Disparities in treatment and outcome of kidney replacement therapy in children with comorbidities: an ESPN/ERA Registry study.

Background: Data on comorbidities in children on kidney replacement therapy (KRT) are scarce. Considering their high relevance for prognosis and treatment, this study aims to analyse the prevalence and implications of comorbidities in European children on KRT. Methods: We included data from patients <20 years of age when commencing KRT from 2007 to 2017 from 22 European countries within the European Society of Paediatric Nephrology/European Renal Association Registry. Differences between patients with and without comorbidities in access to kidney transplantation (KT) and patient and graft survival were estimated using Cox regression. Results: Comorbidities were present in 33% of the 4127 children commencing KRT and the prevalence has steadily increased by 5% annually since 2007. Comorbidities were most frequent in high-income countries (43% versus 24% in low-income countries and 33% in middle-income countries). Patients with comorbidities had a lower access to transplantation {adjusted hazard ratio [aHR] 0.67 [95% confidence interval (CI) 0.61-0.74]} and a higher risk of death [aHR 1.79 (95% CI 1.38-2.32)]. The increased mortality was only seen in dialysis patients [aHR 1.60 (95% CI 1.21-2.13)], and not after KT. For both outcomes, the impact of comorbidities was stronger in low-income countries. Graft survival was not affected by the presence of comorbidities [aHR for 5-year graft failure 1.18 (95% CI 0.84-1.65)]. Conclusions: Comorbidities have become more frequent in children on KRT and reduce their access to transplantation and survival, especially when remaining on dialysis. KT should be considered as an option in all paediatric KRT patients and efforts should be made to identify modifiable barriers to KT for children with comorbidities.

Mixed-methods research in nephrology.

Mixed-methods research involves the mixing of at least 1 qualitative and 1 quantitative method in the same research project or set of related projects. Combined use of qualitative and quantitative research methods in nephrology has increased over the last 10 years. In this review, we aim to advance the understanding of mixed-methods research within the kidney community. Qualitative and quantitative techniques provide different but noncompeting representations of what exists in the world; findings from qualitative research do not generalize to a large population, whereas those from quantitative research may not apply to individuals within the diverse and heterogeneous larger population. Mixed-methods research combines these complementary representations, allowing the strengths of each method to be combined and the strengths of 1 method to address the limitations of the other. Mixed-methods approaches can be used to: (i) gain a more complete understanding of a research problem, (ii) explain initial results from one method with results from another, (iii) generate instruments, for example, survey tools and interventions, (iv) evaluate services, and (v) optimize clinical trial design and delivery. There are 3 core mixed-methods designs: explanatory sequential, exploratory sequential, and convergent parallel, which can be combined. We discuss each design in turn before discussing analysis and integration of findings from the different methods. We provide case studies that illustrate the application of these study designs to kidney research questions. We briefly discuss mixed-methods systematic reviews and evidence synthesis before finally highlighting guidance on how to appraise published mixed-methods research.

Associations between Deprivation, Geographic Location, and Access to Pediatric Kidney Care in the United Kingdom.

BACKGROUND AND OBJECTIVES: Pre-emptive kidney transplantation is advocated as best practice for children with kidney failure who are transplant eligible; however, it is limited by late presentation. We aimed to determine whether socioeconomic deprivation and/or geographic location (distance to the center and rural/urban residence) are associated with late presentation, and to what degree these factors could explain differences in accessing pre-emptive transplantation. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A cohort study using prospectively collected United Kingdom Renal Registry and National Health Service Blood and Transplant data from January 1, 1996 to December 31, 2016 was performed. We included children aged >3 months to ≤16 years at the start of KRT. Multivariable logistic regression models were used to determine associations between the above exposures and our outcomes: late presentation (defined as starting KRT within 90 days of first nephrology review) and pre-emptive transplantation, with a priori specified covariates. RESULTS: Analysis was performed on 2160 children (41% females), with a median age of 3.8 years (interquartile range, 0.2-9.9 years) at first nephrology review. Excluding missing data, 478 were late presenters (24%); 565 (26%) underwent pre-emptive transplantation, none of whom were late presenting. No association was seen between distance or socioeconomic deprivation with late presentation, in crude or adjusted analyses. Excluding late presenters, greater area affluence was associated with higher odds of pre-emptive transplantation, (odds ratio, 1.20 per quintile greater affluence; 95% confidence interval, 1.10 to 1.31), with children of South Asian (odds ratio, 0.52; 95% confidence interval, 0.36 to 0.76) or Black ethnicity (odds ratio, 0.31; 95% confidence interval, 0.12 to 0.80) less likely to receive one. A longer distance to the center was associated with pre-emptive transplantation on crude analyses; however, this relationship was attenuated (odds ratio, 1.02 per 10 km; 95% confidence interval, 0.99 to 1.05) in the multivariable model. CONCLUSIONS: Socioeconomic deprivation or geographic location are not associated with late presentation in children in the United Kingdom. Geographic location was not independently associated with pre-emptive transplantation; however, children from more affluent areas were more likely to receive a pre-emptive transplant.

