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Background: Oral health conditions are common in children and young people (CYP) with kidney disorders. There is currently limited literature on how confident paediatric nephrology teams feel to identify and manage oral health concerns for their patients. Method: An exploratory mixed-method survey was distributed across all 13 UK specialist paediatric nephrology centres with responses received from consultants, registrars, specialist nurses and special interest (SPIN) paediatricians. Results: Responses received from 109 multidisciplinary team members of 13/13 (100%) UK tertiary units. Ninety-two percent (n = 100) of respondents reported they had never received any training in oral health and 87% (n = 95) felt that further training would be beneficial to optimise care for patients and improve communication between medical and dental teams. Most respondents reported that they did not regularly examine, or enquire about, their patients' oral health. Only 16% (n = 17) reported that all their paediatric kidney transplant recipients underwent routine dental assessment prior to transplant listing. Severe adverse oral health outcomes were rarely reported and only 11% (n = 12) of respondents recalled having a patient who had a kidney transplant delayed or refused due to concerns about oral infection. Seventy-eight percent (n = 85) felt that joint working with a dental team would benefit patients at their unit; however, 17% (n = 18) felt that current infrastructure does not currently support effective joint working. Conclusions: Across the UK, paediatric kidney health professionals report lack of confidence and training in oral health. Upskilling subspecialty teams and creating dental referral pathways are recommended to maximise oral health outcomes for CYP with kidney diseases. [ABSTRACT FROM AUTHOR]

Background: Kidney transplantation is the treatment of choice in chronic kidney disease (CKD) stage 5. It is often delayed in younger children until a target weight is achieved due to technical feasibility and historic concerns about poorer outcomes. Methods: Data on all first paediatric (aged < 18 years) kidney only transplants performed in the United Kingdom between 1 January 2006 and 31 December 2016 were extracted from the UK Transplant Registry (n = 1,340). Children were categorised by weight at the time of transplant into those < 15 kg and those ≥ 15 kg. Donor, recipient and transplant characteristics were compared between groups using chi-squared or Fisher's exact test for categorical variables and Kruskal–Wallis test for continuous variables. Thirty day, one-year, five-year and ten-year patient and kidney allograft survival were compared using the Kaplan–Meier method. Results: There was no difference in patient survival following kidney transplantation when comparing children < 15 kg with those ≥ 15 kg. Ten-year kidney allograft survival was significantly better for children < 15 kg than children ≥ 15 kg (85.4% vs. 73.5% respectively, p = 0.002). For children < 15 kg, a greater proportion of kidney transplants were from living donors compared with children ≥ 15 kg (68.3% vs. 49.6% respectively, p < 0.001). There was no difference in immediate graft function between the groups (p = 0.54) and delayed graft function was seen in 4.8% and 6.8% of children < 15 kg and ≥ 15 kg respectively. Conclusions: Our study reports significantly better ten-year kidney allograft survival in children < 15 kg and supports consideration of earlier transplantation for children with CKD stage 5. [ABSTRACT FROM AUTHOR]

Background: Transplantation is widely considered the gold standard method of kidney replacement therapy. Despite compelling evidence for biological sexual dimorphisms, the role of donor and recipient sex matching in transplantation is undefined. Methods: The UK historical cohort study explores the impact of donor and recipient sex on allograft survival, in children receiving their first deceased donor transplant. Nationwide registry data were collected for 1316 transplant procedures performed from January 1, 1999, to December 31, 2019. Results: Male donor–male recipient transplantation occurred most frequently (35%), followed by female donor–male recipient (23%), male donor–female recipient (22%), and female donor–female recipient (20%). The median follow-up time was 7.03 years (IQR: 2.89–12.4 years), with a total of 10,326 person-years. Male donor–male recipients were associated with the highest 10-year kidney allograft survival (72.8% [95% CI 68.3–77.8]) and male donor–female recipients with the lowest (64% [95% CI 57.7–71.1]). Multivariable Cox regression demonstrated for male donor transplantation, the risk of kidney allograft failure was 1.46 times greater for female (compared to male) recipients, after adjusting for acquired recipient age, recipient/donor age at transplantation, mismatched HLA A/B/DR, waitlist time, cold ischemia time, CMV seropositivity, donor hypertension, and donor diabetes (HR 1.46 [95% CI. 1.06–2.01], p = 0.02). There was no evidence for an independent effect of donor or recipient sex in other combinations. Conclusion: This study highlights the complex relationship between donor and recipient sex and pediatric kidney allograft survival, which require further mechanistic evaluation. [ABSTRACT FROM AUTHOR]

