School attendance and sport participation amongst children with chronic kidney disease: a cross-sectional analysis from the Kids with CKD (KCAD) study.

BACKGROUND: School attendance and life participation, particularly sport, is a high priority for children with chronic kidney disease (CKD). This study is aimed at assessing the association between CKD stage, sports participation, and school absences in children with CKD. METHODS: Using data from the binational Kids with CKD study (ages 6-18 years, n = 377), we performed multivariable regression to evaluate the association between CKD stage, school absences, and sports participation. RESULTS: Overall, 62% of participants played sport with the most frequent sport activities engaged in being swimming (17%) and soccer (17%). Compared to children with CKD 1-2, the incidence rate ratios (IRR) (95% CI) for sports participation amongst children with CKD 3-5, dialysis, or transplant were 0.84 (0.64-1.09), 0.59 (0.39-0.90), and 0.75 (0.58-0.96), respectively. The median (IQR) days of school absences within a four-week period were 1 day (0-1), with children on dialysis reporting the highest number of school absences (9 days (5-15)), followed by transplant recipients (2 days (1-7)), children with CKD 3-5 (1 day (0-3)), and with CKD 1-2 (1 day (0-3)). Duration of CKD modified the association between CKD stage and school absences, with children with a transplant experiencing a higher number of missed school days with increasing duration of CKD, but not in children with CKD 1-5 or on dialysis (p-interaction < 0.01). CONCLUSIONS: Children receiving dialysis and with a kidney transplant had greater school absences and played fewer sports compared to children with CKD stages 1-2. Innovative strategies to improve school attendance and sport participation are needed to improve life participation of children with CKD.

Association between socioeconomic status and academic performance in children and adolescents with chronic kidney disease.

BACKGROUND: Lower socioeconomic status (SES) is associated with lower academic achievement; however, this relationship is understudied in children with chronic kidney disease (CKD). This study examined the relationship between SES and academic performance in children and adolescents with CKD. METHODS: A total of 377 participants aged 6-18 years with CKD stages 1-5 (n = 199), on dialysis (n = 43) or with a kidney transplant (n = 135) were recruited. Five SES measures and a composite SES index were examined for associations with parent-rated average or above average academic performance in numeracy and literacy using multivariable logistic regression. RESULTS: Participants' median age was 12.6 years (IQR 8.9-15.5). Adjusted odds ratios (aOR) (95%CI) for better performance in numeracy and literacy, respectively, were 0.71 (0.44-1.15) and 0.75 (0.45-1.23) for children whose caregivers had lower educational attainment; 0.46 (0.26-0.80) and 0.53 (0.30-0.93) for lower household income; 0.52 (0.32-0.85) and 0.44 (0.26-0.73) for caregivers who were unemployed; 0.68 (0.41-1.12) and 0.59 (0.35-1.00) for caregivers with poor self-rated financial status; and 0.93 (0.53-1.64) and 1.00 (0.56-1.79) for caregivers who did not own their own home. Compared with the highest SES index quartile, the aORs for better performance by SES quartile in descending order were 1.24 (0.60-2.54), 0.76 (0.37-1.58), and 0.39 (0.18-0.86) for numeracy and 0.88 (0.41-1.85), 0.77 (0.35-1.66), and 0.32 (0.14-0.72) for literacy. No interactions were identified between SES and CKD stage, child age, or gender. CONCLUSIONS: Across all CKD stages, children from lower SES families are less likely to perform well in literacy and numeracy than those from higher SES households. A higher resolution version of the Graphical abstract is available as Supplementary information.

Cognitive and academic outcomes in children with chronic kidney disease.

