Demographics of childhood hypertension in the UK: a report from the Southeast England.

We aimed to describe hypertensive phenotype and demographic characteristics in children and adolescents referred to our paediatric hypertension service. We compared age, ethnicity and BMI in primary hypertension (PH) compared to those with secondary hypertension (SH) and white coat hypertension (WCH). Demographic and anthropometric data were collected for children and adolescents up to age 18 referred to our service for evaluation of suspected hypertension over a 6 year period. Office blood pressure (BP) and out of office BP were performed. Patients were categorised as normotensive (normal office and out of office BP), WCH (abnormal office BP, normal out of office BP), PH (both office and out of office BP abnormal, no underlying cause identified) and SH (both office and out of office BP abnormal, with a secondary cause identified). 548 children and adolescents with mean ± SD age of 10.1 ± 5.8 years and 58.2% girls. Fifty seven percent (n = 314) were hypertensive; of these, 47 (15%), 84 (27%) and 183 (58%) had WCH, PH and SH, respectively. SH presented throughout childhood, whereas PH and WCH peaked in adolescence. Non-White ethnicity was more prevalent within those diagnosed with PH than both the background population and those diagnosed with SH. Higher BMI z-scores were observed in those with PH compared to SH. Hypertensive children <6 years are most likely to have SH and have negligible rates of WCH and PH. PH accounted for 27% of hypertension diagnoses in children and adolescents, with the highest prevalence in adolescence, those of non-White Ethnicity and with excess weight.

Acute Kidney Injury in Critically Ill Children Is Not all Acute: Lessons Over the Last 5 Years.

Acute kidney injury (AKI) in the pediatric intensive care unit (PICU) is an important risk factor for increased morbidity and mortality during hospitalization. Over the past decade, accumulated data on children and young people indicates that acute episodes of kidney dysfunction can have lasting consequences on multiple organ systems and health outcomes. To date, there are no guidelines for follow-up of surviving children that may be at risk of long-term sequelae following AKI in the PICU. This narrative review aims to describe literature from the last 5 years on the risk of medium and long-term kidney and non-kidney outcomes after AKI in the PICU. More specifically, we will focus on outcomes in children and young people following AKI in the general PICU population and children undergoing cardiac surgery. These outcomes include mortality, hypertension, proteinuria, chronic kidney disease, and healthcare utilization. We also aim to highlight current gaps in knowledge in medium and long-term outcomes in this pediatric population. We suggest a framework for future research to develop evidence-based guidelines for follow-up of children surviving an episode of critical illness and AKI.

Acute kidney injury in children with chronic kidney disease is associated with faster decline in kidney function.

BACKGROUND: This study aimed to investigate the association of acute kidney injury (AKI) with change in estimated glomerular filtration rate (eGFR) in children with advanced chronic kidney disease (CKD). METHODS: Single centre, retrospective longitudinal study including all prevalent children aged 1-18 years with nondialysis CKD stages 3-5. Variables associated with CKD were analysed for their potential effect on annualised eGFR change (ΔGFR/year) following multiple regression analysis. Composite end-point including 25% reduction in eGFR or progression to kidney replacement therapy was evaluated. RESULTS: Of 147 children, 116 had at least 1-year follow-up in a dedicated CKD clinic with mean age 7.3 ± 4.9 years with 91 (78.4%) and 77 (66.4%) with 2- and 3-year follow-up respectively. Mean eGFR at baseline was 29.8 ± 11.9 ml/min/1.73 m2 with 79 (68%) boys and 82 (71%) with congenital abnormalities of kidneys and urinary tract (CAKUT). Thirty-nine (33.6%) had at least one episode of AKI. Mean ΔGFR/year for all patients was - 1.08 ± 5.64 ml/min/1.73 m2 but reduced significantly from 2.03 ± 5.82 to - 3.99 ± 5.78 ml/min/1.73 m2 from youngest to oldest age tertiles (P < 0.001). There was a significant difference in primary kidney disease (PKD) (77% versus 59%, with CAKUT, P = 0.048) but no difference in AKI incidence (37% versus 31%, P = 0.85) between age tertiles. Multiple regression analysis identified age (ß = - 0.53, P < 0.001) and AKI (ß = - 3.2, P = 0.001) as independent predictors of ΔGFR/year. 48.7% versus 22.1% with and without AKI reached composite end-point (P = 0.01). CONCLUSIONS: We report AKI in established CKD as a predictor of accelerated kidney disease progression and highlight this as an additional modifiable risk factor to reduce progression of kidney dysfunction. Graphical abstract.

Vitamin and trace element concentrations in infants and children with chronic kidney disease.

