National study on the risks of COVID-19 infection for paediatric kidney transplant recipients: a retrospective, cross-sectional study.

INTRODUCTION: During the COVID-19 pandemic, evidence emerged that immunosuppressed children were less affected by COVID-19 infections compared with immunosuppressed adults. The aim of our study was to investigate how COVID-19 infections affected paediatric kidney transplant recipients (pKTR) in the UK. METHODS: Questionnaires regarding COVID-19 infection data and care of pKTR during the COVID-19 pandemic were sent to all 13 UK paediatric nephrology centres examining asymptomatic and symptomatic pKTR with positive COVID-19 PCR testing from 1 April 2020 to 1 December 2021. RESULTS: 63 pKTR who were 3.1 (range 0.1-15) years post-transplantation had COVID-19 infection with positive SARS-CoV-2 PCR RNA. Classical COVID-19 symptoms were present in half of the patients; with atypical presentations including diarrhoea (13%) and lethargy (13%) also noted, while a third of patients were asymptomatic. Eighteen patients (28%) were hospitalised including five asymptomatic patients admitted for other reasons. No patients needed ventilation or intensive care admission, and one patient received supplemental oxygen. There was evidence of acute kidney injury (AKI) in 71% of patients, but no patients needed kidney replacement therapy with haemofiltration or dialysis. CONCLUSION: We report 10.4% of the UK paediatric renal transplantation population had documented COVID-19 infections with positive SARS-CoV-2 PCR RNA with 28% of those affected requiring hospitalisation. The increased incidence of AKI, particularly after the first wave of the COVID-19 pandemic, was possibly due to increased testing. There was low morbidity and mortality compared with the adult population.

Use of a donor kidney with known autosomal dominant polycystic kidney disease in a highly sensitised paediatric recipient.

We report the use of an autosomal-dominant polycystic kidney disease (ADPKD) donor kidney in a paediatric recipient. A 14-year-old boy on haemodialysis for 4 years following loss of a first kidney transplant, highly sensitised, and with limited vascular options for ongoing dialysis access, was offered a deceased brain death donor transplant from a mid-30s donor with known ADPKD but normal kidney function and negligible proteinuria. After extensive discussion with the patient and family, discussing all alternative options and review of available literature, the kidney was accepted and implanted. Graft function was immediate. An early post-transplant creatinine rise was attributed to possible antibody-mediated rejection, treated with plasmapheresis and rituximab. Ten months post-transplant, the patient remains dialysis-free with stable function. Extended criteria kidneys are already considered for highly sensitised or long-waiting dialysis patients. Though the literature is limited, kidneys from patients with ADPKD could be considered within extended criteria offers on a case-by-case basis.

A pragmatic, open-label, randomized controlled trial of Plasma-Lyte-148 versus standard intravenous fluids in children receiving kidney transplants (PLUTO).

Acute electrolyte and acid-base imbalance is experienced by many children following kidney transplant. This is partly because doctors give very large volumes of artificial fluids to keep the new kidney working. When severe, fluid imbalance can lead to seizures, cerebral edema and death. In this pragmatic, open-label, randomized controlled trial, we randomly assigned (1:1) pediatric kidney transplant recipients to Plasma-Lyte-148 or standard of care perioperative intravenous fluids (predominantly 0.45% sodium chloride and 0.9% sodium chloride solutions). We then compared clinically significant electrolyte and acid-base abnormalities in the first 72 hours post-transplant. The primary outcome, acute hyponatremia, was experienced by 53% of 68 participants in the Plasma-Lyte-148 group and 58% of 69 participants in the standard fluids group (odds ratio 0·77 (0·34 - 1·75)). Five of 16 secondary outcomes differed with Plasma-Lyte-148: hypernatremia was significantly more frequent (odds ratio 3·5 (1·1 - 10·8)), significantly fewer changes to fluid prescriptions were made (rate ratio 0·52 (0·40-0·67)), and significantly fewer participants experienced hyperchloremia (odds ratio 0·17 (0·07 - 0·40)), acidosis (odds ratio 0·09 (0·04 - 0·22)) and hypomagnesemia (odds ratio 0·21 (0·08 - 0·50)). No other secondary outcomes differed between groups. Serious adverse events were reported in 9% of participants randomized to Plasma-Lyte-148 and 7% of participants randomized to standard fluids. Thus, perioperative Plasma-Lyte-148 did not change the proportion of children who experienced acute hyponatremia compared to standard fluids. However fewer fluid prescription changes were made with Plasma-Lyte-148, while hyperchloremia and acidosis were less common.