Associations with kidney transplant survival and eGFR decline in children and young adults in the United Kingdom: a retrospective cohort study.

BACKGROUND: Although young adulthood is associated with transplant loss, many studies do not examine eGFR decline. We aimed to establish clinical risk factors to identify where early intervention might prevent subsequent adverse transplant outcomes. METHODS: Retrospective cohort study using UK Renal Registry and UK Transplant Registry data, including patients aged < 30 years transplanted 1998-2014. Associations with death-censored graft failure were investigated with multivariable Cox proportional hazards. Multivariable linear regression was used to establish associations with eGFR slope gradients calculated over the last 5 years of observation per individual. RESULTS: The cohort (n = 5121, of whom n = 371 received another transplant) was 61% male, 80% White and 36% had structural disease. Live donation occurred in 48%. There were 1371 graft failures and 145 deaths with a functioning graft over a 39,541-year risk period. Median follow-up was 7 years. Fifteen-year graft survival was 60.2% (95% CI 58.1, 62.3). Risk associations observed in both graft loss and eGFR decline analyses included female sex, glomerular diseases, Black ethnicity and young adulthood (15-19-year and 20-24-year age groups, compared to 25-29 years). A higher initial eGFR was associated with less risk of graft loss but faster eGFR decline. For each additional 10 mL/min/1.73m2 initial eGFR, the hazard ratio for graft loss was 0.82 (95% CI 0.79, 0.86), p < 0.0001. However, compared to < 60 mL/min/1.73m2, higher initial eGFR was associated with faster eGFR decline (> 90 mL/min/1.73m2; - 3.55 mL/min/1.73m2/year (95% CI -4.37, - 2.72), p < 0.0001). CONCLUSIONS: In conclusion, young adulthood is a key risk factor for transplant loss and eGFR decline for UK children and young adults. This study has an extended follow-up period and confirms common risk associations for graft loss and eGFR decline, including female sex, Black ethnicity and glomerular diseases. A higher initial eGFR was associated with less risk of graft loss but faster rate of eGFR decline. Identification of children at risk of faster rate of eGFR decline may enable early intervention to prolong graft survival.

Paediatric anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis: an update on renal management.

The anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV) are a group of disorders characterized by necrotizing inflammation of the small to medium vessels in association with autoantibodies against the cytoplasmic region of the neutrophil. Included in this definition are granulomatosis with polyangiitis (GPA, formerly known as Wegener's granulomatosis), microscopic polyangiitis (MPA) and eosinophilic granulomatosis with polyangiitis (formerly known as Churg-Strauss syndrome). AAV are chronic, often relapsing diseases that can be organ or life threatening. Despite immunosuppression, the morbidity and mortality remain high. Renal involvement contributes significantly to the morbidity with high numbers of patients progressing to end-stage kidney disease. Current therapies have enabled improvements in renal function in the short term, but evidence for long-term protection is lacking. In MPA, renal involvement is common at presentation (90%) and often follows a more severe course than that seen in paediatric GPA. Renal biopsy remains the 'gold standard' in diagnosing ANCA-associated glomerulonephritis. While GPA and MPA are considered separate entities, the two are managed identically. Current treatment regimens are extrapolated from adult studies, although it is encouraging to see recruitment of paediatric patients to recent vasculitis trials. Traditionally more severe disease has been managed with the 'gold standard' treatment of glucocorticoids and cyclophosphamide, with remission rates achieved of between 70 and 100%. Other agents employed in remission induction include anti-tumor necrosis factor-alpha therapy and mycophenolate mofetil. Recently, however, increasing consideration is being given to rituximab as a therapy for children in severe or relapsing disease, particularly for those at risk for glucocorticoid or cyclophosphamide toxicity. Removal of circulating ANCA through plasma exchange is a short-term measure reserved for severe or refractory disease. Maintenance therapy usually involves azathioprine. The aim of this article is to provide a comprehensive review of paediatric AAV, with a focus on renal manifestations, and to highlight the recent advances made in therapeutic management.

