Using the multivariate Hawkes process to study interactions between multiple species from camera trap data.

Interspecific interactions can influence species' activity and movement patterns. In particular, species may avoid or attract each other through reactive responses in space and/or time. However, data and methods to study such reactive interactions have remained scarce and were generally limited to two interacting species. At this time, the deployment of camera traps opens new opportunities but adapted statistical techniques are still required to analyze interaction patterns with such data. We present the multivariate Hawkes process (MHP) and show how it can be used to analyze interactions between several species using camera trap data. Hawkes processes use flexible pairwise interaction functions, allowing us to consider asymmetries and variations over time when depicting reactive temporal interactions. After describing the theoretical foundations of the MHP, we outline how its framework can be used to study interspecific interactions with camera trap data. We design a simulation study to evaluate the performance of the MHP and of another existing method to infer interactions from camera trap-like data. We also use the MHP to infer reactive interactions from real camera trap data for five species from South African savannas (impala Aepyceros melampus, greater kudu Tragelaphus strepsiceros, lion Panthera leo, blue wildebeest Connochaetes taurinus and Burchell's zebra Equus quagga burchelli). The simulation study shows that the MHP can be used as a tool to benchmark other methods of interspecific interaction inference and that this model can reliably infer interactions when enough data are considered. The analysis of real data highlights evidence of predator avoidance by prey and herbivore-herbivore attraction. Lastly, we present the advantages and limits of the MHP and discuss how it can be improved to infer attraction/avoidance patterns more reliably. As camera traps are increasingly used, the multivariate Hawkes process provides a promising framework to decipher the complexity of interactions structuring ecological communities.

Prevalence of mycophenolate mofetil discontinuation and subsequent outcomes in pediatric kidney transplant recipients: A PNRC study.

BACKGROUND: Mycophenolate Mofetil (MMF) is an effective immunosuppressant used in kidney transplant recipients to prevent acute rejection. Complications such as diarrhea, leukopenia, and infections may necessitate the reduction or discontinuation of MMF. The objective of the study was to investigate the prevalence, timing, and reasons for MMF discontinuation and its association with outcomes in pediatric kidney transplant recipients. METHODS: Seven Pediatric Nephrology Research Consortium (PNRC) centers participated in a retrospective analysis of kidney transplant recipients <21 years of age. Characteristics and outcomes of patients in whom MMF was discontinued were compared to those who continued taking MMF throughout the first 2 years post-transplant. RESULTS: The study population included 288 participants (mean age 11.2 years) from 7 North American transplant centers. MMF was discontinued in 93/288 (32%) of participants. Common reasons for discontinuation included infections (35%), diarrhea (32%), leukopenia (15%), and others (18%). Increased cumulative alloimmunity (55% vs. 42%, p = .02), increased number of hospitalizations (82% vs. 67%, p = .01), and viral replications (79% vs. 47%, p < .0001) were observed in the MMF discontinuation group compared to the continuation group. Greater eGFR decline also occurred in the MMF discontinuation group over 2 years of follow-up (-7 vs. -1 mL/min/1.73 m2 , p = .05). CONCLUSIONS: Almost a third of pediatric kidney transplant recipients who begin MMF for maintenance immunosuppression have it discontinued within the first 2 years post-transplant, and this subset of patients is more likely to experience adverse outcomes. New strategies are needed to manage MMF therapy and improve post-transplant outcomes.

Ensuring our exstrophy-epispadias complex patients and families thrive.

Individuals with bladder exstrophy-epispadias complex (EEC) need long-term integrated medical/surgical and psychosocial care. These individuals are at risk for medical and surgical complications and experience social and psychological obstacles related to their genitourinary anomaly. This care needs to be accessible, comprehensive, and coordinated. Multiple surgical interventions, reoccurring hospitalizations, urinary and fecal incontinence, extensive treatment regimens for continent diversions, genital differences, and sexual health implications affect the quality of life for the EEC patient. Interventions must include psychosocial support, medical literacy initiatives, behavioral health services, school and educational consultation, peer-to-peer opportunities, referrals to disease-specific camps, mitigation of adverse childhood events (ACEs), formal transition of care to adult providers, family and teen advisory opportunities, and clinical care coordination. The priority of long-term kidney health will necessitate strong collaboration among urology and nephrology teams. Given the rarity of these conditions, multi-center and global efforts are paramount in the trajectory of improving care for the EEC population. To achieve the highest standards of care and ensure that individuals with EEC can thrive in their environment, multidisciplinary and integrated medical/surgical and psychosocial services are imperative.