Clinical Experience of a Long-acting Pegylated Erythropoietin-Stimulating Agent in Pediatric Chronic Kidney Disease.

OBJECTIVE: Management of anemia of chronic kidney disease (CKD) often includes subcutaneous or intravenous administration of erythropoietin-stimulating agents (ESAs). Mircera, a pegylated continuous erythropoietin receptor agonist, has a longer duration of action and requires less frequent administration than other ESAs. Pediatric experience with Mircera is limited. We retrospectively reviewed our long-term experience of Mircera in a national pediatric nephrology center. METHODS: Patients were identified via an electronic patient record database. Data collected included demographics (sex, age, etiology of CKD, CKD stage, dialysis modality), dosing information, and laboratory data-hemoglobin (Hb), parathormone (PTH), ferritin, hematinics prior to commencing Mircera and all subsequent values associated with dose adjustments. RESULTS: Seventy-seven patients aged 2 to 18 years, with CKD stages 2 to 5T had received at least 1 dose of Mircera, with 75 patients having sufficient data and a total of 1473 doses. No patients discontinued Mircera owing to adverse effects. One patient experienced a potential severe adverse drug reaction. Mircera was effective in improving or maintaining Hb ≥10.0 g/dL in most (58/75, 77.3%) patients. The median dose to achieve Hb ≥10.0 g/dL was 2.1 µg/kg/4 wk. Most doses (1039, 71.5%) were administered 4-weekly. The doses (161, 11.1%) that were administered 6-weekly remained efficacious. Thirty-two patients started Mircera with Hb <10.0 g/dL; 26 (81%) achieved Hb ≥10.0 g/dL within a median time of 4 months. Mircera was less effective if given every 8 weeks, or in the presence of hyperparathyroidism or hyperferritinemia. CONCLUSION: Mircera appears safe and effective in pediatric patients with CKD.

The UK kidney donor risk index poorly predicts long-term transplant survival in paediatric kidney transplant recipients.

Background: The UK kidney offering scheme introduced a kidney donor risk index (UK-KDRI) to improve the utility of deceased-donor kidney allocations. The UK-KDRI was derived using adult donor and recipient data. We assessed this in a paediatric cohort from the UK transplant registry. Methods: We performed Cox survival analysis on first kidney-only deceased brain-dead transplants in paediatric (<18 years) recipients from 2000-2014. The primary outcome was death-censored allograft survival >30 days post-transplant. The main study variable was UK-KDRI derived from seven donor risk-factors, categorised into four groups (D1-low risk, D2, D3 and D4-highest risk). Follow-up ended on 31-December-2021. Results: 319/908 patients experienced transplant loss with rejection as the main cause (55%). The majority of paediatric patients received donors from D1 donors (64%). There was an increase in D2-4 donors during the study period, whilst the level of HLA mismatching improved. The KDRI was not associated with allograft failure. In multi-variate analysis, increasing recipient age [adjusted HR and 95%CI: 1.05(1.03-1.08) per-year, p<0.001], recipient minority ethnic group [1.28(1.01-1.63), p<0.05), dialysis before transplant [1.38(1.04-1.81), p<0.005], donor height [0.99 (0.98-1.00) per centimetre, p<0.05] and level of HLA mismatch [Level 3: 1.92(1.19-3.11); Level 4: 2.40(1.26-4.58) versus Level 1, p<0.01] were associated with worse outcomes. Patients with Level 1 and 2 HLA mismatches (0 DR +0/1 B mismatch) had median graft survival >17 years regardless of UK-KDRI groups. Increasing donor age was marginally associated with worse allograft survival [1.01 (1.00-1.01) per year, p=0.05]. Summary: Adult donor risk scores were not associated with long-term allograft survival in paediatric patients. The level of HLA mismatch had the most profound effect on survival. Risk models based on adult data alone may not have the same validity for paediatric patients and therefore all age-groups should be included in future risk prediction models.

