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Author(s): Damien G. Noone [sup.1] [sup.2] , Magdalena Riedl [sup.3] , Christoph Licht [sup.1] [sup.2] [sup.3] [sup.4] [sup.5] Author Affiliations: (Aff1) 0000 0004 0473 9646, grid.42327.30, Division of Nephrology, The [...], Thrombotic microangiopathy (TMA) is caused by thrombus formation in the microvasculature. The disease spectrum of TMA includes, amongst others, thrombotic thrombocytopenic purpura (TTP) and atypical haemolytic uraemic syndrome (aHUS). TTP is caused by defective cleavage of von Willebrand factor (VWF), whereas aHUS is caused by overshooting complement activation and subsequent endothelial cell (EC) injury. Despite their distinct pathophysiology, the clinical manifestation of TTP and aHUS consisting of microangiopathic haemolytic anaemia and thrombocytopenia is often similar and difficult to distinguish. Recent evidence hints at both a genetic and functional link between TTP and aHUS, especially between VWF and the complement system. There is novel in vitro evidence that complement activation not only results in VWF release from ECs, but that VWF also functions as a negative complement regulator, thus protecting the EC surface from ongoing complement attack. Although contrary to previous experimental work suggesting that complement can be activated on VWF multimers, there may be an explanation in vivo that rationalizes these apparently contradictory findings, whereby a system primarily meant to regulate becomes overwhelmed or pathologic in the disease state. The importance of unravelling these recent findings for our understanding of TMA pathology becomes even more evident considering that glomerular ECs express VWF in a heterogeneous pattern with an overall decreased expression level, thus potentially leaving the glomerular ECs vulnerable to complement-mediated injury. Taken together, these findings support the concept that TTP and aHUS represent two extreme ends of a TMA disease spectrum rather than isolated disease entities.

Objective The objective of this study was to identify nephrology topics of lowest perceived competency and importance for general paediatricians. Methods Surveys were distributed to general paediatricians, paediatric residents, paediatric residency program directors, and paediatric nephrologists. Perceived importance and competence were rated on a 5-point Likert scale. Means and 95% confidence intervals were calculated. Results Mean perceived competency from general paediatricians across all nephrology domains was 3.0, 95%CI (2.9 to 3.1) and mean importance was 3.2, 95%CI (3.1 to 3.3). Domains scoring below the means for competence and importance, respectively were kidney stones (2.5, 95%CI [2.2 to 2.7]) and 2.6, 95%CI [2.3 to 2.8]), acute kidney injury (2.5, 95%CI [2.2 to 2.8] and 2.4, 95%CI [2.1 to 2.8]), chronic kidney disease (1.9, 95%CI [1.7 to 2.2] and 2.1, 95%CI [1.8 to 2.4]), tubular disorders (1.8, 95%CI [1.6 to 2.0] and 2.0, 95%CI [1.8 to 2.3]), and kidney transplant (1.6, 95%CI [1.4 to 1.8] and 1.7, 95%CI [1.4 to 1.9]). Residents, program directors, and paediatric nephrologists agreed that stones, chronic kidney disease, tubular disorders, and transplant were of lower importance. However, acute kidney injury was the domain with the largest discrepancy in perceived importance between residents (4.4, 95%CI [4.2 to 4.6]), nephrologists (4.2, 95%CI [3.8 to 4.6]), and program directors (4.2, 95%CI [3.7 to 4.7]) compared to general paediatricians ([2.4, 95%CI [2.1 to 2.8]; P<0.05). Conclusion Paediatricians did not believe acute kidney injury was important to their practice, despite expert opinion and evidence of long-term consequences. Educational interventions must address deficits in crucial domains of renal health in paediatrics. [ABSTRACT FROM AUTHOR]