Outcome of Biological Therapies and Small Molecules in Ulcerative Proctitis: A Belgian Multicenter Cohort Study.

BACKGROUND & AIMS: Several advanced therapies (biologic therapies and small molecules) have been approved for the treatment of moderate-to-severe ulcerative colitis. The registration trials for these agents typically excluded patients with isolated proctitis, leaving an evidence gap. We evaluated efficacy and safety of advanced therapies in patients with ulcerative proctitis (UP). METHODS: This multicenter retrospective cohort study included consecutive patients with active UP (Mayo endoscopy subscore of ≥2, rectal inflammation up to 15 cm) initiating advanced therapy, after failing conventional therapy. The primary end point was short-term steroid-free clinical remission (total Mayo score ≤2 with no individual subscore >1). In addition, drug persistence and relapse-free and colectomy-free survival were assessed. Both binary logistic and Cox regression analyses were performed. RESULTS: In total, 167 consecutive patients (52.0% female; median age 41.0 years; 82.0% bionaive) underwent 223 courses of therapy for UP (38 adalimumab, 14 golimumab, 54 infliximab, 9 ustekinumab, 99 vedolizumab, 9 tofacitinib). The primary end point was achieved with 36.3% of the treatment courses, and based on multivariate analysis, more commonly attained in bionaive patients (P = .001), patients treated with vedolizumab (P = .001), patients with moderate endoscopic disease activity (P = .002), and a body mass index <25 kg/m2 (P = .018). Drug persistence was significantly higher in patients treated with vedolizumab (P < .001) and patients with a shorter disease duration (P = .006). No new safety signals were observed. CONCLUSIONS: Advanced therapies are also efficacious and safe in patients with ulcerative colitis limited to the rectum. Therefore, the inclusion of patients with UP in future randomized-controlled trials should be considered.

Prospective Study of the Multisite Spread of a Medication Safety Intervention: Factors Common to Hospitals With Improved Outcomes.

Context and implementation approaches can impede the spread of patient safety interventions. The objective of this article is to characterize factors associated with improved outcomes among 9 hospitals implementing a medication safety intervention. Nephrotoxic Injury Negated by Just-in-Time Action (NINJA) is a pharmacist-driven intervention that led to a sustained reduction in nephrotoxic medication-associated acute kidney injury (NTMx-AKI) at 1 hospital. Using qualitative comparative analysis, the team prospectively assessed the association between context and implementation factors and NTMx-AKI reduction during NINJA spread to 9 hospitals. Five hospitals reduced NTMx-AKI. These 5 had either (1) a pharmacist champion and >2 pharmacists working on NINJA (Scon 1.0, Scov 0.8) or (2) a nephrologist-implementing NINJA with minimal competing organizational priorities (Scon 1.0, Scov 0.2). Interviews identified ways NINJA team leaders obtained pharmacist support or successfully implemented without that support. In conclusion, these findings have implications for future spread of NINJA and suggest an approach to study spread of safety interventions more broadly.

Post-transplant recurrence of focal segmental glomerular sclerosis: consensus statements.

Focal segmental glomerular sclerosis (FSGS) is 1 of the primary causes of nephrotic syndrome in both pediatric and adult patients, which can lead to end-stage kidney disease. Recurrence of FSGS after kidney transplantation significantly increases allograft loss, leading to morbidity and mortality. Currently, there are no consensus guidelines for identifying those patients who are at risk for recurrence or for the management of recurrent FSGS. Our work group performed a literature search on PubMed/Medline, Embase, and Cochrane, and recommendations were proposed and graded for strength of evidence. Of the 614 initially identified studies, 221 were found suitable to formulate consensus guidelines for recurrent FSGS. These guidelines focus on the definition, epidemiology, risk factors, pathogenesis, and management of recurrent FSGS. We conclude that additional studies are required to strengthen the recommendations proposed in this review.