Increasing SARS-CoV-2 seroprevalence among UK pediatric patients on dialysis and kidney transplantation between January 2020 and August 2021.

BACKGROUND: Coronavirus disease 2019 (COVID-19) was officially declared a pandemic by the World Health Organisation (WHO) on 11 March 2020, as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spread rapidly across the world. We investigated the seroprevalence of anti-SARS-CoV-2 antibodies in pediatric patients on dialysis or kidney transplantation in the UK. METHODS: Excess sera samples were obtained prospectively during outpatient visits or haemodialysis sessions and analysed using a custom immunoassay calibrated with population age-matched healthy controls. Two large pediatric centres contributed samples. RESULTS: In total, 520 sera from 145 patients (16 peritoneal dialysis, 16 haemodialysis, 113 transplantation) were analysed cross-sectionally from January 2020 until August 2021. No anti-SARS-CoV-2 antibody positive samples were detected in 2020 when lockdown and enhanced social distancing measures were enacted. Thereafter, the proportion of positive samples increased from 5% (January 2021) to 32% (August 2021) following the emergence of the Alpha variant. Taking all patients, 32/145 (22%) were seropositive, including 8/32 (25%) with prior laboratory-confirmed SARS-CoV-2 infection and 12/32 (38%) post-vaccination (one of whom was also infected after vaccination). The remaining 13 (41%) seropositive patients had no known stimulus, representing subclinical cases. Antibody binding signals were comparable across patient ages and dialysis versus transplantation and highest against full-length spike protein versus spike subunit-1 and nucleocapsid protein. CONCLUSIONS: Anti-SARS-CoV-2 seroprevalence was low in 2020 and increased in early 2021. Serological surveillance complements nucleic acid detection and antigen testing to build a greater picture of the epidemiology of COVID-19 and is therefore important to guide public health responses. A higher resolution version of the Graphical abstract is available as Supplementary information.

Long term outcomes following kidney transplantation in children who weighed less than 15 kg - report from the UK Transplant Registry.

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. A higher resolution version of the Graphical abstract is available as Supplementary information.

Establishment of Pediatric Subspecialty Advanced Practice Provider Fellowship Training Programs to Optimize Advanced Practice Utilization in Pediatric Specialty Care and Facilitate Interprofessional Integration.

In the setting of demand for health care providers exceeding the supply of physicians, shift toward value-based care, and institutional gaps in the understanding of advanced practice provider (APP) scope of practice, one urban academic pediatric hospital developed 12-month subspecialty post-graduate fellowship programs for APPs in 18 subspecialties in an effort to optimize APP utilization at top of license and increase access to high-quality care. [J Contin Educ Nurs. 2022;53(11):478-480.].

Use of erythropoiesis-stimulating agents in children with chronic kidney disease: a systematic review.

