Developing a trigger tool to monitor adverse events during haemodialysis in children: a pilot project.

BACKGROUND: We developed a paediatric haemodialysis trigger tool (pHTT) for application per haemodialysis (HD) session in children receiving intermittent in-centre HD and systematically monitored adverse events. METHODS: Single-centre quality improvement study performed over two 8-week cycles. Data collected prospectively using a 'per-dialysis session' pHTT tool including 54 triggers across six domains, adapted from a recently described haemodialysis trigger tool (HTT) for adults. Each trigger was evaluated for level of harm following assessment by two authors. Following a period of training, HD nurses completed the HTT at the end of each dialysis session. RESULTS: There were 241 triggers over 182 dialysis sessions, with 139 triggers in 91 HD sessions for 15 children, age range 28-205 months, over an 8-week period (first cycle) and 102 triggers in 91 HD sessions for 13 children, age range 28-205 months, over a further 8-week period (second cycle). After interventions informed by the pHTT, the harm rate per session was significantly reduced from 1.03 (94/91) to 0.32 (29/91), P < 0.001. There was a significant difference between the distribution of triggers by harm category (P < 0.001) and between the proportion of triggers across the various domains of the pHTT (P = 0.004) between the two cycles. No triggers were evaluated as causing permanent harm. CONCLUSIONS: This pilot study demonstrates potential benefits of a bedside tool to monitor adverse events during haemodialysis in children. Thus, following interventions informed by the pHTT, the harm rate per session was significantly reduced. Under standard patient safety systems, the vast majority of triggers identified by the pHTT would remain unreported and perhaps lead to missed opportunities to improve patient safety. We propose the use of a paediatric HTT as part of standard care by centres providing HD to children in the future. A higher resolution version of the Graphical abstract is available as Supplementary information.

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.

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.

Vitamin B6 blood concentrations in paediatric dialysis patients.

OBJECTIVES: We investigated vitamin B6 blood concentrations in children on long-term dialysis at our centre. METHODS: Retrospective cross-sectional review of vitamin B6 blood concentrations in children on maintenance dialysis [peritoneal dialysis (PD), intermittent haemodialysis (IHD)]. RESULTS: We reviewed 28 children (16 boys), 15 IHD and 13 PD with median (interquartile range, IQR) age of 9.4 (2.4, 14.3) years. The median (IQR) vitamin B6 concentration was 223.4 (74.2, 392.8) nmol/L measured a median (IQR) of 9 (4, 16.5) months following commencement of dialysis. None of the children had vitamin B6 deficiency. Vitamin B6 concentrations were raised in 17 (61%), eight of these received a supplement. Nineteen (68%) received vitamin B6 and/or a supplement containing vitamin B6 whilst 11 (39%) received an enteral feed and a supplement. In those with normal vitamin B6 concentrations who were not receiving an enteral feed or an oral nutritional supplement (n = 6), all achieved normal concentrations without need for vitamin B6 supplementation. There were no differences between those on PD versus IHD (269.2 nmol/L vs. 130 nmol/L, P = 0.65). CONCLUSIONS: We report no children with vitamin B6 deficiency although > 50% had elevated vitamin B6 concentrations. We suggest if dietary assessment of vitamin B6 intake indicates insufficient intake, measurement of blood concentrations will help confirm if supplementation is required. Routine vitamin B6 supplementation and monitoring is currently not indicated in children on chronic dialysis.

Trace element and vitamin concentrations in paediatric dialysis patients.

BACKGROUND: There are few recent data regarding blood micronutrient concentrations and supplementation in children on maintenance dialysis. We investigated micronutrient concentrations following dialysis commencement. METHODS: Retrospective review, including all children on maintenance dialysis (peritoneal dialysis, PD; intermittent haemodialysis, IHD), for nutritional blood concentrations measured over the first 12 months. Patients received pyridoxine and Dialyvit® daily with planned 3-monthly micronutrient concentration monitoring including selenium, manganese, copper, zinc, folate and vitamins A, D, B12 and E. RESULTS: We reviewed 47 children (24 girls) including 19 PD and 28 IHD, median age (IQR) 11.4 (2.8,14.4) years. 33 were white, 5 Asian, 5 black and 4 of other ethnic origins. Vitamin A, B12 and E concentrations were within range in 6%, 20% and 13% respectively, with all others above normal range. Serum folate and vitamin D concentrations were within the desired range of 55%, with the rest above or below target. For trace elements, 37%, 60%, 65% and 89% achieved normal ranges for zinc, manganese, copper and selenium respectively. Deficiencies were seen for zinc (43%), copper (28%), folate (6%) and selenium (4%), whereas 7%, 7%, 20% and 40% had copper, selenium, zinc and manganese levels above normal ranges. Despite standard pyridoxine supplementation, only 6 children were monitored during the study period. CONCLUSIONS: Concentrations of several trace elements and vitamins were outside reference ranges. Response to systematic monitoring and targeted supplementation should be evaluated in future studies. Paediatric dialysis centres should consider undertaking routine nutritional bloods monitoring, particularly for vitamin D, zinc and copper.

