The effects of hospital and dialysis unit characteristics on hospitalizations for access-related complications among children on maintenance dialysis: a European, multicenter, observational, cross-sectional study.

BACKGROUND: Previous studies investigating hospitalizations in dialysis patients have focused primarily on patient-centered factors. We analyzed the impact of hospital and dialysis unit characteristics on pediatric dialysis patients' hospitalizations for access-related complications (ARCs). METHODS: This cross-sectional study involved 102 hemodialysis (HD) and 163 peritoneal dialysis (PD) patients. Data between July 2017 and July 2018 were analyzed. RESULTS: Children's hospitals (CHs) had more pediatric nephrologists and longer PD experience (years) than general hospitals (GHs) (p = 0.026 and p = 0.023, respectively). A total of 53% of automated PD (APD) and 6% of continuous ambulatory PD (CAPD) patients were in CHs (p < 0.001). Ninety-three percent of APD and 69% of CAPD patients were treated in pediatric-specific PD units (p = 0.001). CHs had a higher prevalence in providing hemodiafiltration (HDF) than GHs (83% vs. 30%). Ninety-seven percent of HDF vs. 66% for conventional HD (cHD) patients, and 94% of patients with arteriovenous fistula (AVF) vs. 70% of those with central venous catheters (CVC), were dialyzed in pediatric-specific HD units (p = 0.001 and p = 0.016, respectively). Eighty patients (51 PD and 29 HD) had 135 (84 PD, 51 HD) hospitalizations. CAPD was an independent risk factor for hospitalizations for infectious ARCs (I-ARCs) (p = 0.009), and a health center's PD experience negatively correlated with CAPD patient hospitalizations for I-ARCs (p = 0.041). cHD and dialyzing in combined HD units significantly increased hospitalization risk for non-infectious (NI-)ARCs (p = 0.044 and p = 0.017, respectively). CONCLUSIONS: CHs and pediatric-specific dialysis units have higher prevalence of APD and HDF use. Hospitalizations for I-ARCs in CAPD are lower in centers with longer PD experience, and pediatric HD units are associated with fewer hospitalizations due to NI-ARCs. A higher resolution version of the Graphical abstract is available as Supplementary information.

Silent and dangerous: catheter-associated right atrial thrombus (CRAT) in children on chronic haemodialysis.

BACKGROUND: Catheter-associated right atrial thrombus (CRAT) is a recognised complication of central venous catheter (CVC) use for haemodialysis (HD) patients. METHODS: This was a single-centre retrospective longitudinal observational study of consecutive children aged 6 months-18 years over a 7-year period receiving in-centre chronic HD. Echocardiograms as per routine cardiac surveillance were performed 6 months or earlier given clinical concerns. RESULTS: Sixty-five children, 36 boys (55.4%), median (IQR) age 11.8 (5.3, 14.7) years, received HD for kidney failure with replacement therapy (KFRT). Initial modality was HD in 45 (69.2%), with CVC as initial access in 42 (93.3%) and AVF in 3 (6.7%); in the remaining 20 (30.8%) patients PD was the initial modality before switching to HD. Seven of 65 (10.8%) developed CRAT at median 2 (0.8, 8.4) months from CVC insertion, with one CRAT detected 3 days following insertion. One child had 2 episodes of CRAT and one additionally thrombosed their AVF. No patient had an underlying primary kidney disease associated with a pro-thrombotic state. Those with CRAT were younger, had more frequent CVC change and received dialysis for longer duration compared to those with no CRAT. Six episodes of CRAT (75%) received anticoagulation therapy. Infective complications were observed in 25% and catheter malfunction in 50%. Five CRAT episodes (62.5%) resulted in CVC loss. One patient died after a haemorrhagic complication of anticoagulation and sepsis, and another developed life-threatening superior vena cava obstruction syndrome. Overall mortality 14% (1/7). CONCLUSIONS: This is the first report of CRAT in a paediatric HD population. There was ~ 11% incidence of CRAT in patients receiving chronic HD detected by surveillance echocardiography. Although frequently asymptomatic, CRAT is associated with serious sequelae. Anticoagulation and surveillance with expert echocardiography remain mainstays of management. Graphical abstract.