Background: Wilson disease (WD) is a disorder of copper metabolism that results in accumulation of copper in tissues. In acute WD, patients present with fulminant hepatic failure, encephalopathy, and hemolytic anemia due to copper release from necrotic hepatocytes. Many will require life-saving liver transplantation. Extracorporeal liver support systems can provide a bridge to transplantation for critically ill patients. We report our experience with 2 patients for whom we used a combination of plasma exchange (PLEX) and single pass albumin dialysis (SPAD), or SPAD alone as a bridge to liver transplantation. Case Reports: A 17-year-old girl (patient 1) and a 12-year-old boy (patient 2) presented with fulminant hepatic failure, hemolytic anemia, and acute kidney injury. Patient 1 received SPAD on days 2 and 3 (total 32 h). Serum copper decreased from 22.3 to 15.9 µmol/L (28.7% decrease), measured after 28 h of continuous SPAD. She underwent successful liver transplantation on day 4 after presentation. Patient 2 was treated with PLEX on days 1, 3, 4, and 5 and with SPAD on days 3–6. Serum copper decreased from 48.7 to 25.8 µmol/L (47% decrease) after the first session of PLEX and from 35.5 to 21.5 µmol/L (39.4% decrease) after the second session. The serum copper level was 16.2 µmol/L after 4 sessions of PLEX (and ongoing SPAD), with an overall 66.7% reduction in copper levels over 5 days combining both therapies. He underwent successful liver transplantation on day 6. Conclusion: We conclude that SPAD, with or without PLEX, is effective in reducing serum copper levels as a bridge to liver transplantation in WD. PLEX may be more efficient at removing copper but is associated with a rebound increase in copper levels between sessions. [ABSTRACT FROM AUTHOR]

Nephrotic syndrome is defined by nephrotic-range proteinuria (≥40 mg/m2/hour or urine protein/creatinine ratio ≥200 mg/mL or 3+ protein on urine dipstick), hypoalbuminaemia (<25 g/L) and oedema. This review focuses on the classification, epidemiology, pathophysiology, management strategies and prognosis of idiopathic nephrotic syndrome of childhood, and includes a brief overview of the congenital forms. [ABSTRACT FROM PUBLISHER]

In contrast to adults where hypertension is a leading cause of chronic kidney disease, in pediatrics, hypertension is predominantly a sequela, however, an important one that, like in adults, is likely associated with a more rapid decline in kidney function or progression of chronic kidney disease to end stage. There is a significant issue with unrecognized, or masked, hypertension in childhood chronic kidney disease. Recent evidence and, therefore, guidelines now suggest targeting a blood pressure of <50th percentile for age, sex, and height in children with proteinuria and chronic kidney disease. This often cannot be achieved by monotherapy and additional agents need to be added. Blockade of the renin angiotensin aldosterone system represents the mainstay of therapy, although often limited by the side effect of hyperkalemia. The addition of a diuretic, at least in the earlier stages of chronic kidney disease, might help mitigate this problem. [ABSTRACT FROM AUTHOR]

Background: Cuffed, double-lumen, tunneled haemodialysis catheters are a common means of vascular access in paediatric haemodialysis, particularly in infants. Haemodialysis catheter fracture with distal embolization is a rare complication. Case Report: A 2-year-old boy was receiving chronic haemodialysis via a right internal jugular cuffed, double-lumen, tunneled haemodialysis catheter, inserted 3 months previously. He was asymptomatic and was incidentally found to have had embolization of a fractured catheter tip into a segmental branch of the left pulmonary artery. The catheter was replaced and the embolized fragment successfully retrieved, non-surgically, using an image-guided endovascular approach with a loop snare device. Conclusion: Haemodialysis catheter fracture with distal embolization is a rare complication in both adults and children and is usually associated with prolonged use and catheter fatigue. Retrieval of the embolized fragment should always be attempted to prevent possible complications. Awareness of this potential complication is important to facilitate diagnosis and management. [ABSTRACT FROM AUTHOR]

Objectives: High-dose glucocorticoids for remission-induction of ANCA-associated vasculitis are recommended and commonly used in adults, but recent studies suggest lower glucocorticoid doses can reduce toxicity without reducing efficacy. No paediatric-specific data exists to inform optimal glucocorticoid dosing in paediatric ANCA-associated vasculitis (pAAV). Our objectives were to describe glucocorticoid use in pAAV-related renal disease, and to explore associations between glucocorticoid dose, baseline patient characteristics and 12-month outcomes., Methods: Youth <18 years with pAAV, biopsy-confirmed pauci-immune glomerulonephritis and 12-month follow-up data were included from an international paediatric vasculitis registry. Presenting features and 12-month outcomes (eGFR, glucocorticoid-related adverse effects), were compared between patients receiving no, low-moderate (≤90mg/kg) and high (>90mg/kg) cumulative intravenous methylprednisolone (IVMP), and low (<0.5mg/kg/day prednisone equivalent), moderate (0.5-1.5mg/kg/day) and high (>1.5mg/kg/day) starting doses of oral glucocorticoids., Results: Among 131 patients (101 granulomatosis with polyangiitis, 30 microscopic polyangiitis), 27 (21%) received no IVMP, 64 (49%) low-moderate and 29 (22%) high-dose IVMP, while 9 (7%) received low, 75 (57%) moderate and 47 (36%) high initial doses of oral glucocorticoids. Renal failure at diagnosis (p=0.022) and plasmapheresis use (p=0.0001) were associated with high-dose IVMP. Rates of glucocorticoid-related adverse effects ranged from 15-31% across dose levels, and glucocorticoid dosing did not associate with 12-month outcomes., Conclusions: Glucocorticoid dosing for pAAV-related renal disease was highly variable, and rates of adverse effects were high across all dosing groups. A significant proportion of patients received oral glucocorticoid or IVMP doses that were discordant with current adult guidelines. Higher glucocorticoid doses did not associate with improved outcomes.