Temporal partitioning and the potential for avoidance behaviour within South African carnivore communities.

Carnivora occupy many ecological niches fundamental to ecosystem functioning. Within this diverse order, carnivore species compete to establish dominance, ensure survival and maintain fitness. Subordinate carnivores must, therefore, adapt their behaviour to coexist with dominant species. One such strategy is the partitioning of temporal activity patterns. We aim to determine interspecific avoidance patterns among sympatric carnivores by examining coexistence along a temporal axis. We compared the temporal activity patterns of 13 carnivore species using multi-seasonal camera trapping data from four protected areas across South Africa: Associated Private Nature Reserves, Madikwe Game Reserve, Mountain Zebra National Park and Tswalu Kalahari Reserve. Interspecific coefficients of overlap in diel and core activity periods were calculated over the study period and during the wet and dry seasons. Furthermore, interspecific spatiotemporal behaviour was examined using time-to-event analyses. Our results showed that complete avoidance of diel activity patterns was rare among South African carnivore species. Most species were predominantly nocturnal and, therefore, diel activity overlap was high, whereas core activity overlap was significantly lower (p < .001). Diel activity overlap was significantly lower during the dry than wet seasons (p = .045). Lastly, evidence of spatiotemporal aggregation revolved around scavenging species. We show the importance of seasonality in the temporal avoidance behaviours of South African carnivores while highlighting the need for fine-scaled behavioural analyses. Overall, we show that the daily activity patterns of most subordinate South African carnivore species are not influenced by top-down forces in the form of competitional suppression and risk exerted by dominant species. If avoidance is required, it is more likely to manifest as fine-scaled avoidance of core activity periods. We suggest that the focus on core activity periods might be a more suitable tool for interspecific temporal partitioning research.

Optimal Care for Kidney Health: Development of a Merit-based Incentive Payment System (MIPS) Value Pathway.

The Merit-based Incentive Payment System (MIPS) is a mandatory pay-for-performance program through the Centers for Medicare & Medicaid Services (CMS) that aims to incentivize high-quality care, promote continuous improvement, facilitate electronic exchange of information, and lower health care costs. Previous research has highlighted several limitations of the MIPS program in assessing nephrology care delivery, including administrative complexity, limited relevance to nephrology care, and inability to compare performance across nephrology practices, emphasizing the need for a more valid and meaningful quality assessment program. This article details the iterative consensus-building process used by the American Society of Nephrology Quality Committee from May 2020 to July 2022 to develop the Optimal Care for Kidney Health MIPS Value Pathway (MVP). Two rounds of ranked-choice voting among Quality Committee members were used to select among nine quality metrics, 43 improvement activities, and three cost measures considered for inclusion in the MVP. Measure selection was iteratively refined in collaboration with the CMS MVP Development Team, and new MIPS measures were submitted through CMS's Measures Under Consideration process. The Optimal Care for Kidney Health MVP was published in the 2023 Medicare Physician Fee Schedule Final Rule and includes measures related to angiotensin-converting enzyme inhibitor and angiotensin receptor blocker use, hypertension control, readmissions, acute kidney injury requiring dialysis, and advance care planning. The nephrology MVP aims to streamline measure selection in MIPS and serves as a case study of collaborative policymaking between a subspecialty professional organization and national regulatory agencies.

Why humans kill animals and why we cannot avoid it.

Killing animals has been a ubiquitous human behaviour throughout history, yet it is becoming increasingly controversial and criticised in some parts of contemporary human society. Here we review 10 primary reasons why humans kill animals, discuss the necessity (or not) of these forms of killing, and describe the global ecological context for human killing of animals. Humans historically and currently kill animals either directly or indirectly for the following reasons: (1) wild harvest or food acquisition, (2) human health and safety, (3) agriculture and aquaculture, (4) urbanisation and industrialisation, (5) invasive, overabundant or nuisance wildlife control, (6) threatened species conservation, (7) recreation, sport or entertainment, (8) mercy or compassion, (9) cultural and religious practice, and (10) research, education and testing. While the necessity of some forms of animal killing is debatable and further depends on individual values, we emphasise that several of these forms of animal killing are a necessary component of our inescapable involvement in a single, functioning, finite, global food web. We conclude that humans (and all other animals) cannot live in a way that does not require animal killing either directly or indirectly, but humans can modify some of these killing behaviours in ways that improve the welfare of animals while they are alive, or to reduce animal suffering whenever they must be killed. We encourage a constructive dialogue that (1) accepts and permits human participation in one enormous global food web dependent on animal killing and (2) focuses on animal welfare and environmental sustainability. Doing so will improve the lives of both wild and domestic animals to a greater extent than efforts to avoid, prohibit or vilify human animal-killing behaviour.

