For decades, pediatric hyperkalemia has been managed largely with non-selective cation-exchange resins, despite limitations in tolerability, palatability, and gastrointestinal safety. This perspective reviews the role of...For decades, pediatric hyperkalemia has been managed largely with non-selective cation-exchange resins, despite limitations in tolerability, palatability, and gastrointestinal safety. This perspective reviews the role of sodium zirconium cyclosilicate (SZC) in children and places the pediatric evidence in the context of broader hyperkalemia management. Current pediatric SZC data remain sparse and are derived from a small retrospective cohort of children with chronic kidney disease (CKD) stages 4-5/5D and an in vitro infant formula pretreatment study. Within those constraints, SZC was associated with potassium reduction in acute and chronic settings, favorable tolerability, stable serum sodium and blood pressure, and high acceptability, which is relevant in pediatrics, where palatability and adherence often determine effectiveness. The available literature also suggests practical pediatric applications, including age-based oral dosing and formula-pretreatment strategies, although no validated weight-based regimen has been established. Beyond potassium lowering, SZC may support a more individualized approach to potassium management in selected children, potentially reducing the need for broad dietary restriction and helping preserve renin-angiotensin-aldosterone system inhibitor therapy when hyperkalemia becomes a limiting factor. However, these broader clinical implications remain preliminary, largely observational, and partly extrapolated from adult data. Accordingly, SZC should not yet be viewed as an established pediatric practice standard, but rather as a promising adjunct for carefully selected patients in whom older resins are poorly tolerated or ongoing hyperkalemia compromises diet quality or cardiorenal therapy. Until prospective pediatric trials better define dosing, safety, and patient-centered outcomes, any off-label use should remain individualized and closely monitored.
BACKGROUND: The prospective pediatric Continuous Renal Replacement Therapy (ppCRRT) registry identified the degree of fluid accumulation (FA) at continuous kidney replacement therapy (CKRT) initiation as a predictor of a...BACKGROUND: The prospective pediatric Continuous Renal Replacement Therapy (ppCRRT) registry identified the degree of fluid accumulation (FA) at continuous kidney replacement therapy (CKRT) initiation as a predictor of adverse outcomes in children. These predate major advancements in CKRT technology and fluid stewardship. We aimed to describe the epidemiology of FA at CKRT initiation and associated outcomes in a contemporary paediatric cohort. METHODS: Secondary analysis of Worldwide Exploration of Renal Replacement Outcomes Collaborative in Kidney Disease (WE-ROCK), a retrospective, multicenter study (35 centers, 9 countries) of patients ≤ 25 years treated with CKRT from 2015 to 2021. PRIMARY OUTCOME: survival to ICU discharge. SECONDARY OUTCOMES: ventilator-free and ICU-free days. RESULTS: A total of 1027 patients were included in this analysis. Survival to ICU discharge was 64.5% (n = 663). Median FA at CKRT initiation was 7.4% (IQR 2.4-18.1). FA differed between ICU survivors and non-survivors (7% [IQR 2-17] vs. 9% [IQR 3-21], p = 0.004). At CKRT initiation, 605 patients (58.9%) had FA < 10%, 194 patients (18.9%) had 10%-20% FA, and 228 patients (22.2%) had > 20% FA. In multivariable analysis, FA at CKRT initiation was not associated with ICU mortality but was associated with fewer ventilator (aOR 0.84, 95%CI 0.76-0.94, p = 0.023) and ICU-free days (aOR 0.6, 95%CI 0.49-0.73, p < 0.001). CONCLUSIONS: The current study provides a contemporary evaluation of the epidemiology and impact of FA at CKRT initiation on outcomes in a cohort of > 1000 children treated with CKRT for FA/AKI. Clinically significant FA remains common at CKRT initiation and is associated with outcomes. This contemporary data can be used to inform clinical care and plan prospective studies.
