Nephron最新文献

{"title":"Renal Endowment in Men and Women: Start from the Beginning.","authors":"Barbara Imberti, Ariela Benigni","doi":"10.1159/000542411","DOIUrl":"10.1159/000542411","url":null,"abstract":"<p><p>The development of the human kidney leads to the establishment of nephron endowment through a process influenced by both genetic and environmental factors. There is individual variability regarding nephron endowment and factors including aging and pathological conditions contribute to the decline in the number of nephrons, impacting renal function. Genetic determinants, such as mutations in crucial developmental genes like Pax2, and epigenetic mechanisms mediated by key enzymes including sirtuin 3, play critical roles in the regulation of the number of nephrons, with implications for kidney disease susceptibility. Sexual dimorphism significantly influences kidney development and function, with the number of nephrons being significantly lower in females, consistent with lower female birth weight, which is considered a surrogate for nephron endowment. Also, although females have fewer nephrons, they experience a slower decline in GFR compared to males. Gender disparity in chronic kidney disease progression has been attributed to factors such as metabolism, oxidative stress, renal hemodynamics, and sex hormones. Understanding the complexities of nephron endowment variability, genetic determinants, and sexual dimorphism in kidney development and function is crucial for elucidating the mechanisms underlying individual kidney disease susceptibility and progression. Further research in this field holds promise for the development of personalized approaches to kidney disease prevention, management, and treatment.</p>","PeriodicalId":18998,"journal":{"name":"Nephron","volume":" ","pages":"207-212"},"PeriodicalIF":2.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142604612","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mendelian Randomization Analysis Reveals a Causal Relationship between Membranous Nephropathy and the Gut Microbiome.","authors":"Dunlu Yuan, Yuelong Chen, Hongyun Zheng, Guiqun Liu, Qing Yang, Ling Chen, Qing Li","doi":"10.1159/000543606","DOIUrl":"10.1159/000543606","url":null,"abstract":"<p><strong>Introduction: </strong>With the increasing prevalence of membranous nephropathy (MN), the gut microbiome (GM) is increasingly implicated in its cause, yet the intricate mechanisms remain unclear. Whether changes in the diversity and richness of gut microbial populations among MN patients contribute to disease prevalence is still unanswered, necessitating further exploration into the potential causative link between the GM and MN.</p><p><strong>Methods: </strong>We conducted a comprehensive bidirectional mendelian randomization (MR) study. We selected 211 bacterial taxa using genome-wide association study (GWAS) data provided by the MiBioGen consortium, while GWAS data relevant to MN were obtained from ebi-a-GCST010005. The inverse-variance weighted (IVW) method was the primary technique used to delineate the causal relationship between exposures and outcomes. To confirm the robustness of our results, we used additional methods, including MR-Egger, weighted median, simple mode, and weighted mode. Sensitivity analyses included tests for pleiotropy, heterogeneity, and leave-one-out sensitivity to ensure the integrity of our conclusions. Finally, reverse MR analyses were conducted to assess the likelihood of reverse causality.</p><p><strong>Results: </strong>Using various analytical methods, including the IVW approach, MR-Egger, weighted median, simple mode, and weighted mode, our study identified six microbial taxa with a statistically significant causal link to MN, as indicated by p values <0.05. The implicated taxa are Butyrivibrio (OR = 1.25, 95% CI: 1.001-1.565, p = 0.048), Butyricicoccus (OR = 2.15, 95% CI: 1.005-4.621, p = 0.048), Catenibacterium (OR = 1.49, 95% CI: 1.043-2.134, p = 0.028), Ruminiclostridium 5 (OR = 1.78, 95% CI: 1.140-2.763, p = 0.03), Ruminococcaceae UCG-003 (OR = 1.78, 95% CI: 1.140-2.763, p = 0.011), and Bacillales (OR = 1.52, 95% CI: 1.135-2.025, p = 0.005). Each of these taxa has been established as a risk factor for MN. Notably, Ruminococcaceae UCG-003 and Bacillales were identified as having a bidirectional causal relationship with the disease.</p><p><strong>Conclusion: </strong>Our MR study has revealed a causal link between six microbial taxa and MN, highlighting their potential involvement in the disease's development. These findings represent an initial step into this complex field and underscore the need for more in-depth research.</p>","PeriodicalId":18998,"journal":{"name":"Nephron","volume":" ","pages":"311-323"},"PeriodicalIF":2.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143008762","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Personalized Care in CKD: Moving Beyond Traditional Biomarkers.","authors":"Thomas McDonnell, Rosamonde E Banks, Maarten W Taal, Nicolas Vuilleumier, Philip A Kalra","doi":"10.1159/000543640","DOIUrl":"10.1159/000543640","url":null,"abstract":"<p><strong>Background: </strong>Traditional biomarkers, such as estimated glomerular filtration rate (eGFR) and urine albumin-to-creatinine ratio (uACR), have long been central to chronic kidney disease (CKD) diagnosis and management, leading to a standardized CKD classification system. However, these biomarkers are non-specific and fail to capture the heterogeneity within CKD and the nuances of an individual's disease mechanism, limiting personalized treatment approaches. There is an increasing need for novel biomarkers that reflect the diverse pathophysiological processes underlying CKD progression, enabling more precise risk prediction and treatment strategies.