Dialysis-associated headache (DAH) is a common and recognized complication of chronic hemodialysis. We report a diagnostically challenging case of severe intradialytic headache in an adolescent with chronic kidney diseas...Dialysis-associated headache (DAH) is a common and recognized complication of chronic hemodialysis. We report a diagnostically challenging case of severe intradialytic headache in an adolescent with chronic kidney disease stage 5 and a history of ventriculoperitoneal shunt. A comprehensive evaluation excluded dialysis disequilibrium syndrome, biochemical and hemodynamic contributors, primary headache disorders, infection, vascular pathology, ophthalmologic causes, and shunt malfunction. Subsequent progression of focal neurological findings revealed a diffuse intramedullary spinal cord glioma. This case highlights the limitations of solely attributing refractory DAH to dialysis-related etiologies and underscores the importance of repeated neurological reassessment and multidisciplinary management in pediatric dialysis patients.
C3 glomerulopathy is an ultra-rare kidney disease driven by dysregulation of the alternative complement pathway fluid phase C3 convertase. We report the case of a previously healthy 13-year-old girl who presented with co...C3 glomerulopathy is an ultra-rare kidney disease driven by dysregulation of the alternative complement pathway fluid phase C3 convertase. We report the case of a previously healthy 13-year-old girl who presented with concurrent nephrotic and nephritic syndrome and low complement C3. Her initial kidney biopsy surprisingly showed mesangioproliferative glomerulonephritis with dominating IgA deposits resulting in a diagnosis of IgA nephropathy. Despite standard immunosuppressive treatment with prednisone and mycophenolic acid plus angiotensin-converting enzyme inhibitors, she achieved only partial remission and subsequently relapsed, exhibiting severe, persistent C3 consumption (6-8 mg/dl) and sustained C5b9 activation (1059 ng/ml). A repeat biopsy 1.2 years later established the definitive diagnosis of C3 glomerulonephritis (C3GN) with a membranoproliferative pattern. C3NEF antibodies were negative, and no pathological variant was detected in the genetic study. After 1 year and 9 months without response to immunosuppressive treatment, the C3 inhibitor pegcetacoplan was initiated. The patient achieved rapid and complete remission within 3 months, marked by normalization of proteinuria, from 2747 mg/day (urine protein-to-creatinine ratio [UPCR] 2.66 mg/mg) pre-treatment to 19 mg/d (UPCR 0.02 mg/mg) and complement activation markers (from 1162 ng/ml pre-treatment to C5b9 92 ng/ml; reference value 30-150 ng/ml). This case highlights the inherent diagnostic complexity of C3GN, suggesting the critical role of repeat biopsies in treatment-refractory, complement-dysregulated glomerulonephritis. It strongly supports the potential efficacy of C3 inhibition as a targeted therapeutic approach for patients with C3GN.
BACKGROUND: Rituximab (RTX) is widely used to prevent relapses in steroid-dependent or frequently-relapsing nephrotic syndrome (SD/FRNS). However, the impact of B-cell depletion duration on long-term outcomes remains unc...BACKGROUND: Rituximab (RTX) is widely used to prevent relapses in steroid-dependent or frequently-relapsing nephrotic syndrome (SD/FRNS). However, the impact of B-cell depletion duration on long-term outcomes remains uncertain. We compared short-term B-cell depletion (limited RTX course) with prolonged depletion maintained by repeated RTX infusions and assessed long-term disease activity. METHODS: In this retrospective multicenter study, we included children with SD/FRNS who received RTX before the age of 18 years between 2007 and 2017. Short-depletion corresponded to one or two RTX infusions, whereas prolonged-depletion reflected repeated infusions over time to maintain B-cell depletion. Prolonged remission was defined as the absence of relapse and immunosuppressive therapy for at least 2 years after the last anti-CD20 infusion. RESULTS: A total of 117 patients were included (median age at first RTX infusion: 11.6 years; 65% were boys), of whom 48 (41%) had short-depletion and 69 (59%) had prolonged-depletion. Baseline characteristics were comparable between groups. At 2 years after the last RTX infusion, 69% of patients in the short-depletion group and 65% in the prolonged-depletion group were in prolonged remission. Overall, 89 patients (75%) relapsed during follow-up. Median time to first relapse was significantly longer in the long-depletion group (36 vs. 19 months, p = 0.04). Prolonged hypogammaglobulinemia was more frequent with prolonged-depletion, whereas infection rates were similar between groups. CONCLUSION: RTX exerts a suspensive rather than curative effect in SD/FRNS. Prolonged B-cell depletion extends relapse-free survival but is associated with more frequent hypogammaglobulinemia, without an increase in severe infections.