Clinical course and management of children with IgA vasculitis with nephritis.

BACKGROUND: IgA vasculitis is the most common vasculitis in children and is often complicated by acute nephritis (IgAVN). Risk of chronic kidney disease (CKD) among children with IgAVN remains unknown. This study aimed to describe the clinical management and kidney outcomes in a large cohort of children with IgAVN. METHODS: This observational cohort study used the PEDSnet database to identify children diagnosed with IgAV between January 1, 2009, and February 29, 2020. Demographic and clinical characteristics were compared among children with and without kidney involvement. For children followed by nephrology, clinical course, and management patterns were described. Patients were divided into four categories based on treatment: observation, renin-angiotensin-aldosterone system (RAAS) blockade, corticosteroids, and other immunosuppression, and outcomes were compared among these groups. RESULTS: A total of 6802 children had a diagnosis of IgAV, of whom 1139 (16.7%) were followed by nephrology for at least 2 visits over a median follow-up period of 1.7 years [0.4,4.2]. Conservative management was the most predominant practice pattern, consisting of observation in 57% and RAAS blockade in 6%. Steroid monotherapy was used in 29% and other immunosuppression regimens in 8%. Children receiving immunosuppression had higher rates of proteinuria and hypertension compared to those managed with observation (p < 0.001). At the end of follow-up, 2.6 and 0.5% developed CKD and kidney failure, respectively. CONCLUSIONS: Kidney outcomes over a limited follow-up period were favorable in a large cohort of children with IgAV. Immunosuppressive medications were used in those with more severe presentations and may have contributed to improved outcomes. A higher resolution version of the Graphical abstract is available as Supplementary information.

IL-22-Activated MUC13 Impacts on Colonic Barrier Function through JAK1/STAT3, SNAI1/ZEB1 and ROCK2/MAPK Signaling.

Overexpression of the transmembrane mucin MUC13, as seen in inflammatory bowel diseases (IBD), could potentially impact barrier function. This study aimed to explore how inflammation-induced MUC13 disrupts epithelial barrier integrity by affecting junctional protein expression in IBD, thereby also considering the involvement of MUC1. RNA sequencing and permeability assays were performed using LS513 cells transfected with MUC1 and MUC13 siRNA and subsequently stimulated with IL-22. In vivo intestinal permeability and MUC13-related signaling pathways affecting barrier function were investigated in acute and chronic DSS-induced colitis wildtype and Muc13-/- mice. Finally, the expression of MUC13, its regulators and other barrier mediators were studied in IBD and control patients. Mucin knockdown in intestinal epithelial cells affected gene expression of several barrier mediators in the presence/absence of inflammation. IL-22-induced MUC13 expression impacted barrier function by modulating the JAK1/STAT3, SNAI1/ZEB1 and ROCK2/MAPK signaling pathways, with a cooperating role for MUC1. In response to DSS, MUC13 was protective during the acute phase whereas it caused more harm upon chronic colitis. The pathways accounting for the MUC13-mediated barrier dysfunction were also altered upon inflammation in IBD patients. These novel findings indicate an active role for aberrant MUC13 signaling inducing intestinal barrier dysfunction upon inflammation with MUC1 as collaborating partner.

Outcomes based on induction regimens in pediatric kidney transplantation: a NAPRTCS and PHIS collaborative study.