Continually improving standards of care: The UK Renal Registry as a translational public health tool.

A disease registry uses observational study methods to collect defined data on patients with a particular condition for a predetermined purpose. By providing comprehensive standardised data on patients with kidney disease, renal registries aim to provide a 'real world' representation of practice patterns, treatment and patient outcomes that may not be captured accurately by other methods, including randomised controlled trials. Additionally, using registries to measure variations in outcomes and audit care against standards is crucial to understanding how to improve quality of care for patients in an efficacious and cost-effective manner. Registries also have the potential to be a powerful scientific tool that can monitor and support the translational process between research and routine clinical practice, although their limitations must be borne in mind. In this review, we describe the role of the UK Renal Registry as a tool to support translational research. We describe its involvement across each stage of the translational pathway: from hypothesis generation, study design and data collection, to reporting of long-term outcomes and quality improvement initiatives. Furthermore we explore how this role may bring about improvements in care for adults and children with kidney disease.

Unilateral hypoplastic kidney - a novel highly penetrant feature of familial juvenile hyperuricaemic nephropathy.

BACKGROUND: Familial juvenile hyperuricaemic nephropathy is a rare inherited nephropathy with genetic heterogeneity. Categorised by genetic defect, mutations in uromodulin (UMOD), renin (REN) and hepatocyte nuclear factor-1ß (HNF-1ß) genes as well as linkage to chromosome 2p22.1-21 have previously been identified. Knowledge of the genetics of this phenotype has provided important clues to developmental pathways in the kidney. CASE PRESENTATION: We report a novel phenotype, with the typical features of hyperuricemia and renal deterioration, but with the additional unexpected feature of unilateral renal hypoplasia. Mutation analyses of the existing known genes and genetic loci were negative indicating a new monogenic cause. Interestingly two cousins of the index case did not share the latter feature, suggesting a modifier gene effect. CONCLUSION: Unilateral renal hypo/aplasia is usually sporadic and relatively common, with no genetic cause to date identified. This reported pedigree reveals the possibility that a new, unknown renal developmental gene may be implicated in the FJHN phenotype.

Longitudinal changes in body mass index following renal transplantation in UK children.

BACKGROUND: Childhood obesity is a significant health problem in the UK. To date, there is little known about the pattern of change in body mass index (BMI) following renal transplantation in UK paediatric patients. Our objectives in this study were to (i) describe trends in BMI seen in UK patients undergoing renal transplantation in the short and medium term and (ii) identify risk factors predisposing children to excessive weight gain following transplantation. METHODS: A retrospective case note review was performed across 12 of 13 paediatric nephrology centres in the UK, with BMI measurements recorded pre-transplantation and for 4 years thereafter. BMI% was used to assess changes in adiposity over time. International Obesity Taskforce definitions of overweight and obesity were used to identify the prevalence of excess weight pre- and post-renal transplantation. RESULTS: A total of 159 patients (113 boys) under the age of 18 with a functioning kidney transplant were included. Fifty-six patients (35.2%) were under the age of 5 at transplantation. Pre-transplantation, 31.4% of patients were classified as overweight or obese, which increased to 52.8% by the end of follow-up. The majority of patients experienced rapid increases in BMI% over the initial four months post-transplantation, which were sustained for the remainder of the follow-up period. The major risk factor for being overweight or obese at the end of follow-up was having excessive weight pre-transplantation. Four years following transplantation, the prevalence rate of overweight and obesity was much higher in our study cohort than the normal UK childhood population. CONCLUSIONS: The prevalence of patients classified as overweight or obese in the UK paediatric renal cohort is high pre-transplantation and rises subsequently. Those at risk can be identified by an unhealthy BMI pre-transplantation and will require timely intervention with close monitoring in the subsequent post-transplantation period.