BACKGROUND: Programmed cell death protein 1 (PD-1) plays a pivotal role in regulating T-cell responses. Its expression profile and clinical significance in pediatric idiopathic nephrotic syndrome (INS), particularly in s...BACKGROUND: Programmed cell death protein 1 (PD-1) plays a pivotal role in regulating T-cell responses. Its expression profile and clinical significance in pediatric idiopathic nephrotic syndrome (INS), particularly in steroid-resistant nephrotic syndrome (SRNS), remain unclear. METHODS: PD-1 expression on CD3⁺, CD4⁺, and CD8⁺T cells was quantified by flow cytometry in 65 treatment-naive children with idiopathic nephrotic syndrome (INS): steroid-sensitive (SSNS, n = 54), steroid-resistant (SRNS, n = 11), as well as in healthy controls (HC, n = 30). Group differences, clinical correlations and PD-1's predictive value for SRNS were analyzed. Circulating T subsets, including CD3⁺PD-1⁺ T cells, CD4⁺PD-1⁺T cells, and CD8⁺PD-1⁺T were detected with multiparameter flow cytometry. RESULTS: The percentage of CD4⁺PD-1⁺ T cells was significantly higher in SRNS (10.77 ± 4.62%) compared to both SSNS (5.14 ± 1.99%, P = 0.000) and HC (6.36 ± 2.02%, P = 0.028). CD3⁺PD-1⁺ T cells were also elevated in SRNS (8.13 ± 3.12%) versus SSNS (4.67 ± 1.82%, P = 0.001). No significant difference was found in CD8⁺PD-1⁺ T cells. Multivariate logistic regression identified an elevated percentage of CD4⁺PD-1⁺ T cells as an independent risk factor for SRNS (OR = 2.236, P = 0.002). Receiver operating characteristic (ROC) analysis showed that CD4⁺PD-1⁺ T cell cutoff > 7.385% predicted SRNS with an area under the curve (AUC) of 0.891, sensitivity of 81.8%, and specificity of 87.0%. CONCLUSIONS: Overexpression of PD-1, predominantly on CD4⁺ T cells, is associated with steroid resistance in pediatric INS. Elevated CD4⁺PD-1⁺ T cells may serve as a predictive biomarker for SRNS, offering a potential tool for early identification and a rationale for exploring PD-1 pathway modulation.
Podocytopathies are kidney diseases caused by podocyte injury or dysfunction that drives proteinuria or nephrotic syndrome. A significant expansion in understanding of the complex causes and mechanisms of podocyte injury...Podocytopathies are kidney diseases caused by podocyte injury or dysfunction that drives proteinuria or nephrotic syndrome. A significant expansion in understanding of the complex causes and mechanisms of podocyte injury, as well as potential therapeutic approaches, has been achieved over the past two decades with rapid advances in genomics in both research and clinical practice. Podocytopathies associated with monogenic mechanisms account for approximately 30% of cases with steroid-resistant nephrotic syndrome (SRNS) or focal segmental glomerulosclerosis lesions (FSGS), with even higher proportions in pediatric patients. Podocytopathies related to each gene mutation are rare. However, recent developments in these rare podocytopathies contribute to an optimistic outcome for the future to eventually avoid kidney failure. This review therefore focuses on aspects of new advances of therapies in rare podocytopathies with monogenic causes.
