Stephen D. Marks

Context: Congenital hyperinsulinism (HI) with polycystic kidney disease (PKD), or HIPKD, is a recently described syndrome caused by a specific promotor variant in PMM2, a gene otherwise associated with PMM2 congenital disorder of glycosylation. Objective: To describe the HIPKD clinical phenotype, expanding our understanding and its distinction from the congenital disorder of glycosylation phenotype. Design: Retrospective multicenter cohort study of individuals with HIPKD identified through an international HI genetic referral center. Patients: Ten individuals from 9 families compound heterozygous for the promoter variant c.-167G > T and a pathogenic intragenic variant in PMM2. Intervention: None. Main Outcome Measures: Observed clinical features and outcomes. Results: Median age of presentation was 5 months (range 0-42). Median age at follow up was 12.7 years (range 5.4-20.1). HI was managed with diazoxide monotherapy (7/10 patients), diazoxide and nifedipine (2/10 patients), and carbohydrate supplementation alone (1/10 patient). PKD age at diagnosis and severity was variable, ranging from antenatal presentation requiring renal transplantation, to incidental detection in mid-childhood. Liver cysts were noted in 6/10 patients (5/6 with normal liver function). Five of 7 patients had systemic hypertension and 3/5 were normotensive on losartan at last follow up. Inflammatory bowel disease (IBD) with gastric antral foveolar hyperplasia occurred in 4/10 patients, and aortic root and/or ascending aortic dilation in 4/7 patients who underwent echocardiography, 3 of whom also had IBD. Conclusion: HIPKD due to a PMM2 promoter variant is associated with broad, multisystem phenotype, including IBD and aortic dilation. These findings support targeted screening for IBD and cardiovascular surveillance in addition to standard endocrine and renal follow up.

Key Points: Among 72 patients with childhood-onset ANCA-associated vasculitis, kidney transplant survival was good (86%). ANCA-associated vasculitis relapse occurred in 8 patients (11%), a median of 71 months after transplantation and resulted in graft failure in only one case. Positive ANCA at the time of transplantation did not predict graft failure but was associated with a higher risk of relapse and worse graft function. Background: ANCA-associated vasculitis (AAV) is rare in children, and results in kidney failure in up to one third of cases. There is very limited knowledge on kidney transplantation in childhood-onset AAV. We assessed kidney transplantation outcomes and prognostic factors in a multicenter cohort of patients with childhood-onset AAV. Methods: Patients diagnosed with AAV during childhood (≤18 years) who received a kidney transplant were included in this retrospective study. We determined patient and graft survival, rates of chronic graft dysfunction (defined as eGFR 2 for ≥3 months) and AAV relapse, and assessed determinants of outcome with logistic regression models. Patients were matched 1:2 for age, sex, and era of transplantation with non-AAV recipients from the Hospital for Sick Children in Toronto, Canada, and their graft survival was compared. Results: We included 72 patients, of whom 53 (74%) had microscopic polyangiitis and 19 (26%) granulomatosis with polyangiitis. Their median age (interquartile range at the time of diagnosis and transplantation was 12 (9–14) and 14 (12–16) years, respectively. After a median post-transplant follow-up of 53 months (interquartile range, 25–97), 70 patients (97%) were alive, 62 (86%) had a functioning graft, 28 (39%) had developed chronic graft dysfunction, and 8 (11%) had experienced AAV relapse. Graft survival was comparable between AAV and non-AAV recipients. Acute rejection was the only independent predictor of graft failure (hazard ratio [HR], 12.11; 95% confidence interval [CI], 1.19 to 122.49). Positive ANCA at the time of transplantation was significantly associated with a chronic graft dysfunction (HR, 4.16; 95% CI, 1.71 to 10.13) and AAV relapse (HR, 23.1; 95% CI, 2.67 to 200.28). Conclusions: Patients with childhood-onset AAV show good overall and graft survival after kidney transplantation and a low rate of post-transplant relapse. Further studies are warranted to confirm whether positive ANCA at the time of transplantation is associated with poorer graft outcomes.