Background: Erythropoiesis-stimulating agents (ESAs) revolutionized the management of anaemia in chronic kidney disease (CKD) when introduced in the late 1980s. A range of ESA types, preparations and administration modalities now exist, with newer agents requiring less frequent administration. Although systematic reviews and meta-analyses have been published in adults, no systematic review has been conducted investigating ESAs in children. Methods: The Preferred Reporting Items for Systematic Reviews and Meta-analyses statement for the conduct of systematic reviews was used. All available literature on outcomes relating to ESAs in children with CKD was sought. A search of the MEDLINE, CINAHL and Embase databases was conducted by two independent reviewers. Inclusion criteria were published trials in English, children with chronic and end-stage kidney disease and use of any ESA studied against any outcome measure. An assessment of risk of bias was carried out in all included randomized trials using the criteria from the Cochrane Handbook for Systematic Reviews of Interventions. Two tables were used for data extraction for randomized and observational studies. Study type, participants, inclusion criteria, case characteristics, follow-up duration, ESA type and dosage, interventions and outcomes were extracted by one author. Results: Of 965 identified articles, 58 were included covering 54 cohorts. Six were randomized trials and 48 were observational studies. A total of 38 studies assessed the efficacy of recombinant human erythropoietin (rHuEPO), 11 of darbepoetin alpha (DA) and 3 of continuous erythropoietin receptor activator (CERA), with 6 studies appraising secondary outcome measures exclusively. Recruitment to studies was a consistent challenge. The most common adverse effect was hypertension, although confounding effects often limited direct correlation. Two large cohort studies demonstrated a greater hazard of death independently associated with high ESA dose. Secondary outcome measures included quality of life measures, growth and nutrition, exercise capacity, injection site pain, cardiovascular function, intelligent quotient, evoked potentials and platelet function. Conclusions: All ESA preparations and modes of administration were efficacious, with evidence of harm at higher doses. Evidence supports individualizing treatments, with strong consideration given to alternate treatments in patients who appear resistant to ESA therapy. Further research should focus on randomized trials comparing the efficacy of different preparations, treatment options in apparently ESA-resistant cohorts and clarification of meaningful secondary outcomes to consolidate patient-relevant indices.

Advanced chronic kidney disease among UK children.

The UK Renal Registry currently collects information on UK children with kidney failure requiring long-term kidney replacement therapy (KRT), which supports disease surveillance and auditing of care and outcomes; however, data are limited on children with chronic kidney disease (CKD) not on KRT. METHODS: In March 2020, all UK Paediatric Nephrology centres submitted data on children aged <16 years with severely reduced kidney function as of December 2019, defined as an estimated glomerular filtration rate <30 mL/min/1.73 m2. RESULTS: In total, 1031 children had severe CKD, the majority of whom (80.7%) were on KRT. The overall prevalence was 81.2 (95% CI 76.3 to 86.3) per million of the age-related population. CONCLUSIONS: The prevalence of severe CKD among UK children is largely due to a high proportion of children on long-term KRT. Expanding data capture to include children with CKD before reaching failure will provide greater understanding of the CKD burden in childhood.

Use of a B-cell depleting regimen for antifactor H autoantibody-mediated membranoproliferative glomerulonephritis in a paediatric patient.

A male child presented initially well with a mixed nephrotic-nephritic syndrome and was commenced on standard high-dose oral corticosteroids. Clinical deterioration occurred 3 weeks later with rapidly progressing renal dysfunction, seizures and diminished urinary output, requiring renal replacement therapy. Once stabilised, renal biopsy demonstrated mesangial and capillary C3, minimal IgG deposition, with mesangial electron dense deposits felt consistent with postinfectious glomerulonephritis or C3 glomerulopathy. Further investigations identified circulating autoantibody directed against factor H, as a plausible aetiology of the membranoproliferative glomerulonephritis (MPGN). Treatment with rituximab and mycophenolate mofetil was associated with a reduction in antibody titres and a concurrent reduction in proteinuria and normalisation of renal function.Subsequent monitoring of antibody titres prompted further administrations of rituximab, with reduction in titres demonstrated after repeat doses. Atypical presentations or complications of nephrotic syndrome or MPGN should prompt detailed investigations for the cause with consideration of antifactor H antibodies.

Genetic evaluation of paediatric nephrocalcinosis: phenotype-driven genetic panels reveal a rare diagnosis.

Monogenic causes of paediatric nephrocalcinosis are associated with extensive phenotypic variability. We report a 14-year-old male who presented at 8 years of age with incidentally identified nephrocalcinosis alongside growth impairment and dental anomalies. Extensive genetic investigation confirmed a molecular diagnosis of Bartter syndrome type II. This is exceptional in both late presentation and the presence of amelogenesis imperfecta, a very rare association of inherited tubulopathies. Details of the nephrocalcinosis gene panel analysed and associated phenotypes are presented to highlight the utility of a phenotype-driven genetic panel in resolving an atypical presentation of nephrocalcinosis, allowing precise diagnosis, tailored therapy and prognostication.