Vitamin B6 blood concentrations in paediatric dialysis patients.

OBJECTIVES: We investigated vitamin B6 blood concentrations in children on long-term dialysis at our centre. METHODS: Retrospective cross-sectional review of vitamin B6 blood concentrations in children on maintenance dialysis [peritoneal dialysis (PD), intermittent haemodialysis (IHD)]. RESULTS: We reviewed 28 children (16 boys), 15 IHD and 13 PD with median (interquartile range, IQR) age of 9.4 (2.4, 14.3) years. The median (IQR) vitamin B6 concentration was 223.4 (74.2, 392.8) nmol/L measured a median (IQR) of 9 (4, 16.5) months following commencement of dialysis. None of the children had vitamin B6 deficiency. Vitamin B6 concentrations were raised in 17 (61%), eight of these received a supplement. Nineteen (68%) received vitamin B6 and/or a supplement containing vitamin B6 whilst 11 (39%) received an enteral feed and a supplement. In those with normal vitamin B6 concentrations who were not receiving an enteral feed or an oral nutritional supplement (n = 6), all achieved normal concentrations without need for vitamin B6 supplementation. There were no differences between those on PD versus IHD (269.2 nmol/L vs. 130 nmol/L, P = 0.65). CONCLUSIONS: We report no children with vitamin B6 deficiency although > 50% had elevated vitamin B6 concentrations. We suggest if dietary assessment of vitamin B6 intake indicates insufficient intake, measurement of blood concentrations will help confirm if supplementation is required. Routine vitamin B6 supplementation and monitoring is currently not indicated in children on chronic dialysis.

Comparative analysis of hospitalizations among patients treated with hemodialysis and peritoneal dialysis in European pediatric nephrology centers: results from a prospective EPDWG/ESPN Dialysis Working Group study.

Background and hypothesis: Hospital admissions in pediatric dialysis patients need to be better studied, and most existing studies are retrospective and based on registry data. This study aimed to analyse and compare hospital admission rates, causes, length of stay (LOS), and outcomes in children treated with peritoneal dialysis (PD) and hemodialysis (HD). Methods: Data from 236 maintenance PD and 138 HD patients across 16 European dialysis centers were collected between 1 July 2017 and 30 June 2018. A total of 178 hospitalized patients (103 PD, 75 HD) were included for further analyses. Results: There were 465 hospitalization events (268 PD, 197 HD) with a rate of 0.39 admissions per 100 patient-days at risk (PDAR) and 2.4 hospital days per 100 PDAR. The admission rates were not significantly different between HD and PD patients. The most common causes of hospitalization were access-related infections (ARI) (17%), non-infectious complications of access (NIAC) (14%), and infections unrelated to access (12%). ARI was the leading cause in PD patients (24%), while NIAC was more common in HD patients (19%). PD patients had more ARIs, diagnostic procedures, and treatment adjustments (P < .05), while HD patients had more NIACs, infections unrelated to access, access placement procedures, and interventional/surgical procedures (P < .001). LOS was longer with acute admissions than non-acute admissions (P < .001). Overall LOS and LOS in the intensive care unit were similar between HD and PD patients. High serum uric acid and low albumin levels were significant predictors of longer LOS (P = .022 and P = .045, respectively). Young age, more significant height deficit, and older age at the start of dialysis were predictors of longer cumulative hospital days (P = .002, P = .001, and P = .031, respectively). Conclusion: Access-related complications are the main drivers of hospitalization in pediatric dialysis patients, and growth and nutrition parameters are significant predictors of more extended hospital stays.