BACKGROUND: Induction agent used at the time of kidney transplant is often based upon center practice and recipient characteristics. We evaluated outcomes across induction therapies among children enrolled in the North American Pediatric Renal Trials and Collaborative Studies (NAPRTCS) transplant registry with data in the Pediatric Health Information System (PHIS). METHODS: This is a retrospective study of merged data from NAPRTCS and PHIS. Participants were grouped by induction agent: interleukin-2 receptor blocker (IL-2 RB), anti-thymocyte/anti-lymphocyte globulin (ATG/ALG), and alemtuzumab. Outcomes assessed included 1-, 3-, and 5-year allograft function and survival, rejection, viral infections, malignancy, and death. RESULTS: A total of 830 children transplanted between 2010 and 2019. At 1 year post-transplant, the alemtuzumab group had higher median eGFR (86 ml/min/1.73 m2) compared to IL-2 RB and ATG/ALG (79 and 75 ml/min/1.73 m2, respectively; P < 0.001); at 3 and 5 years, there was no difference. Adjusted eGFR over time was similar across all induction agents. Rejection rates were lower among the alemtuzumab group vs. IL-2RB and ATG (13.9% vs. 27.3% and 24.6%, respectively; P = 0.006). Adjusted ATG/ALG and alemtuzumab had higher hazard ratio for time to graft failure compared to IL-2 RB (HR 2.48 and HR 2.11, respectively; P < 0.05). Incidence of malignancy, mortality, and time to first viral infection was similar. CONCLUSION: Although rejection and allograft loss rates were distinct, the incidences of viral infection and malignancy were comparable across induction agents. By 3 years post-transplant, there was no difference in eGFR. A higher resolution version of the Graphical abstract is available as Supplementary information.

Position statement on the management of the immune checkpoint inhibitor-induced colitis via multidisciplinary modified Delphi consensus.

INTRODUCTION: The use of immune checkpoint inhibitors (ICIs) in cancer immunotherapy has shown increased overall survival in a wide range of cancer types with the associated risk of developing severe immune-mediated adverse events, commonly involving the gastrointestinal tract. AIM: The aim of this position statement is to provide an updated practice advice to the gastroenterologists and oncologists on the diagnosis and management of ICI-induced gastrointestinal toxicity. METHODOLOGY: The evidence reviewed in this paper includes a comprehensive search strategy of English language publications. Consensus was reached using a three-round modified Delphi methodology and approved by the members of the Belgian Inflammatory Bowel Disease Research and Development Group (BIRD), Belgian Society of Medical Oncology (BSMO), Belgian group of Digestive Oncology (BGDO), and Belgian Respiratory Society (BeRS). CONCLUSIONS: The management of ICI-induced colitis requires an early multidisciplinary approach. A broad initial assessment is necessary (clinical presentation, laboratory markers, endoscopic and histologic examination) to confirm the diagnosis. Criteria for hospitalisation, management of ICIs, and initial endoscopic assessment are proposed. Even if corticosteroids are still considered the first-line therapy, biologics are recommended as an escalation therapy and as early treatment in patients with high-risk endoscopic findings.

Evaluating Kidney Function Decline in Children with Chronic Kidney Disease Using a Multi-Institutional Electronic Health Record Database.

