Increasing trends in hemodialysis and living donor kidney transplantation for children and young people in the United Kingdom.

BACKGROUND: The UK Renal Registry is responsible for the national collection and reporting of data on all children receiving long-term kidney replacement therapy [KRT], including kidney transplantation. METHODS: All 13 UK pediatric nephrology centers contributed to providing individual patient data from the pediatric population incident to and prevalent to KRT as per the date 31 December 2018. Data for children aged 16-<18 years were presented separately as some were managed under adult care settings with different methods of data collection. Demographics and biochemical data, including kidney function and prevalence of cardiovascular risk factors [hypertension, hypercholesterolemia, BMI] were reported. RESULTS: Eight hundred and twenty-six children (65.4 per million age-related population [pmarp]) and 199 young people (139.4pmarp) in the United Kingdom were prevalent to KRT on 31 December 2018. Overall, the incidence of KRT during 2018 was 9.1 pmarp and 12.6 pmarp in children and young people, respectively. Congenital anomalies of the kidney and urinary tract (CAKUT) were the most prevalent primary diagnoses (52%). Living and deceased donor transplantation was the most common treatment modality (78%). Patients on dialysis had lower age standardized mean height and weight ranges recorded in comparison to transplant patients [median height z score -1.8 vs. -1.1]. 73.1% patients had one or more cardiovascular disease risk factors. CONCLUSIONS: This study highlights increasing prevalence of hemodialysis and living donor transplantation as modalities for KRT. Of those incident to KRT, the highest patient survival was seen among 8-12 years and lowest <2 years. Moreover, there was a demographic shift from Caucasian toward Asian/other ethnicity and from CAKUT to other primary kidney diseases.

The clinical and radiological cerebrovascular abnormalities associated with renovascular hypertension in children: a systematic review.

Renovascular disease is an important secondary cause of hypertension in childhood. In this cohort, many may have undiagnosed cerebrovascular disease, and some children present acutely with cerebrovascular complications. However, these associations are yet to be defined in the literature.A systematic review of clinical and radiological abnormalities associated with renovascular hypertension in the global pediatric (< 18 years) population. The MEDLINE, Embase, and Google Scholar databases were searched, from database inception to 26 January 2021. Primary articles were unrestricted by study design and geographical location but were limited to those published in English.A total of 303 individuals (median age: 7.6 years [range 10 days-17.9 years]; M:F, 174:129) from 34 studies were included, across 13 countries. Twenty-seven individual cases were published for children with coexisting renovascular hypertension and cerebrovascular disease. Most children had bilateral renal artery stenosis, secondary to fibromuscular dysplasia and had coexisting occlusive cerebrovascular disease. The majority presented with neurological symptoms, and cerebral complication ranged from asymptomatic cerebrovascular stenosis to acute stroke and posterior reversible encephalopathy syndrome. The location or underlying etiology of the renovascular disease did not predict the location or extent of the cerebrovascular disease. The evidence from the cohort studies was limited, as none specifically established a cohort of children with coexisting disease. Furthermore, the conclusions drawn were subjected to considerable bias from the treating clinicians.A prospective cohort of children with renovascular hypertension and cerebrovascular complications should be established so the long-term prognosis and impact of treatment may be better understood.

The impact of donor and recipient sex on kidney allograft survival in pediatric transplant recipients.

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.

Acute kidney injury in paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS) is not associated with progression to chronic kidney disease.

BACKGROUND: Paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS) is a rare complication of SARS-CoV-2 associated with single or multiorgan dysfunction. OBJECTIVE: We aimed to evaluate the incidence of acute kidney injury (AKI) and risk factors for kidney dysfunction in PIMS-TS, with reporting of 6-month renal follow-up data. We also evaluated renal involvement between first and second waves of the SARS-CoV-2 pandemic in the UK, the latter attributed to the Alpha variant. DESIGN: A single-centre observational study was conducted through patient chart analysis. SETTING: Data were collected from patients admitted to Great Ormond Street Hospital, London, UK, between April 2020 and March 2021. PATIENTS: 110 patients <18 years of age. MAIN OUTCOME MEASURE: AKI during hospitalisation. AKI classification was based on upper limit of reference interval (ULRI) serum creatinine (sCr) values. RESULTS: AKI occurred in 33 (30%) patients. Hypotension/hypoperfusion was associated with almost all cases. In univariate analysis, the AKI cohort had higher peak levels of triglycerides (OR, 1.27 (95% CI, 1.05 to 1.6) per 1 mmol/L increase) and C reactive protein (OR, 1.06 (95% CI, 1.02 to 1.12) per 10 mg/L increase), with higher requirement for mechanical ventilation (OR, 3.8 (95% CI, 1.46 to 10.4)) and inotropic support (OR, 15.4 (95% CI, 3.02 to 2.81)). In multivariate analysis, triglycerides were independently associated with AKI stages 2-3 (adjusted OR, 1.26 (95% CI, 1.04 to 1.6)). At follow-up, none had macroalbuminuria and all had sCr values

The new UK SARS-CoV-2 variant and lockdown - causes and consequences.