BACKGROUND: There are limited data regarding vitamin and trace element blood concentrations and supplementation needs in children with non-dialysis stages 3-5 of chronic kidney disease (CKD). METHODS: Retrospective cross-sectional review for nutritional blood concentrations measured over a recent 2-year period. In our CKD clinics, nutritional bloods including copper, zinc, selenium and vitamin A, vitamin E, active vitamin B12 and folate are monitored annually. Vitamin D status is monitored every 6-12 months. RESULTS: We reviewed 112 children (70 boys) with median (IQ1, IQ3) age 8.97 (4.24, 13.80) years. Estimated median (IQ1, IQ3) GFR (mL/min/1.73 m2) was 28 (21, 37). Vitamin A, active vitamin B12 and vitamin E concentrations were within normal range in 19%, 23% and 67% respectively, with all others being above normal range. Vitamin D blood concentrations were within desired range for 85% (15% had low levels) and folate blood concentrations were within normal range in 92%, with the remainder above or below target. For trace elements, 60%, 85% and 87% achieved normal ranges for zinc, selenium and copper respectively. Deficiencies were seen for zinc (35%), copper (7%), folate (3%) and selenium (1%), whilst 5%, 6% and 14% had zinc, copper and selenium levels above normal ranges. CONCLUSIONS: Several vitamin and trace element blood concentrations were outside normal reference ranges. Monitoring vitamin D and zinc blood concentrations is indicated due to the percentages with low levels in this group. Targeted vitamin and trace element supplementation should be considered where indicated rather than commencing multivitamin and/or mineral supplementation. Graphical abstract Vitamin and trace element concentrations in infants and children with non-dialysis chronic kidney disease.

The Incidence of Paediatric Acute Kidney Injury Identified Using an AKI E-Alert Algorithm in Six English Hospitals.

Objective: Acute kidney injury (AKI) is a significant cause of morbidity and mortality among hospitalised patients. The objectives in this study were (i) to investigate the incidence of AKI using the National Health Services (NHS) AKI e-alert algorithm as a means of identifying AKI; and (ii) in a randomly selected sub-group of children with AKI identified using the algorithm, to evaluate the recognition and management of AKI. Patients and Methods: Retrospective cross-sectional study with initial electronic retrieval of creatinine measurements at six hospitals in England over a six-month period. Results were evaluated using the NHS AKI e-alert algorithm with recognition and management of AKI stages 1, 2 and 3 reviewed in a sub-set of randomly selected patient case notes. Patients aged 29 to 17 years were included. AKI stage 1 was defined as a rise of 1.5 - ≤2x baseline creatinine level; AKI stage 2 a rise of ≤ 2.0 and < 3.0; AKI stage 3 a rise of ≥ 3.0. Urine output was not considered for AKI staging. Results: 57,278 creatinine measurements were analysed. 5,325 (10.8%) AKI alerts were noted in 1,112 patients with AKI 1 (62%), AKI 2 (16%) and AKI 3 (22%). There were 222 (20%) <1y, 432 (39%) 1 ≤ 6y, 192 (17%) 6 ≤ 11y, 207 (19%) 11 ≤ 16y, and 59 (5%) 16-17y. Case notes of 123 of 1,112 [11.1%] children with AKI alerts were reviewed. Confirmed AKI was recognised with a documented management plan following its identification in n = 32 [26%] patients only. Conclusions: In this first multicentre study of the incidence of AKI in children admitted to selected hospitals across England, the incidence of AKI was 10.8% with most patients under the age of 6 years and with AKI stage 1. Recognition and management of AKI was seen in just over 25% children. These data highlight the need to improve recognition of AKI in hospitalised children in the UK.

Improved blood pressure and left ventricular remodelling in children on chronic intermittent haemodialysis: a longitudinal study.

OBJECTIVES: We aimed to examine longitudinal changes in left ventricular (LV) structure and function and evaluate factors associated with LV remodelling in children on chronic haemodialysis. METHODS: Retrospective longitudinal study including all children from the start of chronic haemodialysis with two or more m-mode 2D echocardiograms and tissue Doppler studies. Left ventricular mass (LVM) in g/m2.7, geometry and LV function were compared at baseline (dialysis start) with follow-up studies at least 6 months following commencement. Left ventricular hypertrophy (LVH) was defined if greater than 95th percentile as per age-specific centiles. We also defined LVH as indexed LV mass index (LVMI) > 51 g/m2.7 and using LV mass-for-height z-scores greater than the 95th percentile. Biochemical data, interdialytic weight change and blood pressure level were assessed for their association with change in indexed LVM. RESULTS: Twenty-three of the 32 children < 18 years were included (n = 5, < 5 years) with last follow-up study performed following dialysis after a median (IQR) of 21 (10-34) months. The prevalence of LVH reduced significantly (69.6%, (n = 16/23) vs. 39.1% (n = 9/23), P = 0.002); LV geometry improved (13% concentric and 56.5% eccentric vs. 8.7% and 17.4% respectively) with mean ± SD reduction in indexed LVM (50.8 ± 23.1 g/m2.7 vs. 38.6 ± 14.7 g/m2.7, P = 0.002) and LV mass-for-height z-scores (0.67 ± 1.66 vs. - 0.46 ± 1.88, P = 0.002) from baseline to last follow-up respectively. There was no change in systolic function (LV fractional shortening, 37% vs. 38%, P = 0.39) and diastolic function (mean E/E' 10.8 vs. 9.0, P = 0.09). Multiple regression analysis identified improved systolic BP control (ß = 0.41, P = 0.04) as an independent predictor for change in indexed LVM. CONCLUSIONS: LV structure and function can improve in children despite long-term chronic intermittent haemodialysis. Cardiovascular health in this population does not always deteriorate but can be stabilised and indeed improved with optimal blood pressure management.