Nail-patella syndrome (NPS) is an autosomal dominant disorder caused by LMX1B mutations and typically associated with glomerular proteinuria. We report three brothers carrying a maternally inherited heterozygous LMX1B mu...Nail-patella syndrome (NPS) is an autosomal dominant disorder caused by LMX1B mutations and typically associated with glomerular proteinuria. We report three brothers carrying a maternally inherited heterozygous LMX1B mutation (NM_001174147.2: c.309C > G (p.Cys103Trp)), all presenting with classical skeletal features of NPS. Two siblings developed early-onset proteinuria predominantly composed of low-molecular-weight proteins, hypercalciuria, and ophthalmologic abnormalities including cataracts and glaucoma; one also exhibited nephrocalcinosis. Further genetic analysis identified a hemizygous OCRL pathogenic mutation (NM_000276.4: c.2209G > A (p.Glu737Lys)) in the two affected brothers but not in the third sibling, who had no renal involvement. This intrafamilial discordance supports a dual genetic diagnosis. Our findings emphasize the importance of reconsidering the initial diagnosis when clinical features are atypical and highlight the value of comprehensive genetic testing in patients with unusual renal presentations.
BACKGROUND: The Standardizing Care to Improve Outcomes in Pediatric End Stage Kidney Disease (SCOPE) collaborative is a quality improvement initiative focused on improving care of children on dialysis. Accurate blood pre...BACKGROUND: The Standardizing Care to Improve Outcomes in Pediatric End Stage Kidney Disease (SCOPE) collaborative is a quality improvement initiative focused on improving care of children on dialysis. Accurate blood pressure (BP) measurement is a focus of SCOPE as cardiovascular disease is a leading cause of morbidity and mortality. METHODS: An analysis of children from 25 pediatric hemodialysis (HD) centers enrolled in SCOPE was conducted to describe prevalence of high BP and hypertension and assess risk factors for hypertension. Data on patient characteristics, including age, renal diagnosis, race, sex, and use of antihypertensive medications was collected. Based on 2017 AAP hypertension guidelines, patients were classified as having uncontrolled, controlled or untreated BP as well as persistent hypertension. Generalized linear modeling was used to evaluate associations between patient characteristics and persistent hypertension. RESULTS: A total of 3532 BP evaluation forms from 407 HD patients were collected, providing 6962 BP measurements. 54.3% of BP measurements were abnormal with 25.4% classified as stage I hypertension and 16.3% as stage II hypertension. Across 3532 forms, 47.7% showed uncontrolled BP, 13.8% showed untreated hypertension and 37.1% had persistent hypertension. There were no significant associations of age, renal diagnosis, race or sex with persistent hypertension. CONCLUSIONS: Prevalence of uncontrolled and untreated hypertension is high among patients on HD in the SCOPE collaborative, despite frequent use of antihypertensive therapy. This mirrors results from other registry studies but is more robust due to use of repeated measurements, standardized measurement procedures and use of post-HD measurements for classification of hypertension.
BACKGROUND: CD163 is a surface marker expressed by M2c macrophages. This study aims to evaluate the level of urinary soluble CD163 (u-sCD163) in children with IgA vasculitis with nephritis (IgAVN) and its potential diagn...BACKGROUND: CD163 is a surface marker expressed by M2c macrophages. This study aims to evaluate the level of urinary soluble CD163 (u-sCD163) in children with IgA vasculitis with nephritis (IgAVN) and its potential diagnostic value. METHODS: U-sCD163 was analyzed in 73 children with IgAVN who underwent a kidney biopsy, 37 children with IgA nephropathy and 50 normal controls. CD163 expression was analyzed by immunohistochemistry. Correlation analyses and inter-group comparison were performed to assess the association between u-sCD163 levels and clinicopathological features of IgAVN. The comparison of u-sCD163 levels before and after treatment was conducted. RESULTS: The level of u-sCD163 was significantly higher in children with IgAVN than healthy controls. Compared with grade II IgAVN subjects, u-sCD163 level was significantly elevated in grade III-IV subjects. There was no difference in u-sCD163 level between IgAVN and IgA nephropathy groups. There was no difference in serum CD163 level among different groups. In the IgAVN group, abundant CD163-positive cells were observed in glomeruli showing endocapillary proliferation, especially in areas of thrombosis and fibrinoid necrosis. In contrast, CD163-positive cells were scarce within cellular crescents, but increased in fibrocellular crescents. Levels of u-sCD163 showed a significant positive correlation with proportions of endocapillary proliferation, and moderately correlated with proteinuria, CD163 score of glomerular area, and weakly correlated with proportions of cellular crescents, D-dimer and fibrin degradation products (FDP). The level of u-sCD163 decreased significantly after treatment. CONCLUSIONS: U-sCD163 emerges as a promising marker associated with endocapillary proliferation and coagulation in pediatric patients with IgAVN.