The new variant of concern (VOC), B.1.1.7, has a distinct set of mutations in nucleotides encoding the spike (S) protein on the surface of SARS-CoV-2. SARS-CoV-2 previously accumulated mutations at a much slower rate, of 1-2 per month; the sudden appearance of a large cluster of mutations was thought to be unusual. We now suspect that VOC may have arisen from immunosuppressed individuals who shed virus for longer periods. Epidemiological analyses estimate VOC to be more infectious; this is of most concern because these estimates were calculated during periods where many regions of the UK were in high social distancing restrictions. Therefore, the previous 'tiered' system implemented in the UK was ineffective at containing VOC. The most likely reason for this is that previous restrictions, no matter how strict, still allowed for gatherings in certain places. VOC also has implications for the national vaccination programme - a higher proportion of people will need to be vaccinated with a more infectious virus. Prolongation of the second dose of vaccines to increase vaccine uptake has understandably caused concern, but is based on sound immunological principles. There is now an urgent need to monitor the effect of new variants on vaccine efficacy - marking a new chapter in the global fight against COVID-19.

Acute Kidney Injury in Pediatric Inflammatory Multisystem Syndrome Temporally Associated With Severe Acute Respiratory Syndrome Coronavirus-2 Pandemic: Experience From PICUs Across United Kingdom.

OBJECTIVES: To study the prevalence, evolution, and clinical factors associated with acute kidney injury in children admitted to PICUs with pediatric inflammatory multisystem syndrome temporally associated with severe acute respiratory syndrome coronavirus-2. DESIGN: Multicenter observational study. SETTING: Fifteen PICUs across the United Kingdom. PATIENTS: Patients admitted to United Kingdom PICUs with pediatric inflammatory multisystem syndrome temporally associated with severe acute respiratory syndrome coronavirus-2 between March 14, 2020, and May 20, 2020. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Deidentified data collected as part of routine clinical care were analyzed. All children were diagnosed and staged for acute kidney injury based on the level of serum creatinine above the upper limit of reference interval values according to published guidance. Severe acute kidney injury was defined as stage 2/3 acute kidney injury. Uni- and multivariable analyses were performed to study the association between demographic data, clinical features, markers of inflammation and cardiac injury, and severe acute kidney injury. Over the study period, 116 patients with pediatric inflammatory multisystem syndrome temporally associated with severe acute respiratory syndrome coronavirus-2 were admitted to 15 United Kingdom PICUs. Any-stage acute kidney injury occurred in 48 of 116 patients (41.4%) and severe acute kidney injury in 32 of 116 (27.6%) patients, which was mostly evident at admission (24/32, 75%). In univariable analysis, body mass index, hyperferritinemia, high C-reactive protein, Pediatric Index of Mortality 3 score, vasoactive medication, and invasive mechanical ventilation were associated with severe acute kidney injury. In multivariable logistic regression, hyperferritinemia was associated with severe acute kidney injury (compared with nonsevere acute kidney injury; adjusted odds ratio 1.04; 95% CI, 1.01-1.08; p = 0.04). Severe acute kidney injury was associated with longer PICU stay (median 5 days [interquartile range, 4-7 d] vs 3 days [interquartile range, 1.5-5 d]; p < 0.001) and increased duration of invasive mechanical ventilation (median 4 days [interquartile range, 2-6 d] vs 2 days [interquartile range, 1-3 d]; p = 0.04). CONCLUSIONS: Severe acute kidney injury occurred in just over a quarter of children admitted to United Kingdom PICUs with pediatric inflammatory multisystem syndrome temporally associated with severe acute respiratory syndrome coronavirus-2. Hyperferritinemia was significantly associated with severe acute kidney injury. Severe acute kidney injury was associated with increased duration of stay and ventilation. Although short-term outcomes for acute kidney injury in pediatric inflammatory multisystem syndrome temporally associated with severe acute respiratory syndrome coronavirus-2 appear good, long-term outcomes are unknown.

Maternal and Fetal Death following Group A Streptococcal Meningitis in Mid-Term Pregnancy.

Background. Group A streptococcal (GAS) meningitis is rarely seen in the antenatal period, but it is associated with significant mortality. We present a case of a mid-trimester woman who developed fulminant meningitis following a rapid onset atypical presentation of infection with this organism. Case. A multiparous 23(+5)-week woman presented with a 10-day history of a non-productive cough associated with pyrexia. Within minutes of her admission she collapsed and lost consciousness; sepsis was suspected and cross-specialty care was initiated. She was managed empirically in extremis with broad-spectrum antibiotics and mannitol with 3% hypertonic saline for suspected infection and raised intracranial pressure, respectively. Despite intensivist management, a CT head revealed diffuse oedema with coning of the cerebellar tonsils. Brainstem death was certified within 19 hours of admission and fetal death ensued. Postmortem bacteriology confirmed GAS meningitis. Conclusion. Through raising awareness of this patient and her disease course, we hope that future policy decisions, primary care, and hospital level management will be informed accordingly for treatment of pregnant women with suspected GAS infection.