BACKGROUND: The objectives of this study were to use electronic health record data from a US national multicenter pediatric network to identify a large cohort of children with CKD, evaluate CKD progression, and examine clinical risk factors for kidney function decline. METHODS: This retrospective cohort study identified children seen between January 1, 2009, to February 28, 2022. Data were from six pediatric health systems in PEDSnet. We identified children aged 18 months to 18 years who met criteria for CKD: two eGFR values <90 and ≥15 ml/min per 1.73 m2 separated by ≥90 days without an intervening value ≥90. CKD progression was defined as a composite outcome: eGFR <15 ml/min per 1.73 m2, ≥50% eGFR decline, long-term dialysis, or kidney transplant. Subcohorts were defined based on CKD etiology: glomerular, nonglomerular, or malignancy. We assessed the association of hypertension (≥2 visits with hypertension diagnosis code) and proteinuria (≥1 urinalysis with ≥1+ protein) within 2 years of cohort entrance on the composite outcome. RESULTS: Among 7,148,875 children, we identified 11,240 (15.7 per 10,000) with CKD (median age 11 years, 50% female). The median follow-up was 5.1 (interquartile range 2.8-8.3) years, the median initial eGFR was 75.3 (interquartile range 61-83) ml/min per 1.73 m2, 37% had proteinuria, and 35% had hypertension. The following were associated with CKD progression: lower eGFR category (adjusted hazard ratio [aHR] 1.44 [95% confidence interval (95% CI), 1.23 to 1.69], aHR 2.38 [95% CI, 2.02 to 2.79], aHR 5.75 [95% CI, 5.05 to 6.55] for eGFR 45-59 ml/min per 1.73 m2, 30-44 ml/min per 1.73 m2, 15-29 ml/min per 1.73 m2 at cohort entrance, respectively, when compared with eGFR 60-89 ml/min per 1.73 m2), glomerular disease (aHR 2.01 [95% CI, 1.78 to 2.28]), malignancy (aHR 1.79 [95% CI, 1.52 to 2.11]), proteinuria (aHR 2.23 [95% CI, 1.89 to 2.62]), hypertension (aHR 1.49 [95% CI, 1.22 to 1.82]), proteinuria and hypertension together (aHR 3.98 [95% CI, 3.40 to 4.68]), count of complex chronic comorbidities (aHR 1.07 [95% CI, 1.05 to 1.10] per additional comorbid body system), male sex (aHR 1.16 [95% CI, 1.05 to 1.28]), and younger age at cohort entrance (aHR 0.95 [95% CI, 0.94 to 0.96] per year older). CONCLUSIONS: In large-scale real-world data for children with CKD, disease etiology, albuminuria, hypertension, age, male sex, lower eGFR, and greater medical complexity at start of follow-up were associated with more rapid decline in kidney function.

Survival of neonates born with kidney failure during the initial hospitalization.

BACKGROUND: Survival to hospital discharge in neonates born with kidney failure has not been previously described. METHODS: This was a retrospective, observational analysis of the Pediatric Health Information System (PHIS) database from 2005 to 2019. Primary outcome was survival at discharge; secondary outcomes were hospital and ICU length of stay (LOS). Univariate analysis was performed to describe the population by birth weight (BW) and characterize survival; multivariable generalized liner mixed modeling assuming a binomial distribution and logit link was performed to identify mortality risk factors. RESULTS: Of 213 neonates born with kidney failure (median BW 2714 g; GA 35 weeks; 68% male), 4 (1.9%) did not receive dialysis or peritoneal dialysis (PD) catheter placement, 152 (72.9%) received PD only, 49 (23.4%) received PD plus extracorporeal dialysis (ECD), and 8 (3.4%) were treated with an undocumented dialysis modality. Median age at dialysis initiation was 7 days; median hospital LOS and ICU LOS were 84 and 69 days, respectively. One-hundred and sixty-two patients (76%) survived to discharge. Non-survivors (n = 51) were more likely to have received ECD and mechanical ventilation, and had a longer duration of mechanical ventilation. Every day of mechanical ventilation increased the mortality odds by 2% (n = 189; adjusted OR 1.02; 1.01, 1.03); in addition, the odds of mortality were 2 times higher in those who received ECD vs. only PD (adjusted OR 2.25; 1.04, 4.86). CONCLUSIONS: Survival to initial hospital discharge occurs in the majority of neonates born with kidney failure. Predictors of increased mortality included longer duration of mechanical ventilation, as well as the requirement for ECD. A higher resolution version of the Graphical abstract is available as Supplementary information.

Skeletal Outcomes in Children and Young Adults with Glomerular Disease.

BACKGROUND: Children with glomerular disease have unique risk factors for compromised bone health. Studies addressing skeletal complications in this population are lacking. METHODS: This retrospective cohort study utilized data from PEDSnet, a national network of pediatric health systems with standardized electronic health record data for more than 6.5 million patients from 2009 to 2021. Incidence rates (per 10,000 person-years) of fracture, slipped capital femoral epiphysis (SCFE), and avascular necrosis/osteonecrosis (AVN) in 4598 children and young adults with glomerular disease were compared with those among 553,624 general pediatric patients using Poisson regression analysis. The glomerular disease cohort was identified using a published computable phenotype. Inclusion criteria for the general pediatric cohort were two or more primary care visits 1 year or more apart between 1 and 21 years of age, one visit or more every 18 months if followed >3 years, and no chronic progressive conditions defined by the Pediatric Medical Complexity Algorithm. Fracture, SCFE, and AVN were identified using SNOMED-CT diagnosis codes; fracture required an associated x-ray or splinting/casting procedure within 48 hours. RESULTS: We found a higher risk of fracture for the glomerular disease cohort compared with the general pediatric cohort in girls only (incidence rate ratio [IRR], 1.6; 95% CI, 1.3 to 1.9). Hip/femur and vertebral fracture risk were increased in the glomerular disease cohort: adjusted IRR was 2.2 (95% CI, 1.3 to 3.7) and 5 (95% CI, 3.2 to 7.6), respectively. For SCFE, the adjusted IRR was 3.4 (95% CI, 1.9 to 5.9). For AVN, the adjusted IRR was 56.2 (95% CI, 40.7 to 77.5). CONCLUSIONS: Children and young adults with glomerular disease have significantly higher burden of skeletal complications than the general pediatric population.