BACKGROUND: About 90% of cases with idiopathic nephrotic syndrome (NS) respond to corticosteroids. The remaining 10%, classified as steroid-resistant nephrotic syndrome (SRNS), typically undergo a kidney biopsy before re...BACKGROUND: About 90% of cases with idiopathic nephrotic syndrome (NS) respond to corticosteroids. The remaining 10%, classified as steroid-resistant nephrotic syndrome (SRNS), typically undergo a kidney biopsy before receiving additional immunosuppression. This study examined the extent to which kidney biopsy findings influenced management in children and young adults with newly diagnosed idiopathic SRNS. METHODS: We conducted a retrospective chart review of patients aged 1-21 years and diagnosed with SRNS at the Detroit Medical Center from January 2000 to December 2024. Exclusion criteria were patients with syndromic diagnoses and presentation with gross hematuria, hypertension, or identifiable systemic disease. RESULTS: The study included 55 patients, 46 underwent kidney biopsy after the diagnosis of SRNS (mean age 10.9 ± 4.6 years), and 9 had elective biopsies based on age before being diagnosed with SRNS (mean age 16 ± 1.7 years). Biopsy diagnoses included focal segmental glomerulosclerosis (72%), minimal change disease (24%), and membranous nephropathy (4%). Sixty-five percent of cases had mild to moderate interstitial fibrosis/tubular atrophy. Most patients (84%) were admitted overnight, 71% had flank or back pain, and 15% had a hematoma. Post-biopsy, 96% of patients received calcineurin inhibitors (CNIs): cyclosporine (n = 38) or tacrolimus (n = 15). At one year, 96% remained on CNIs. CONCLUSIONS: Kidney biopsy did not significantly alter immunosuppressive management in newly diagnosed patients with SRNS at our center. Larger multicenter studies are needed to confirm these findings and evaluate whether more selective biopsy criteria could spare patients from a potentially avoidable invasive procedure, improve clinical management, and reduce healthcare costs.
BACKGROUND: Few studies have compared the long-term survival of children by their first modality of kidney replacement therapy (KRT). This study aimed to compare the mortality outcomes of children starting dialysis as th...BACKGROUND: Few studies have compared the long-term survival of children by their first modality of kidney replacement therapy (KRT). This study aimed to compare the mortality outcomes of children starting dialysis as their first KRT modality to those who received a pre-emptive kidney transplant (PKT). METHODS: Historical cohort analyses of UK children starting KRT between 1997-2020 were undertaken, using data from the UK Renal Registry linked to Hospital Episodes Statistics. Crude and multivariable Cox proportional hazards regression analyses were performed to compare mortality amongst children with complete records who received (i) haemodialysis (HD) and (ii) peritoneal dialysis (PD) for ≥ 3 months with those receiving PKT, stratified by the time-period of KRT initiation. Mortality estimates were adjusted for sociodemographic, time-period, primary kidney disease and comorbidity-related covariates. RESULTS: 242 deaths were recorded amongst 2440 children included in complete-case analyses. Adjusted mortality amongst children was highest (HR 3.70, 95% CI: 1.41-9.74), when compared to PKT) for those starting HD in 1997-2008. Evidence for a difference in mortality amongst children receiving HD (compared to PKT) was weak in later time-periods (2009-14, 2015-20). Mortality did not differ amongst children receiving PD first compared to those who had been pre-emptively transplanted. CONCLUSIONS: Whilst adjusted mortality was highest for children starting HD at KRT onset in the earliest time-period, there were no differences in long-term survival amongst those starting dialysis (HD or PD) to those pre-emptively transplanted in more recent years.