BACKGROUND: Few data exist on the cognitive and academic functioning of children with chronic kidney disease (CKD) over the trajectory of their illness. We aimed to determine the association between CKD stages and cognitive and academic performance in children over time. METHODS: We included 53 participants (aged 6-18 years) with CKD stages 1-5 (n = 37), on dialysis (n = 3), or with functioning kidney transplant (n = 22) from three units in Australia from 2015 to 2019. Participants undertook a series of psychometric tests and were invited for repeated assessments annually. We used linear regression and linear mixed models to investigate the effect of CKD stage, adjusted for socioeconomic status. RESULTS: At baseline, full-scale intelligence quotient (FSIQ) (95%CI) of children on kidney replacement therapy (KRT) was in the low average range (87: 78, 96) and average (101: 95, 108) for children with CKD 1-5. Mean (95%CI) FSIQ, word reading, numerical operations, and spelling scores for children on KRT were 14.3 (- 25.3, - 3.3), 11 (- 18.5, - 3.6), 8.5 (- 17.6, 0.76), and 10 (- 18.6, - 1.3) points lower than children with CKD Stages 1-5. Spelling and numerical operations scores declined by 0.7 (- 1.4, - 0.1) and 1.0 (- 2.0, 0.2) units per year increase in age, regardless of CKD stage. CONCLUSIONS: Children treated with KRT have low average cognitive abilities and lower academic performance for numeracy and literacy compared to both children with CKD 1-5 and to the general population. However, the rate of decline in academic performance over time is similar for children across the full spectrum of CKD. A higher resolution version of the Graphical abstract is available as Supplementary information.

Thrombotic Microangiopathy Following Onasemnogene Abeparvovec for Spinal Muscular Atrophy: A Case Series.

Spinal muscular atrophy is treated with onasemnogene abeparvovec, which replaces the missing survival motor neuron 1 gene via an adeno-associated virus vector. As of July 1, 2020, we had identified 3 infants who developed thrombotic microangiopathy following onasemnogene abeparvovec. Early recognition and treatment of drug-induced thrombotic microangiopathy may lessen mortality and morbidity.

Long term follow up of persistence of immunity following quadrivalent Human Papillomavirus (HPV) vaccine in immunocompromised children.

BACKGROUND: Human Papillomavirus (HPV) causes significant burden of HPV-related diseases, which are more prevalent in immunosuppressed compared to immunocompetent people. We conducted a multi-centre clinical trial to determine the immunogenicity and reactogenicity of HPV vaccine in immunocompromised children. Here we present the immunogenicity results 5 years post vaccination. METHODS: We followed up immunocompromised children (5-18 years) with a range of specified underlying conditions who were previously recruited from three Australian paediatric hospitals. Participants received three doses of quadrivalent HPV vaccine (Gardasil Quadrivalent HPV Types 6, 11, 16, 18) and were followed up between 2007 and 2016 (60 months post-vaccination). The immunogenicity primary outcome was seroconversion and geometric mean titres (GMT) of the quadrivalent HPV vaccine serotypes in the study. RESULTS: Of the 59 original participants, 37 were followed up at 60 months. The proportion of participants who seroconverted were: 86.5%, 89.2%, 89.2%, 91.9% by competitive Luminex immunoassay (cLIA) and 83.8%, 83.8%, 94.6%, 78.4% by total immunoglobulin G assays (IgG) for serotypes 6, 11, 16 and 18 respectively. GMT values ranged from 118 (95%CI: 79-177) for serotype 11, to 373 (95%CI: 215-649) for serotype 16 by cLIA. For IgG, serotype 16 had the highest GMT of 261 (95%CI: 143-477) and serotype 18 had the lowest value of 37 (95%CI: 21-68). All antibody titres were lower in females compared to males but the difference was not statistically significant except for serotype 16. No serious adverse event was reported during this follow-up period. CONCLUSION: Our evidence, although limited by small numbers, is reassuring that a three dose schedule of HPV vaccine remains immunogenic in immunocompromised children to five years post vaccination. Large scale studies are required to determine long term protection in immunocompromised children. CLINICAL TRIAL REGISTRATION: NCT02263703 (ClinicalTrials.gov).

Attitude towards deceased donation in Ho Chi Minh City, Vietnam.