UK experience of ofatumumab in recurrence of focal segmental glomerulosclerosis post-kidney transplant.

BACKGROUND: Steroid-resistant nephrotic syndrome (SRNS), commonly caused by focal segmental glomerulosclerosis (FSGS), is associated with progression to stage 5 chronic kidney disease, requirement for kidney replacement therapy and a risk of disease recurrence post-kidney transplantation. Ofatumumab (OFA) is a fully humanised monoclonal antibody to CD20, with similar mechanisms of action to rituximab (RTX). METHODS: We report a case series of seven UK patients (five paediatric, two adult), all of whom developed FSGS recurrence after kidney transplantation and received OFA as part of their therapeutic intervention. All also received concomitant plasmapheresis. The 2-year outcome of these seven patients is reported, describing clinical course, kidney function and proteinuria. RESULTS: Four patients (all paediatric) achieved complete urinary remission with minimal proteinuria 12 months post-treatment. Three of those four also had normal graft function. Two patients showed partial remission-brief improvement to non-nephrotic proteinuria (197 mg/mmol) in one patient, maintained improvement in kidney function (estimated glomerular filtration rate 76 ml/min/1.73 m2) in the other. One patient did not demonstrate any response. CONCLUSIONS: OFA may represent a useful addition to therapeutic options in the management of FSGS recurrence post-transplantation, including where RTX has shown no benefit. Concomitant plasmapheresis in all patients prevents any definitive conclusion that OFA was the beneficial intervention.

UK national study of barriers to renal transplantation in children.

AIMS: To investigate access to paediatric renal transplantation and examine potential barriers within the process. METHODS: Cross-sectional, multicentre, observational study where paediatric nephrology centres in the UK were requested to provide data on transplantation plans for all children (<18 years) with end-stage kidney disease (ESKD). RESULTS: 308 children with ESKD were included in this study from 12 out of 13 UK paediatric nephrology centres. 139 (45%) were being prepared for living donor transplantation and 82 (27%) were listed for deceased donor transplantation. The most common cited factors delaying transplantation from occurring in children were disease factors (36%), donor availability (27%) and size of the child (20%). Psychosocial factors were listed as a barrier in 19% of children. CONCLUSIONS: In this study we have documented the main barriers to renal transplantation in children. Some identified factors may be modifiable through local or national intervention, including donor availability and patient psychosocial factors.

Thromboprophylaxis in congenital nephrotic syndrome: 15-year experience from a national cohort.

INTRODUCTION: Congenital nephrotic syndrome (CNS) is an ultra-rare disease associated with a pro-thrombotic state and venous thromboembolisms (VTE). There is very limited evidence evaluating thromboprophylaxis in patients with CNS. This study aimed to determine the doses and duration of treatment required to achieve adequate thromboprophylaxis in patients with CNS. METHODS: From 2005 to 2018 children in Scotland with a confirmed genetic or histological diagnosis of CNS were included if commenced on thromboprophylaxis. The primary study endpoint was stable drug monitoring. Secondary outcomes included VTE or significant haemorrhage. RESULTS: Eight patients were included; all initially were commenced on low-molecular weight heparin (enoxaparin). Four patients maintained therapeutic anti-Factor Xa levels (time 3-26 weeks, dose 3.2-5.07 mg/kg/day), and one patient developed a thrombosis (Anti-Factor Xa: 0.27 IU/ml). Four patients were subsequently treated with warfarin. Two patients maintained therapeutic INRs (time 6-11 weeks, dose 0.22-0.25 mg/kg/day), and one patient had two bleeding events (Bleed 1: INR 6, Bleed 2: INR 5.5). CONCLUSIONS: Achieving thromboprophylaxis in CNS is challenging. Similar numbers of patients achieved stable anticoagulation on warfarin and enoxaparin. Enoxaparin dosing was nearly double the recommended starting doses for secondary thromboprophylaxis. Bleeding events were all associated with supra-therapeutic anticoagulation.