Objectives: Transitioning from paediatric to adult care can be challenging. Whereas transition models of care have been shared in some rheumatological conditions, reported experience in vasculitis is lacking., Methods: Retrospective chart review of adolescents aged 16-18 years assessed at the vasculitis transition clinic by paediatric and adult rheumatologists, and then scheduled for follow-up at the Adult Vasculitis Clinic (Toronto, Canada) from January 2013 until May 2020., Results: Twenty-eight patients were seen at the transition clinic and included. Mean age at transition was 17 years and 11 (± SD 2) months, with a mean follow up from diagnosis of 32 (± 24) months. Most patients had ANCA-associated vasculitis (N=19, 39%), followed by Takayasu's arteritis (N=4, 14%); all but one were in remission at the time of transition. Twenty-six (93%) patients showed up for their first booked adult visit (two did not, were called and rebooked), after a mean of 4 (± 2) months after transition clinic. Subsequently, two patients missed 1 appointment, and three missed ≥ 2 appointments; only one (4%) stopped coming, while in remission for >2 years post-transition. Five (18%) patients were identified to have medication non-adherence after transition. With a mean follow up post-transition of 32 (± 25) months, 7 (25%) patients had minor and five (18%) had major relapses, at a mean of 17 (± 9) and 25 (± 15) months post-transition, respectively (compared to 12 (43%) and 9 (32%) prior to transition). At their last visit, all were in remission, 18 (64%) off glucocorticoids, and damage had remained stable., Conclusions: This model of care of vasculitis transition clinic resulted in favourable outcomes, as reflected by continuity of follow-up, and no increased risk of relapse.

Background and Objectives: A proposed histopathologic classification for ANCA-associated GN is predictive of long-term renal outcome in adult populations. This study sought to validate this system in a pediatric cohort., Design, Setting, Participants, & Measurements: This was a retrospective, single-center, cohort study of 40 children diagnosed and followed until their transition to adult care at one institution between 1987 and 2012. Renal biopsy specimens were reviewed by a pathologist blinded to patient outcome and were classified using the new histopathologic classification system of focal, crescentic, mixed, and sclerotic groups. Time to the composite outcome of CKD stages 3 and 4 (determined by eGFR with repeated creatinine measures using the Schwartz equation) or ESRD (defined as dialysis dependence or transplantation) were ascertained., Results: The study population consisted of 40 children (70% female), followed for a median of 2.4 years. The biopsy specimens were categorized as focal in 13 patients (32.5%), crescentic in 20 (50%), mixed in two (5%), and sclerotic in five (12.5%). Mixed and crescentic were combined for analyses. Survival analysis of time to the composite renal endpoint of at least 3 months of eGFR<60 ml/min per 1.73 m(2) or ESRD differed significantly among the three biopsy groups log-rank P<0.001), with an adjusted hazard ratio of 3.14 (95% confidence interval, 0.68 to 14.4) in the crescentic/mixed group and 23.6 (95% confidence interval, 3.9 to 144.2) in the sclerotic category compared with the focal category. The probability of having an eGFR>60 ml/min per 1.73 m(2) at 2 years was 100% for the focal, 56.5% for the crescentic/mixed, and 0% for the sclerotic biopsy categories., Conclusions: This study showed the clinical utility of this histopathologic classification system and its ability to discriminate renal outcomes among children with ANCA GN., (Copyright © 2014 by the American Society of Nephrology.)