Renal malformations associated with mutations of developmental genes: messages from the clinic.

Renal tract malformations (RTMs) account for about 40% of children with end-stage renal failure. RTMs can be caused by mutations of genes normally active in the developing kidney and lower renal tract. Moreover, some RTMs occur in the context of multi-organ malformation syndromes. For these reasons, and because genetic testing is becoming more widely available, pediatric nephrologists should work closely with clinical geneticists to make genetic diagnoses in children with RTMs, followed by appropriate family counseling. Here we highlight families with renal cysts and diabetes, renal coloboma and Fraser syndromes, and a child with microdeletion of chromosome 19q who had a rare combination of malformations. Such diagnoses provide families with often long-sought answers to the question "why was our child born with kidney disease". Precise genetic diagnoses will also help to define cohorts of children with RTMs for long-term clinical outcome studies.

UK Renal Registry 12th Annual Report (December 2009): chapter 14: demography of the UK paediatric renal replacement therapy population in 2008.

AIMS: To describe the demographics of the paediatric RRT population in the UK and analyse changes in demographics with time. METHODS: Extraction and analysis of data from the UK Paediatric Renal Registry and the UK Renal Registry (UKRR). RESULTS: The UK paediatric established renal failure (ERF) population in December 2008 was 905 patients. The prevalence under the age of 16 years was 56 per million age related population (pmarp) and the incidence 7.4 pmarp. The incidence and prevalence for South Asian patients was much higher than that of the White and Black populations. Renal dysplasia was the most common cause of ERF accounting for 33% of prevalent cases. Diseases with autosomal recessive inheritance were a common cause of ERF in all ethnic groups, 23.5% of prevalent and 18% of incident cases. Whilst the incidence and prevalence of diseases with autosomal recessive inheritance in the South Asian population was 3 times that of the white population, this was not the sole reason for the increased proportion of South Asian patients with ERF, as diseases with no defined inheritance were twice as common in this ethnic group than in White patients. Prevalent mortality stood at 9.4%. Most deaths were in patients presenting with ERF early in life and mortality varied markedly according to the aetiology of ERF. The proportion with new grafts from living donors has steadily risen to 54%. Children from ethnic minority groups were less likely to have an allograft and living donation was less frequent in this population. For those on dialysis, 56% were receiving peritoneal dialysis. This was the main treatment modality for patients under 4 years of age. CONCLUSIONS: The paediatric ERF population continued to expand slowly. Incidence and prevalence rates were stable and similar to other developed nations. The high incidence in patients from ethnic minority groups will lead to a greater proportion of the population being from these groups in time. To maintain the high proportion of engrafted patients it will be necessary to encourage living donation in the ethnic minority population. Case note analysis of the factors involved in mortality would be valuable.

HNF1B mutations associate with hypomagnesemia and renal magnesium wasting.

Mutations in hepatocyte nuclear factor 1B (HNF1B), which is a transcription factor expressed in tissues including renal epithelia, associate with abnormal renal development. While studying renal phenotypes of children with HNF1B mutations, we identified a teenager who presented with tetany and hypomagnesemia. We retrospectively reviewed radiographic and laboratory data for all patients from a single center who had been screened for an HNF1B mutation. We found heterozygous mutations in 21 (23%) of 91 cases of renal malformation. All mutation carriers had abnormal fetal renal ultrasonography. Plasma magnesium levels were available for 66 patients with chronic kidney disease (stages 1 to 3). Striking, 44% (eight of 18) of mutation carriers had hypomagnesemia (<1.58 mg/dl) compared with 2% (one of 48) of those without mutations (P < 0.0001). The median plasma magnesium was significantly lower among mutation carriers than those without mutations (1.68 versus 2.02 mg/dl; P < 0.0001). Because hypermagnesuria and hypocalciuria accompanied the hypomagnesemia, we analyzed genes associated with hypermagnesuria and detected highly conserved HNF1 recognition sites in FXYD2, a gene that can cause autosomal dominant hypomagnesemia and hypocalciuria when mutated. Using a luciferase reporter assay, we demonstrated HNF1B-mediated transactivation of FXYD2. These results extend the phenotype of HNF1B mutations to include hypomagnesemia. HNF1B regulates transcription of FXYD2, which participates in the tubular handling of Mg(2+), thus describing a role for HNF1B not only in nephrogenesis but also in the maintenance of tubular function.