BACKGROUND: Vancomycin-induced nephrotoxicity is associated with an increased risk of neonatal mortality and prolonged neonatal intensive care unit (NICU) stay. This retrospective cohort study aimed to assess the inciden...BACKGROUND: Vancomycin-induced nephrotoxicity is associated with an increased risk of neonatal mortality and prolonged neonatal intensive care unit (NICU) stay. This retrospective cohort study aimed to assess the incidence of vancomycin-associated nephrotoxicity and its risk factors in neonates. METHODS: The study included neonates admitted to the NICU of the Maternity and Children Hospital (Makkah, Saudi Arabia) from January 2018 to December 2020 who received intravenous vancomycin for more than 48 h. The primary outcome was the incidence of newly developed acute kidney injury (AKI) after the initiation of vancomycin therapy, defined according to the neonatal modified Kidney Disease: Improving Global Outcomes criteria. Analyses included AKI incidence, comparison of clinical parameters between neonates with and without AKI, and multivariable logistic regression to identify predictors of AKI and mortality. RESULTS: Among 362 neonates treated with vancomycin, 11.3% developed AKI. Neonates with AKI had a lower postmenstrual age (31.3 vs. 34.1 weeks, p = 0.01) and higher rates of extreme prematurity (31.7% vs. 14.3%, p = 0.02) and extremely low birth weight (43.9% vs. 18.7%, p = 0.00). Vancomycin trough levels > 15 mg/L were more frequent in the AKI group (26.8%, 11/41) than in others (11.8%, 35/321) (p = 0.00). Only one-third of vancomycin trough measurements were obtained according to guideline-recommended timing. In multivariable analysis, each additional week of postmenstrual age was independently associated with a 10% reduction in the odds of AKI (OR 0.90; p = 0.00). Higher weight was associated with lower mortality (OR = 0.26; p < 0.001), while AKI incidence was associated with increased mortality (OR = 5.88; p < 0.001). Caffeine citrate use was associated with lower odds of mortality, but was not associated with AKI (OR = 0.21; p < 0.001). CONCLUSION: Lower postmenstrual age independently predicted vancomycin-associated AKI. Lower neonatal weight and AKI were associated with increased mortality, reinforcing the importance of individualized monitoring during vancomycin therapy.
Pediatric obesity is a growing public health crisis with profound cardiometabolic and kidney consequences extending into adulthood. Emerging frameworks now distinguish preclinical obesity from clinical obesity, emphasizi...Pediatric obesity is a growing public health crisis with profound cardiometabolic and kidney consequences extending into adulthood. Emerging frameworks now distinguish preclinical obesity from clinical obesity, emphasizing excess adiposity-related organ dysfunction or functional limitations in activities of daily living. Obesity is a central driver of cardiovascular-kidney-metabolic syndrome, underscoring the need for integrated treatment approaches. This narrative review summarizes current evidence for lifestyle interventions and pharmacologic therapies for pediatric obesity, with a focus on implications for hypertension and chronic kidney disease. Intensive health behavior and lifestyle treatment remains first-line therapy, but access and sustainability barriers limit effectiveness. Pharmacotherapy is increasingly used as adjunctive treatment, with five medications currently approved for non-syndromic obesity in children. Among available agents, glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and combination phentermine/topiramate demonstrate the greatest efficacy in adolescents, while older agents and off-label therapies offer modest benefit with greater limitations. Emerging data suggest GLP-1 RAs may improve blood pressure and kidney outcomes, although pediatric evidence remains limited. Lack of long-term safety data, durability of weight loss, cost, and access remain substantial barriers in the use of obesity pharmacotherapy for children. Sustained, coordinated care across the lifespan is essential to effectively manage pediatric obesity and its cardiometabolic and kidney sequelae.