An unusual cause of severe persistent neutropenia in a child with nephrotic syndrome.

A 5-year-old boy presented with neutropenia 9 weeks following the administration of rituximab for management of his steroid-dependent nephrotic syndrome. Extensive investigations failed to identify any underlying cause. In keeping with adult reports, rituximab was thought to be the likely cause for this 'late-onset' neutropenia (LOP). He was treated successfully with granulocyte-colony-stimulating factor. Patients treated with rituximab need to be carefully monitored for LOP.

The demographic characteristics of children with chronic kidney disease stages 3-5 in South East England over a 5-year period.

OBJECTIVE: To analyse the demographics of children with moderate to severe chronic kidney disease (CKD) stages 3-5 over a 5-year period for the population of South East England. METHODS: Retrospective study of all children <18 years of age with estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m(2) managed at Evelina Children's Hospital, London from 2005 to 2009. eGFR was estimated using the Schwartz formula, and stages of CKD were defined using Kidney Disease Outcome Quality Initiative criteria. We excluded all patients with a functioning kidney transplant. RESULTS: There were 293 children (58% male) with a median (IQR) age of 6.7 (2.3, 12.1) years; 288 were aged <16 years and five 16-18 years at first presentation. The mean incidence and prevalence of children <16 years with CKD stage 3-5 during the 5-year study period was 17.5 and 90.0 per million age-related population (pmarp), respectively. There was a marked increase in incidence and prevalence over the 5 years (incidence 8.4 to 25.2 pmarp; prevalence 79.5 to 104.7 pmarp). There was an initial peak in children presenting under 2 years of age (48/141, 34%) due to congenital renal disease, and a second peak in the 12-15.9-year age group (32/141, 23%) due to glomerulonephritides. Forty-five children (15%) were transplanted, and 22 (8%) transitioned to adult care. There were seven deaths giving a death rate of 0.84 per 100 patient-years. CONCLUSIONS: We observed a steady increase in the incidence and prevalence of children with CKD stage 3-5. As a result of improved management, the majority of children with CKD will proceed to kidney transplantation, transition to adult nephrology services, and continue to require lifelong medical care.

Distribution of ABO blood group antibody titers in pediatric patients awaiting renal transplantation: implications for organ allocation policy.

BACKGROUND: Blood group-incompatible transplantation is one strategy used when a potential recipient does not have a compatible living donor. Current practice includes desensitization strategies to reduce antibody titers. However, when antibodies are low, in cardiac transplantation in neonates for example, no desensitization is required. This study is the first to examine the distribution of ABO blood group antibody titers in a population of pediatric patients on the deceased-donor renal transplantation waiting list. METHODS: All patients from two pediatric nephrology centers active on the national deceased-donor waiting list had antibody titers (total immunoglobulin load) measured. A simulation modeling the effect of allocating blood group-incompatible deceased-donor kidneys to those patients with titers of 16 or lower was developed. RESULTS: Twenty-four children were screened; eight (33.3%) had titers of either anti-A or anti-B antibodies of 8 or lower. A further three (12.5%) had either an anti-A or anti-B antibody titer of 16. Blood group A or B patients had lower antibody levels than blood group O patients. In blood group O patients, levels of anti-A antibodies were higher than anti-B antibodies (Wilcoxon signed rank test, P=0.028). The simulation model showed that a change in organ allocation policy would increase pediatric transplant activity by 2.2% and reduce the median waiting time for a transplant. CONCLUSION: This allocation strategy may be of particular benefit to those pediatric patients who have been on the deceased-donor waiting list for a long time or those with a high calculated reaction frequency.

Systemic arterial hypertension in children following renal transplantation: prevalence and risk factors.

