Frontiers in nephrology最新文献

{"title":"Short-term outcome of levamisole in frequently relapsing nephrotic syndrome: a single-center prospective cohort study.","authors":"Sabeeta Khatri, Irshad Ali Bajeer, Aasia Zubair, Ali Asghar Anwar Lanewala, Seema Hashmi","doi":"10.3389/fneph.2025.1539776","DOIUrl":"10.3389/fneph.2025.1539776","url":null,"abstract":"<p><strong>Introduction: </strong>This study aims to describe the outcome of levamisole (LEVA) treatment in children with frequently relapsing nephrotic syndrome (FRNS).</p><p><strong>Methods: </strong>This prospective cohort study was conducted at the Department of Pediatric Nephrology, Sindh Institute of Urology and Transplantation from 1 January 2019 to 31 December 2020. Children aged 1-18 years diagnosed with FRNS were included. LEVA was started with a dose of 2-2.5 mg/kg every other day for 2 years along with low-dose prednisolone in the first year.</p><p><strong>Results: </strong>A total of 70 children with FRNS were enrolled in the study. The median age was 7.5 [interquartile range (IQR) 5.0-9.6 years] with a slight predominance of boys (42, 60%). The mean number of relapses and cumulative dose of steroids significantly decreased after 2 years of LEVA therapy and during the 1-year follow-up. LEVA non-response was observed in half of the studied participants (28, 46%). The responders and non-responders were comparable in terms of cumulative dose of steroids and number of relapses in the year prior to starting LEVA [5,242 ± 1,738 versus 4,910 ± 1,469 (p-value = 0.52) and 5.4 ± 2.4 versus 5.2 ± 2.1 (p-value = 0.85)].</p><p><strong>Conclusion: </strong>LEVA therapy resulted in a substantial reduction in the frequency of relapses and cumulative dosage, indicating its potential as an alternative option for children with relapsing disease.</p>","PeriodicalId":73091,"journal":{"name":"Frontiers in nephrology","volume":"5 ","pages":"1539776"},"PeriodicalIF":0.0,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11969797/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143797181","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Editorial: Novel diagnostic and prognostic methods in acute kidney injury among patients in intensive care unit.","authors":"Marco Fiorentino","doi":"10.3389/fneph.2025.1586794","DOIUrl":"10.3389/fneph.2025.1586794","url":null,"abstract":"","PeriodicalId":73091,"journal":{"name":"Frontiers in nephrology","volume":"5 ","pages":"1586794"},"PeriodicalIF":0.0,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11965580/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143782118","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The kidney injury biomarker profile of patients with lupus nephritis remains unchanged with the second-generation calcineurin inhibitor voclosporin.","authors":"Biff F Palmer, James A Tumlin, Jai Radhakrishnan, Linda M Rehaume, Jennifer L Cross, Robert B Huizinga","doi":"10.3389/fneph.2025.1540471","DOIUrl":"10.3389/fneph.2025.1540471","url":null,"abstract":"<p><strong>Objectives: </strong>Kidney injury in patients with lupus nephritis (LN) results in pro-fibrotic biomarker expression, a manifestation also observed with calcineurin inhibitor (CNI) therapy. The second-generation CNI, voclosporin, is approved in the United States and Europe for the treatment of patients with active LN in combination with background immunosuppression, based on successful outcomes from the global phase 2 AURA-LV and phase 3 AURORA 1 studies, which demonstrated the efficacy of voclosporin across diverse racial and ethnic populations, and encompassing multiple biopsy classes of LN, alongside a favorable safety profile. This <i>post hoc</i> analysis examined changes from baseline levels of serum and urinary biomarkers, including pro-fibrotic biomarkers, in a cohort of patients from the parent AURORA 1 study.</p><p><strong>Methods: </strong>Samples were analyzed from a cohort of patients in AURORA 1 treated with voclosporin (23.7 mg twice daily, n=57) or placebo (n=59) in combination with mycophenolate mofetil (MMF) and low-dose glucocorticoids, including in a subgroup of patients that experienced a ≥30% decline from baseline in estimated glomerular filtration rate (voclosporin, n=26; placebo, n=20).</p><p><strong>Results: </strong>The addition of voclosporin to MMF and low-dose glucocorticoids for the treatment of LN did not result in significant differences in normalized urinary concentrations of KIM-1, TGF-β1, MCP-1, or NGAL, biomarkers indicative of renal fibrosis and kidney damage, when compared to MMF and low-dose glucocorticoids alone.