Pediatric Nephrology最新文献

{"title":"The role of the complement system in Shiga toxin-associated hemolytic uremic syndrome.","authors":"Victoria Bocanegra, Mariana Luna, Valeria V Costantino, Andrea F Gil Lorenzo, Raul Marino, Roberto Miatello, Valeria Cacciamani, M Eugenia Benardon, Clara Pott Godoy, Sheila Pinto, Santiago Rodríguez de Córdoba, Patricia G Vallés","doi":"10.1007/s00467-024-06629-6","DOIUrl":"10.1007/s00467-024-06629-6","url":null,"abstract":"<p><strong>Background: </strong>This research explores complement activation products involvement and risk and protective polymorphisms in the complement alternative pathway genes in Shiga toxin-associated hemolytic uremic syndrome (STEC-HUS) pathogenesis.</p><p><strong>Methods: </strong>We analyzed the levels of complement activation products, C3a, C5a and soluble C5b-9 (sC5b-9) and plasma concentrations of Factor H (FH) and FH-related protein 1 (FHR-1) in 44 patients with STEC-HUS, 12 children with STEC-positive diarrhea (STEC-D), and 72 healthy controls (HC). STEC-HUS cases were classified as \"severe\" or \"non-severe\". Genetic analysis was performed for complement genes (CFH, CFB, MCP, C3).</p><p><strong>Results: </strong>No significant differences in the frequency of atypical HUS (aHUS) complement risk polymorphisms were found between groups. In severe STEC-HUS, the risk haplotypes CFH-H3 and MCPggaac were identified in three patients each, all in homozygosity. Patients with STEC-HUS had significantly elevated C3a, C5a and sC5b-9 levels at admission compared to HC and STEC-D, with higher sC5b-9 levels in severe cases. Increased ratio between FHR-1 and FH (FHR-1/FH) was demonstrated in STEC-HUS vs. HC, with significantly higher FHR-1/FH ratio in severe STEC-HUS patients. Principal component analysis revealed significant changes in sC5b-9 direction and magnitude in STEC-HUS. Pearson correlation showed a significant relationship between FH and sC5b-9. Logistic regression indicated sC5b-9, leukocytosis, creatinine, and anuria duration as independent factors for severe STEC- HUS.</p><p><strong>Conclusions: </strong>This study highlights the significant activation of the alternative complement pathway in STEC-HUS, particularly sC5b-9 in severe cases, and suggests a limited contribution of complement risk polymorphisms in STEC-HUS. FHR-1 may represent a promising target for future investigations related to STEC-HUS pathogenesis.</p>","PeriodicalId":19735,"journal":{"name":"Pediatric Nephrology","volume":" ","pages":"1711-1722"},"PeriodicalIF":2.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142952601","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhancing kidney assessment in pediatric neurogenic bladder: addressing gaps in body composition and GFR monitoring.","authors":"Hamza Bin Ahmed","doi":"10.1007/s00467-024-06593-1","DOIUrl":"10.1007/s00467-024-06593-1","url":null,"abstract":"","PeriodicalId":19735,"journal":{"name":"Pediatric Nephrology","volume":" ","pages":"1817"},"PeriodicalIF":2.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142581398","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanisms of podocyte injury in genetic kidney disease.","authors":"Nina Mann, Hua Sun, Amar J Majmundar","doi":"10.1007/s00467-024-06551-x","DOIUrl":"10.1007/s00467-024-06551-x","url":null,"abstract":"<p><p>Glomerular diseases are a leading cause of chronic kidney disease worldwide. Both acquired and hereditary glomerulopathies frequently share a common final disease mechanism: disruption of the glomerular filtration barrier, podocyte injury, and ultimately podocyte death and detachment. Over 70 monogenic causes of proteinuric kidney disease have been identified, and most of these genes are highly expressed in podocytes, regulating key processes such as maintenance of the slit diaphragm, regulation of actin cytoskeleton remodeling, and modulation of downstream transcriptional pathways. Collectively, these are increasingly being referred to as hereditary \"podocytopathies,\" in which podocyte injury is the central feature driving proteinuria and kidney dysfunction. In this review, we provide an overview of the monogenic podocytopathies and discuss the molecular mechanisms by which single-gene defects lead to podocyte injury and ultimately glomerulosclerosis. We review how advances in genomic technology and a better understanding of the cell biological basis of disease have led to the development of more targeted and personalized therapeutic strategies, including an overview of small molecule and gene therapy approaches.</p>","PeriodicalId":19735,"journal":{"name":"Pediatric Nephrology","volume":" ","pages":"1523-1538"},"PeriodicalIF":2.