BACKGROUND: Uroflowmetry is a non-invasive test that measures changes in urinary flow rate over time and facilitates the recognition of lower urinary tract dysfunction. Most pediatric uroflowmetry studies have been condu...BACKGROUND: Uroflowmetry is a non-invasive test that measures changes in urinary flow rate over time and facilitates the recognition of lower urinary tract dysfunction. Most pediatric uroflowmetry studies have been conducted in healthy children to construct nomograms. This study aimed to evaluate the uroflowmetric parameters of children with non-neurogenic voiding dysfunction in a tertiary pediatric hospital. METHODS: This single-center retrospective study included children aged 5-18 years with lower urinary tract symptoms who underwent uroflowmetry and pelvic floor electromyography (EMG) and met predefined functional criteria, while those with neurogenic bladder, anatomical obstruction, or neurological disorders were excluded. Uroflowmetric parameters were compared according to sex, age groups, and voiding patterns. RESULTS: A total of 1152 patients (median age: 9 years; 61.8% female) were included. Normal voiding patterns were observed in 64.3% of patients, followed by plateau (21.5%), staccato (7.6%), tower-shaped (3.6%), and interrupted (3.0%) patterns. Plateau patterns were more common in males, while tower-shaped patterns predominated in females (p < 0.001). Females had higher Qmax and voided volume than males (p < 0.001 and p = 0.003, respectively), whereas no difference was observed in post-void residual urine (p > 0.05). Qmax was lower in plateau and staccato patterns but higher in tower-shaped patterns (all p < 0.001). Post-void residual urine was significantly higher in staccato and interrupted patterns (p = 0.001 and p < 0.001, respectively). CONCLUSIONS: Uroflowmetric parameters in children with non-neurogenic voiding dysfunction differ according to sex, age, and voiding pattern. Recognition of these differences may facilitate early identification of high-risk subgroups and support the development of more targeted diagnostic and therapeutic strategies.
BACKGROUND: Pediatric Castleman disease (CD) is a rare lymph node disorder, and renal involvement is uncommon in pediatric CD. This study aimed to investigate the clinical features of pediatric CD with renal involvement....BACKGROUND: Pediatric Castleman disease (CD) is a rare lymph node disorder, and renal involvement is uncommon in pediatric CD. This study aimed to investigate the clinical features of pediatric CD with renal involvement. METHODS: Clinical data from Beijing Children's Hospital for pediatric patients with CD were analyzed retrospectively. All included cases were confirmed by lymph node biopsy, with one patient also undergoing renal biopsy. RESULTS: A total of 42 pediatric patients with CD were included, of whom 20 (47.6%) presented with renal involvement, with a median age of 10.9 years. Renal manifestations included proteinuria (11 cases), acute nephritis (4 cases), nephrotic syndrome (2 cases), and acute renal failure (3 cases). Renal involvement generally coincided with CD onset and improved following etiological treatment of CD. One patient who underwent renal biopsy was diagnosed with minimal change disease. Notably, isolated nephrotic syndrome could occur during the remission phase of CD, presenting as steroid-resistant disease that responded to the addition of immunosuppressive agents. CONCLUSIONS: Pediatric CD with renal involvement included proteinuria, nephrotic syndrome, acute nephritis, and acute renal failure. Renal involvement occurred simultaneously with CD and improved rapidly in all patients after etiological treatment of CD and immunosuppressants.