Circulating anti-nephrin antibodies have recently been identified as mediators in many cases of childhood nephrotic syndrome. After binding of the antibody to nephrin, a key component of the slit diaphragm, different int...Circulating anti-nephrin antibodies have recently been identified as mediators in many cases of childhood nephrotic syndrome. After binding of the antibody to nephrin, a key component of the slit diaphragm, different intracellular signaling mechanisms lead to foot process effacement. These new insights into the pathophysiology of nephrotic syndrome may have the potential to influence clinical treatment strategies. First, the measurement provides a pathomechanism-specific serological biomarker of a previously clinically diagnosed renal disease. Second, it may have additional value for diagnosis and prognostication, as anti-nephrin antibodies are more common in steroid-sensitive forms and less frequently associated with multidrug-resistant forms. Furthermore, anti-nephrin autoantibodies have the potential to be used as biomarkers for disease activity and to estimate the risk of relapse before kidney transplantation, after conduction of appropriate clinical trials. Additionally, the detection of autoantibodies strengthens the role of B-cell targeting therapies and provides a potential rationale for further multicenter, prospective, randomized clinical trials using B-cell depletion to potentially reduce corticosteroid use and relapse rates in children. In the future, more targeted therapies such as the interference with downstream effects of antibody binding or the depletion of autoantigen-specific antibody producing cells might become possible. Finally, the detection of anti-nephrin autoantibodies provides an explanation for patients and their families with a previously elusive "idiopathic" disease in antibody positive patients. In summary, the identification of anti-nephrin antibodies in nephrotic syndrome now opens up new questions and paves the way for further experimental and clinical studies to improve diagnostic and therapeutic approaches.
Rejuso A, Asif H, Howell M
… +13 more, Guha C, Kim S, Jaure A, Hughes A, Nicholl K, Mallit KA, Bouroumad F, Craig J, Teixeira-Pinto A, Francis A, Larkins N, van Zwieten A, Wong G
CONTEXT: Children with chronic kidney disease (CKD) experience complex challenges affecting their physical, emotional and quality of life outcomes. Patient-reported outcome measures (PROMs) and experience measures (PREMs...CONTEXT: Children with chronic kidney disease (CKD) experience complex challenges affecting their physical, emotional and quality of life outcomes. Patient-reported outcome measures (PROMs) and experience measures (PREMs), collectively known as patient-reported measures (PRMs) are essential to capture these impacts, but their validation and suitability in pediatric CKD research remain underexplored. OBJECTIVE: To identify and evaluate the psychometric properties of PRMs used in research in children with CKD. DATA SOURCES: Medline, Embase, CINAHL and PSYCinfo searched from inception to March 2025. STUDY SELECTION: Studies that reported the results of at least one PRM completed by patients or proxies in children aged 0-18 years with CKD were included. DATA EXTRACTION: Study and measure characteristics and psychometric properties of PRMs were extracted. RESULTS: One hundred seventy-five studies involving 21,423 children from 39 countries were eligible and included. 307 PRMs were identified, representing 121 unique tools across 23 outcome domains. Pediatric Quality of Life Inventory (PedsQL) was the most frequently used measure (50%). Approximately 40% were applied in the pediatric CKD population without evidence of external validation. Internal consistency was the most frequently reported psychometric property, assessed for 19 of all identified PRMs (6%). Disease-specific instruments (PRO-KID, TECAVNER) had good internal consistency (α ≥ 0.8). CONCLUSIONS: There is firm reliance on using generic PRMs in children with CKD; however, most lack robust external validation in this population. Co-development and comprehensive validation of disease-specific instruments that reflect outcomes valued by patients and families are required to enhance the relevance of outcome assessment in pediatric CKD care.
Patients with kidney disease face a markedly increased risk of developing cardiovascular disease (CVD) which manifests in multiple forms, including: left ventricular hypertrophy, heart failure, atherosclerosis, and vascu...Patients with kidney disease face a markedly increased risk of developing cardiovascular disease (CVD) which manifests in multiple forms, including: left ventricular hypertrophy, heart failure, atherosclerosis, and vascular inflammation, all of which are associated in clinical studies to well-characterized morbidity and mortality reported throughout disease progression. These patients also exhibit disturbances in mineral metabolism and in the network of signals that regulate mineral balance, that we collectively refer to as the "mineralostat." This review aims to summarize the links between mineralostat alterations and its potential implications for the onset and progression of CVD, as disruptive signals are transmitted to the heart and vascular system. Over the past decade, studies using sophisticated preclinical models have identified new proteins and signaling pathways of the mineralostat as candidates contributing to CVD. Here, we discuss the pathophysiological conditions reported to disrupt the mineralostat, the hormones involved in mineral metabolism, and the minerals. We also summarize the mechanisms through which each of these factors may promote CVD, with attention to their relevance for patients.