Describe the current state of deceased kidney donation in Southern Vietnam and to explore the knowledge, attitude and behaviour towards kidney donation after death. Factors associated with the decision to donate among selective populations in HoChi Minh city were explored. Self-administered questionnaire of 30 questions to people over 18 years in three different communities were studied, n = 1068; 77% and 63.8% agreed they would donate their own kidney and that of their relatives respectively after death. Factors associated with positive donation wishes were knowledge of the national shortage of organs and brain death as well as positive previous family conversations. Main reason for refusal was lack of agreement within families about donation. The desire for equitable distribution of organs was frequently expressed. The majority of people interviewed in this large study agreed with deceased organ donation. Despite this, few deceased donor kidney transplants are performed in adults and none in children in Southern Vietnam, therefore greater efforts in the donation process and coordination of deceased donor lists is required. Given the correlation between positive donation wishes and knowledge with desire to donate, widespread public education campaigns are critical to the promotion and development of a successful deceased organ donation programme in Southern Vietnam.

The efficacy of valganciclovir for prevention of infections with cytomegalovirus and Epstein-Barr virus after kidney transplant in children.

This study evaluated the efficacy of prophylactic ValGCV in preventing CMV and EBV infections in a single-center pediatric kidney transplant population (2008-2014). Therapy duration was determined according to donor/recipient serostatus. EBV monitoring was performed using monthly plasma PCR for 18 months post-transplant and for CMV, monthly for 6 months after prophylaxis cessation. Data were collected on 35 children, median age 10.6 years. There were 15 (42.9%) and 11 (31.4%) recipients seronegative for CMV or EBV, respectively, who received a kidney from a seropositive donor. Prophylaxis was ceased by 6 months in 24 (69%), between seven and 13 months in 10 (29%) children. Fourteen (40%) and eight (23%) children experienced CMV and EBV DNAemia, respectively. Ten of the 14 (71%) episodes of CMV DNAemia occurred in the first 6 months following cessation of prophylaxis. Shorter prophylaxis was associated with increased CMV DNAemia (P = 0.044). There was an inverse correlation between adjusted ValGCV dose and EBV incidence/timing. Neutropenia was more common if ValGCV dosage was ≥10% of the dose predicted (by BSA and creatinine clearance). ValGCV prevents CMV and may modify EBV infection risk. Frequent dosing adjustment for BSA and creatinine clearance is required to optimize safety and efficacy.

Socio-economic status and quality of life in children with chronic disease: A systematic review.

Reduced quality of life (QoL) is a known consequence of chronic disease in children, and this association may be more evident in those who are socio-economically disadvantaged. The aims of this systematic review were to assess the association between socio-economic disadvantage and QoL among children with chronic disease, and to identify the specific socio-economic factors that are most influential. MEDLINE, Embase and PsycINFO were searched to March 2015. Observational studies that reported the association between at least one measure of social disadvantage in caregivers and at least one QoL measure in children and young people (age 2-21 years) with a debilitating non-communicable childhood disease (asthma, chronic kidney disease, type 1 diabetes mellitus and epilepsy) were eligible. A total of 30 studies involving 6957 patients were included (asthma (six studies, n = 576), chronic kidney disease (four studies, n = 796), epilepsy (14 studies, n = 2121), type 1 diabetes mellitus (six studies, n = 3464)). A total of 22 (73%) studies reported a statistically significant association between at least one socio-economic determinant and QoL. Parental education, occupation, marital status, income and health insurance coverage were associated with reduced QoL in children with chronic disease. The quality of the included studies varied widely and there was a high risk of reporting bias. Children with chronic disease from lower socio-economic backgrounds experience reduced QoL compared with their wealthier counterparts. Initiatives to improve access to and usage of medical and psychological services by children and their families who are socio-economically disadvantaged may help to mitigate the disparities and improve outcomes in children with chronic illnesses.

Immunogenicity and persistence of immunity of a quadrivalent Human Papillomavirus (HPV) vaccine in immunocompromised children.