Background: Modern immunosuppressive regimens in paediatric kidney transplant recipients have contributed to improved long-term allograft survival, but at the expense of an increased incidence of viral infections. Here, we describe, for the first time, the incidence, risk factors and clinical outcome of CMV, EBV, BKV and JCV viraemia in a cohort of paediatric allograft recipients treated with a corticosteroid-minimisation immunosuppressive regimen (CMR). Methods: We retrospectively analysed 98 children treated with a CMR (basiliximab induction, corticosteroids until day 4, long-term tacrolimus and mycophenolate mofetil), who received a kidney transplant in our centre between 2009 and 2019. Results: Over the first 4 years post-transplant, the incidences of viraemia were as follows: CMV, 25.5%; EBV, 52.0%; JCV, 16.3%; BKV, 26.5%. Younger children at time of transplant were more likely to develop EBV and BKV viraemia. EBV viraemia was also associated with a regimen involving corticosteroids, but lacking MMF. Recipient CMV serology predicted the development of EBV, BKV and CMV viraemia. Fifty-six percent of CMV viraemia episodes in high-risk patients occurred whilst the graft recipients were still receiving anti-viral prophylaxis or within 3 months of cessation. There was no difference in graft function at latest follow-up between those with and without viraemia. Conclusions: Judicious monitoring of viraemia, coupled with timely clinical intervention, can result in similar long-term outcomes for graft recipients compared to controls. The high incidence of CMV viraemia observed within a short period of cessation of anti-viral prophylaxis supports an extension of the length of prophylactic treatment in high-risk allograft recipients. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to investigate whether dalteparin is a safe and effective anticoagulant for paediatric home haemodialysis (HD) and to assess the determinants of dosing.Methods: Data were collected for all children (< 18 years) undergoing home HD from 2011 to 2017 at one large paediatric nephrology centre in the UK. All children had anticoagulation with dalteparin sodium according to a standardised protocol. Dalteparin safety was assessed by monitoring for accumulation, adequate clearance of dalteparin and adverse events. Dalteparin efficacy was assessed through monitoring for clot formation in dialysis circuits. Potential determinants of dalteparin dosing were assessed.Results: Eighteen children were included, their median age at start was 12 years, and 50% were male. Eighty-three percent of children had four home HD sessions each week, with a median total dialysis hours of 20 h/week. Thirty-three percent of children had nocturnal home HD. Median dalteparin dose at 12-month follow-up was 40 IU/kg (range 8-142 IU/kg). Factors associated with higher dalteparin dosing requirements included a younger age of the child (p < 0.01), a lower blood flow rate (p < 0.01) and the use of a central venous line for dialysis access (p = 0.038). No children had evidence of bioaccumulation of dalteparin or inadequate clearance. No significant bleeding or adverse events were reported.Conclusions: Dalteparin is a safe and effective anticoagulant when used for paediatric home HD. In this study, there was no evidence of bioaccumulation or significant adverse events. Further research is required to directly compare dalteparin with unfractionated heparin (UFH) and evaluate anticoagulant choice for paediatric home HD. [ABSTRACT FROM AUTHOR]

Background: Primary hyperoxaluria (PH) is a rare, genetic disorder which involves the overproduction of endogenous oxalate, leading to hyperoxaluria, recurrent urolithiasis and/or progressive nephrocalcinosis and eventually resulting in kidney failure and systemic oxalosis. The aim of this trial was to investigate whether treatment involving an oxalate-metabolising bacterium ( Oxalobacter formigenes) could reduce urinary oxalate excretion in PH patients. Methods: The efficacy and safety of O. formigenes (Oxabact® OC5; OxThera AB, Stockholm, Sweden) was evaluated in a randomised, placebo-controlled, double-blind study for 8 weeks. The primary objective was reduction in urinary oxalate excretion (Uox). Secondary objectives included faecal O. formigenes count and decrease in plasma oxalate concentration (Pox). Results: Twenty-eight patients randomised 1:1 to the treatment group (OC5) or the placebo group completed the study. After 8 weeks of treatment, there was no significant difference in the change in Uox (mmol/24 h/1.73 m) between the groups (OC5: +0.042, placebo: −0.140). Post-hoc analysis showed a statistically significant increase in Uox per urinary creatinine excretion in the OC5 group (OC5: +5.41, placebo: −15.96; p = 0.030). Change in Pox from baseline was not significantly different between groups ( p = 0.438). The O. formigenes cell count was significantly increased in OC5-treated patients ( p < 0.001) versus placebo. The treatment response to O. formigenes was related to individual stage of kidney deterioration, and Pox was directly correlated to kidney function, even for early-stage patients (chronic kidney disease stage 1). No safety issues were observed. Conclusions: Treatment with OC5 did not significantly reduce Uox or Pox over 8 weeks of treatment. The treatment was well tolerated and successfully delivered to the gastrointestinal tract. [ABSTRACT FROM AUTHOR]

