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Background Limited data suggest children with secondary steroid-resistant nephrotic syndrome (secondary SRNS) have increased risk of recurrence post transplantation. There are no data on the association between secondary steroid resistance and risk of transplant loss. Methods Children who received kidney transplantation between 2000 and 2019 for either primary or secondary SRNS in Australia and New Zealand were included. Children presenting with nephrotic syndrome before 12 months were excluded. Data were gathered from chart reviews and ANZDATA. Transplant survival was estimated using the Kaplan-Meier estimator with Cox modelling used to explore predictors of survival. Results There were seventy children, 38 (55%) male, median age at presentation 4 years (IQR 2-7) and 46 (66%) Caucasian. Median age at transplant was 11 years (IQR 7-15) and 39 (55%) received living donor transplant. Secondary SRNS occurred in 20/70 (29%). For those with secondary SRNS, 18/20 (90%) had recurrence post-transplant, compared to 18/50 (36%) with primary SRNS (p = 0.001). Every child with history of atopy (n = 11) or with hypoalbuminaemia at time of transplant (n = 13) experienced immediate recurrence. For children with secondary SRNS, 8/18 (44%) with post-transplant recurrence had no response to therapy. For children with primary SRNS, 4/18 (22%) with recurrence had no response to therapy (p = 0.3). Overall, 10-year transplant survival was 47% (95%CI 29-77%) for those with secondary SRNS, compared to 71 (95%CI 57-88%) for those with primary SRNS (p = 0.05). Conclusions Secondary steroid resistance is strongly associated with SRNS recurrence. Atopy and hypoalbuminaemia at transplant may be novel risk factors for recurrence. Further research is needed to assess if secondary steroid resistance is associated with poorer transplant outcomes. Graphical abstract 'A higher resolution version of the Graphical abstract is available as Supplementary information'., Author(s): Anna Francis [sup.1] , Chanel Prestidge [sup.2] , Joshua Kausman [sup.3] , Amelia Le Page [sup.4] , Nicholas Larkins [sup.5] , Hugh McCarthy [sup.6] Author Affiliations: (1) grid.240562.7, Department [...]

Background Young children starting kidney replacement therapy (KRT) suffer high disease burden with unique impacts on growth and development, timing of transplantation and long-term survival. Contemporary long-term outcome data and how these relate to patient characteristics are necessary for shared decision-making with families, to identify modifiable risk factors and inform future research. Methods We examined outcomes of all children [less than or equal to] 5 years enrolled in the Australia and New Zealand Dialysis and Transplant Registry, commencing KRT 1980-2017. Primary outcomes were patient and graft survival. Final height attained was also examined. We used generalized additive modelling to investigate the relationship between age and graft loss over time post-transplant. Results In total, 388 children were included, of whom 322 (83%) received a kidney transplant. Cumulative 1-, 5- and 10-year patient survival probabilities were 93%, 86% and 83%, respectively. Death censored graft survival at 1, 5 and 10 years was 93%, 87% and 77%, respectively. Most children were at least 10 kg at transplantation (n = 302; 96%). A non-linear relationship between age at transplantation and graft loss was observed, dependent on time post-transplant, with increased risk of graft loss among youngest recipients both initially following transplantation and subsequently during adolescence. Graft and patient survival have improved in recent era. Conclusions Young children commencing KRT have good long-term survival and graft outcomes. Early graft loss is no reason to postpone transplantation beyond 10 kg, and among even the youngest recipients, late graft loss risk in adolescence remains one of the greatest barriers to improving long-term outcomes., Author(s): Nicholas G. Larkins [sup.1] [sup.2] [sup.3] , Germaine Wong [sup.3] [sup.4] [sup.5] , Stephen I. Alexander [sup.5] [sup.6] , Stephen McDonald [sup.7] [sup.8] , Chanel Prestidge [sup.9] , Anna [...]

