Pediatric Nephrology最新文献

Background: Levamisole is a commonly used steroid-sparing medication in pediatric nephrotic syndrome. While use of this agent is associated with development of antineutrophil cytoplasmic antibodies (ANCA), there is limited data on their prevalence and antigen specificity.

Methods: This cross-sectional study, conducted from October 2020 to June 2022, included 117 patients, aged 2-18 years, with steroid-sensitive nephrotic syndrome and receiving levamisole at a dose of 2-2.5 mg/kg on alternate days for ≥ 6-months. All patients were screened for ANCA by indirect immunofluorescence and conventional ELISA. Patients positive on screening underwent profile ELISA to determine its antigen specificity.

Results: Twenty (17.1%) patients tested positive for ANCA by either screening method. On profile ELISA, antibodies showed specificity to myeloperoxidase (n = 13), human neutrophil elastase (n = 6), proteinase-3 (n = 4), and/or their combination (n = 3). Risk factors independently associated with presence of ANCA included female sex [adjusted odds ratio (aOR) 3.1; 95% CI 1.0-9.3; P = 0.044] and cumulative prednisolone intake in the last 6-months [aOR 0.0041; 0.0001-0.21; P = 0.006]. Following levamisole discontinuation, ANCA was negative in all 16 patients who were retested at 40.6 (3-67.2) months. Antinuclear and anticardiolipin antibodies were present in 19 and 8 patients, respectively, and leukopenia in 4 patients.

Conclusions: A significant proportion of patients with steroid-sensitive nephrotic syndrome receiving > 6-months' therapy with levamisole show positive ANCA, with antigen specificity against myeloperoxidase, neutrophil elastase and/or proteinase-3. The risk was higher in girls and lower in those receiving concurrent therapy with prednisolone in the past 6-months. Stopping levamisole therapy was associated with resolution of ANCA.

Background: Chronic kidney disease (CKD) causes significant morbidity and mortality among children with heart failure. Although the survival benefit of a simultaneous heart-kidney transplant has been demonstrated in children with heart failure undergoing dialysis [1], the optimal intervention, simultaneous heart-kidney transplant or heart-only transplant, in those with advanced CKD but not requiring dialysis remains uncertain (Choudhry et al. Pediatr Transplant 26:e14149, 2022).

Methods: Using the Scientific Registry of Transplant Recipients (SRTR), we identified all pediatric heart transplant recipients (age ≤ 18 years) who were transplanted between 1989 and 2022 with an estimated glomerular filtration rate (eGFR) of less than 45 mL/min/1.73 m² at the time of transplant. We categorized the cohort into simultaneous heart-kidney (n = 21) and heart-only recipients (n = 839). To compare patient and graft survival between these groups, we created a weighted comparison group of heart-only recipients using covariate-balancing propensity scores. The characteristics balanced included the year of transplant, age at transplant, sex, race, HLA mismatch, cause of heart disease, previous heart transplant, and immunosuppression. Survival was analyzed using weighted Cox regression.

Results: We observed significantly higher patient survival (HR: 0.29; 95% CI: 0.1-0.81; p = 0.02) and heart graft survival (HR: 0.24; 95% CI: 0.08-0.67; p = 0.002) in simultaneous heart-kidney recipients compared to propensity-score-weighted heart-only recipients.

Conclusions: In children awaiting a heart transplant with advanced non-dialysis-dependent CKD (eGFR < 45 ml/min/1.73 m²), a simultaneous heart-kidney transplant is associated with higher patient and heart graft survival compared to a heart-only transplant.

Background: Caregivers of children with nephrotic syndrome may experience psychological challenges due to the disease's unpredictability and home monitoring burden. Prevalence and risk factors of distress, anxiety, and depression among these caregivers are unknown.