Background: Relapses of nephrotic syndrome are common and are treated with a course of prednisolone (2 mg/kg/day or 60 mg/m/day). This is associated with major adverse effects including diabetes, weight gain, hypertension and behavioural problems. This study is a retrospective review examining the success of treating relapses in steroid-sensitive nephrotic syndrome (SSNS) with low-dose prednisolone and the consequences on subsequent relapse rates. Furthermore, a follow-up study looked at the side-effect profile during treatment with high- versus low-dose prednisolone. Methods: Between January 2012 and July 2013, all well children with SSNS presenting with a relapse were advised to start 1 mg/kg prednisolone daily for a maximum of 7 days. In July 2015, we compared the side-effect profile of prednisolone therapy using the parent proxy PedsQL questionnaire for quality of life (QoL). Results: Fifty patients were included in the study, with a total of 87 relapses. Sixty-one of the 87 relapses (70 %) responded within a week. Treating relapses with a reduced dose of steroids did not adversely affect the relapse rate in the 6 months preceding and following the current relapse (1.01 vs 0.86, p = 0.3). Fifteen parents completed the PedsQL questionnaire. Comparison of scores in each category showed significantly higher values in each domain during treatment with low-dose prednisolone compared with high-dose treatment (35.6 vs 18.3, p < 0.0001; 31.1 vs 15.0, p < 0.001; 38.3 vs 20.1, p < 0.0001). Conclusion: A low-dose prednisolone regimen was successful in achieving remission in 70 % of relapses of children with SSNS, without adversely affecting the relapse rate. Parent-completed QoL questionnaires showed significantly higher scores on low-dose treatment, indicating better QoL. [ABSTRACT FROM AUTHOR]

Background: Critically ill children and neonates are at high risk of developing acute kidney injury (AKI). AKI is associated with short- and long-term renal impairment and increased mortality. Current methods of diagnosing AKI rely on measurements of serum creatinine, which is a late and insensitive marker. Few studies to date have assessed AKI biomarkers in a heterogeneous patient cohort. Methods: We conducted a prospective feasibility study in a paediatric intensive care setting over a 6-month period to describe the relationship between AKI (defined according to pRIFLE criteria) and new AKI biomarkers. Results: In total, 49 patients between the ages of 16 days and 15 years were recruited for measurement of plasma cystatin C (Cys-C) and neutrophil gelatinase-associated lipocalin (pNGAL) concentrations, as well as for urinary kidney injury molecule-1 (KIM-1) and urinary NGAL (uNGAL) concentrations. Almost one-half (49 %) of the patient cohort experienced an AKI episode, and Cys-C and pNGAL were the strongest candidates for the detection of AKI. Our data suggest that the widely used estimated baseline creatinine clearance value of 120 mL/min/1.73 m underestimates actual baseline function in patients admitted to paediatric intensive care units. Conclusions: This investigation demonstrates the feasibility of new AKI biomarker testing in a mixed patient cohort and provides novel biomarker profiling for further evaluation. [ABSTRACT FROM AUTHOR]