Renal disease in pregnancy: Fetal, neonatal and long-term outcomes.

Renal disease in women of childbearing age is estimated to be approximately 3%; consequently, renal disease is not an uncommon comorbidity in pregnancy. There has been considerable evidence published over the last 20 years to suggest that renal disease in pregnancy is associated with higher maternal, fetal, and offspring morbidity. Studies published are largely heterogeneous; include unmatched cohort studies; and focus on early neonatal outcomes such as prematurity, small for gestational age, and neonatal unit admission. There appears to be an inverse relationship between maternal renal function and likelihood of neonatal morbidity using these outcome measures. Overall though, data regarding medium-to long-term outcomes for children born to mothers with renal disease are scarce. However, in view of emerging epidemiological evidence regarding cardiovascular programming in intrauterine life in those born premature or small for gestational age, it is likely that this population of children remain at high risk of cardiovascular disease as adults. The scope of this review is to amalgamate and summarize existing evidence regarding the outcomes of infants born to mothers with renal disease. Focus will be given to pregnancy-related acute kidney injury, chronic kidney disease, dialysis, and transplantation.

Chronic kidney disease following twin-to-twin transfusion syndrome-long-term outcomes.

BACKGROUND: Amongst other sequelae, acute kidney injury (AKI) is a well-recognised post-natal complication of twin-to-twin transfusion syndrome (TTTS). Despite this, there has been a lack of data reporting long-term renal outcomes. Our aim was to report the long-term renal outcomes of infants born with TTTS. METHODS: We performed a retrospective case note review of all infants referred to our centre between 1998 and 2018 with a primary diagnosis of TTTS. Subjects with confirmed TTTS were divided into a chronic kidney disease (CKD) group and a non-CKD group for comparison. RESULTS: Twenty-six infants with TTTS were included for analysis. Eight (31%) subjects developed CKD. Within the CKD group, 50% went on to require long-term renal replacement therapy (RRT) of whom all underwent renal transplantation. For subjects who had neonatal AKI, cumulative survival rate before RRT at 5 and 10 years was 79% and 70%, respectively. Subjects with CKD had a significantly higher incidence of AKI in the neonatal period and were more likely to be the donor twin. Gestational age at birth, gender, antenatal interventions and comorbidities did not affect long-term renal outcome between the two groups. CONCLUSION: This is the first long-term follow-up study demonstrating that CKD progressing to the need for RRT can develop after TTTS. Donor-twin status and neonatal AKI associated with adverse long-term outcomes warranting long-term surveillance in this group.

Intensified home haemodialysis for managing severe cardiac failure.

BACKGROUND: Conventional thrice weekly haemodialysis (HD) provides adequate dialysis to prevent mortality, but morbidity is prevalent in both the paediatric and adult population. There has been growing interest in the potential of intensive dialysis regimes entering the realm of optimal dialysis, with superior health and quality of life outcomes. CASE DIAGNOSIS/TREATMENT: We present the case of a 13-year-old girl who had bilateral nephrectomies as a result of bilateral Wilms tumors. In the third year of treatment with conventional HD, she presented with symptomatic progressive cardiac failure, presumably secondary to anthracycline-induced cardiomyopathy. Consequently, she was taken off the renal transplant list and became increasingly dependent on frequent in-centre dialysis sessions to manage her symptoms. Five months after switching to a frequent and extended home HD regime, we observed a tremendous improvement in her health and well-being, with complete reversal of her cardiac dysfunction. CONCLUSIONS: Home HD is a practically viable option in children with severe cardiac dysfunction. Gentler, more intensive dialysis will draw out and improve the ureamic component of heart disease. This may translate into improved cardiac function.

Toxin-produced Purkinje cell death: a model for neural stem cell transplantation studies.

Purkinje cell loss is the hallmark of the cerebellar ataxias. Here the fungal neurotoxin Penitrem A was used to create partially Purkinje-cell-deficient cerebella in neonate and young adult rats suitable for use in neural stem cell transplantation studies. I.p. administration of Penitrem A to P3, P6 and 11-week old rats caused noticeable tremor in all treated animals that lasted between 1 and 3 days and was more immediate in the rat pups than in the 11-week old rats. Quantification of cresyl violet stained sections showed that Purkinje cells were preferentially lost in the cerebellar vermis and specifically in folia VI to IX (P<0.001-0.05). No change occurred in Purkinje cell number in folia I-III and folium X. These results were confirmed by the loss of calbindin binding cells in the Purkinje cell layer and the appearance of enlarged vacuolated mitochondria. The results of the present study show that the Penitrem A can remove Purkinje cells in the immature rat cerebellum and thus provide a potential model to study the micro-environmental cues in vivo for the differentiation of Purkinje cells from transplanted and/or intrinsic neural stem cells.