UK Renal Registry 11th Annual Report (December 2008): Chapter 13 Demography of the UK paediatric renal replacement therapy population.

AIMS: To describe the demographics of the paediatric RRT population in the UK and analyse changes in demographics with time. METHODS: Extraction and analysis of data from the UK paediatric Renal Registry. RESULTS: The UK paediatric established renal failure (ERF) population in April 2008 was 875 patients. The prevalence under the age of 16 years was 55 per million age related population (pmp) and the incidence 7.92 pmp. The incidence and prevalence for South Asian and Other ethnic groups were 3 times that of the White and Black populations. Renal dysplasia was the most common cause of ERF accounting for 33% of prevalent cases. Diseases with autosomal recessive inheritance were more common in patients from ethnic minority groups. The spectrum of diseases seen has changed over a generation. Overall 5 year survival for children with ERF was 91.8%. Five year survival of infants starting dialysis was just 62%. Transplanted patients accounted for 74% of the current population. The proportion with grafts from living donors has steadily risen to 34%. Children from ethnic minority groups were less likely to have an allograft and living donation was less frequent in this population. For those on dialysis, 57% were receiving peritoneal dialysis. This was the main treatment modality for patients under 4 years of age. CONCLUSIONS: The paediatric ERF population continued to expand slowly. Incidence and prevalence rates were stable and similar to other developed nations. The high incidence in patients from ethnic minority groups will lead to a greater proportion of the population being from these groups in time. To maintain the high proportion of engrafted patients it will be necessary to encourage living donation in the ethnic minority population. The spectrum of diseases seen has already changed over a generation with the treatment of young children with diseases such as congenital nephrosis. The incidence of cystinosis causing ERF was reduced, probably reflecting better early treatment.

Medical pediatric inpatients and outpatients are at risk of influenza and pneumococcal disease.

Influenza and pneumococcal vaccines are recommended for certain risk groups. All children admitted to the Children's wards or attending Children's Outpatients were studied for these risk factors. Risk factors for influenza were present in 78 (41%) of 193 admissions and 93 (27%) of 348 outpatients. Risk factors for pneumococcal infection were present in 22 (11.5%) admissions and 42 (12%) outpatients. Only 29 of these children had been given influenza (n = 19) or pneumococcal (n = 10) vaccines. Pediatricians could improve the coverage of influenza and pneumococcal vaccines by identifying children with risk factors in hospital discharge summaries and outpatient clinic letters.

HNF1B Mutations Are Associated With a Gitelman-like Tubulopathy That Develops During Childhood.

BACKGROUND: Mutations in the transcription factor hepatocyte nuclear factor 1B (HNF1B) are the most common inherited cause of renal malformations, yet also associated with renal tubular dysfunction, most prominently magnesium wasting with hypomagnesemia. The presence of hypomagnesemia has been proposed to help select appropriate patients for genetic testing. Yet, in a large cohort, hypomagnesemia was discriminatory only in adult, but not in pediatric patients. We therefore investigated whether hypomagnesemia and other biochemical changes develop with age. METHODS: We performed a retrospective analysis of clinical, biochemical, and genetic results of pediatric patients with renal malformations tested for HNF1B mutations, separated into 4 age groups. Values were excluded if concurrent estimated glomerular filtration rate (eGFR) was <30 ml/min per 1.73 m2, or after transplantation. RESULTS: A total of 199 patients underwent HNF1B genetic testing and mutations were identified in 52 (mut+). The eGFRs were comparable between mut+ and mut- in any age group. Although median plasma magnesium concentrations differed significantly between mut+ and mut- patients in all age groups, overt hypomagnesemia was not present until the second half of childhood in the mut+ group. There was also a significant difference in median potassium concentrations in late childhood with lower values in the mut+ cohort. CONCLUSIONS: The abnormal tubular electrolyte handling associated with HNF1B mutations develops with age and is not restricted to magnesium, but consistent with a more generalized dysfunction of the distal convoluted tubule, reminiscent of Gitelman syndrome. The absence of these abnormalities in early childhood should not preclude HNF1B mutations from diagnostic considerations.

