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Yaira Hamama-Raz,1 Yaacov Frishberg,2 Menachem Ben-Ezra,1 Yafit Levin1 1School of Social Work, Ariel University, Ariel, Israel; 2Division of Pediatric Nephrology, Shaare Zedek Medical Center, Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, IsraelCorrespondence: Yaira Hamama-Raz, Email yairahr@ariel.ac.ilBackground: Medication adherence among adolescents and emerging adults following kidney transplantation was found to be lower with harmful consequences. The current study aimed to examine associations between illness cognition of helplessness, family relationships, and perceived barriers to medication adherence among post-kidney transplant adolescent and emerging adult recipients and their parents by applying a dyadic perspective.Methods: Fifty-nine dyads of adolescents and emerging adults aged 11– 26 years and their parents, were recruited from a pediatric nephrology department in a medical center in Israel. Both adolescents and emerging adults and parents completed self-report questionnaires addressing illness cognition of helplessness (subscale of Illness Cognition Questionnaire), family relationships related to conflict and cohesion (Brief Family Relationship Scale), and the adolescents’ perceived barriers (Adolescent Medication Barriers Scale) to taking their prescribed medications.Results: Adolescents’ and emerging adults’ perceptions of family conflicts moderated the link between illness cognition of helplessness among parents and barriers to medication adherence via the illness cognition of helplessness among adolescents and emerging adults. However, only the adolescents’ and emerging adults’ perceptions of family cohesion had a direct association with barriers to medication adherence. Parents’ perceived family conflict and cohesion did not directly associate with barriers to medication adherence. Findings highlight the complex interplay between family dynamics, illness cognition, and barriers to medication adherence in adolescents and emerging adults.Conclusion: Parents’, adolescents’ and emerging adults’ perceptions of family conflicts and cohesion, as well as their illness cognitions, can play important roles in understanding and addressing barriers to medication adherence in this population. The study reveals findings that highlight the dyadic transference process of illness cognition of helplessness among both adolescent and emerging adult kidney recipients and their parents in assessing barriers to medical treatment.Keywords: illness cognition of helplessness, family relationships, barriers to medication adherence, adolescents, parents, kidney transplantation

A novel point mutation(I137T) was identified in the hypoxanthine-guanine phosphoribosyltransferase(HPRT) encoding gene, in a patient with partial deficiency of the enzyme. The mutation, ATT to ACT(substitution of isoleucine to threonine), occurred at codon 137, which is within the region encoding the binding site for 5-phosphoribosyl-1-pyrophosphate(PRPP). The mutation caused decreased affinity for PRPP, manifested clinically as a Lesch–Nyhan variant(excessive purine production and delayed acquisition of language skills). The partial HPRT deficiency could be detected only by measuring HPRT activity in intact fibroblasts(uptake of hypoxanthine into nucleotides). [ABSTRACT FROM AUTHOR]

Unlabelled: Acute interstitial nephritis is uncommon in children and has very rarely been described with naproxen treatment. We report the occurrence of severe acute renal failure in a 10-year-old girl with juvenile rheumatoid arthritis after 1 month of naproxen therapy. Renal biopsy showed severe acute interstitial nephritis. The patient recovered completely after discontinuation of naproxen and administration of methylprednisolone. A review of the literature regarding non-steroidal anti-inflammatory drug-associated acute interstitial nephritis is provided.Conclusion: In an era of increasing popularity of non-steroidal anti-inflammatory drugs for use in children, paediatricians should be aware of the potential renal complications of this class of drugs. [ABSTRACT FROM AUTHOR]