Background: Medication-related problems (MRPs) are the undesirable effects of pharmacotherapy that can potentially lead to harm. The epidemiology of MRPs in paediatric renal patients is unknown. We aimed to characterise MRPs in this population at two tertiary care hospitals in the UK. Methods: Prescription charts for children (≤18 years) were reviewed to identify MRPs, and characterised using a specific proforma with a standard operational definition. MRP predictors were evaluated by logistic regression and severity was assessed using a validated scale. Results: Two hundred and sixty-seven MRPs were identified from 266 prescription chart reviews. The incidence was 51.2 % (203 MRPs, 166 charts; 95 % CI 43.2-60.6 %) of hospitalised patients and 32 % (64 MRPs, 100 charts; 95 % CI 22.9-41.1 %) in outpatients. The number of prescribed medications was the only independent predictor during inpatient treatment (OR 1.06, 95 % CI 1.02-1.10, p = 0.002) with no significant predictors identified at outpatient clinics. The severity level of the MRPs was minor: 53.9 %, (144 out of 267); or moderate: 46.1 %, (123 out of 267). Sub-optimal drug effect was the predominant MRP (inpatient: 68 %; outpatient: 39 %). Prescribing error and patients' medicine-taking behaviour were the main contributory factors. The majority of the MRPs in the inpatient setting were resolved. Conclusion: Many factors are associated with MRPs in children; the associations are cumulative and interdependent. Investment in preventive strategies and extending the support from the acute health care setting into the community are invaluable for optimising pharmacotherapy. [ABSTRACT FROM AUTHOR]

Background: Vitamin A accumulates in renal failure, but the prevalence of hypervitaminosis A in children with predialysis chronic kidney disease (CKD) is not known. Hypervitaminosis A has been associated with hypercalcemia. In this study we compared dietary vitamin A intake with serum retinoid levels and their associations with hypercalcemia. Methods: We studied the relationship between vitamin A intake, serum retinoid levels, and serum calcium in 105 children with CKD stages 2-5 on dialysis and posttransplant. Serum retinoid measures included retinol (ROH), its active retinoic acid (RA) metabolites [all-trans RA (at-RA) and 13-cis RA] and carrier proteins [retinol-binding protein-4 (RBP4) and transthyretin (TTR)]. Dietary vitamin A intake was assessed using a food diary. Results: Twenty-five children were in CKD 2-3, 35 in CKD 4-5, 23 on dialysis and 22 posttransplant; 53 % had vitamin A intake above the Reference Nutrient Intake (RNI) value. Children receiving supplemental feeds compared with diet alone had higher vitamin A intake ( p = 0.02) and higher serum ROH ( p < 0.001). Notably, increased ROH was seen as early as CKD stage 2. For every 10 ml/min/1.73 m fall in estimated glomerular filtration rate (eGFR), there was a 13 % increase in ROH. RBP4 levels were increased in CKD 3-5 and dialysis patients. The lowest ratios of ROH:RBP4 were seen in dialysis compared with CKD 2-3 ( p = 0.03), suggesting a relative increase in circulating RBP4. Serum ROH, RBP4 and at-RA were associated with serum calcium. On multivariable analysis RBP4 levels and alfacalcidol dose were significant predictors of serum calcium (model R 32 %) in dialysis patients. Conclusions: Hypervitaminosis A is seen in early CKD, with highest levels in children on supplemental feeds compared with diet alone. Serum retinoid levels significantly predict hypercalcemia. [ABSTRACT FROM AUTHOR]

Background: Guillain-Barre syndrome (GBS) causes acute motor, sensory and autonomic dysfunction. There is a relative paucity of published data regarding the autonomic features of GBS. The aims of this study were to describe the incidence, management and outcome of bladder dysfunction and hypertension in GBS and to ascertain whether these features relate to muscle weakness severity. Case-Diagnosis/Treatment: Twenty-seven patients with a median (interquartile range) age of 5.7 (3.5-8.4) years were included, of whom 18 (67 %) were male and 14 (52 %) had autonomic dysfunction. One patient presented with and three subsequently developed urinary retention necessitating catheterisation for a median of 7.5 (7-14.5) days. Univariate analysis demonstrated that urinary retention was associated with weakness in all four limbs [retention: MRC muscle grade 2 (2-2.75); no retention: MRC grade 4 (3-4); p = 0.02], possibly reflecting more severe disease. Patients with hypertension (12 patients, 44 %) had a longer hospital stay [median 32.5 (15.5-53.5) days; rho = 0.65; p = 0.02], and those with worse muscle weakness required more anti-hypertensive medications (upper limb rho = −0.71, p = 0.03; lower limb rho = −0.72, p = 0.03]. The majority of blood pressure treatments involved calcium channel and beta blockers. Conclusion: In children with GBS, bladder dysfunction and hypertension are common. The presence of severe muscle weakness may predict those at greatest risk of these complications. [ABSTRACT FROM AUTHOR]