</p><p><strong>Conclusion: </strong>These findings further support the safety of voclosporin for the treatment of LN in adult patients.</p><p><strong>Clinical trial registration: </strong>ClinicalTrials.gov <b>, identifier NCT03021499; EudraCT, identifier 2016-004045-81.</b></p>","PeriodicalId":73091,"journal":{"name":"Frontiers in nephrology","volume":"5 ","pages":"1540471"},"PeriodicalIF":0.0,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11955810/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143756387","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of kidney transplantation in long-term cardiac reverse remodeling and interconnecting mechanisms in type 4 cardiorenal syndrome.","authors":"Jose Luis Salas-Pacheco, Jose Manuel Arreola-Guerra, Ricardo Marquez-Velasco, Israel Perez-Torres, Sergio Casarez-Alvarado, Giovanny Fuentevilla-Alvarez, Verónica Guarner-Lans, Randall Cruz-Soto, María Elena Soto","doi":"10.3389/fneph.2024.1455036","DOIUrl":"10.3389/fneph.2024.1455036","url":null,"abstract":"<p><strong>Background: </strong>Type 4 cardiorenal syndrome (CRS) involves cardiovascular alterations caused by chronic kidney disease (CKD). Fibroblast growth factor-23 (FGF23), carboxy-terminal propeptide of procollagen type I (PIP), and parathyroid hormone (PTH) have been proposed as biomarkers of pathological cardiac remodeling in CKD. In contrast, it has been suggested that MicroRNA 221 has a cardioprotective role. Available evidence shows that, 12 months after kidney transplantation (KT), type 4 CRS reverts in only half of the patients.</p><p><strong>Objective: </strong>To assess long-term cardiac reverse remodeling after KT and its association with FGF23, PIP, and PTH levels.</p><p><strong>Methods: </strong>Patients with end-stage renal disease were assessed before and 28 months after KT using FGF23, PIP, and PTH serum concentrations and transthoracic echocardiography.</p><p><strong>Results: </strong>Fifty-three patients were followed for 28 months after KT. All the patients showed cardiac abnormalities upon inclusion. A follow-up assessment showed a reduction in left ventricle (LV) mass (121 ± 48 vs. 65 ± 14 gr/m²) and left atrial volume (46 vs. 30 ml/m²). The LV ejection fraction (53 vs. 63%), LV global longitudinal strain (-15.9 vs.-19.4%), and LV diastolic function improved. miR-221 expression increased after KT (8.73 RIQ= 3.7-25 vs. 40.16 RIQ= 24-223, p=0.001) and was correlated with the Ee´ratio (r= -0.32, p= 0.02). Multivariate analysis showed that post-KT LV mass was determined by pre-KT LV mass, serum Cr level, post-KT PIP, and hypertension (R² = 0.65, F=12.1, p=0.001).</p><p><strong>Conclusions: </strong>Contrary to other evidence, this study demonstrated that type 4 CRS is reversible over the long term. This is a paramount finding because KT normalizes cardiac structure and function independently of the severity of basal cardiac abnormalities.</p>","PeriodicalId":73091,"journal":{"name":"Frontiers in nephrology","volume":"4 ","pages":"1455036"},"PeriodicalIF":0.0,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11922888/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143671774","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The value of the phase angle of bioelectrical impedance analysis to predict malnutrition in hemodialysis patients.","authors":"Qingxuan Xiao, Na Xie, Xinyang Xiang, Ting Cao, Yingye Xie, Xiang Liang, Xiaoyan Su","doi":"10.3389/fneph.2025.1478367","DOIUrl":"10.3389/fneph.2025.1478367","url":null,"abstract":"<p><strong>Objectives: </strong>To investigate the validity of bioelectrical impedance analysis (BIA)-derived phase angle (PhA) as a predictor of malnutrition in maintenance hemodialysis (MHD) patients.</p><p><strong>Methods: </strong>A single-center, cross-sectional study of 126 MHD patients was conducted. A diagnosis of malnutrition was based on the 7-point Subjective Global Assessment (7-p-SGA) criteria. A Bioelectrical Impedance Analyzer was used to determine the PhA, fat mass (FM), muscle mass, and extracellular water/total body water (ECW/TBW) ratio. Biochemical indices and anthropometric measurements were also assessed. Using 7-p-SGA criteria, the patients were categorized into two groups: well-nourished and malnourished. General patient characteristics and the PhA values were compared between the two groups. A correlation analysis examined the relationship between PhA and the nutritional index. Logistic regression models and receiver operating characteristic curve analyses were used to identify independent factors for predicting malnutrition and determining their respective cutoff values.