Chronic kidney disease (CKD) in childhood, although uncommon, has profound lifelong consequences. Because disease onset occurs early, even modest slowing of CKD progression may translate into decades free from dialysis,...Chronic kidney disease (CKD) in childhood, although uncommon, has profound lifelong consequences. Because disease onset occurs early, even modest slowing of CKD progression may translate into decades free from dialysis, transplantation, and premature death. Progressive proteinuria is a central driver of nephron loss in pediatric CKD, making early and sustained antiproteinuric strategies particularly impactful. Despite heterogeneous etiologies, including congenital and immune-mediated kidney diseases, CKD progression in children converges on shared mechanisms such as glomerular hypertension, podocyte injury, tubular epithelial dysfunction, and fibrosis. Targeting these final common pathways offers the greatest opportunity to modify long-term outcomes. Several emerging pharmacological strategies are reshaping the therapeutic landscape of CKD. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) reduce intraglomerular pressure by restoring tubuloglomerular feedback and exert additional natriuretic, metabolic, and anti-inflammatory effects. Endothelin A (ETA) receptor antagonists counteract endothelin-1-mediated vasoconstriction, inflammation, and fibrotic remodeling, key drivers of proteinuric kidney damage. Dual endothelin-angiotensin receptor antagonists (DEARAs) integrate selective ETA blockade with angiotensin II type 1 receptor inhibition, simultaneously suppressing two tightly interconnected pathways that amplify glomerular hypertension, podocyte injury, and fibrosis. Robust randomized trials support the efficacy and safety of these agents in adults, whereas pediatric evidence remains limited, particularly regarding long-term safety. In this review, we summarize the mechanistic rationale and available clinical data for these novel antiproteinuric therapies in children, highlighting ongoing trials and key knowledge gaps relevant to future pediatric CKD management.
BACKGROUND: Trehalase is a brush-border glycoprotein enzyme found in the small intestine and in renal proximal tubules, where it breaks down trehalose into glucose. We examined whether a non-invasive urine measurement of...BACKGROUND: Trehalase is a brush-border glycoprotein enzyme found in the small intestine and in renal proximal tubules, where it breaks down trehalose into glucose. We examined whether a non-invasive urine measurement of trehalase could help with earlier recognition of acute kidney injury (AKI) in children presenting with acute dehydration. METHODS: We included 80 children who were evaluated in the Pediatric Emergency Department for acute dehydration and 40 healthy controls from the general pediatric outpatient clinic. Baseline laboratory data were extracted from the hospital information system. At time of presentation, blood and urine specimens were collected from all participants. Urinary trehalase and urinary creatinine levels were analyzed, and the urinary trehalase/creatinine ratio was subsequently computed. RESULTS: Participants were analyzed in three groups: dehydrated with AKI (n = 40), dehydrated without AKI (n = 40), and healthy controls (n = 40). Baseline urea and creatinine and presentation creatinine values were similar between all groups (p > 0.05). At presentation, however, urea, urinary trehalase, and the trehalase-to-creatinine ratio were higher in dehydrated children than in controls (p = 0.001, p = 0.001 and p = 0.026 respectively). Within the dehydrated cohort, children with AKI had higher urinary trehalase, a higher trehalase-to-creatinine ratio, and higher presentation urea than those without AKI (p = 0.023, p = 0.049, and p = 0.001, respectively). Urinary trehalase showed high diagnostic accuracy (AUC 0.925); at a cut-off > 9.55 mg/dL specificity reached 100%. CONCLUSIONS: Urinary trehalase, particularly when adjusted for urinary creatinine may capture early tubular injury in dehydrated children before serum creatinine rises. Larger studies are needed to establish clinically useful cut-offs and to confirm diagnostic performance.
