Insights in Pediatric Nephrology: An Editorial overview

Michael L Moritz^1,2*Agnieszka Swiatecka-Urban³Vera Hermina Koch^4,5

• ¹Pediatrics/ Pediatric Nephrology, Division of Nephrology, Akron Children's Hospital, Akron, Pennsylvanion, United States
• ²Northeast Ohio Medical University, Rootstown, United States
• ³University of Virginia School of Medicine, Charlottesville, United States
• ⁴Universidade de Sao Paulo, São Paulo, Brazil
• ⁵Universidade de Sao Paulo Instituto da Crianca, São Paulo, Brazil

The field of pediatric nephrology continues to evolve, marked by both significant advancements and ongoing challenges. This collection of articles, assembled under the research topic "Insights in Pediatric Nephrology", highlights emerging discoveries, innovative approaches, and evolving perspectives that are shaping the future of kidney care in children. Below is an overview of the thematic content of the collection, highlighting significant findings and emerging trends that are poised to shape the future of pediatric nephrology.Two articles report on the treatment of primary hyperoxaluria type 1 (PH1) with Lumasiran, an RNA interference (RNAi) therapeutic agent that reduces the hepatic production of oxalate by targeting glyoxylate metabolism. 1,2 PH1 is a rare autosomal recessive inborn disorder in glyoxylate metabolism that is particularly devastating in young children as it results in kidney failure due to kidney stones and nephrocalcinosis which then leads to systemic oxalosis with deposition of calcium oxalate crystals throughout the body. Frishberg et al report on the efficacy and safety of 30-months of Lumasiran treatment in 18 patients under 6 years of age enrolled in the phase 3 ILLUMINATE-B trial. 1 Lumasiran was remarkably effective with a sustained reduction in urine oxalate of approximately 70%, stable renal function, improvements in medullary nephrocalcinosis ,and low kidney stone events rate. In addition, there were no serious adverse events related to Lumasiran. Taroni et al describe a fascinating report on Lumasiran initiated at 10 days of age in a newborn prenatally diagnosed with PH1, as an older sibling presented with PH1 at 2 months of age and later required a liver and kidney transplant. 2 Despite early initiation of therapy, the child developed nephrocalcinosis and nephrolithiasis with elevated urine oxalate levels. It took approximately 9 months for urinary oxalate levels to normalize. At 20-month follow up, renal function and urine oxalate levels were normal, with improvement in nephrocalcinosis and no evidence of systemic oxalosis. These studies demonstrate the remarkable impact that biological drugs have had in pediatric rare diseases.Two articles reported on the clinical utility of radiological imaging in assessing hemolytic uremic syndrome and vesicoureteral reflux, respectively. 3,4 Hemolytic uremic syndrome (HUS) is an important cause of acute kidney injury in children which frequently requires acute dialysis and can result in CKD. It can be difficult to predict if a child with HUS will have a severe clinic course requiring dialysis. Rink et al retrospectively evaluated if a renal sonogram provided clinical meaningful information in 30 children with HUS and predictive of the need for acute dialysis. 3 They found that both increased kidney size and elevated resistive indices were predictive of the need for acute dialysis. Increased kidney size was most predictive, with a kidney size > 130% compared to mean values associated with a 67% need for dialysis and combination of both kidney size > 130% and resistive index > 1.0 associated with a 73% need for dialysis. Interestingly, no children with a kidney size < 130% required dialysis. This data suggests that renal sonography may be clinically useful in predicting the need for dialysis in children with HUS. Zhu et al retrospectively evaluated renal damage using both Dimercaptosuccinic acid (DMSA) renal scintigraphy and Technetium-99m-Ethylenedicysteine (99mTc-EC) dynamic renal scintigraphy in 226 children diagnosed with primary vesicoureteral reflux. 4 They demonstrated that scintigraphic abnormalities were common, and that split renal function was much lower in kidneys which had reflux.There were two review articles, one discussing sodium glucose co-transporter 2 inhibitors and the other renal abscesses in children. 5,6 Portalatin et al discuss the growing interest in SGLT2 inhibitors as renoprotective agents in pediatric nephrology. 5 Originally developed for glycemic control in adults with type 2 diabetes, these agents have shown substantial kidney and cardiovascular benefits in major adult chronic kidney disease (CKD) trials independent of glycemic status. Proposed mechanisms underlying renal benefit include restoration of tubulo glomerular feedback, reduction in intraglomerular pressure, attenuation of inflammatory and fibrotic signaling, and stabilization of podocyte and mesangial cell function. Pediatric data remain limited, but extrapolation from adult studies suggests a strong rationale for use in selected children and adolescents with proteinuric CKD and progressive glomerular diseases (e.g., IgA nephropathy, FSGS, Alport syndrome). They advocate for disease-specific pediatric trials and provide interim recommendations for cautious use in adolescents with close monitoring of renal function and volume status. Sun et al reviewed pediatric renal abscesses and report on 12 cases. 6 Patient's present with non-specific symptoms, such as fever and abdominal pain, typically require abdominal cat scan or magnetic resonance urography to make a diagnosis. Abscess sizes are typically less than 3 cm and respond to antibiotics without the need for surgical intervention.Finally, the European Society for Paediatric Nephrology (ESPN) conducted a multi-institutional cross-sectional analysis evaluating the organization, workforce, and delivery of pediatric nephrology care in 48 European countries. 7 Despite progress in establishing specialized centers, transplant programs, and dialysis services, wide disparities persist. Over 50% of countries experience shortages in pediatric nephrologists, dialysis nurses, and clinical support. Common challenges include limited access to dialysis, inadequate transplant services for younger children, and lack of multidisciplinary teams. They call for initiatives to standardize care, optimize training, and reduce inequities across regions. Their findings underscore the need for coordinated policies and investment to ensure equitable access to quality pediatric kidney care across Europe.In conclusion, we congratulate the authors for their invaluable contributions to the field of pediatric nephrology. Their research and insights not only advance our understanding of complex kidney-related disorders in children but also highlight innovative therapeutic strategies and systemic improvements necessary for enhancing patient care. Despite these significant strides, much work remains to be done to further advance the care of children with kidney diseases.Continued research, collaboration, and investment are essential to address the existing challenges and disparities in pediatric nephrology, ensuring that all children have access to the highest quality of care. We look forward to future developments and the ongoing commitment of the pediatric nephrology community to improve outcomes for young patients worldwide. Frishberg