</p><p><strong>Results: </strong>The malnourished group had a significantly lower PhA than the well-nourished group (5.19° (5.81°, 4.09°) vs 6.13° (6.80°, 5.49°), <i>P</i> < 0.001). The PhA correlated positively with body mass index (BMI), albumin (Alb), and handgrip strength (HGS) (<i>P</i> < 0.05). However, there were no significant associations between PhA and FM or triceps skinfold thickness (TSF) (P > 0.05). Multivariate logistic regression analysis revealed that PhA, Alb, and BMI were independent predictors of malnutrition. Of these, BMI was the strongest predictor [odds ratio (OR) = 0.68; <i>P</i> < 0.001]. PhA also served as a secondary predictor of malnutrition (OR = 0.588; <i>P</i> = 0.035). Receiver operating characteristic curve analysis indicated that a PhA threshold value of approximately 5.78° was optimal for predicting malnutrition.</p><p><strong>Conclusion: </strong>PhA is a straightforward and reliable predictor of malnutrition in MHD patients, with an optimal cut-off value of 5.78° identified for diagnosing this condition.</p>","PeriodicalId":73091,"journal":{"name":"Frontiers in nephrology","volume":"5 ","pages":"1478367"},"PeriodicalIF":0.0,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11911513/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143652311","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Introducing the \"urine biochemical approach\": an alternative tool for improving acute kidney injury monitoring in critically ill patients.","authors":"Alexandre Toledo Maciel","doi":"10.3389/fneph.2025.1525551","DOIUrl":"10.3389/fneph.2025.1525551","url":null,"abstract":"<p><p>Urine electrolytes and indices assessment as a tool for acute kidney injury (AKI) pathophysiological understanding and management is, until these days, a matter of debate. The classic division of AKI in \"pre-renal\" (functional/transient) and \"renal\" (structural/persistent) based on the urinary concentration of sodium and the fractional excretions of sodium and urea has gained popularity for decades and is still present in medical textbooks. Nevertheless, the conclusions of the studies that have used these parameters are very heterogenous and controversial. In the last decade, the pre-renal paradigm has been questioned since urine biochemistry (UB) compatible with \"pre-renal AKI\" was retrieved from experimental animals with increased renal blood flow, leading some authors to conclude that this approach is not useful for AKI monitoring. Our group has also studied the use of UB in AKI and we think that the key point for adequate use of this tool in clinical practice is a complete mindset change in the way we look and interpret data. In this article, we present the \"urine biochemical approach\" as an alternative way for UB assessment, which we believe that makes more sense and seems to be more useful for AKI monitoring than the traditional approach. Although the real utility of this alternative approach needs to be confirmed in large, prospective studies, the aim of the present article is to open the mind of critical care practitioners for a potential reappraisal of ancient concepts and ideas regarding the use of urine electrolytes in AKI monitoring.</p>","PeriodicalId":73091,"journal":{"name":"Frontiers in nephrology","volume":"5 ","pages":"1525551"},"PeriodicalIF":0.0,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11879783/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143569044","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Artificial intelligence and pediatric acute kidney injury: a mini-review and white paper.","authors":"Jieji Hu, Rupesh Raina","doi":"10.3389/fneph.2025.1548776","DOIUrl":"10.3389/fneph.2025.1548776","url":null,"abstract":"<p><p>Acute kidney injury (AKI) in pediatric and neonatal populations poses significant diagnostic and management challenges, with delayed detection contributing to long-term complications such as hypertension and chronic kidney disease. Recent advancements in artificial intelligence (AI) offer new avenues for early detection, risk stratification, and personalized care. This paper explores the application of AI models, including supervised and unsupervised machine learning, in predicting AKI, improving clinical decision-making, and identifying subphenotypes that respond differently to interventions. It discusses the integration of AI with existing risk scores and biomarkers to enhance predictive accuracy and its potential to revolutionize pediatric nephrology. However, barriers such as data quality, algorithmic bias, and the need for transparent and ethical implementation are critical considerations. Future directions emphasize incorporating biomarkers, expanding external validation, and ensuring equitable access to optimize outcomes in pediatric AKI care.