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11945604/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142562954","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Re: Vanadium exposure and kidney markers in a pediatric population.","authors":"Fathimathul Henna, Faaizah Ahmed, Reda Iqbal","doi":"10.1007/s00467-024-06647-4","DOIUrl":"10.1007/s00467-024-06647-4","url":null,"abstract":"","PeriodicalId":19735,"journal":{"name":"Pediatric Nephrology","volume":" ","pages":"1823"},"PeriodicalIF":2.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142882647","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Response letter to UTI in infants: less is more, together is better.","authors":"Magnus Lindén, Therese Rosenblad, Sverker Hansson, Per Brandström","doi":"10.1007/s00467-024-06610-3","DOIUrl":"10.1007/s00467-024-06610-3","url":null,"abstract":"","PeriodicalId":19735,"journal":{"name":"Pediatric Nephrology","volume":" ","pages":"1821-1822"},"PeriodicalIF":2.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142716386","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic and clinical spectrum of steroid-resistant nephrotic syndrome with nuclear pore gene mutation.","authors":"Huihui Yang, Gaohong Zhu, Wenjun Shao, Panli Liao, Yuan Yan, Chun Wang, Xiaowen Wang","doi":"10.1007/s00467-024-06618-9","DOIUrl":"10.1007/s00467-024-06618-9","url":null,"abstract":"<p><strong>Background: </strong>Steroid-resistant nephrotic syndrome (SRNS) is insensitive to steroid therapy and overwhelmingly progresses to kidney failure (KF), the known pathogenic genes of which include key subunits of the nuclear pore complex (NPC), a less-recognized contributor to glomerular podocyte injury.</p><p><strong>Methods: </strong>After analyzing their clinical characterizations and obtaining parental consent, whole-exome sequencing (WES) was performed on patients with SRNS. Several nucleoporin (NUP) biallelic pathogenic variants were identified and further analyzed by cDNA-PCR sequencing from white cells of peripheral blood, minigene assay, immunohistochemical (IHC) staining, and electron microscopy (EM) ultrastructure observation of kidney biopsy, as well as multiple in silico prediction tools, including 3D protein modeling.</p><p><strong>Results: </strong>Here, in six families with SRNS, we identified pathogenic mutations in NUP85/93/107/160 genes. Specifically, the patient with NUP93 mutation developed KF six months after diagnosis at 1 year 2 months. Two missense mutations, c.1655A > G and c.1604A > C, disrupted the protein stability of NUP93 by IHC staining of kidney biopsy. Ultrastructurally, the above mutations led to severe vacuolization and deformed nucleus in podocytes, torn and dissolved glomerular basement membrane, and diffuse foot process effacement. The patient with NUP85 mutation reached chronic kidney disease (CKD) stage 3 after 4 years follow-up, with exons 2-5 in-frame loss and a missense variant at c.511C > T, not affecting NUP85 expression but possibly weakened interaction with Seh1. Additionally, an extended endoplasmic reticulum (ER) tubule was readily observed under EM. Meanwhile, dilated ER was also found in two children with NUP160 mutations (c.3330 delA and c.2407 G > A; c.2241 + 1 (IVS17) G > T and c.3656 T > G), one of which has undergone kidney transplantation. Compound heterozygous variants in NUP107, c.1695 G > C and c.1360 C > T, were found in a 14-year-old girl initially diagnosed with CKD stage 5, with the former variant causing exon 19 skipping and early translation termination. c.1311 + 1(IVS15) G > A and c.1790 C > T were identified in the second affected girl, with the former causing exon 15 skipping and an in-frame loss of aa417-438, which disrupted the stability of NUP107 and interaction with NUP133.</p><p><strong>Conclusions: </strong>Our findings expand the spectrum of phenotypes and genotypes of NUPs-associated SRNS and suggest its possible pathogenic mechanism in nuclear and ER homeostasis.</p>","PeriodicalId":19735,"journal":{"name":"Pediatric Nephrology","volume":" ","pages":"1663-1676"},"PeriodicalIF":2.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143009355","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ambulatory blood pressure profiles of children with asthma compared to healthy controls.","authors":"Adem Yasin Köksoy, Yurda Şimşek, Serdar Epçaçan, Umut Selda Bayrakci","doi":"10.1007/s00467-024-06615-y","DOIUrl":"10.1007/s00467-024-06615-y","url":null,"abstract":"<p><strong>Background: </strong>Studies suggest that asthma and hypertension may be comorbid conditions. Most of these studies are epidemiological research. However, data on the relationship between asthma and hypertension in childhood are limited. We aimed to evaluate ambulatory blood pressure profiles of children with asthma.