The primary hyperoxalurias (PH 1, 2, and 3) are rare autosomal recessive disorders of glyoxylate metabolism resulting in hepatic overproduction of oxalate. Clinical presentations that should prompt consideration of PH include kidney stones, nephrocalcinosis, and kidney failure of unknown etiology, especially with echogenic kidneys on ultrasound. PH1 is the most common and severe of the primary hyperoxalurias with a high incidence of kidney failure as early as infancy. Until the recent availability of a novel RNA interference (RNAi) agent, PH care was largely supportive of eventual need for kidney/liver transplantation in PH1 and PH2. Together with the Oxalosis and Hyperoxaluria Foundation, the authors developed a diagnostic algorithm for PH1 and in this report outline best clinical practices related to its early diagnosis, supportive treatment, and long-term management, including the use of the novel RNAi. PH1-focused approaches to dialysis and kidney/liver transplantation for PH patients with progression to chronic kidney disease/kidney failure and systemic oxalosis are suggested. Therapeutic advances for this devastating disease heighten the importance of early diagnosis and informed treatment., (© 2024. The Author(s), under exclusive licence to International Pediatric Nephrology Association.)

Background: Primary hyperoxaluria type 1 (PH1) is a genetic disorder resulting in overproduction of hepatic oxalate, potentially leading to recurrent kidney stones, nephrocalcinosis, chronic kidney disease, and kidney failure. Lumasiran, the first RNA interference therapeutic approved for infants and young children, is a liver-directed treatment that reduces hepatic oxalate production. Lumasiran demonstrated sustained efficacy with an acceptable safety profile over 12 months in infants and young children (age <6 years) with PH1 in ILLUMINATE-B (clinicaltrials.gov: NCT03905694), an ongoing, Phase 3, multinational, open-label, single-arm study., Methods: Here, we report interim efficacy and safety findings from ILLUMINATE-B following 30 months of lumasiran treatment. Eligible patients had an estimated glomerular filtration rate (eGFR) >45 ml/min/1.73 m 2 if ≥12 months old or normal serum creatinine if <12 months old, and a urinary oxalate to creatinine ratio (UOx:Cr) greater than the upper limit of normal. All 18 patients enrolled in ILLUMINATE-B completed the 6-month primary analysis period, entered an extension period of up to 54 months, and continue to participate in the study., Results: At Month 30, mean percent change from baseline in spot UOx:Cr was -76%, and mean percent change in plasma oxalate was -42%. eGFR remained stable through Month 30. In 14 patients (86%) with nephrocalcinosis at baseline, nephrocalcinosis grade improved at Month 24 in 12; no patient worsened. In the 4 patients without baseline nephrocalcinosis, nephrocalcinosis was absent at Month 24. Kidney stone event rates were ≤0.25 per person-year through Month 30. Mild, transient injection site reactions were the most common lumasiran-related adverse events (17% of patients)., Conclusion: In infants and young children with PH1, long-term lumasiran treatment resulted in sustained reductions in urinary and plasma oxalate that were sustained for 30 months, with an acceptable safety profile. Kidney function remained stable, low kidney stone event rates were observed through Month 30, and nephrocalcinosis grade improvements were observed through Month 24., Clinical Trial Registration: https://clinicaltrials.gov, identifier NCT03905694., Competing Interests: YF: consultancy fees from Alnylam Pharmaceuticals and membership in the safety review committee. WH: principal investigator for Alnylam Pharmaceuticals; travel and accommodation expenses from Alnylam Pharmaceuticals to attend an international investigators’ meeting. HS-L: principal investigator for Alnylam Pharmaceuticals; travel and accommodation expenses from Alnylam Pharmaceuticals to attend international investigators’ meetings. DJS: grants and other from Alnylam Pharmaceuticals and Dicerna Pharmaceuticals, and personal fees from Advicenne. MM: principal investigator for Alnylam Pharmaceuticals; served on advisory board for Novo Nordisk, Inc. ALS-L: consultancy fees from Alnylam Pharmaceuticals and Dicerna Pharmaceuticals, and principal investigator for research funded by OxThera. JH: consultancy fees from Alnylam Pharmaceuticals. RW and JMG: employees of and shareholders in Alnylam Pharmaceuticals; contributed to study design, data analysis, and (in partnership with all other authors) review and revision of the manuscript in accordance with the ethical principles of Good Publication Practice (GPP 2022) guidelines. DM: research funding, consultancy fees, and non-financial support from Alnylam Pharmaceuticals. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (© 2024 Frishberg, Hayes, Shasha-Lavsky, Sas, Michael, Sellier-Leclerc, Hogan, Willey, Gansner and Magen.)