BACKGROUND: Control of blood pressure (BP) following renal transplantation may improve allograft and patient survival. Our aims were (i) to describe the distribution of BP and the prevalence of systolic and/or diastolic hypertension in children over the first 5 years following renal transplantation and (ii) to evaluate clinical risk factors and centre-specific factors associated with hypertension in this population. METHODS: We conducted a retrospective case note review of all current paediatric kidney transplant patients in the UK, with data collected at 6 months, 1, 2 and 5 years following transplantation in subjects with hypertension (systolic and/or diastolic BP > 95th > ) and non-hypertensive subjects BP ≤ 95th > . RESULTS: In total, 27.3% (117/428), 27.6% (118/428), 26.0% (95/365) and 25.6% (50/195) of the patients were hypertensive (systolic and/or diastolic BP > 95th > ) at 6 months, 1, 2 and 5 years following transplantation, respectively. A total of 58.4% of the patients at 6 months, 52.8% at 1 year, 48.2% at 2 years and 48.2% at 5 years were receiving anti-hypertensive therapy, of whom 31.6-36.6% remained hypertensive. When subjects were identified as being hypertensive, on anti-hypertensive medication or had untreated hypertension (systolic and/or diastolic BP > 95th > ), 66.4, 61.0, 56.4 and 55.9% of patients were hypertensive at 6 months, 1, 2 and 5 years, respectively. In a multivariate model, odds ratios for systolic hypertension were 4.16 (deceased versus living donor), 2.65 (lowest versus highest quartile of height z-score) and 2.07 (if on anti-hypertensive; yes versus no). There was significant variation in prevalent rates of hypertension between centres (P < 0.0001) that remained significant (P = 0.003) after adjustment for all the factors in the multivariate model. CONCLUSIONS: Control of BP after kidney transplantation remains sub-optimal in paediatric centres in the UK. Just over 25% of patients remain hypertensive 5 years following transplantation. Significant differences between centres remain unexplained and may reflect differences in assessment and management of hypertension.

Progression to hypertension in non-hypertensive children following renal transplantation.

BACKGROUND: The aim of this study was to evaluate in non-hypertensive children following renal transplantation (TX) the rates and determinants of transition to hypertension. METHODS: Retrospective case note review of all current paediatric kidney transplant patients in the UK. At baseline (6 months following TX), all included subjects were non-hypertensive with systolic and/or diastolic clinic blood pressure (BP) ≤95th percentile while on no anti-hypertensive therapy. We assessed progression from optimal (systolic and/or diastolic clinic BP<50th percentile), normal (systolic and/or diastolic clinic BP≥50th but <90th percentile) and pre-hypertension (systolic and/or diastolic clinic BP 90th-95th percentile) to hypertension (systolic and/or diastolic clinic BP>95th percentile). If systolic and diastolic BP levels belonged to different categories, the higher of the two levels were used for categorization. RESULTS: At baseline, 146 of 524 (27.9%) children (106 male) median [inter-quartile range (IQR)] age 7.8 years (4.8, 11.8) were non-hypertensive and not on any anti-hypertensive therapy; there were 34 patients (23.2%) with optimal BP, 90 (61.6%) with normal BP and 22 (15.1%) with pre-hypertension. They were followed up for a median of 2.0 (1.0, 4.0) years post-TX. At the end of follow-up, BP was optimal in 37 patients (25.3%), normal in 35 (24.0%), high normal in 2 (1.4%) and 72 (49.3%) had progressed to hypertension. The Kaplan-Meier estimated time at which 50% of patients developed hypertension was 2.0 years for the pre-hypertension and 3.0 years in the normal BP group as opposed to 40% risk at 7-year post-TX in the optimal group (P=0.001 between the three groups). The differences between BP groups remained significant after adjustment for all risk factors on multivariate analysis. CONCLUSIONS: Just over 49% of our initially non-hypertensive patients progressed to hypertension following TX. BP needs careful monitoring post-TX and ideally should be maintained in the 'normal' and 'optimal' range.

Factors affecting success of blood pressure measurements during ambulatory blood pressure monitoring in children with renal disease.

AIM: To analyse blood pressure characteristics during 24-hour ambulatory blood pressure monitoring in children and to assess factors that influence its success over 24 hours and during patient-recorded awake (DAY) and sleep (NIGHT) periods. METHODS: A total of 169 consecutive ambulatory blood pressure monitoring studies were conducted in 154 patients over 30 months. For each ambulatory study, we measured the percentage of successful measurements both at the first attempt (S-initial%) and following any automated repeat attempt if initial attempts had failed (S-final%). These were measured over 24-hour, DAY, and NIGHT periods. RESULTS: We found that blood pressure measurements at NIGHT were more successful than measurements attempted during the DAY (p<0.05). There was no influence of age, gender, height, weight, body mass index and estimated glomerular filtration rate with the proportion of successful measurements during the 24-hour, DAY, and NIGHT periods. On stepwise multiple regression analysis, the indexed mean systolic blood pressure over 24 hours was the only factor having a significant influence on the proportion of successful measurements over the 24-hour and DAY periods, although it only accounted for three-tenths of the variance; it had no influence on the overall success of measurements at NIGHT. CONCLUSION: Ambulatory blood pressure monitoring in children provides reliable data both during the patient's awake and sleep periods with higher success of measurements at NIGHT as opposed to DAY periods.