</p><p><strong>Methods: </strong>Children aged 5-18 with asthma were evaluated using ABPM. The control group included healthy age- and sex-matched volunteers. A total of 26 patients with asthma and 20 controls were enrolled.</p><p><strong>Results: </strong>Children with asthma had higher mean 24-h systolic blood pressure (SBP) SDS (standard deviation score) compared to controls (mean difference: 0.84, 0.19 ± 1.14 vs. - 0.65 ± 1.09, p = 0.015). Daytime SBP SDS was higher in those with asthma (mean difference: 0.83, 0.009 ± 1.22 vs. - 0.82 ± 1.09, p = 0.021), as was nighttime SBP SDS (mean difference: 0.74, 0.64 ± 1.09 vs. - 0.10 ± 0.79, p = 0.013). Median nighttime SBP load was higher in those with asthma (p = 0.006). Nondipping status was found in 23.1% of patients with asthma (none in controls, p = 0.021). One patient (3.8%) had ambulatory hypertension and six (23.1%) had masked hypertension (none in controls, p = 0.042). Extended use of inhaled corticosteroids was associated with a 2% increase in the odds of developing hypertension (OR 1.02, p = 0.025).</p><p><strong>Conclusions: </strong>Children with asthma may be at greater risk for developing hypertension compared to healthy counterparts. Ambulatory blood pressure tends to be higher in children with asthma than healthy peers. Inhaled steroids potentially contribute to elevated BP levels in children with asthma.</p>","PeriodicalId":19735,"journal":{"name":"Pediatric Nephrology","volume":" ","pages":"1723-1729"},"PeriodicalIF":2.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142927555","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Risk factors and retreatment for relapse in childhood primary nephrotic syndrome treated with rituximab.","authors":"Yuanzhao Zhi, Lu Cao, Rui Gu, Qin Wang, Peipei Shi, Lin Zhu, Wai W Cheung, Ping Zhou, Jianjiang Zhang","doi":"10.1007/s00467-024-06622-z","DOIUrl":"10.1007/s00467-024-06622-z","url":null,"abstract":"<p><strong>Background: </strong>The effectiveness of rituximab (RTX) for steroid-dependent/frequently relapsing nephrotic syndrome (SDNS/FRNS) in children is well documented. However, there are insufficient data on relapse risk factors. Additionally, the retreat regimen for relapsed children requires further investigation.</p><p><strong>Methods: </strong>We administered single dose RTX (375 mg/m², maximum 500 mg) to children with SDNS/FRNS between May 2020 and December 2022. An additional single dose of RTX was administered when B-cell depletion (CD19 + B cells < 1%) was incomplete or B-cell recovery (CD19 + B cells ≥ 1%) occurred. Primary and secondary outcomes were the first and second relapse, respectively.</p><p><strong>Results: </strong>Eighty-nine patients were included and the observation period was 12.2-43.2 months. Thirty-three patients (37.1%) relapsed after RTX treatment. Multivariate analysis showed that previous steroid-resistant nephrotic syndrome (SRNS) history and low NK-cell percentage at initial RTX treatment were independent risk factors for first relapse. In the relapse group, 26 patients (78.8%) continued RTX treatment upon B-cell recovery. During mean follow-up period of (15.4 ± 8.1) months, 15 patients (45.5%) experienced a second relapse. Compared with non-continued RTX treatment group, the continued RTX treatment group had a lower relapse rate (34.6% (9/26) versus 85.7% (6/7); P = 0.047) and fewer relapses (0.0 (0.0, 0.6) versus 1.8 (0.9, 2.7) times/year; P = 0.004). Multivariate analysis showed that continued RTX treatment was the protective factor for second relapse.</p><p><strong>Conclusion: </strong>Previous SRNS history and low NK-cell percentage at initial RTX treatment may be associated with higher risk of relapse. Despite the possibility of relapse during RTX treatment, continued RTX treatment is effective in reducing relapse.</p>","PeriodicalId":19735,"journal":{"name":"Pediatric Nephrology","volume":" ","pages":"1635-1644"},"PeriodicalIF":2.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142927581","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Optimal functioning of hypothalamic-pituitary-adrenal axis after cessation of prednisolone therapy: a cross-sectional study in children with nephrotic syndrome.","authors":"Jaiganesh M, Kirtisudha Mishra, Shikha Sharma, Manish Kumar, Ankita Patel","doi":"10.1007/s00467-024-06645-6","DOIUrl":"10.1007/s00467-024-06645-6","url":null,"abstract":"<p><strong>Background: </strong>Hypothalamic-pituitary-adrenal (HPA) axis recovery after cessation of steroid therapy in children with nephrotic syndrome (NS) has hardly been studied in the literature.