Hyperoxaluria is a condition in which there is a pathologic abundance of oxalate in the urine through either hepatic overproduction (primary hyperoxaluria [PH]) or excessive enteric absorption of dietary oxalate (enteric hyperoxaluria [EH]). Severity can vary with the most severe forms causing kidney failure and extrarenal manifestations. To address the current challenges and innovations in hyperoxaluria, the 14th International Hyperoxaluria Workshop convened in Perugia, Italy, bringing together international experts for focused presentation and discussion. The objective of the following report was to disseminate an overview of the proceedings and provide substrate for further thought. The format of this paper follows the format of the meeting, addressing, "PH type 1" (PH1) first, followed by "surgery, genetics, and ethics in PH", then "PH types 2 and 3," (PH2 and PH3) and, finally, "EH." Each session began with presentations of the current clinical challenges, followed by discussion of the latest advances in basic and translational research, and concluded with interactive discussions about prioritizing the future of research in the field to best serve the need of the patients., (© 2024 International Society of Nephrology. Published by Elsevier Inc.)

Introduction: Patients with primary hyperoxaluria type 1 (PH1), a genetic disorder associated with hepatic oxalate overproduction, frequently experience recurrent kidney stones and worsening kidney function. Lumasiran is indicated for the treatment of PH1 to lower urinary and plasma oxalate (POx)., Methods: ILLUMINATE-A (NCT03681184) is a phase III trial in patients aged ≥6 years with PH1 and estimated glomerular filtration rate (eGFR) ≥30 ml/min per 1.73 m 2 . A 6-month double-blind placebo-controlled period is followed by an extension period (≤54 months; all patients receive lumasiran). We report interim data through month 36., Results: Of 39 patients enrolled, 24 of 26 (lumasiran/lumasiran group) and 13 of 13 (placebo/lumasiran group) entered and continue in the extension period. At month 36, in the lumasiran/lumasiran group (36 months of lumasiran treatment) and placebo/lumasiran group (30 months of lumasiran treatment), mean 24-hour urinary oxalate (UOx) reductions from baseline were 63% and 58%, respectively; 76% and 92% of patients reached a 24-hour UOx excretion ≤1.5× the upper limit of normal (ULN). eGFR remained stable. Kidney stone event rates decreased from 2.31 (95% confidence interval: 1.88-2.84) per person-year (PY) during the 12 months before consent to 0.60 (0.46-0.77) per PY during lumasiran treatment. Medullary nephrocalcinosis generally remained stable or improved; approximately one-third of patients (both groups) improved to complete resolution. The most common lumasiran-related adverse events (AEs) were mild, transient injection-site reactions., Conclusion: In patients with PH1, longer-term lumasiran treatment led to sustained reduction in UOx excretion, with an acceptable safety profile and encouraging clinical outcomes.See for Video Abstract., (© 2024 International Society of Nephrology. Published by Elsevier Inc.)

Background: Post infectious glomerulonephritis is the most common glomerulopathy in children, occurring several weeks after nephritogenic streptococcal throat or skin infection. Reports of acute glomerulonephritis (AGN) occurring during active bacterial pneumonia in children are rare. The aim of this study was to evaluate the incidence of AGN concurrent with bacterial pneumonia in children., Methods: We reviewed records of all children admitted with a diagnosis of pneumonia to the pediatric department in a single tertiary medical center between January 2015 and April 2023. Patients with bacterial pneumonia and concurrent glomerulonephritis were included., Results: Eleven (0.98%) of 1,123 patients with bacterial pneumonia had concurrent AGN. All were males with a median age of 2.7 years (range 1-13). Mean time from bacterial pneumonia onset to acute glomerulonephritis symptoms was 2.7 ± 1.5 days. Five (45%) patients had evidence of pneumococcal infection. Hypertension was found in 10 (91%) patients. Mean trough eGFR was 43.5 ± 21.4 ml/min/1.73 m 2 (range 11-73). Ten patients (91%) had low C3 levels. Median urinary protein-to-creatinine ratio was 2.5 mg/mg (IQR 2.15-14.75). All patients fully recovered. Microscopic hematuria was the last finding to normalize after a median of 29.5 days (IQR 17.25-38)., Conclusion: AGN during bacterial pneumonia may be more frequent than previously recognized. Kidney prognosis was excellent in all patients. Prospective studies are needed to evaluate the impact of this condition., (© 2023. The Author(s), under exclusive licence to International Pediatric Nephrology Association.)