AIM: The aim of this study was to determine the immunogenicity and reactogenicity of HPV vaccine in immunocompromised children. METHODS: A multi-centre clinical trial was conducted in three paediatric hospitals in Australia. Unvaccinated children 5-18years of age attending one of three paediatric hospitals with a range of specified conditions associated with immunosuppression were included. Quadrivalent HPV vaccine (Gardasil) was given to the participants and serum anti-HPV antibody levels were measured at baseline (before first dose), 7 and 24months after the first dose of vaccine. RESULTS: Fifty-nine participants were enrolled across the three paediatric hospitals and among those one was seropositive to types 6, 11 and 16 at baseline. Seven months after the first dose, seroconversion rates were 93.3%, 100%, 100% and 88.9% for type 6, 11, 16 and 18 respectively. The corresponding rates at 24month follow up were 82.2%, 91.1%, 91.1% and 68.9%. The greatest increase in geometric mean titre (GMT) was for type 16, followed by type 11. GMTs declined over the following months, but remained more than fourfold higher for all serotypes compared to baseline titres at 24months post vaccination. Injection site erythema, pain and swelling were commonly reported local adverse events and were less common after each dose. Few participants reported systemic adverse events, and minor disease flare occurred in two participants. One child developed a squamous cell oral carcinoma during follow up, but tissue was unable to be tested for HPV. CONCLUSION: Immunosuppressed children had an adequate immunogenic response to Quadrivalent HPV vaccine regardless of age and the cause of immunosuppression. HPV related cancers occur at higher frequency and earlier in immunosuppressed patients, so early vaccination and optimal scheduling should be further studied in such children. CLINICAL TRIAL REGISTRATION: NCT02263703 (ClinicalTrials.gov).

Surveillance biopsies after paediatric kidney transplantation: A review.

Kidney transplantation is the most effective means of treating children with end-stage kidney disease, and yet, there continues to be a limited "life span" of transplanted kidneys in paediatric recipients. Early graft monitoring, using the surveillance biopsy, has the potential to extend renal allograft survival in paediatric recipients. The surveillance biopsy provides important and timely information about acute and chronic graft pathology, particularly SCR and calcineurin inhibitor-induced nephrotoxicity, which can subsequently guide management decisions and improve long-term graft survival. The ostensible value of the surveillance biopsy is furthered by the limitations of conventional renal functional studies. However, there is still much debate surrounding the surveillance biopsy in paediatric recipients, particularly in regard to its overall utility, safety and timing. This review discusses the current literature regarding the utility, safety, and potential predictive value of surveillance biopsies for guiding post-transplant management in paediatric renal allograft recipients, as well as the viability of other potentially newer non-invasive strategies for renal allograft monitoring.

A systematic review of acute kidney injury in pediatric allogeneic hematopoietic stem cell recipients.

The process of allogeneic HSCT in children is associated with frequent AKI and mortality, but the epidemiology is not widely reported. The aim of this review was to summarize the available evidence on incidence, risk factors, timing, and prognosis of AKI in children following HSCT. We systematically reviewed all observational studies reporting incidence and outcomes of AKI in pediatric allogenic HSCT recipients. The minimum criteria for AKI were defined as an increase in sCr ≥ x1.5 or urine output ≤0.5 mL/kg/min over six h. Medline and Embase were searched until March 2014. From 993 electronic records, five were eligible for inclusion (n = 571 patients). The average incidence of AKI within the first 100 days following HSCT was 21.7% (range 11-42%), and the average time of onset was 4-6 wk post-transplant. Risk factors for AKI included cyclosporine toxicity, amphotericin B and foscarnet, SOS, and having a mismatched donor. There were conflicting reports on whether AKI was associated with the development of CKD. AKI is a common and potentially life-threatening complication following HSCT in children. Further quality observational studies are needed to accurately determine the epidemiology and prognosis of AKI in this population.

Ten-year single-center experience of the ketogenic diet: factors influencing efficacy, tolerability, and compliance.

OBJECTIVES: To evaluate the efficacy, tolerability, and compliance of 3 ketogenic diets, the classical ketogenic diet, medium-chain triglyceride (MCT), and modified Atkins diet. STUDY DESIGN: A single-center, retrospective study of 48 children with intractable epilepsy receiving ketogenic diets from 2003 to 2012. Patient demographics, epilepsy history, nutritional management, and side effects were collated. Compliance and tolerability were assessed by recording reasons for diet modification and cessation. The value of potassium citrate supplementation for preventing nephrolithiasis was reviewed. RESULTS: Median age at ketogenic diet initiation was 3.8 years (IQR: 2.3-7 years). The majority had intractable epilepsy, and 33 of the 48 children (69%) had epileptic encephalopathies. Three (6%) patients became seizure free, 35 (73%) reported <50%-90% reduction, and 10 (21%) had 0%-50% reduction during a 2-year period. Diet duration or ketogenic diet type did not predict reduction in seizures (P = .381; P = .272). Constipation (n = 31, 65%) was very common. Food refusal (n = 3, 6%) and poor parental compliance (n = 5, 10%) were common reasons cited for cessation. There were lower rates of side effects for modified Atkins diet. Diet cessation was greatest for MCT; however, 3 patients on MCT ceased therapy because adequate seizure control was achieved. Nephrolithiasis was reported in 1 patient before potassium citrate was used and 2 patients noncompliant with potassium citrate supplementation developed hypercalciuria. CONCLUSION: The 3 ketogenic diets were comparably effective in seizure control and generally well-tolerated. Potassium citrate supplementation is an effective prophylactic supplement for the prevention of nephrolithiasis.