</p>","PeriodicalId":73091,"journal":{"name":"Frontiers in nephrology","volume":"5 ","pages":"1548776"},"PeriodicalIF":0.0,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11876175/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143560144","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Predictive value of early neutrophil-to-lymphocyte ratio and C-reactive protein in pediatric steroid-sensitive nephrotic syndrome.","authors":"Gulinuer Maimaititusvn, Nilupaer Jvnaiti, Maierhaba Kulaixi, Fang Liu","doi":"10.3389/fneph.2025.1524231","DOIUrl":"10.3389/fneph.2025.1524231","url":null,"abstract":"<p><strong>Objective: </strong>This study aims to investigate the predictive value of early neutrophil-to-lymphocyte ratio (NLR) and C-reactive protein (CRP) levels for relapse and adverse prognosis within one year in children diagnosed with steroid-sensitive nephrotic syndrome (SSNS).</p><p><strong>Methods: </strong>This study included a total of 145 pediatric patients diagnosed with steroid-sensitive nephrotic syndrome (SSNS) between January 2016 and December 2021. We collected early neutrophil-to-lymphocyte ratio (NLR) and C-reactive protein (CRP) levels, along with relevant clinical data, and conducted a one-year follow-up of the patients. Based on the follow-up outcomes, the patients were categorized into two groups: those who experienced a relapse and those who did not. We assessed the diagnostic and predictive value of NLR and CRP for relapse within one year using receiver operating characteristic (ROC) curve analysis and the Cox proportional hazards regression model.</p><p><strong>Results: </strong>After an average follow-up period of one year, 95 patients (65.52%) experienced relapse, while 50 patients (34.48%) did not. Significant differences were noted between the relapse and non-relapse groups regarding neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), C-reactive protein (CRP), 24-hour urinary protein levels, age at onset, and parental education level (P < 0.05). Cox proportional hazards regression analysis identified age at onset, NLR, CRP, and 24-hour urinary protein levels as significant risk factors for relapse in patients with steroid-sensitive nephrotic syndrome (SSNS). Receiver operating characteristic (ROC) curve analysis for the combined prediction of relapse using NLR, CRP, and 24-hour urinary protein levels demonstrated good predictive value, with an area under the curve (AUC) of 0.858 (95% CI: 0.80-0.916, P < 0.001). Kaplan-Meier survival analysis indicated that patients with elevated NLR (≥ 2.90) and CRP (≥ 25.30) exhibited the highest relapse rates and shorter survival times. Further Cox proportional hazards analysis revealed that children in the high NLR and high CRP groups were at an increased risk of relapse, rehospitalization, infection, prolonged cumulative steroid use, renal insufficiency, secondary hypertension, and other adverse outcomes within one year.</p><p><strong>Conclusion: </strong>Early levels of Neutrophil-to-Lymphocyte Ratio (NLR) and C-Reactive Protein (CRP) demonstrate significant predictive value for relapse and adverse prognosis within one year in children with Steroid-Sensitive Nephrotic Syndrome (SSNS). These markers can serve as effective tools for auxiliary clinical assessment.</p>","PeriodicalId":73091,"journal":{"name":"Frontiers in nephrology","volume":"5 ","pages":"1524231"},"PeriodicalIF":0.0,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11897826/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143617812","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The road ahead: emerging therapies for primary IgA nephropathy.","authors":"Edward J Filippone, Rakesh Gulati, John L Farber","doi":"10.3389/fneph.2025.1545329","DOIUrl":"10.3389/fneph.2025.1545329","url":null,"abstract":"<p><p>Primary IgA nephropathy (IgAN) is the most common form of primary glomerulopathy. A slowly progressive disease presenting in the young to middle-aged, most patients with reduced eGFR or proteinuria will progress to end-stage kidney disease (ESKD) in their lifetimes. The pathogenesis involves increased production of galactose-deficient IgA1 (Gd-IgA1) that forms immune complexes that deposit in the glomerulus, eliciting mesangial cell proliferation, inflammation, and complement activation. The backbone of therapy is supportive, including