Diaper dermatitis-frequency and contributory factors in hospital attending children.

The incidence and prevalence of diaper dermatitis varies widely between published studies. It is a condition which causes considerable parental anxiety. To better understand the frequency of diaper dermatitis, treatment practices, and the current importance of previously identified etiologic factors, a questionnaire survey of parents who had children wearing diapers (n = 532) attending a large United Kingdom district general hospital was undertaken. At the time of survey, only 16% of the study population had diaper dermatitis. Forty-eight percent of the study population had never had an episode of diaper dermatitis. In a multivariate analysis, current diaper dermatitis was independently associated with four factors: presence of oral thrush, number of previous episodes, frequency of diaper changes, and diarrhea. Recurrent episodes of diaper dermatitis were associated with increasing age, lack of barrier cream use, current diaper rash, and frequency of diaper changes. In the majority of children with diaper dermatitis at the time of survey, treatment had been instituted in the community. Diaper dermatitis usually presents and is treated successfully outside the hospital setting and is not a common clinical problem in secondary care.

Uncovering genomic causes of co-morbidity in epilepsy: gene-driven phenotypic characterization of rare microdeletions.

BACKGROUND: Patients with epilepsy often suffer from other important conditions. The existence of such co-morbidities is frequently not recognized and their relationship with epilepsy usually remains unexplained. METHODOLOGY/PRINCIPAL FINDINGS: We describe three patients with common, sporadic, non-syndromic epilepsies in whom large genomic microdeletions were found during a study of genetic susceptibility to epilepsy. We performed detailed gene-driven clinical investigations in each patient. Disruption of the function of genes in the deleted regions can explain co-morbidities in these patients. CONCLUSIONS/SIGNIFICANCE: Co-morbidities in patients with epilepsy can be part of a genomic abnormality even in the absence of (known) congenital malformations or intellectual disabilities. Gene-driven phenotype examination can also reveal clinically significant unsuspected condition.

Successful treatment with azithromycin and rifampicin of penicillin and cephalosporin insensitive pneumococcal osteomyelitis in a child with HIV infection: a case report.

Pneumococcal infection is common in children with HIV infection, but osteomyelits is unusual. The best treatment for bone and joint infection due to antibiotic resistant pneumococci is not known, especially in immunocompromised children.A 6 month old girl, infected with HIV by mother to child transmission, had recently started combination antiretroviral therapy (cART). She presented with osteomyelitis of the left radius confirmed on bone scan. Blood cultures grew Streptococcus pneumoniae 9S resistant to penicillin, with reduced susceptibility to ceftriaxone.Osteomyelitis was treated with parenteral teicoplanin, oral rifampicin and azithromycin. After two weeks of treatment she developed rash and fever. These were thought to be a drug eruption and resolved when teicoplanin was stopped. She completed a 3 month course of rifampicin and azithromycin and continued on cART. She has normal function of her left wrist 18 months after treatment. She remains on her original cART regimen with an undetectable viral load and normal CD4 count (34%; 1398 x 106/l).The combination of rifampicin and azithromycin was well tolerated, simple to administer and effective. This combination deserves further study in bone and joint infection caused by antibiotic resistant Gram positive bacteria.