Blood pressure control and left ventricular mass in children with chronic kidney disease.

BACKGROUND AND OBJECTIVES: Heart disease is a major cause of death in young adults with chronic kidney disease (CKD). Left ventricular hypertrophy (LVH) is common and is associated with hypertension. The aims of this study were to evaluate whether there is a relationship between LVH and BP in children with CKD and whether current targets for BP control are appropriate. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: In this single-center cross-sectional study, 49 nonhypertensive children, (12.6 ± 3.0 years, mean GFR 26.1 ± 12.9 ml/min per 1.73 m²) underwent echocardiographic evaluation and clinic and 24-hour ambulatory BP monitoring. LVH was defined using age-specific reference intervals for left ventricular mass index (LVMI). Biochemical data and clinic BP for 18 months preceding study entry were also analyzed. RESULTS: The mean LVMI was 37.8 ± 9.1 g/m²·7, with 24 children (49%) exhibiting LVH. Clinic BP values were stable over the 18 months preceding echocardiography. Patients with LVH had consistently higher BP values than those without, although none were overtly hypertensive (> 95th percentile). Multiple linear regression demonstrated a strong relationship between systolic BP and LVMI. Clinic systolic BP showed a stronger relationship than ambulatory measures. Of the confounders evaluated, only elemental calcium intake yielded a consistent, positive relationship with LVMI. CONCLUSIONS: LVMI was associated with systolic BP in the absence of overt hypertension, suggesting that current targets for BP control should be re-evaluated. The association of LVMI with elemental calcium intake questions the appropriateness of calcium-based phosphate binders in this population.

Evaluation of blood pressure in children.

PURPOSE OF REVIEW: This review briefly highlights origins of hypertension with emphasis on the influences of gestation, birth weight, salt intake, and adiposity. We focus on the role of ambulatory blood pressure monitoring, and the assessment of comorbidity and target organ change in hypertensive children and adolescents. RECENT FINDINGS: Low birth weight, prematurity and uric acid levels are associated with hypertension early in childhood and in young adult life, not just in later adult life. Reduction of dietary salt intake leads to significant reductions in blood pressure in infants and young children. Newly applied techniques for assessment of target organ damage in children include arterial studies using retinal photography, ultrasound assessment of arterial intima-media thickness, and applanation tonometry. SUMMARY: Overweight and obesity are increasingly common, and are major determinants of high blood pressure in children, in both the developed and developing world. Initial evaluation of the hypertensive child must include carefully confirming if they are hypertensive using published reference data for blood pressure in children, and increasingly through ambulatory blood pressure monitoring. Left ventricular hypertrophy based on echocardiography remains the most widely used indirect marker of hypertensive end organ change. New techniques for assessing target organ damage are being developed.

Management of congenital nephrotic syndrome.

We reviewed the medical records of seven children with congenital nephrotic syndrome (CNS) treated by unilateral nephrectomy, captopril, and indomethacin since 1990. Clinical response to the treatment was analyzed using the Students' t-test. After a median period of 54 months (range 36-88 months) follow-up, five patients were alive at a median age of 74 (range 43-88) months. Median (range) plasma albumin rose from 11 (6-17) g/l at the start of treatment to 18 (15-22) g/l and 21 (18-25) g/l after 6 and 12 months treatment, respectively ( P=0.001 and P=0.0006). Albumin infusions per patient per month decreased from 7 (0-18) to 0 (0-30) in the 6 months post treatment ( P=0.017). The median (range) height standard deviation scores at 12 months and 30 months from onset of treatment were -1.56 (-2.96 to 0.41) and -1.43 (-2.40 to 0.90), respectively. In conclusion, management of CNS with captopril and indomethacin therapy in combination with unilateral nephrectomy achieves significant improvements in plasma albumin and reduces the need for albumin infusions and time in hospital, while growth is maintained. Second nephrectomy, dialysis, and transplantation can be delayed until the 3rd year of life or longer.