Cytomegalovirus & Epstein Barr Virus serostatus as a predictor of the long-term outcome of kidney transplantation.

AIM: Cytomegalovirus (CMV) and Epstein Barr Virus (EBV) disease and asymptomatic infection have been associated with poor outcomes in kidney transplantation. Recipients who acquire primary infection through transplantation from a seropositive donor may be at particular risk of complications. The primary aim of this study was to evaluate the relationship between donor/recipient (D/R) CMV and EBV serostatus pretransplant and allograft and patient survival in a large cohort of kidney transplant recipients. METHODS: Data were obtained from the Australian and New Zealand Dialysis and Transplant Registry and the Australian and New Zealand Organ Donation Registry on 4516 first deceased donor kidney transplants performed between 1998 and 2010. Graft and patient survival were analysed using the Kaplan-Meier method. RESULTS: Pretransplant CMV D/R serostatus was available for the whole cohort, with EBV D/R serostatus available for 2566 transplants (56.8%). Serostatus for both viruses was significantly associated with donor and recipient age and recipient smoking status. For both viruses the majority of transplants were in a D+/R+ serostatus setting: 45.3% for CMV and 77.9% for EBV. D/R serostatus for either virus did not have a significant effect on graft or patient survival. CONCLUSION: We conclude that in the current era of viral prophylaxis and surveillance, long-term outcome for the kidney transplant population is unaffected by D/R CMV and EBV serostatus.

A qualitative study investigating knowledge and attitudes regarding human papillomavirus (HPV) and the HPV vaccine among parents of immunosuppressed children.

Barriers influencing the willingness of parents to vaccinate immunocompetent children include a lack of knowledge about human papillomavirus (HPV) and low perception of risk regarding their child's acquisition of HPV infection. However, it cannot be assumed that the facilitators and barriers of HPV vaccination are the same for parents/guardians of children who are immunocompromised, or who have chronic medical conditions. This study aimed to document the knowledge and attitudes of parents/guardians of immunosuppressed children and adolescents towards HPV infection and the vaccine. A study using qualitative methods which incorporated 27 semi-structured interviews was undertaken with parents/guardians of immunosuppressed children vaccinated against HPV at three hospitals in two states of Australia. Thematic analysis revealed that while participants acknowledged that they had heard of HPV, they did not have a strong sense of what it actually was. The level of concern held about their child acquiring an HPV infection (prior to vaccination) ranged from 'not at all' to 'extremely'. Some believed that their child was at increased risk of developing a severe HPV-related illness because of their underlying condition. The participants supported their child receiving the HPV vaccine, as they did not want to take a risk with a disease that may cause their child to return to hospital for treatment. The majority had little apprehension about the use of the HPV vaccine but expressed some concern that potential adverse effects would be more severe for immunosuppressed children. However, they stressed their belief in the safety of the vaccine and their trust in the child's health team. Our study results show that parents of children with impaired immunity would benefit from further information about the safety of the vaccine and about the important role of the vaccine for boys as well as girls.

Nationwide survey of adolescents and young adults with end-stage kidney disease.