</p><p><strong>Methods: </strong>This 22-month cross-sectional study recruited children (2-14 years) with NS, having received a minimum 3 months of prednisolone, now in remission, and off steroids for 1, 3, or 6 months. Serum cortisol-basal and stimulated (with long-acting intramuscular adrenocorticotropic hormone), and factors affecting them, were assessed. Low basal and stimulated cortisol were taken as < 138 nmol/L and < 500 nmol/L, respectively.</p><p><strong>Results: </strong>Of 80 (60 males) children, median (IQR) age 64 (43, 91.7) months, most were infrequently relapsing (34; 42.5%) or had a single episode of NS (35; 43.8%). As per duration since discontinuation, 23 (28.8%), 35 (43.8%), and 22 (27.4%) children were off steroids for 1, 3, and 6 months, respectively. Overall, 8 (10%) and 26 (32.5%) had low basal and stimulated cortisol levels, respectively. Proportions of children with HPA axis suppression (low peak cortisol) were 9/23 (39%), 12/35 (34%), and 5/22 (23%) in the groups off steroids for 1, 3, and 6 months, respectively. Optimal peak cortisol level, indicating adrenal recovery, was independently associated with duration since cessation of prednisolone [odds ratio (6 months vs. 1 month) was 10.07 (95%CI 1.46 to 69.51); P = 0.019] and basal cortisol levels > 138 nmol/L (odds ratio 25.0 (95%CI 2.94 to 200); P = 0.03).</p><p><strong>Conclusions: </strong>Nearly two-thirds of children with mild courses of NS demonstrate optimal HPA axis function between 1 and 6 months post cessation of steroids. Duration since cessation and basal cortisol independently predict optimal adrenal response.</p>","PeriodicalId":19735,"journal":{"name":"Pediatric Nephrology","volume":" ","pages":"1645-1651"},"PeriodicalIF":2.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142952576","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Progression of serum creatinine and glomerular filtration rate in neonatal critical care patients during the first seven days of life.","authors":"María Medina Muñoz, Mario Cantó Cerdán, Vanesa Matías Del Pozo, Asunción Pino Vázquez, Andrés José Alcaraz Romero, Pedro Juan Tárraga López","doi":"10.1007/s00467-024-06631-y","DOIUrl":"10.1007/s00467-024-06631-y","url":null,"abstract":"<p><strong>Background: </strong>Serum creatinine and estimated glomerular filtration rate (GFR) are key indicators of kidney function.</p><p><strong>Methods: </strong>This descriptive, retrospective study included neonatal patients admitted to a tertiary hospital's neonatal intensive care unit from January 2013 to December 2016. Data on kidney function were collected from birth to 7 days of life. Patients were stratified into four gestational age groups: below 28 weeks, 28-31 weeks, 32-36 weeks, and term neonates. Qualitative variables were expressed as percentages. Quantitative variables were assessed using the Kruskal-Wallis/Wilcoxon tests. Chi-square analysis was performed for categorical variables. Statistical analysis was conducted using SPSS (Version 22.0), with significance set at p < 0.05.</p><p><strong>Results: </strong>Among 138 patients, 99 (71.7%) were premature. Term neonates showed a gradual postnatal decline in creatinine, while premature infants exhibited an initial rise followed by a decline, with values inversely proportional to gestational age (at seven days: 0.70 ± 0.19 mg/dL in below 28 weeks vs. 0.39 ± 0.08 mg/dL in term, p < 0.001). Among the clinical-epidemiological variables of the included patients, seven significantly influenced serum creatinine. GFR decreased in premature neonates at 24 h, then increased throughout the study. Term neonates demonstrated a progressive GFR increase, with higher values associated with greater gestational age (at seven days:16.8 ± 5.0 ml/min/1.73m² in below 28 weeks vs. 41.8 ± 8.0 ml/min/1.73m² in term, p < 0.001).</p><p><strong>Conclusions: </strong>Evaluating kidney function in neonates, based on serum creatinine and GFR, requires special attention during the first days of life, particularly in critically ill neonates due to multiple physiological changes and clinical factors that may influence these parameters.</p>","PeriodicalId":19735,"journal":{"name":"Pediatric Nephrology","volume":" ","pages":"1783-1793"},"PeriodicalIF":2.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142952578","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}