BACKGROUND: Chronic kidney disease (CKD) in children exposes the developing brain to uremic and vascular insults, yet blood-based markers of the pediatric kidney-brain axis remain underexplored. We characterized neuron-s...BACKGROUND: Chronic kidney disease (CKD) in children exposes the developing brain to uremic and vascular insults, yet blood-based markers of the pediatric kidney-brain axis remain underexplored. We characterized neuron-specific enolase (NSE) and brain-derived neurotrophic factor (BDNF) across the spectrum of pediatric kidney disease. METHODS: Prospective cohort of 75 children with measured GFR: 12 comparators with normal kidney function, 31 with non-dialysis CKD stages G2-G5, and 32 kidney transplant recipients (KTx). Biomarkers were measured by ELISA at baseline and after 3.2 years. Cross-sectional and longitudinal analyses adjusted for age and group. RESULTS: NSE correlated inversely with age (r = - 0.46, p < 0.001) and did not differ between groups after age adjustment. NSE-age slopes were comparable in comparators and CKD but flat in transplanted children, indicating loss of the developmental decline in this group. BDNF correlated positively with measured GFR (r = 0.31, p = 0.018) and was lower in CKD than in comparators, consistent with reduced neurotrophic reserve in pediatric uremia. CONCLUSIONS: Circulating NSE in childhood reflects developmental stage rather than CKD status. Group comparisons in pediatric biomarker studies require age adjustment. Transplantation alters the NSE-age relationship beyond what kidney function explains. BDNF tracks kidney function in pediatric CKD. Age-stratified reference intervals are required before either marker can guide clinical decisions.
Hyponatraemia is one of the most common electrolyte abnormalities encountered in clinical practice, seen in up to 30% of hospitalised children. A key part of the evaluation of hyponatraemia concerns the assessment of vol...Hyponatraemia is one of the most common electrolyte abnormalities encountered in clinical practice, seen in up to 30% of hospitalised children. A key part of the evaluation of hyponatraemia concerns the assessment of volume status. Whereas hypovolaemia indicates a deficit in salt, euvolaemic hyponatraemia is most commonly associated with excess water. An important yet often forgotten differential diagnosis in chronic euvolaemic hyponatraemia is a reset osmostat, where patients regulate their plasma osmolality around a set point below the normal range. Here we present a case of an adolescent with chronic hyponatraemia and how we arrived at a diagnosis of a reset osmostat through simple diagnostic tests.
BACKGROUND: For pediatric patients with IgA vasculitis nephritis (IgAVN), therapeutic decisions during relapse are often guided by empirical adjustments based on clinical manifestations, lacking timely pathological evide...BACKGROUND: For pediatric patients with IgA vasculitis nephritis (IgAVN), therapeutic decisions during relapse are often guided by empirical adjustments based on clinical manifestations, lacking timely pathological evidence. We aimed to investigate the dynamic evolution of kidney pathology in children with IgAVN and evaluate the clinical utility of repeat kidney biopsy in treatment decisions. METHODS: Retrospective analysis was conducted on 30 children with IgAVN who underwent repeat kidney biopsy. We summarized demographic characteristics, clinical relapse features, and indications for repeat kidney biopsy. Clinical indicators and kidney pathological changes were compared from initial to repeat kidney biopsy, and correlation between clinical indicators and pathological progression was analyzed. Longitudinal progression after treatment adjustments based on repeat kidney biopsy findings was assessed using linear mixed-effects model (LMM). RESULTS: Median interval between the two kidney biopsies was 39.95 months. During this period, despite no significant changes in 24-h urinary protein (24 h UTP) and urinary red blood cell (URBC) levels, estimated glomerular filtration rate (eGFR) showed a slight increasing trend (141.68 vs. 167.37 mL/min/1.73 m, P = 0.031). In contrast, pathological findings revealed significant deterioration of ISKDC grades (P < 0.001), with proportion of grade IIIb lesions rising from 26.67% at initial biopsy to 50.00% at repeat biopsy. Concurrently, incidence of chronicity indicators, including global glomerulosclerosis, tubular atrophy, and interstitial fibrosis, significantly increased (all P < 0.05). Fluctuations in 24 h UTP and URBC failed to sensitively reflect deterioration of intrarenal activity (all P > 0.05); only fluctuations in eGFR correlated with global sclerosis progression (P = 0.019). Consequently, 80.00% of children had treatment regimen adjustment based on repeat biopsy results. Following adjustments, both 24 h UTP (P < 0.001) and URBC (P < 0.001) decreased significantly, while serum creatinine (SCr) levels remained stable (P = 0.109), indicating a positive therapeutic response. CONCLUSION: A distinct dissociation exists between clinical presentation and kidney pathological progression during relapse in children with IgAVN. Repeat kidney biopsy is particularly beneficial for pediatric patients with clinical relapse whose conditions cannot be accurately assessed by conventional indicators; it facilitates enhanced treatment precision and improves long-term kidney outcomes.
Teixeira A, Stabouli S, Topaloglu R
… +15 more, Bayazit AK, Boyer O, Drozdz D, Shroff R, Christian M, Arslan Z, Bacchetta J, Harambat J, Printza N, Oni L, Erez DL, Platt C, Haffner D, Oh J, Levtchenko E
BACKGROUND: Subspecialty recognition and certification in Pediatric Nephrology remain heterogeneous across Europe and globally, resulting in variations in training standards and professional mobility. To address this gap...BACKGROUND: Subspecialty recognition and certification in Pediatric Nephrology remain heterogeneous across Europe and globally, resulting in variations in training standards and professional mobility. To address this gap, the European Society for Paediatric Nephrology (ESPN) launched the European Board Certification in 2020 as a pan-European and curriculum-based assessment of knowledge and clinical reasoning in Pediatric Nephrology. METHODS: We performed a descriptive and analytical evaluation of candidates who applied for the ESPN Board Certification in Pediatric Nephrology between 2020 and 2025. Candidate characteristics, examination performance, and factors associated with success were analyzed. The exam consisted of 100 case-based multiple-choice questions developed according to a predefined blueprint. Multivariable logistic regression was used to identify factors independently associated with passing. Additionally, a cross-sectional survey assessed candidates' perceptions of the examination and its professional impact. RESULTS: A total of 349 pediatric nephrologists from 52 countries and four continents completed the examination. Median age was 38.2 years (IQR 34.7-43.5), and 59.9% were female. The overall pass rate was 54.7%, with significant variation by continent (p = 0.014). Attendance at the International Pediatric Nephrology Association (IPNA)-ESPN Junior Master Class was associated with higher odds of success (OR 3.76, 95% CI 1.65-5.87, p < 0.001), whereas increasing age was associated with lower odds of success (OR 0.66 per additional year, 95% CI 0.55-0.78, p = 0.002). Among 74 survey respondents, perceptions regarding the examination were highly positive: 93.2% considered the content clinically relevant, 89.2% reported increased self-confidence, and 75.6% perceived a positive professional impact. CONCLUSIONS: Since its launch, the ESPN Board Examination has emerged as an internationally acknowledged benchmark of key knowledge and clinical reasoning in Pediatric Nephrology. Structured preparatory education enhances examination success, and certification is widely perceived as professionally meaningful. The examination plays a vital role in standardizing subspecialty criteria and reinforcing the professional identity within Pediatric Nephrology.