AIM: To better understand the health-care needs of adolescents and young adults (AYA) with end-stage kidney disease (ESKD), we sought to describe the demographic characteristics of a national cohort. METHODS: Data were retrieved from the Australia and New Zealand Dialysis and Transplant Registry. We included all patients aged 15-25 years, living in Australia and receiving renal replacement therapy (RRT) on 31 December 2009. Data included race, aetiology of kidney disease, postal code, transition and migration history. RESULTS: A total of 495 AYA were receiving RRT in Australia giving a prevalence of 143 per million age-related population. Sixty-three per cent had a functioning transplant, 24% were receiving haemodialysis and 13% peritoneal dialysis. Median current age was 22 years (interquartile range (IQR) 19-24). The most prevalent cause of ESKD was glomerulonephritis (33%). The majority of patients lived in capital cities. Indigenous patients were more likely to live in more remote areas. Eighty-five per cent of patients were currently receiving care at an adult unit and 35% of these patients had transitioned from a paediatric unit since starting RRT. The median number of patients per adult unit was 5 (IQR 3-10). CONCLUSIONS: The majority of Australian AYA with ESKD are managed in adult units; however, the number at any one unit is low. As most live in the capital cities there may be an opportunity to establish centralized services designed to cater for the needs of AYA patients. However, the needs of patients living in more remote areas, including a significant proportion of Indigenous patients, may not be met by such a model.

Waiting time and outcome of kidney transplantation in adolescents.

BACKGROUND: The major cause of late graft failure in adolescent kidney transplant recipients is thought to be nonadherence with medications. Delaying transplantation in adolescents may lead to improved adherence but at the cost of longer time on dialysis. To determine if waiting time on dialysis is a risk factor for graft survival in adolescents, we compared the outcomes of kidney transplants according to age and time on dialysis. METHODS: We analyzed data from the Australian and New Zealand Dialysis and Transplant Registry on 2,739 primary kidney transplants performed between 1980 and 2004 in recipients less than 30 years old. Outcomes according to age at transplantation and waiting time were analyzed by Kaplan-Meier curves, log-rank tests, and Cox proportional hazard tests. RESULTS: Overall five- and 10-year graft survival rates were significantly worse in adolescents (65% and 50%, respectively) compared to recipients aged two to 10 years (74% and 58%) and 20 to 29 years (72% and 57%). Waiting time on dialysis was an independent risk factor for failure of living donor grafts in adolescents (hazard ratio 0.53, P = 0.03). Five- and 10-year graft survival of preemptive grafts in adolescents were 82% and 70%, respectively, which were similar to survival rates of preemptive grafts in other age groups. CONCLUSIONS: Reduced graft survival rates in adolescent recipients are not seen after preemptive transplants. Preemptive grafts are associated with a 50% reduction in the risk of graft failure. Delaying transplantation in adolescents may expose them to increased risk of poorer outcomes.

The choice of threshold limits for pediatric ambulatory blood pressure monitoring influences clinical decisions.

OBJECTIVES: Hypertension in children may be defined by blood pressure elevated above the 95th percentile according to sex and age. Population data for ambulatory blood pressure provide different age-related and sex-related threshold limits to office-derived data. We sought to determine whether, when using ambulatory blood pressure monitoring in a clinical setting, changing 95th percentile threshold limit sets from office-derived to ambulatory blood pressure-derived would lead to different diagnostic decisions. METHODS: Three nephrologists who were blinded as to patient identity and limit setting method reported on 42 ambulatory blood pressure records from a mixed group of patients aged 5-18 years by using both office-derived threshold limits for the 95th centile of blood pressure and ambulatory blood pressure-derived limits. Decisions regarding the presence or absence of hypertension were compared for each patient according to the limit set. RESULTS: Thirty-five (83%) patients were considered to be hypertensive when office-derived threshold limits were used and 20% (P=0.005) fewer records were reported as showing hypertension when ambulatory blood pressure-derived threshold limits were used. When ambulatory blood pressure limits were applied, there were fewer records with an awake systolic blood pressure load >50% (P=0.004) and the average awake systolic blood pressure load was significantly lower (P<0.001). CONCLUSION: Ambulatory blood pressure normative data tend to provide higher blood pressure limits for age and sex. Consequently, when ambulatory blood pressure data are used to set threshold limits, clinical decisions based on ambulatory blood pressure may be different than when office limits are used. These findings demonstrate the importance of using the most appropriate limit sets to analyze ambulatory blood pressure and when interpreting ambulatory blood pressure-based research.