BackgroundTreatment decisions in kidney transplantation requires patients and clinicians to weigh the benefits and harms of a broad range of medical and surgical interventions, but the heterogeneity and lack of patient-relevant outcomes across trials in transplantation makes these trade-offs uncertain, thus, the need for a core outcome set that reflects stakeholder priorities.MethodsWe convened 2 international Standardized Outcomes in Nephrology-Kidney Transplantation stakeholder consensus workshops in Boston (17 patients/caregivers; 52 health professionals) and Hong Kong (10 patients/caregivers; 45 health professionals). In facilitated breakout groups, participants discussed the development and implementation of core outcome domains for trials in kidney transplantation.ResultsSeven themes were identified. Reinforcing the paramount importance of graft outcomes encompassed the prevailing dread of dialysis, distilling the meaning of graft function, and acknowledging the terrifying and ambiguous terminology of rejection. Reflecting critical trade-offs between graft health and medical comorbidities was fundamental. Contextualizing mortality explained discrepancies in the prioritization of death among stakeholders-inevitability of death (patients), preventing premature death (clinicians), and ensuring safety (regulators). Imperative to capture patient-reported outcomes was driven by making explicit patient priorities, fulfilling regulatory requirements, and addressing life participation. Specificity to transplant; feasibility and pragmatism (long-term impacts and responsiveness to interventions); and recognizing gradients of severity within outcome domains were raised as considerations.ConclusionsStakeholders support the inclusion of graft health, mortality, cardiovascular disease, infection, cancer, and patient-reported outcomes (ie, life participation) in a core outcomes set. Addressing ambiguous terminology and feasibility is needed in establishing these core outcome domains for trials in kidney transplantation.

Evidence-informed decision making in clinical care and policy in nephrology is undermined by trials that selectively report a large number of heterogeneous outcomes, many of which are not patient centered. The Standardized Outcomes in Nephrology-Hemodialysis (SONG-HD) Initiative convened an international consensus workshop on November 7, 2015, to discuss the identification and implementation of a potential core outcome set for all trials in hemodialysis. The purpose of this article is to report qualitative analyses of the workshop discussions, describing the key aspects to consider when establishing core outcomes in trials involving patients on hemodialysis therapy. Key stakeholders including 8 patients/caregivers and 47 health professionals (nephrologists, policymakers, industry, and researchers) attended the workshop. Attendees suggested that identifying core outcomes required equitable stakeholder engagement to ensure relevance across patient populations, flexibility to consider evolving priorities over time, deconstruction of language and meaning for conceptual consistency and clarity, understanding of potential overlap and associations between outcomes, and an assessment of applicability to the range of interventions in hemodialysis. For implementation, they proposed that core outcomes must have simple, inexpensive, and validated outcome measures that could be used in clinical care (quality indicators) and trials (including pragmatic trials) and endorsement by regulatory agencies. Integrating these recommendations may foster acceptance and optimize the uptake and translation of core outcomes in hemodialysis, leading to more informative research, for better treatment and improved patient outcomes.

Objective Hypertension is increasingly recognized as a disease spanning the entire life course. Continued efforts to refine the diagnosis and management of hypertension in children are highlighted by the recent American Academy of Pediatrics (AAP) guidelines, which include lower threshold values than the previous reference standard (Fourth Report). We aimed to determine the population-based prevalence of children exceeding thresholds for hypertension using these two guidelines. We also sought to identify the correlates of blood pressure (BP) among Australian children. Methods Cross-sectional data from the Growing Up in Australia: Longitudinal Survey of Australian Children were analyzed. Blood pressure was measured in 7139 Australian children aged 10-12 years and sampled using population-based methodology. The association between BP and explanatory variables linked to BP in other populations was examined using multiple linear regression with fractional polynomial terms for continuous, non-linear relationships. Results The threshold for hypertension was exceeded in 3.1% and 5.4%, and prehypertension in 3.0% and 3.7% of children, using the Fourth Report and AAP guidelines respectively. Children at the threshold for obesity had a 9.1 mmHg higher adjusted BP than those on the 50th centile for body mass index (BMI) (95% CI 8.4 to 9.9). BMI had a non-linear relationship with BP, and the magnitude of association between BMI and BP increased with BMI. Socioeconomic status, hypertension during pregnancy, birth weight, and sports participation were also independently associated with BP. Conclusions Using the AAP guidelines is likely to substantially increase the population prevalence of hypertension. The association between BMI and BP was strongest and non-linear for obese children, who should be the focus of interventional trials., Author(s): Nicholas G. Larkins [sup.1] [sup.2] [sup.3] , Armando Teixeira-Pinto [sup.2] [sup.3] , Siah Kim [sup.4] [sup.5] , David P. Burgner [sup.6] [sup.7] [sup.8] , Jonathan C. Craig [sup.2] [sup.3] [...]