Hematuria is a common manifestation in hemophilia A, whereas upper urinary tract bleeding is rare and diagnostically challenging. We report a patient with severe hemophilia A presenting with gross hematuria due to sponta...Hematuria is a common manifestation in hemophilia A, whereas upper urinary tract bleeding is rare and diagnostically challenging. We report a patient with severe hemophilia A presenting with gross hematuria due to spontaneous renal pelvic hemorrhage (Antopol-Goldman lesion), initially mimicking a urothelial tumor on imaging. The diagnosis was supported by clinical context, imaging characteristics, and response to factor VIII replacement therapy. This case highlights the importance of considering benign hemorrhagic causes in hemophilia patients with atypical imaging findings to avoid unnecessary invasive procedures.
BACKGROUND: Cardiac complications are among the most common causes of death in patients after pediatric kidney transplantation (KTx), but defined diagnostic procedures identifying young patients at risk are not establish...BACKGROUND: Cardiac complications are among the most common causes of death in patients after pediatric kidney transplantation (KTx), but defined diagnostic procedures identifying young patients at risk are not established. Cardiovascular magnetic resonance (CMR) imaging with native T1 mapping allows detection of diffuse myocardial alterations but is not routinely available for cardiovascular screening. Whether abnormalities detected by echocardiography reflect underlying myocardial structural changes remains unclear. METHODS: Pediatric KTx recipients underwent comprehensive transthoracic echocardiography and CMR imaging with native T1 mapping. Associations between echocardiographic measures and T1 values were analyzed using multivariable linear regressions. Receiver operating characteristics analyses assessed the ability of septal E/e' to identify elevated T1 values, with area under the curve (AUC) and optimal cut-offs determined using positive likelihood ratios (LR +). RESULTS: Forty-six pediatric KTx recipients (16 ± 3.5 years old; time since KTx 7.9 ± 5.3 years) were included. Diastolic echocardiographic abnormalities were common, with 87% exhibiting at least one abnormal diastolic parameter. Septal T1 was associated with septal E/e', A-wave, and pulmonary venous atrial reversal, while lateral T1 was associated only with septal E/e'. Optimal septal E/e' cut-offs were 10.550 for detecting an elevated septal T1 (LR + = 7.143) and 10.630 for detecting an elevated lateral T1 (LR + = 9). CONCLUSIONS: Pediatric KTx recipients with structural myocardial alterations on CMR imaging exhibit detectable abnormalities in routine echocardiographic diastolic parameters. Especially a markedly elevated septal E/e' could identify patients at increased risk for underlying myocardial involvement and justify the use of CMR imaging in post-transplant follow-up.
BACKGROUND: Preterm birth affects approximately 10% of U.S. births, and children born preterm face twice the lifetime risk of chronic kidney disease (CKD). Despite this, kidney health surveillance after preterm birth is...BACKGROUND: Preterm birth affects approximately 10% of U.S. births, and children born preterm face twice the lifetime risk of chronic kidney disease (CKD). Despite this, kidney health surveillance after preterm birth is uncommon. Although clinical decision support (CDS) tools are widely used in pediatric practice, none address CKD risk stratification after preterm birth. This study assessed pediatric clinician perspectives on facilitators and barriers to CDS tool use, in general and for pediatric CKD risk stratification. METHODS: We conducted a qualitative descriptive study using semistructured interviews with neonatologists, general pediatricians, and pediatric nephrologists in the United States (December 2023-April 2024). Interviews were conducted by video or teleconference, digitally recorded, and professionally transcribed. Thematic analysis followed COREQ guidelines, and sampling continued until thematic saturation was confirmed. RESULTS: Twenty-five pediatric clinicians participated (44% neonatologists, 44% general pediatricians, and 12% nephrologists; median age 39 years, 76% female, 52% White, 88% non-Hispanic, and 80% academic practice). Clinicians reported strong preferences for CDS tools that efficiently support workflows, integrate with the electronic health record (EHR), and provide actionable recommendations with caregiver education. Key concerns included unintended consequences such as false reassurance, over-referral to nephrology, and care burden for families with limited subspecialty access. All participants endorsed the need for a pediatric CKD risk stratification tool. CONCLUSIONS: Pediatric clinicians prefer EHR-integrated, evidence-based, family-centered CDS tools to guide CKD risk identification after preterm birth. These findings represent an important step toward developing a pediatric kidney disease risk stratification CDS tool.
