Michael L. Moritz

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...

There is little known about the impact of maintenance fluid choice in children with critical asthma on clinical outcomes. Our primary study objectives were to determine the differences in the serum chloride and bicarbonate levels based on the receipt of 0.9% saline or a balanced solution. The secondary study objectives included differences in acute kidney injury (AKI) and intensive care unit (ICU)/hospital length of stay (LOS). In this retrospective cohort study, we included 1166 patients admitted to a quaternary children’s hospital with critical asthma between 2017 and 2019. The patients were stratified based on if they received 0.9% saline or a balanced solution (Lactated Ringer’s or Plasma-lyte) for maintenance therapy. The study outcomes were determined using independent sample t-tests, multivariable logistic regression, and negative binomial regression. The patients who received 0.9% saline maintenance therapy had a significantly higher increase in their serum chloride levels when compared to those who received balanced solutions (0.9% saline: +4 mMol/L, balanced: +2 mMol/L, p = 0.002). There was no difference in the decrease in the serum bicarbonate levels (0.9% saline: −0.4 mMol/L, balanced: −0.5 mMol/L, p = 0.830). After controlling for age, race, sex, and the Pediatric Logistic Organ Dysfunction (PELOD-2) score, there was no association between the type of fluid received and the development of AKI (OR 0.87, 95% CI: 0.46–1.63, p = 0.678). Additionally, there was no association between the type of fluid and hospital or ICU LOS. Thus, despite higher serum chloride levels in the patients that received 0.9% saline, the choice of fluid therapy did not have an impact on the serum bicarbonate values, the development of AKI or hospital and ICU LOS, suggesting there is little difference between 0.9% saline and balanced solutions as maintenance therapy in children with critical asthma.

Three-percent sodium chloride (3% NaCl) is a hyperosmolar agent used to treat hyponatremic encephalopathy or other cases of increased intracranial pressure. A barrier to the use of 3% NaCl is the perceived risk of local infusion reactions when administered through a peripheral vein. We sought to evaluate reports of local infusion reactions associated with 3% NaCl over a 10-year period throughout a large healthcare system. A query was conducted through the Risk Master database to determine if there were any local infusion reactions associated with peripheral 3% NaCl administration throughout the entire UPMC health system, which consists of 40 hospitals with 8400 licensed beds, over a 10-year time period from 14 May 2010 to 14 May 2020. Search terms included infiltrations, extravasations, phlebitis, IV site issues, and IV solutions. There were 23,714 non-chemotherapeutic and non-contrast-associated intravenous events, of which 4678 (19.7%) were at UPMC Children’s Hospital. A total of 2306 patients received 3% NaCl, of whom 836 (35.8%) were at UPMC Children’s Hospital. There were no reported local infusion reactions with 3% NaCl. There were no reported local infusion reaction events associated with 3% NaCl in a large healthcare system over a 10-year period. This suggests that 3% NaCl can be safely administered through a peripheral IV or central venous catheter.

Primary hyperoxaluria type 1 (PH1) is a rare genetic disease that results in oxalate overproduction leading to nephrolithiasis (NL), nephrocalcinosis (NC), kidney failure, and systemic oxalosis. Infantile PH1 is its most severe form, and it may require intensive hemodialysis followed by a liver-kidney transplant. Lumasiran is an RNA interference (RNAi) therapeutic agent that reduces hepatic oxalate production, which has been recently approved for the treatment of PH1. In this report, we present a case of twin males with infantile PH1 and bilateral NL and NC who were treated with lumasiran at 12 months of age. Their symptoms abated after therapy was started without disease progression. To the best of our knowledge, this is the first report of PH1 occurring in twins and the first report on using lumasiran to treat infantile PH1 outside of a clinical trial. Lumasiran appears to be a successful therapeutic option for infantile PH1.

Three percent sodium chloride (3% NaCl) is the treatment of choice for symptomatic hyponatremia. A barrier to the use of 3% NaCl is the perceived risk of both local infusion reactions and neurologic complications from overcorrection. We examine whether children’s hospital pharmacies have policies or practice guidelines for the administration of 3% NaCl and whether these pharmacies have restrictions on the administration of 3% NaCl in terms of rate, route, volume and setting. An Internet survey was distributed to the pharmacy directors of 43 children’s hospitals participating in the Children’s Hospital Association (CHA) network. The response rate was 65% (28/43). Ninety-three percent (26/28) of pharmacy directors reported a restriction for the administration of 3% NaCl, with 57% restricting its use through a peripheral vein or in a non-intensive care unit setting, 68% restricting the rate of administration and 54% restricting the volume of administration. Seventy-one percent (20/28) reported having written policy or practice guidelines. Only 32% of hospital pharmacies allowed 3% NaCl to be administered through a peripheral IV in a non-intensive care unit setting. The majority of children’s hospital pharmacies have restrictions on the administration of 3% NaCl. These restrictions could prevent the timely administration of 3% NaCl in children with symptomatic hyponatremia.

Background: Primary hyperoxaluria type 1 (PH1) is a rare genetic disease that can result in irreversible damage to the kidneys and, eventually, extrarenal organs. While kidney failure is a known consequence of PH1, few studies to date have characterized clinical consequences of PH1 prior to kidney failure, and data on healthcare resource use outcomes across different stages of disease severity in PH1 are also limited. To help fill this knowledge gap, this study characterized the clinical and healthcare resource use (HRU) burden in patients with PH1 with varying stages of kidney disease.Methods: Nephrologists in the United States, Canada, United Kingdom, France, Germany, and Italy abstracted chart data from patients with PH1 under their care via an online questionnaire. Eligible patients had confirmed PH1 and ≥2 office visits from 2016 to 2019.Results: A total of 120 patients were analyzed (median age at diagnosis, 17.4 years old, median age at index 19.5 years old, median eGFR at index 45 ml/min/1.73 m²; median follow-up 1.7 years). During follow-up, the most common PH1 manifestations were kidney stones and urinary tract infections (UTIs, both 56.8%), and the most common symptoms were fatigue/weakness (71.7%) and pain (64.6%). With regard to HRU during follow-up, 37.4% required lithotripsy, 31.3% required ureteroscopy, and 9.6% required nephrolithotomy. PH1-related hospitalizations and emergency/urgent care visits were noted for 84.0 and 81.6% of patients, respectively.Conclusions: The current study demonstrated that patients with PH1 across various stages of kidney disease exhibited a substantial clinical burden, including kidney stones, UTIs, fatigue/weakness, and pain, and required frequent HRU, including kidney stone procedures, hospitalizations, and emergency visits. These findings highlight the significant morbidity and HRU burden in patients with PH1.