INTRODUCTION: Renal artery stenosis is one of the severe secondary hypertension (HTN) causes in children and may lead to hypertension-mediated organ damage (HMOD), including left ventricle hypertrophy (LVH). CASE REPORT/...INTRODUCTION: Renal artery stenosis is one of the severe secondary hypertension (HTN) causes in children and may lead to hypertension-mediated organ damage (HMOD), including left ventricle hypertrophy (LVH). CASE REPORT/TREATMENT: We describe a case of a 4-year-old boy with severe renovascular HTN and LVH during infancy. Genetic testing revealed variant of unknown significance in SMAD3, a gene linked to Loeys-Dietz syndrome. The patient was treated with intensive pharmacotherapy and percutaneous intravascular intervention. CONCLUSIONS: Early onset of HTN and HMOD should prompt consideration of genetic evaluation to aid diagnosis and management. In this case, a heterozygous SMAD3 variant coexisted with renal artery stenosis without the development of aortic aneurysms.
BACKGROUND: Selective Fetoscopic Laser Photocoagulation (SFLP) is used to treat Twin-Twin Transfusion Syndrome (TTTS), affecting 10-15% of monochorionic twin pregnancies. Historical data have reported neonatal acute kidn...BACKGROUND: Selective Fetoscopic Laser Photocoagulation (SFLP) is used to treat Twin-Twin Transfusion Syndrome (TTTS), affecting 10-15% of monochorionic twin pregnancies. Historical data have reported neonatal acute kidney injury (AKI) as high as 50% following TTTS; however, the incidence of AKI following SFLP remains poorly characterized. METHODS: We conducted a single-center retrospective study of monochorionic diamniotic twins who underwent SFLP for TTTS between 2010 and 2023. The primary outcome was the development of AKI during the first two weeks of life, defined by the Neonatal Modified KDIGO criteria. Mixed-effects logistic regression was performed to identify associations with AKI. RESULTS: Among 103 infants included, 15 (14.6%) developed AKI. Twins with AKI were born at earlier gestational age (26 weeks vs. 30 weeks, p < 0.001) and had lower birth weights (923 vs. 1320 g, p = 0.01). Adjusted analysis demonstrated longer latency to delivery (OR 0.69, 95% CI 0.54-0.88) and greater total number of arteriovenous (AV) anastomoses (OR 0.78, 95% CI 0.64-0.94) were associated with decreased odds of AKI. CONCLUSION: Our postnatal incidence of AKI following SFLP for TTTS is less common than previously described. Our findings suggest that a more extensive AV anastomotic network and/or longer latency to delivery may allow for improved hemodynamic balance and kidney maturation.
BACKGROUND: Atypical hemolytic uremic syndrome (aHUS) is a rare, potentially life-threatening condition; however, the evidence currently guiding therapeutic strategies remains inconsistent across countries. OBJECTIVES: I...BACKGROUND: Atypical hemolytic uremic syndrome (aHUS) is a rare, potentially life-threatening condition; however, the evidence currently guiding therapeutic strategies remains inconsistent across countries. OBJECTIVES: In this meta-analysis, we evaluated the effectiveness and safety of key therapeutic strategies, including plasma therapy (PT) and complement inhibitors (CIs), with the goal of informing treatment decision-making for aHUS in real-world settings. DATA SOURCES: PubMed, Embase, and the Cochrane Library were searched, without date or language restrictions. STUDY ELIGIBILITY CRITERIA: Observational cohort studies examining the effectiveness and safety of PT and CIs in patients with aHUS were included. STUDY APPRAISAL AND SYNTHESIS METHODS: Study quality was assessed using the Newcastle-Ottawa Scale. Target outcomes included initial treatment responsiveness (hematologic and renal remission) as well as progression and prognosis, including chronic kidney disease (CKD), kidney failure, relapse, death, and adverse events. RESULTS: Data were obtained from 106 observational cohort studies. No significant difference was observed between PT and CIs in terms of overall effectiveness or safety, with the exception of a lower relapse rate for CIs (0% vs. 15.5%, p < 0.001). Subgroup analysis revealed no significant differences between patients receiving CIs as first-line therapy, switching from PT to CIs, or receiving PT alone. In adults, no significant