Kidney transplantation is the gold standard treatment for children and young people (CYP) with stage 5 chronic kidney disease (CKD). However, psychosocial and structural factors including race, socioeconomic status and family context can delay or limit access to transplantation. This systematic review explores the breadth of psychological, social and societal factors influencing transplant access, outcomes and quality of life. We included peer-reviewed quantitative, qualitative and mixed-method studies with primary data. Medline, PsychInfo, CINAHL and Web of Science were searched for papers published in English between January 1964 and November 2022. A total of 66 studies (52 quantitative, 10 qualitative and 4 mixed-methods) were identified and analysed. A wide breadth of psychosocial factors were identified: mental health, adjustment to CKD, non-adherence, beliefs, motivation, cognitive status, family structure, family relationships, trust in or relationship with healthcare professionals, health insurance, infrastructure, education, geography, socioeconomic status (SES), social support, housing, religion or culture, national or regional wealth, migrant status-driven or racialised health inequities and kidney allocation policies. Among these studies, 13 qualified for meta-analysis regarding SES and race. CYP experiencing lower SES as a potential stressor were more likely to access deceased donor transplantation, less likely to access pre-emptive transplantation and more likely to experience allograft failure. CYP from racially minoritised groups had reduced access to living donor and pre-emptive transplantation, and higher rates of allograft loss. These inequities were often mediated by structural racism, implicit bias, allocation policies and overlapping systems of disadvantage. There is a wide breadth of psychosocial factors that influence the lived experience of CKD and access to and outcomes after transplantation. Race, as a proxy for racism, interacts with SES, geography and other social determinants through an intersectional process that deepens inequities. Some factors are modifiable at the clinical or family level, while others require systemic change. Addressing these inequities will require multi-tiered strategies, from clinician education on bias to reforms in allocation policy and broader social structures. Further studies are needed to better understand the complex relationship between these psychosocial factors and kidney transplantation outcomes. Prospero Registration. number CRD42020210506. Graphical Abstract A higher resolution version of the Graphical abstract is available as Supplementary information

In the context of limited donor availability and long waiting times for deceased donor transplantation, ABO-incompatible kidney transplantation (ABOiKT) do

Pediatric anti-phospholipid syndrome (APS) is a rarely diagnosed multisystem autoimmune inflammatory disorder resulting in recurrent vascular thrombosis with serious clinical implications. We highlight a case of an adolescent female who presented with Catastrophic APS (CAPS) in hypertensive emergency and end organ damage. She developed reduced kidney function, fluid overload and neurological manifestations. Neuroimaging and kidney biopsy confirmed micro-angiopathic thrombosis. Her blood results showed high titers of triple positive anti-phospholipid antibodies with negative serology for other immunological conditions. She was managed with dual anti-coagulation and immunosuppression and remains under pediatric subspecialist follow-up for ongoing multisystem involvement. APS should be considered as a differential diagnosis in children presenting with sepsis and multi-organ dysfunction. Pediatric focused diagnostic criteria and long-term management is needed to cater to needs of the pediatric population.

PURPOSE: Childhood, adolescent, and young adult (CAYA) survivors of cancer are at risk of nephrotoxicity. Surveillance guidelines are important for timely diagnosis and treatment of these survivors, which could slow the progression to higher stages of kidney dysfunction. METHODS: The International Late Effects of Childhood Cancer Guideline Harmonization Group established a multidisciplinary panel of 34 experts from 11 countries. The panel performed systematic literature reviews for articles published between 1990 and June 2023, graded the evidence using Grading of Recommendations Assessment, Development, and Evaluation methodology, and formulated recommendations based on evidence, clinical judgment, and consideration of benefits and harms of surveillance. Recommendations were critically appraised by two independent external experts and patient representatives. RESULTS: Glomerular dysfunction surveillance is recommended every 2-5 years for survivors treated with ifosfamide, cisplatin, abdominal radiotherapy, total body irradiation, or nephrectomy and is reasonable after carboplatin treatment. We recommend screening for glomerular dysfunction using an estimated glomerular filtration rate (eGFR) equation that includes serum creatinine, preferably combined with serum cystatin C if available. Tubular dysfunction surveillance is recommended once at entry into long-term follow-up and with follow-up as clinically indicated for survivors treated with ifosfamide and is reasonable after cisplatin treatment. CONCLUSION: These recommendations inform routine, uniform long-term follow-up care for CAYA survivors of cancer at risk of nephrotoxicity.

Childhood-onset systemic lupus erythematosus (cSLE) is a severe lifelong and life-threatening autoimmune disease with multi-organ involvement. Compared to those with adult-onset disease, cSLE patients have more aggressive disease with a higher prevalence of early lupus nephritis (LN) causing worse kidney and patient outcomes. The transfer of adolescent patients to adult healthcare poses several major challenges, from a disease as well as a psychosocial perspective. Transitional care even in tertiary centers can be heterogenous, suboptimal, and often even non-existent. In this comprehensive review of the literature, we synthesize the obstacles adolescents and young adults (AYA) with systemic lupus erythematosus (SLE) and LN face and how these challenges impact the transfer to adult health care. Finally, we propose a framework for a structured and individually modifiable transitional care plan, tailored to the unique needs of this population and taking into account their social and cultural background. This framework includes suggestions for the timing of the preparatory phase and the transfer itself, the composition of the transitional care team, increasing transition readiness and treatment adherence, and establishing a supportive network of peers. Efficient transitional care will optimize long-term patient outcomes. Graphical Abstract