Nephrotic syndrome (NS) is the most common chronic glomerular disorder in pediatric populations, yet its manifestation during the neonatal or infantile period often portends a severe, treatment-resistant monogenic form....Nephrotic syndrome (NS) is the most common chronic glomerular disorder in pediatric populations, yet its manifestation during the neonatal or infantile period often portends a severe, treatment-resistant monogenic form. While recent studies reveal marked heterogeneity in the clinical course and severity of congenital and infantile NS, critical gaps remain in understanding its underlying mechanisms. This review synthesizes current evidence on the genetic landscape of the early-onset NS, highlighting how advances in next-generation sequencing and molecular diagnostics have refined genotype-phenotype correlations. We discuss how these insights are reshaping disease classification, enabling early prognostic stratification, and informing personalized management strategies. Emphasis is placed on the transformative role of genetic testing in guiding clinical care and uncovering novel therapeutic avenues for this complex pediatric kidney disorder.
BACKGROUND: Although acetazolamide is the main medical treatment for idiopathic intracranial hypertension (IIH), data on acetazolamide-induced metabolic acidosis and its long-term outcomes are limited. This study aimed t...BACKGROUND: Although acetazolamide is the main medical treatment for idiopathic intracranial hypertension (IIH), data on acetazolamide-induced metabolic acidosis and its long-term outcomes are limited. This study aimed to investigate the severity of acetazolamide-related metabolic acidosis, associated risk factors, and its effects on bone mineral density (BMD), growth, and kidney function. METHODS: This retrospective cohort study included pediatric patients with IIH treated with acetazolamide between 2018 and 2025. Demographic and clinical characteristics, anthropometric and laboratory findings at diagnosis and during follow-up, BMD measurements, and ultrasonography findings were collected. Metabolic acidosis was categorized by severity. Minimum and mean serum bicarbonate levels during follow-up were recorded. RESULTS: Forty-one patients (65.9% female; mean age 11.2 ± 3.1 years) were included. Metabolic acidosis was observed in all patients (39.0% mild, 53.7% moderate, 7.3% severe). Patients with moderate-to-severe acidosis had significantly lower BMI Z-scores and younger ages at diagnosis compared with those with mild acidosis. In multivariable analysis, cumulative acetazolamide dose remained independently associated with moderate/severe metabolic acidosis (OR 1.30, 95% CI 1.00-1.69; p = 0.049). BMD was assessed in 35 patients after a median acetazolamide exposure of 14 months and mildly reduced/low BMD was detected in 22.9%. Higher cumulative acetazolamide exposure and lower minimum bicarbonate levels were associated with mildly reduced/low BMD in univariable analyses; however, these associations did not remain significant after multivariable adjustment. Although estimated glomerular filtration rate declined modestly from baseline to the last visit, this change was not associated with acidosis severity, treatment duration, or cumulative acetazolamide dose. CONCLUSIONS: Metabolic acidosis is highly prevalent among children receiving acetazolamide for IIH, and greater cumulative acetazolamide exposure appears to be associated with more severe acidosis. Lower bicarbonate levels and higher cumulative acetazolamide exposure were associated with mildly reduced/low BMD in univariable analyses; however, these associations did not remain significant after multivariable adjustment. The limited number of patients undergoing BMD assessment, the relatively short exposure duration in some patients, and the absence of baseline BMD measurements limit definitive conclusions regarding the skeletal effects of acetazolamide.