Introduction: Prematurity is associated with incomplete nephrogenesis and an increased incidence of acute kidney injury, that may increase the risk of future kidney disease, including hypertension, proteinuria and reduced glomerular filtration rate. The aim of this study was to evaluate the risk of hypertension or proteinuria in adolescents born prematurely or small for gestational age, in a nationwide cohort., Methods: The study cohort included potential recruits examined in the Israel Defense Forces (IDF) medical facilities, between November 2005 and October 2018. Clinical and anthropometric data, including blood pressure (BP) measurement, were retrieved from the IDF medical files. Adolescents born between January 1993 and December 2000 had additional data on gestational age at birth, retrieved from the Israeli Ministry of Health database., Results: The study cohort included 513,802 participants, aged 17.3 ± 0.9 years, of whom 48,994 had gestational age data. Adolescents born as very preterm, as extremely preterm infants, those born with very low birthweight (VLBW), or with extremely low birthweight (ELBW) had higher incidence of hypertensive-range BP (55%, 47%, 19% and 12%, respectively). No significant association between birthweight (BW) adjusted to gestational age and hypertension was observed. Within the overweight and obese adolescents, those born with VLBW and ELBW, had further increased hypertensive-range BP rate. Proteinuria was diagnosed in 0.33% of the study cohort, with no significant difference between BW or gestational age categories., Conclusion: Adolescents born with VLBW or as significant preterm were associated with high BP and should be monitored for hypertension development and its potential complications., (© 2024 International Society of Nephrology. Published by Elsevier Inc.)

Introduction: Genetic etiologies are estimated to account for a large portion of chronic kidney diseases (CKD) in children. However, data are lacking regarding the true prevalence of monogenic etiologies stemming from an unselected population screen of children with advanced CKD., Methods: We conducted a national multicenter prospective study of all Israeli pediatric dialysis units to provide comprehensive "real-world" evidence for the genetic basis of childhood kidney failure in Israel. We performed exome sequencing and assessed the genetic diagnostic yield., Results: Between 2019 and 2022, we recruited approximately 88% ( n  = 79) of the children on dialysis from all 6 Israeli pediatric dialysis units. We identified genetic etiologies in 36 of 79 (45%) participants. The most common subgroup of diagnostic variants was in congenital anomalies of the kidney and urinary tract causing genes (e.g., EYA1 , HNF1B , PAX2 , COL4A1, and NFIA ) which together explain 28% of all monogenic etiologies. This was followed by mutations in genes causing renal cystic ciliopathies (e.g., NPHP1 , NPHP4 , PKHD1 , and BBS9 ), steroid-resistant nephrotic syndrome (e.g., LAGE3 , NPHS1 , NPHS2 , LMX1B , and SMARCAL1 ) and tubulopathies (e.g., CTNS and AQP2 ). The genetic diagnostic yield was higher among Arabs compared to Jewish individuals (55% vs. 29%) and in children from consanguineous compared to nonconsanguineous families (63% vs. 29%). In 5 participants (14%) with genetic diagnoses, the molecular diagnosis did not correspond with the pre-exome diagnosis. Genetic diagnosis has a potential influence on clinical management in 27 of 36 participants (75%)., Conclusion: Exome sequencing in an unbiased Israeli nationwide dialysis-treated kidney failure pediatric cohort resulted in a genetic diagnostic yield of 45% and can often affect clinical decision making., (© 2023 International Society of Nephrology. Published by Elsevier Inc.)