Methods: We analyzed data from Insight into Nephrotic Syndrome: Investigating Genes, Health, and Therapeutics, a prospective observational childhood nephrotic syndrome cohort. We included children (1-18 years) diagnosed from 1996-2023 from the greater Toronto area, Canada, and their caregivers. Children had annual study visits for five years. Caregivers were screened for anxiety and depression using the Patient Health Questionnaire-4 annually. We evaluated risk factors for psychological distress using mixed effects models.

Results: We analyzed data from 733 children with nephrotic syndrome (median age at diagnosis: 4 [IQR 3-6] years; 460 [73%] male; 242 [33%] South Asian; 690 [94%] steroid-sensitive). Median follow-up was 5.4 (IQR 3.0-9.3) years. Caregivers of 261 (36%) children experienced ≥ mild, 101 (14%) experienced ≥ moderate, and 38 (5%) experienced severe psychological distress. Caregivers of 167 (23%) children screened positive for anxiety and 90 (12%) for depression during follow-up. Risk factors for psychological distress were younger child age, parental unemployment, worse child quality-of-life, worse family functioning, language barrier, active steroid treatment, and lack of steroid-sparing treatment. Distress was associated with a higher probability of subsequent steroid-sparing medication initiation (adjusted odds ratio 1.08, 95%CI 1.02-1.15), although residual confounding and reverse causation cannot be excluded.

Conclusions: Over one-third of caregivers experienced mild or greater psychological distress, 23% screened positive for anxiety, and 12% for depression. Child and caregiver demographics, treatment response, and socioeconomic elements were predictive of caregiver distress.

Background: Ultrasonography (US) is the preferred first-line imaging modality for suspected urinary calculi in children because it is non-invasive and avoids radiation exposure. However, its diagnostic accuracy compared with non-contrast computed tomography (CT) remains variable, depending on stone location and secondary findings. This study evaluated the diagnostic accuracy of US for pediatric urinary calculi, using CT as the reference, and explored the predictive role of secondary sonographic markers.

Methods: We retrospectively analyzed 47 children (0-18 years) who underwent both US and non-contrast CT for suspected urinary tract calculi (June 2023-2025). Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of US were calculated separately for kidney and ureteral calculi. Logistic regression assessed whether hydronephrosis or ureteral dilatation predicted CT-confirmed stones.

Results: US showed moderate specificity (84.8%) and NPV (82.4%) overall but limited sensitivity (57.1%) and a high false-negative rate (42.9%) for kidney calculi. Performance was notably poorer for ureteral calculi, with very low sensitivity. Hydronephrosis was significantly associated with ureteral calculi, increasing stone likelihood nearly seven-fold (OR 7.02, 95% CI 1.25-39.40; p = 0.027), while it was not predictive for kidney stones. Ureteral dilatation was not predictive for either kidney (OR 0.34, 95% CI 0.03-3.18; p = 0.349) or ureteral calculi (OR 0.57, 95% CI 0.06-5.41; p = 0.628).

Conclusions: US remains a valuable first-line tool for pediatric urinary calculi but shows limited sensitivity, particularly for ureteral stones. CT should be reserved for cases with inconclusive or negative US but persistent clinical suspicion or secondary signs suggestive of obstruction, ensuring diagnostic accuracy while minimizing unnecessary radiation exposure.

Background: Monosymptomatic nocturnal enuresis (MNE) affects 10-15% of children at school age. Influences on psychological well-being and self-confidence were repeatedly described, but effects on health-related quality of life (HRQoL) have been rarely reported. The aim of this study is to examine the HRQoL under therapy by using KINDL-R and to compare it with three recognized chronic diseases.

Methods: Questionnaires were sent to all patients with MNE of the special outpatient clinic for enuresis (age 7-17 years; groups: I: 7-13, II: 14-17 years; at least 3 months of therapy, no achieved dryness). Simultaneously, patients from special outpatient clinics for allergic bronchial asthma (ABA), diabetes mellitus type I (DMI), and juvenile idiopathic arthritis (JIA) were asked to take part in the study.