Treatment and long-term outcome in primary nephrogenic diabetes insipidus.

BACKGROUND: Primary nephrogenic diabetes insipidus (NDI) is a rare disorder and little is known about treatment practices and long-term outcome. METHODS: Paediatric and adult nephrologists contacted through European professional organizations entered data in an online form. RESULTS: Data were collected on 315 patients (22 countries, male 84%, adults 35%). Mutation testing had been performed in 270 (86%); pathogenic variants were identified in 258 (96%). The median (range) age at diagnosis was 0.6 (0.0-60) years and at last follow-up 14.0 (0.1-70) years. In adults, height was normal with a mean (standard deviation) score of -0.39 (±1.0), yet there was increased prevalence of obesity (body mass index >30 kg/m2; 41% versus 16% European average; P < 0.001). There was also increased prevalence of chronic kidney disease (CKD) Stage ≥2 in children (32%) and adults (48%). Evidence of flow uropathy was present in 38%. A higher proportion of children than adults (85% versus 54%; P < 0.001) received medications to reduce urine output. Patients ≥25 years were less likely to have a university degree than the European average (21% versus 35%; P = 0.003) but full-time employment was similar. Mental health problems, predominantly attention-deficit hyperactivity disorder (16%), were reported in 36% of patients. CONCLUSION: This large NDI cohort shows an overall favourable outcome with normal adult height and only mild to moderate CKD in most. Yet, while full-time employment was similar to the European average, educational achievement was lower, and more than half had urological and/or mental health problems.

Bilateral primary renal diffuse large B-cell lymphoma: a rare presentation of paediatric renal disease mimicking juvenile nephronophthisis.

A 12-year-old boy presented with a prolonged history of headache, fatigue and hypertension. Initial investigations were consistent with presumed non-oliguric end-stage renal disease, leading to a provisional diagnosis of juvenile nephronophthisis. Subsequent imaging demonstrated bilaterally enlarged kidneys without cystic change. Mutation analysis was negative for nephronophthisis, causing diagnostic uncertainty which prompted renal biopsy. Histology revealed a primary renal diffuse large B-cell lymphoma which was highly responsive to chemotherapy, including the anti-CD20 monoclonal agent, rituximab. Renal function improved during lymphoma treatment, with residual chronic kidney disease stage 3a once chemotherapy was completed. Atypical diagnostic features should always prompt re-evaluation of a patient. In this case, the delayed malignancy diagnosis did not have an adverse effect on patient survival or morbidity. The outcome for primary renal lymphoma (PRL) has improved markedly following the introduction of rituximab.

Association of Time-Varying Blood Pressure With Chronic Kidney Disease Progression in Children.