difference was observed between PT and CIs in terms of initial treatment response, prognosis, or safety. However, in children, CI therapy was associated with lower rates of CKD (24.6% vs. 56.6%, p < 0.001), relapse (6.2% vs. 25.5%, p = 0.02), and mortality (0.3% vs. 7.6%, p = 0.002) compared with PT. In patients with positive anti-complement factor H antibodies, CI therapy was associated with a higher rate of renal remission compared with PT (90% vs. 41.8%, p = 0.02), with no significant differences observed in any other outcomes. In patients with complement gene mutations, no significant differences in outcomes were observed between CIs and PT. CONCLUSIONS AND IMPLICATIONS OF KEY FINDINGS: No significant difference was noted between PT and CIs in terms of overall effectiveness and safety, excluding a higher rate of relapse associated with PT. CI therapy appears to be a more favorable therapeutic option for pediatric patients. PROSPERO REGISTRATION: CRD420251239582.
This report describes the case of a 12-year-old female patient with severe lupus nephritis and refractory thrombotic microangiopathy, who required dialysis for several months despite receiving intensive immunosuppressive...This report describes the case of a 12-year-old female patient with severe lupus nephritis and refractory thrombotic microangiopathy, who required dialysis for several months despite receiving intensive immunosuppressive treatment, including terminal complement blockade with eculizumab. Following a switch in therapy from eculizumab to pegcetacoplan, there was a significant reduction in haemolytic activity and steady improvement in kidney function. After more than 8 months of haemodialysis, the patient could be weaned off dialysis. This case study highlights the therapeutic potential of pegcetacoplan in the treatment of thrombotic microangiopathy in systemic lupus erythematosus.
BACKGROUND: Hydroxychloroquine (HCQ) has been identified as an interesting treatment option in adult IgA nephropathy. HCQ targets the active toll-like receptors in IgA nephropathy. The purpose of this study was to explor...BACKGROUND: Hydroxychloroquine (HCQ) has been identified as an interesting treatment option in adult IgA nephropathy. HCQ targets the active toll-like receptors in IgA nephropathy. The purpose of this study was to explore the effects and potential benefits of HCQ for childhood-onset IgA nephropathy (cIgAN). METHODS: We conducted a retrospective multicenter cohort study including 16 children with biopsy-proven cIgAN treated with HCQ in tertiary pediatric nephrology centers in Canada and France. HCQ was prescribed as an adjunctive therapy for persistent proteinuria despite standard-of-care treatment and/or with a steroid-sparing intent. Clinical and histological data were collected at baseline, and urine protein-to-creatinine ratios (UPCR) and estimated glomerular filtration rates (eGFR) were documented at HCQ initiation, 3, 6, 9, and 12 months of follow-up. Iterative biopsies before and after the introduction of HCQ (n = 8) were compared. Steroid exposure was assessed in both groups, and safety monitoring data for HCQ therapy were documented. RESULTS: Median age was 12.74 [11.33-14.07] years, with 37.5% male participants. Most (15/16, 93.8%) participants received steroid therapy, and all (16/16, 100%) were treated with renin-angiotensin-aldosterone system blockers. HCQ was initiated within a median time of 519 [249-1016.5] days from initial diagnosis. UPCR at 3, 6, 9, and 12 months after HCQ initiation significantly decreased, both in absolute and relative metrics. A decrease of 50% was noted at 12 months of follow-up. eGFR remained stable over the follow-up period. Follow-up biopsies in the HCQ-treated group showed stability or improvement of the Oxford score. No complications of HCQ were documented. CONCLUSIONS: In this first pediatric cohort reporting on real-life experience with HCQ, HCQ use was associated with a sustained reduction in proteinuria and stable kidney function in children with difficult-to-control cIgAN, with an excellent safety profile. Although causality cannot be inferred due to the observational design and concomitant therapies, these findings support further prospective evaluation of HCQ as a safe adjunctive treatment in selected cases of cIgAN.