Results: Included patients: 47 MNE (I:41/II:6)/59 ABA (I:34/II:25)/57 DMI (I:31/II:26)/37 JIA (I:18/II:19). Patient reports showed no significant differences between the cohorts in both age groups examined with regard to the total score and six individual dimensions. In the additional "chronic-generic" module, patients with MNE in the age of 7-13 years showed significantly lower values than all other study cohorts (p < 0.001).

Conclusions: Patients under therapy for MNE without achieving dryness showed no significant differences in overall HRQoL or individual dimensions compared to the reference groups, but a significantly lower HRQoL in the chronic-generic module in children and parents (group 7-13 years) and in adolescents (14-17 years of age). This result is consistent with reported limitations in self-esteem and HRQoL before therapy and supports the need and importance of adequate therapy for MNE.

Frequently relapsing, steroid-dependent nephrotic syndrome (FRNS/SDNS) remains a therapeutic challenge. Rituximab, a B-cell-depleting agent, is effective and widely used for FRNS/SDNS, but its use can be limited by rare, serious adverse effects. Belimumab, a monoclonal antibody targeting B-cell activating factor (BAFF), is approved for treating adult systemic lupus erythematosus (SLE) and lupus nephritis (LN). We report a pediatric case of FRNS/SDNS refractory to conventional immunosuppressive regimens and intolerant of rituximab due to serious complications, who subsequently maintained complete remission for nearly one year after steroid withdrawal while receiving belimumab added to ongoing mycophenolate mofetil (MMF). This case suggests that belimumab combined with MMF is effective for refractory NS. However, as a single case report, its efficacy requires further strengthening through more cases.

Background: Nephropathy in nail-patella syndrome (NPS) has limited therapeutic options. Progressive nephrotic-range proteinuria often persists despite maximal renin-angiotensin-aldosterone system inhibitor (RAASi) therapy. Calcineurin inhibitors such as cyclosporine A (CsA) are unexplored in NPS. We therefore evaluated the efficacy and safety of CsA in a patient with NPS.

Methods: A 15-year-old boy with genetically confirmed NPS (novel LMX1B missense variant, c.796T>G, p. W266G) was studied. Clinical, pathological, and follow-up data were analyzed. Bioinformatic screening (GSE12008 dataset) identified LMX1B-regulated podocyte genes. Functional assays (immunofluorescence, dual luciferase reporter, and molecular dynamics analyses) assessed the mutation's impact.

Results: The patient presented with classical NPS features, including nail dysplasia, limited elbow motion, patellar dysplasia, and proteinuria. Kidney biopsy revealed focal glomeruli immaturity with small foci of foamy cells, diffuse foot process effacement, and heterogeneous glomerular basement membrane (GBM) abnormalities (predominantly thinned with segmental thickening and loosening), demonstrating Alport-like kidney pathology. Despite resistance to RAASi and sodium-glucose cotransporter inhibitor (SGLT2i), CsA therapy for 7 months significantly reduced proteinuria from 3.74 to 0.697 g/24 h, increased serum albumin from 28.8 to 39.4 g/L, and maintained normal serum creatinine (54-63 μmol/L). Immunofluorescence analysis of the patient's kidney tissue indicated reduced expressions of PTPRO, NPHS2, and COL4A3. The W266G mutation severely impaired LMX1B binding to the promoters, reducing the transcriptional activity of PTPRO, NPHS2, and COL4A3.

Conclusions: CsA effectively reduced nephrotic-range proteinuria in genetically confirmed NPS, suggesting the therapeutic potential of calcineurin inhibitors in for NPS-associated nephropathy.

Background: Childhood-onset systemic lupus erythematosus (SLE) poses unique challenges compared to adult-onset SLE, with higher rates of kidney involvement, tissue damage, and mortality. Despite this, data on the effectiveness of immunomodulatory therapies, particularly for lupus nephritis (LN), in pediatric populations are limited. We leveraged a U.S. national learning health system to describe induction treatment in children with LN.