BACKGROUND: Adolescents and adults born preterm are at increased risk for kidney dysfunction, possibly secondary to incomplete nephrogenesis. However, few long-term follow-up studies are available from U.S.-born preterm...BACKGROUND: Adolescents and adults born preterm are at increased risk for kidney dysfunction, possibly secondary to incomplete nephrogenesis. However, few long-term follow-up studies are available from U.S.-born preterm cohorts. METHODS: Using the Parkland Hospital Neonatal Intensive Care Unit Registry (Dallas, TX), patients aged 12-40 years born ≤ 32 weeks gestation or < 1500 g were recruited, along with healthy term-born similarly aged participants. Study procedures included anthropometrics, vitals, and basic laboratory testing. Glomerular filtration rate (eGFR) was calculated using the CKD-Epi Creatinine Equation (2021). Least squares regressions were used to determine the main effect of neonatal and adult factors on markers of kidney function. RESULTS: Participants included 103 preterm (GA 29.5 ± 2.5 wks, current age 26.1 ± 6.0 yrs) and 43 term (GA 39.2 ± 1.1 wks; current age 29.1 ± 7.3 yrs) individuals. Patients born prematurely had similar creatinine (0.73 ± 0.21 vs. 0.82 ± 0.21 mg/dL; p = 0.112), higher eGFR (120.5 ± 17.76 vs. 112.4 ± 16.28 mL/min/1.73 m; p = 0.003), and higher cystatin C (12.15 ± 3.17 vs. 11.46 ± 2.66 µg/mL; p = 0.035) in adolescence/adulthood compared to term, respectively. Multivariate linear regression demonstrated that gestational age was significantly related to eGFR and cystatin C, where lower GA was associated with higher eGFR but also higher cystatin C. CONCLUSION: Despite similar creatinine, individuals born prematurely had higher eGFR and higher cystatin C. The elevated eGFR suggests a potential hyperfiltrative state, while the elevated cystatin C suggests increased risk for progression to chronic kidney disease.
BACKGROUND: The neonatal-modified Kidney Disease: Improving Global Outcomes acute kidney injury (KDIGO-AKI) serum creatinine (SCr) definition is widely used to characterize neonatal AKI. In extremely preterm neonates bor...BACKGROUND: The neonatal-modified Kidney Disease: Improving Global Outcomes acute kidney injury (KDIGO-AKI) serum creatinine (SCr) definition is widely used to characterize neonatal AKI. In extremely preterm neonates born < 28 weeks' gestational age (GA), this definition has limitations. We evaluated whether GA- and postnatal age-specific SCr thresholds during the first postnatal week could identify additional neonates at risk for mortality. METHODS: In a secondary analysis of prospectively collected data from the Preterm Erythropoietin Neuroprotection Trial, daily 95th percentile SCr thresholds were derived over the first week of life for two GA groups (24-25 and 26-27 weeks) using neonates without KDIGO-AKI. Neonates were classified sequentially into three cohorts: KDIGO-AKI; 95th-AKI, defined by at least one SCr exceeding the daily 95th percentile thresholds in the absence of KDIGO-AKI; and controls with no AKI. Time-varying Cox proportional hazards models assessed associations with in-hospital mortality. RESULTS: Among 918 extremely preterm neonates, 106 (12%) had KDIGO-AKI, 72 (8%) had 95th-AKI, and 740 (81%) had no AKI in the first postnatal week. In-hospital mortality was higher with 95th-AKI (18%) or KDIGO-AKI (18%) than with no AKI (9%) (p = 0.003). After adjusting for confounding factors, 95th-AKI was associated with an increased in-hospital mortality (adjusted HR 2.16, 95% CI 1.12-4.18), but KDIGO-AKI was not (adjusted HR 0.99, 95% CI 0.49-2.02). CONCLUSIONS: Extremely preterm neonates without KDIGO-AKI but with elevated SCr in the first postnatal week had an increased risk of in-hospital mortality. GA- and postnatal age-specific SCr thresholds may improve early detection of at-risk neonates. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01378273.