Importance: Optimal blood pressure (BP) management in children with chronic kidney disease (CKD) slows progression to end-stage renal disease. Studies often base progression risk on a single baseline BP measurement, which may underestimate risk. Objective: To determine whether time-varying BP measurements are associated with a higher risk of progression of CKD than baseline BP measurements. Design, Setting, and Participants: The ongoing longitudinal, prospective cohort study Chronic Kidney Disease in Children (CKID) recruited children from January 19, 2005, through March 19, 2014, from pediatric nephrology centers across North America, with data collected at annual study visits. Participants included children aged 1 to 16 years with a diagnosis of CKD and a glomerular filtration rate (GFR) of 30 to 90 mL/min/1.73 m2. Data were analyzed from February 11, 2005, through February 13, 2018. Exposures: Office BP measurement classified as less than 50th percentile, 50th to less than 90th percentile, or at least 90th percentile. Blood pressure categories were treated as time fixed (baseline) or time varying (updated at each visit) in models. Main Outcomes and Measures: A composite renal outcome (50% GFR reduction from baseline, estimated GFR less than 15 mL/min/1.73 m2, or dialysis or transplant). Pooled logistic models using inverse probability weighting estimated the hazard odds ratio (HOR) of the composite outcome associated with each BP category stratified by CKD diagnosis. Results: A total of 844 children (524 [62.1%] male; median age, 11 [interquartile range, 8-15] years; 151 [17.9%] black; 580 [68.7%] with nonglomerular CKD; and 264 [31.3%] with glomerular CKD) with complete baseline data and median follow-up of 4 (interquartile range, 2-6) years were included. One hundred ninety-six participants with nonglomerular diagnoses (33.8%) and 99 with glomerular diagnoses (37.5%) reached the composite outcome. Baseline systolic BP in at least the 90th percentile was associated with a higher risk of the composite outcome (HOR for nonglomerular disease, 1.58 [95% CI, 1.07-2.32]; HOR for glomerular disease, 2.85 [95% CI, 1.64-4.94]) compared with baseline systolic BP in less than the 50th percentile. Time-fixed estimates were substantially lower compared with time-varying systolic BP percentile categories (HOR among those with nonglomerular CKD, 3.75 [95% CI, 2.53-5.57]; HOR among those with glomerular diagnoses, 5.96 [95% CI, 3.37-10.54]) comparing those at or above the 90th percentile vs below the 50th percentile. Adjusted models (adjusted for proteinuria and use of antihypertensives) attenuated the risk in nonglomerular CKD (adjusted HOR for baseline measurement, 1.52 [95% CI, 0.98-2.36]; adjusted HOR for time-varying measurement, 2.25 [95% CI, 1.36-3.72]) and in glomerular CKD (adjusted HOR for baseline, 0.97 [95% CI, 0.39-2.36]; adjusted HOR for time-varying measurement, 1.41 [95% CI, 0.65-3.03]). Similar results were observed for diastolic BP. Conclusions and Relevance: Among children with nonglomerular CKD included in this study, elevated time-varying BP measurements were associated with a greater risk of CKD progression compared with baseline BP measurement. This finding suggests that previous studies using only baseline BP likely underestimated the association between BP and CKD progression.

Prevalence of Acute Kidney Injury in Neonates with Congenital Diaphragmatic Hernia.

BACKGROUND: Congenital diaphragmatic hernia (CDH) often presents with severe cardio-respiratory impairment in the neonatal period. Affected infants may be exposed to multiple nephrotoxic insults, predisposing them to acute kidney injury (AKI). The prevalence of AKI in a CDH cohort has not previously been described. OBJECTIVES: The primary aim of this study was to quantify the prevalence of AKI in patients with CDH treated in a single national centre. Secondarily, we investigated the association between AKI, select neonatal outcomes, and recognised AKI risk factors. METHODS: This was a retrospective analysis of all patients with CDH treated at our regional neonatal surgical centre between September 2011 and December 2017. Data was collected on demographics, CDH Study Group stage (size), laboratory and physiological parameters, medications, mortality, and duration of hospitalisation. AKI severity was stratified using the modified paediatric RIFLE criteria, determined by comparing the percentage increase in serum creatinine from baseline. Statistical analysis was performed using Fisher's exact and Pearson's χ2 tests for parametric analysis and Mann-Whitney U testing for non-parametric analysis. RESULTS: Fifty-four CDH patients met the inclusion criteria, 37% of whom developed AKI. The development of AKI was significantly associated with larger CDH defect (type C/D; p = 0.014), extracorporeal membranous oxygenation support (p = 0.003), patch repair (p = 0.004), and exposure to vancomycin, corticosteroids and diuretics (p = 0.004, p = 0.007, and p ≤ 0.001, respectively). There was no statistical association between AKI and gentamicin administration, umbilical arterial catheter insertion, or significant infection. Prolonged hospitalisation and patient mortality were significantly associated with AKI (p = 0.01 and p = 0.001, respectively). CONCLUSIONS: AKI is common in CDH cases treated in our centre and is associated with adverse outcomes. Potentially modifiable risk factors include nephrotoxic medication exposure. Prevention and early recognition of contributory factors for AKI may improve outcomes in CDH.