Methods: A previously validated LN case-finding algorithm was used to identify patients. Index date was the date of the first LN diagnosis code or the date of the first kidney biopsy, whichever came first. Induction medications included corticosteroids (IV and PO), cytotoxic agents (cyclophosphamide, IV), antimetabolites (mycophenolate mofetil, mycophenolic acid) and biologics (rituximab, belimumab).

Results: 575 children with LN were identified. Median age at entry was 15.1 years, 78.6% had evidence of a kidney biopsy, and 56.3% of patients received at least one non-corticosteroid immunosuppressive medication within 6 months of the index date. Prescribed or administered agents during the induction period were: corticosteroids (85%), antimetabolite (61.6%), biologic agent (13.7%), cytotoxic agent (21%). Among the 15% not prescribed or administered corticosteroids, but prescribed or administered an additional immunosuppressive medication, 100% were prescribed or administered antimetabolites. The most common first non-corticosteroid agents were antimetabolites (61.6%), cytotoxic agents (21%) and biologics (13.7%), while biologics were the most common second-line agent.

Conclusions: We utilized a validated, sensitive and specific computable phenotype to identify children and adolescents with LN and subsequently characterize their induction therapy regimens, a critical first step in designing future pragmatic clinical trials.

Kidney biopsy is the standard of diagnosis for many kidney diseases and conditions. Severe bleeding following a kidney biopsy is a complication for which limited therapeutic interventions exist. The use of recombinant activated factor VII (rFVIIa) is described in pediatric patients to control severe intra-operative hemorrhage and has been used in at least one adult patient to manage post-kidney biopsy hemorrhage. We present a 10-year-old female who presented with acute kidney injury, thrombocytopenia, and hypertension, ultimately diagnosed with ANCA-vasculitis. Following a kidney biopsy, the patient experienced a large, expanding hematoma with active bleeding that did not improve despite pre-biopsy desmopressin, 90 min of pressure to the biopsy site, and platelet transfusions. Recombinant activated FVIIa was administered, and the bleeding immediately stopped. This case supports the use of recombinant FVIIa in post-kidney biopsy hemorrhage when bleeding is not controlled using conventional strategies.

Background: In pediatric kidney transplant, recipients' long-term graft survival remains variable necessitating methods to predict the timing of graft failure. Studies in adults have identified post-transplant serum creatinine (sCr) as a biomarker for graft survival. Our goal was to investigate the predictive value of 1-year sCr levels on long-term graft survival in pediatric kidney recipients.

Methods: We performed a retrospective cohort study of Organ Procurement and Transplantation Network data. We identified 8733 pediatric kidney transplant recipients between 2008 and 2021 with reported 1-year sCr levels. Patients were grouped by sCr level: ≤ 1.0, 1.0-1.5, 1.5-2.0, and ≥ 2.0 mg/dL. We analyzed long-term graft survival with a Kaplan-Meier curve and a multivariable Cox proportional hazards model. We developed a predictive score derived from a sCr-based model and an estimated glomerular filtration rate (eGFR)-based model and compared them using DeLong's test.

Results: Mean 1-year sCr was 0.88 mg/dL, and higher 1-year sCr predicted long-term graft failure (sCr 1.0-1.5 adjusted hazard ratio (aHR) 1.73, sCr 1.5-2.0 aHR 2.64, sCr ≥ 2.0 aHR 6.92, p < 0.001 for all). The mean 1-year eGFR was 71.66 mL/min/1.73 m². Compared to patients with eGFR ≥ 90, the risk of graft failure increased stepwise with lower eGFR (eGFR 60-90 aHR 1.27, eGFR 45-60 aHR 1.70, eGFR 30-45 aHR 2.62, eGFR < 30 aHR 9.05, p < 0.004 for all). Predictive ability was similar between eGFR- and sCr-based models (p = 0.116).

Conclusions: Utilizing 1-year sCr may allow for early identification of patients at risk of graft failure for careful surveillance and prognostication for patients' expectations.