BACKGROUND: Primary hyperoxaluria type 1 (PH1) is a rare autosomal recessive disorder caused by pathogenic variants in the AGXT gene. In regions with a high prevalence of consanguinity, the burden of PH1 is expected to b...BACKGROUND: Primary hyperoxaluria type 1 (PH1) is a rare autosomal recessive disorder caused by pathogenic variants in the AGXT gene. In regions with a high prevalence of consanguinity, the burden of PH1 is expected to be increased; however, data on its epidemiology in Tunisia remain scarce. This study aimed to estimate the minimum observed clinical prevalence of PH1 in Tunisia, to assess the expected genetic burden based on published pathogenic allele frequency data, and to describe the clinical and molecular spectrum of the disease in this cohort. METHODS: We retrospectively analyzed genetically confirmed PH1 patients referred to a major national tertiary referral center in Tunisia between 2011 and 2025, in whom molecular diagnosis was established by systematic Sanger sequencing of the AGXT gene. The minimum observed clinical prevalence was estimated using national population data. The expected genetic burden was derived using Hardy-Weinberg equilibrium based on published gene-based pathogenic AGXT allele frequency estimates from large population databases (gnomAD). A sensitivity analysis incorporating population-level consanguinity was performed. RESULTS: A total of 104 PH1 patients from 55 unrelated families were identified. Most patients presented during childhood (at least 77%), mainly with nephrolithiasis or nephrocalcinosis, while kidney failure (CKD stage 5) was already present in at least half of the probands. The minimum observed clinical prevalence of PH1 in Tunisia was estimated at 8.7 cases per million inhabitants. By contrast, gene-based estimates suggested that approximately 200-300 individuals would be expected to be affected in an outbred population of 12 million. A marked founder effect was observed for the c.731 T>C (p.Ile244Thr) variant. CONCLUSIONS: PH1 represents a significant cause of pediatric kidney disease in Tunisia and is likely underdiagnosed. These findings support the need for increased clinical awareness, early genetic testing, and timely diagnosis to optimize patient management in the era of disease-modifying therapies.
Podocytopathies, including minimal change disease and focal segmental glomerulosclerosis, represent the leading causes of nephrotic syndrome in children and adolescents. Although traditionally considered T-cell-mediated...Podocytopathies, including minimal change disease and focal segmental glomerulosclerosis, represent the leading causes of nephrotic syndrome in children and adolescents. Although traditionally considered T-cell-mediated disorders, growing evidence over the last decade has reshaped this paradigm, highlighting a central role for B-cells, plasma cells, and humoral immune mechanisms in podocyte injury. The identification of pathogenic autoantibodies, particularly anti-nephrin IgG, and the involvement of complement activation have provided a strong mechanistic rationale for B-cell-targeted therapies. Rituximab, an anti-CD20 monoclonal antibody, has become an established steroid-sparing agent in steroid-dependent and frequently relapsing nephrotic syndrome, significantly reducing relapse rates and cumulative steroid exposure in pediatric patients. However, its efficacy is limited in steroid-resistant disease and in settings characterized by persistent autoantibody production or post-transplant recurrence. These limitations have prompted the exploration of next-generation anti-CD20 agents, such as obinutuzumab, which achieve deeper and more sustained B-cell depletion, as well as therapies targeting long-lived plasma cells, including anti-CD38 monoclonal antibodies. Emerging clinical data suggest that combined B-cell and plasma cell targeting may induce durable remission in refractory podocytopathies and recurrent post-transplant focal segmental glomerulosclerosis, while maintaining an acceptable safety profile. In parallel, novel strategies targeting the BAFF/APRIL axis and cellular therapies such as CAR-T cells are under investigation. This review summarizes current evidence on B-cell-directed therapies in podocytopathies, mostly in pediatrics, discusses unmet clinical needs, and outlines future perspectives toward precision, mechanism-based immunotherapy.