lifestyle modifications, strict blood pressure control, and renin-angiotensin system inhibition targeting proteinuria < 300 mg/day. Sodium-glucose transporter 2 inhibitors are indicated for persisting proteinuria or declining eGFR. Sparsentan is indicated for persisting proteinuria. Immunosuppression should be considered for all patients at risk for progression (persisting proteinuria and/or declining eGFR). To reduce Gd-IgA1 production, targeted-release budesonide is approved. Agents targeting B cell survival factors APRIL or BAFF/APRIL have significantly reduced Gd-IgA1 production and proteinuria in phase 2 trials but await phase 3 data for approval. To reduce inflammation, high-dose steroids are ineffective and toxic in Caucasian patients, although lower-dose regimens may be effective in Chinese patients. Complement inhibition is being actively studied. The factor B inhibitor iptacopan has conditional approval. The terminal pathway inhibitors cemdisiran and ravulizumab show promise in phase 2 studies. Our current approach for those requiring immunosuppression involves combining the reduction of Gd-IgA1 (nefecon) with suppressing the effects of inflammation (iptacopan). The optimal duration of such therapy is uncertain. Clearly, there is more to be learned with many trials underway.</p>","PeriodicalId":73091,"journal":{"name":"Frontiers in nephrology","volume":"5 ","pages":"1545329"},"PeriodicalIF":0.0,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11832374/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143451160","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Case report: Novel <i>ACTN4</i> variant of uncertain significance in a pediatric case of steroid-resistant nephrotic syndrome requesting kidney transplantation.","authors":"Ignacio Alarcón, Carolina Peralta, Francisco Cammarata-Scalisi, Maykol Araya Castillo, Francisco Cano, Angélica Rojo, María Luisa Ceballos, Paola Krall","doi":"10.3389/fneph.2024.1375538","DOIUrl":"10.3389/fneph.2024.1375538","url":null,"abstract":"<p><strong>Background: </strong>Steroid-resistant nephrotic syndrome (SRNS) is a rare kidney disease commonly characterized histopathologically by focal and segmental glomerulosclerosis (FSGS) or minimal change disease. One-third of SRNS-FSGS cases are attributed to a genetic cause ultimately leading to end-stage kidney disease (ESKD) during childhood or adulthood. <i>ACTN4</i> variants, although rare, typically manifest in early adulthood as SRNS-FSGS with autosomal dominant inheritance pattern and are associated with variable progression toward ESKD.</p><p><strong>Case–diagnosis/treatment: </strong>A 10-year-old Chilean male patient, born to a complicated pregnancy without any history of prenatal care, was incidentally found to have mild proteinuria during pre-surgery analysis. He was diagnosed with nephrotic syndrome and treatment with prednisone was started, but 12 months later, he persisted with hyperlipidemia, hypoalbuminemia, and proteinuria. Within a few weeks, proteinuria rapidly increased, and a kidney biopsy exhibited FSGS features. At the age of 12, he reached ESKD and initiated peritoneal dialysis, experiencing an episode of posterior reversible encephalopathy syndrome. Exome sequencing identified a novel variant of uncertain significance (VUS), <i>ACTN4</i> c.625_633del that predicted the in-frame deletion p.L209_E211del in a highly conserved functional domain. He requested to be considered for kidney transplantation and the VUS in <i>ACTN4</i> was re-analyzed to assess potential risks, resulting in a reclassification as likely pathogenic (PM1+PM2+PM4 criteria). At 14 years old, he received a deceased donor kidney allograft without recurrence during the subsequent 5 months.</p><p><strong>Conclusions: </strong>Identifying VUS is a recurring challenge in routine clinical genetics, particularly for patients with rare diseases or atypical phenotypes in underrepresented populations. This case underscores the benefit of timely genetic diagnosis taking into account the patient's request. VUS reassessment becomes more relevant when considering a kidney transplant not only as an appropriate procedure, but as the therapy of choice, especially considering the patient's history of complications with variable long-term consequences.</p>","PeriodicalId":73091,"journal":{"name":"Frontiers in nephrology","volume":"4 ","pages":"1375538"},"PeriodicalIF":0.0,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11826236/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143434338","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}