Missing data is an important and common source of bias in clinical research. Readers should be alert to and consider the impact of missing data when reading studies. Beyond preventing missing data in the first place, through good study design and conduct, there are different strategies available to handle data containing missing observations. Complete case analysis is often biased unless data are missing completely at random. Better methods of handling missing data include multiple imputation and models using likelihood-based estimation. With advancing computing power and modern statistical software, these methods are within the reach of clinician-researchers under guidance of a biostatistician. As clinicians reading papers, we need to continue to update our understanding of statistical methods, so that we understand the limitations of these techniques and can critically interpret literature., Author(s): Nicholas G. Larkins [sup.1] [sup.2] , Jonathan C. Craig [sup.2] [sup.3] , Armando Teixeira-Pinto [sup.2] [sup.3] Author Affiliations: (Aff1) 0000 0004 0625 8600, grid.410667.2, Department of Nephrology, Princess Margaret [...]

Objectives To determine the population-based prevalence of albuminuria in Australian children and validate any negative correlation with body mass index (BMI). Methods Data from the Australian Health Survey 2011-2013 were used. This is a large-scale survey of the health of the Australian population, conducted by the Australian Bureau of Statistics, and uses a stratified, multistage area design with replicate weights attached to observations to allow for the derivation of accurate population estimates. We considered children aged 5-18 years, and defined albuminuria as an albumin-to-creatinine ratio (ACR) >30 mg/g (3.4 mg/mmol). Results A total of 975 children provided urine samples for determination of ACR. The prevalence of albuminuria was 10.2% for males (95% confidence interval [CI] 6.1-14.2) and 15.5% for females (95% CI 10.7-20.3). After adjusting for age and gender, the odds ratio for albuminuria associated with being overweight or obese was 0.34 (95% CI 0.15-0.75). This relationship also held for waist-to-height ratio, where the adjusted odds ratio for each 0.1 increase was 0.46 (95% CI 0.26-0.82). Conclusions Albuminuria, using a measurement suitable for population-based and clinical screening, occurs in 12.8% of school-aged Australian children, and is less common in overweight and obese children., Author(s): Nicholas Larkins [sup.1] [sup.2] , Armando Teixeira-Pinto [sup.2] [sup.3] , Jonathan Craig [sup.2] [sup.3] Author Affiliations: (1) Department of Nephrology, Princess Margaret Hospital, 0000 0004 0625 8600, grid.410667.2, , [...]

Background The Kidney Donor Profile Index (KDPI) is routinely reported by the donation agencies in Australia. We determined the association between KDPI and short-term allograft loss and assessed if this association was modified by the estimated post-transplant survival (EPTS) score and total ischaemic time. Methods Using data from the Australia and New Zealand Dialysis and Transplant Registry, the association between KDPI (in quartiles) and 3-year overall allograft loss was examined using adjusted Cox regression analysis. The interactive effects between KDPI, EPTS score and total ischaemic time on allograft loss were assessed. Results Of 4006 deceased donor kidney transplant recipients transplanted between 2010 and 2015, 451 (11%) recipients experienced allograft loss within 3 years post-transplant. Compared with recipients of kidneys with a KDPI of 0–25%, recipients who received donor kidneys with a KDPI >75% experienced a 2-fold increased risk of 3-year allograft loss {adjusted hazard ratio [HR] 2.04 [95% confidence interval (CI) 1.53–2.71]}. The adjusted HRs for kidneys with a KDPI of 26–50% and 51–75% were 1.27 (95% CI 0.94–1.71) and 1.31 (95% CI 0.96–1.77), respectively. There were significant interactions between KDPI and EPTS scores (P -value for interaction <.01) and total ischaemic time (P -value for interaction <.01) such that the associations between higher KDPI quartiles and 3-year allograft loss were strongest in recipients with the lowest EPTS scores and longest total ischaemic time. Conclusion Recipients with higher post-transplant expected survival and transplants with longer total ischaemia who received donor allografts with higher KDPI scores experienced a greater risk of short-term allograft loss compared with those recipients with reduced post-transplant expected survival and with shorter total ischemia. [ABSTRACT FROM AUTHOR]