1.73m