Treatment of primary hyperoxaluria type 1.

Supportive treatment for primary hyperoxaluria type 1 (PH1) focuses on high fluid intake and crystallization inhibitors. A subset of patients with specific PH1 genotypes (c.508G>A and c.454T>A) will respond to pyridoxine, defined as a >30% reduction in urinary oxalate excretion. Response to pyridoxine is variable and in some patients, urinary oxalate may normalize. The first focused treatment for PH1 using an RNA interference agent to reduce urinary oxalate was approved in 2020, and such therapies may significantly alter treatment approaches and long-term outcomes in PH1. Currently PH1 often presents with kidney function impairment and frequently results in end-stage kidney disease (ESKD). With kidney dysfunction, urinary oxalate clearance decreases and multisystem deposition of oxalate (oxalosis) occurs, commonly in bones, eyes, heart and skin. Once plasma oxalate levels exceed 30 µmol/L, aggressive haemodialysis is indicated to prevent oxalosis, even if the glomerular filtration rate (GFR) remains better than for typical dialysis initiation. Peritoneal dialysis alone does not achieve the needed oxalate clearance. Dialysis is a bridge to future transplantation. Liver transplantation restores hepatic alanine-glyoxylate transaminase enzyme activity, allowing glyoxylate detoxification and preventing further oxalosis. The native liver must be removed as part of this process to avoid ongoing pathologic oxalate production. The timing and type of liver transplantation are dependent on pyridoxine sensitivity, age, weight, residual GFR and evidence of systemic oxalate deposition in extrarenal organs. Liver transplant can be isolated or combined with kidney transplantation in a sequential or simultaneous fashion. Isolated kidney transplantation is generally reserved for pyridoxine-sensitive patients only. Although liver transplantation is curative for PH1 and kidney transplantation treats ESKD, ensuing necessary immunosuppression and potential allograft dysfunction impart significant long-term risks.

Treatment of post-transplant recurrent FSGS in children using plasmapheresis and augmentation of immunosuppression.

BACKGROUND: Up to 60% of pediatric renal transplant recipients with end-stage renal disease due to primary focal and segmental glomerulosclerosis (FSGS) may develop recurrent disease. Such recurrence is associated with poor prognosis if no remission is achieved. We report a single center experience with a protocol based on plasmapheresis and increased immunosuppression that resulted in a high long-lived remission rate. METHODS: This retrospective cohort study included consecutive pediatric renal transplant patients with recurrent FSGS treated with a standardized protocol using plasmapheresis and cyclophosphamide to supplement usual post-transplant immunosuppression with calcineurin inhibitors and steroids. Relapse was defined as urinary protein/creatinine ratio > 1.0 g/g and remission as < 0.5 g/g. RESULTS: Seventeen patients with FSGS recurrence post-transplant were treated. All had therapy resistant FSGS in native kidneys and had been on dialysis from 4 to 10 years. Of the 17, one died perioperatively from a pulmonary thromboembolism. Fifteen others achieved a complete remission within 3 months of treatment for FSGS recurrence. After a median follow-up period of 4 years, there were no recurrences of significant proteinuria. One patient achieved remission with rituximab. CONCLUSION: The addition of plasmapheresis and cyclophosphamide to a calcineurin- and steroid-based immunosuppression regime was highly successful in inducing high remission rates with recurrent FSGS. Prospective trials are needed to evaluate further the efficacy of increased immunosuppression along with plasmapheresis in this setting.