Adenine phosphoribosyltransferase (APRT) deficiency is a rare autosomal recessive disorder of purine metabolism causing 2,8-dihydroxyadenine urinary tract stones and crystal nephropathy. Disease manifestations include ac...Adenine phosphoribosyltransferase (APRT) deficiency is a rare autosomal recessive disorder of purine metabolism causing 2,8-dihydroxyadenine urinary tract stones and crystal nephropathy. Disease manifestations include acute kidney injury (AKI), progressive chronic kidney disease (CKD), and not infrequently, kidney failure. A significant proportion of affected individuals remain asymptomatic into adulthood. The diagnosis of APRT deficiency should be considered in all children presenting with renal colic, radiolucent urinary stones and/or AKI, as well as in infants with a history of reddish-brown diaper stain. Indeed, the disorder should be considered in any person with radiolucent urinary stones and in young and middle-aged individuals with progressive CKD, particularly when a kidney biopsy reveals tubulointerstitial nephropathy of unknown cause. The presence of biallelic pathogenic APRT mutations identified through targeted multi-gene panels or single-gene testing confirms the diagnosis of APRT deficiency. As kidney stone analysis can be false-positive, this method can only be considered suggestive of APRT deficiency, and confirmatory testing must be carried out in all cases. Timely diagnosis and treatment with a xanthine oxidoreductase inhibitor, either allopurinol or febuxostat, have in several studies, based on different levels of evidence, been found to be both highly effective and safe in APRT deficiency. Appropriate pharmacotherapy significantly reduces kidney stone recurrence, slows CKD progression and appears to prevent the development of kidney failure. The outcome of kidney transplantation in individuals with APRT deficiency is comparable to those with other causes of kidney failure when allopurinol or febuxostat therapy is initiated before the transplant procedure.
BACKGROUND: Biological sex plays a crucial role in the pathophysiology of morbidities related to preterm birth. Studies specifically investigating the role of biological sex in neonatal kidney disease are lacking. This s...BACKGROUND: Biological sex plays a crucial role in the pathophysiology of morbidities related to preterm birth. Studies specifically investigating the role of biological sex in neonatal kidney disease are lacking. This study aimed to determine the association between biological sex and kidney outcomes in preterm infants. We hypothesized that male infants would be more likely to have poor kidney outcomes, including acute kidney injury (AKI), hypertension and chronic kidney disease. Given data on the relationship between sex, AKI and lung disease, we also evaluated lung disease as a secondary outcome. METHODS: Retrospective analysis of the Preterm Erythropoietin Neuroprotection Trial data. For adjusted models, we used covariates associated with adverse outcomes a priori (gestational age, SGA status) and a lasso regression. AKI was defined using creatinine only neonatal modified KDIGO criteria and bronchopulmonary dysplasia (BPD) by Neonatal Research Network criteria. RESULTS: Of the 923 infants included, 479 (51.8%) were male. AKI was more common among males (aOR 1.31, 95%CI 1.00-1.74). Hypertension was nearly twice as common in males (66.4% vs. 51.5%, p < 0.001) and remained after adjustment (aOR 1.91, 95%CI 1.32-2.77). Severe BPD was more common in males (33.4% vs. 24.3%, p = 0.0024), which persisted after adjustment (aOR 1.65, 95%CI 1.22-2.23). This association was not fully mitigated by AKI exposure. CONCLUSIONS: We describe differences in kidney outcomes and BPD by sex. Male sex is associated with an increased risk of AKI and hypertension. Research efforts focused on the mechanisms underlying sex-specific differences are needed for the identification of novel therapies that benefit both sexes.