</p><p><strong>Summary: </strong>This review examines the limitations of current CKD biomarkers and classification systems, highlighting the need for a precision medicine approach. While traditional markers like eGFR and uACR are foundational, they inadequately capture CKD's complexity. Emerging biomarkers offer insights into specific disease processes, such as inflammation, oxidative stress, fibrosis, and tubular injury, which are crucial for personalized care. The article discusses the potential benefits of integrating these novel biomarkers into clinical practice, including more accurate risk prediction, tailored treatments, and personalized clinical trial designs, as well as the barriers to their implementation. Furthermore, advancements in multi-omics and high-throughput techniques offer opportunities to identify novel causative proteins with druggable targets, pushing CKD care towards greater precision.</p><p><strong>Key messages: </strong>Current CKD classification systems, based on non-specific biomarkers, fail to capture CKD's heterogeneity. Incorporating biomarkers reflecting diverse pathophysiological mechanisms can enhance risk prediction, customized treatments, and personalized clinical trials. High-throughput multi-omic techniques present a promising path towards precision medicine in nephrology.</p>","PeriodicalId":18998,"journal":{"name":"Nephron","volume":" ","pages":"339-357"},"PeriodicalIF":2.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12136532/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143029225","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Membranoproliferative Glomerulonephritis with Striated Ultrastructural Deposits with Significantly Elevated Fibrinogen and Fibronectin on Mass Spectrometry Analysis: A Case Report and Literature Review.","authors":"Manna Ishida, Shinya Yamamoto, Yohei Iwashige, Shuma Miyazawa, Hirosuke Nakata, Koichi Seta, Kensei Yahata, Sachiko Minamiguchi, Yoko Endo, Akiko Mii, Akira Shimizu, Motoko Yanagita","doi":"10.1159/000544709","DOIUrl":"10.1159/000544709","url":null,"abstract":"<p><p>Glomerular diseases with organized deposits can be classified into various etiologies. A diagnostic algorithm based on clinical and pathological findings has been proposed. However, some cases cannot be diagnosed using existing algorithms. Here, we report the case of a 77-year-old man diagnosed with membranoproliferative glomerulonephritis (MPGN) with striated ultrastructural deposits, micro-filament-like substructures with straight bands arranged in parallel in the subendothelial space by two sequential renal biopsies. His examinations and clinical findings were incompatible with known glomerular diseases with organized deposits. Dialysis was initiated 10 months after the second biopsy procedure. Furthermore, we report the first mass spectrometry analysis of laser micro-dissected glomeruli with striated ultrastructural deposits, which revealed significant levels of fibrinogen and fibronectin. Immunostaining was positive for fibrinogen, fibrin, and fibronectin in the subendothelial space. These findings suggest that the deposits were composed of a fibrin-fibronectin complex and that accumulation of these fibrin-fibronectin complexes possibly induced endothelial injury, leading to MPGN. We also reviewed the literature on the clinical and pathological characteristics of the four cases with striated ultrastructural deposits. Our investigation showed that all patients had the MPGN pattern and striated ultrastructural deposits in the subendothelial space, and all underwent hemodialysis within 3 years of renal biopsy. Clinicians should be aware of the findings of glomerulonephritis with striated ultrastructural deposits since this disease may be a new entity and has a poor prognosis.</p>","PeriodicalId":18998,"journal":{"name":"Nephron","volume":" ","pages":"411-421"},"PeriodicalIF":2.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12215155/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143414626","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy and Safety of Telitacicept in IgA Nephropathy: A Retrospective, Multicenter Study.","authors":"Lijun Liu, Yimeng Liu, Juan Li, Chen Tang, Huiming Wang, Cheng Chen, Haibo Long, Xiaowen Chen, Guolan Xing, Jingru Cheng, Jianbo Liang, Xuan Peng, Liang Wang, Sijia Shao, Yongqiang Lin, Tianmu Chen, Ying Tang, Shizhong Shen, Lingyun Sun, Henglan Wu, Yuan Yu, Xuanyi Du, Hong Liu, Liyu He, Hong Liu, Meixing Ye, Wei Chen, Qiong Wen, Hong Zhang, Hongmin Cao, Jing Yuan, Hong Chen, Ming Wang, Jicheng Lv, Hong Zhang","doi":"10.1159/000540326","DOIUrl":"10.1159/000540326","url":null,"abstract":"<p><strong>Introduction: </strong>The efficacy of telitacicept treatment in reducing proteinuria in patients with IgA nephropathy (IgAN) was indicated in a phase II clinical trial with small sample size. In this study, we conducted a large multicenter retrospective study to explore the efficacy and safety of telitacicept in patients with IgAN.</p><p><strong>Methods: </strong>This study recruited patients with IgAN from 19 sites from China who were treated with telitacicept and had been followed up at least once or with side effect reported, since April 1, 2021, to April 1, 2023. The primary outcomes of the study were the changing in proteinuria and eGFR over time.</p><p><strong>Results: </strong>A cohort of 97 patients with IgAN who were treated with telitacicept were recruited, with a median follow-up duration of 3 months. The median baseline proteinuria was 2.3 [1.3, 3.9] g/day and eGFR was 45.0 [26.8, 73.7] mL/min/1.73 m2. There was a significant reduction of proteinuria at 2, 4, 6 months when compared with baseline (2.3 [1.5, 4.1] vs. 1.5 [0.8, 2.3] g/day; 2.3 [1.1, 3.7] vs. 1.1 [0.6, 1.9] g/day; 2.1 [1.0, 2.7] vs. 0.9 [0.5, 1.7] g/day, all p values <0.01). The level of eGFR were comparable between at the baseline and 2, 4, 6 months of follow-up time (41.5 [29.7, 72.0] vs. 42.5 [28.8, 73.3] mL/min/1.73 m2; 41.0 [26.8, 67.7] vs. 44.7 [31.0, 67.8] mL/min/1.73 m2; 33.7 [24.0, 58.5] vs. 32.6 [27.8, 57.5] mL/min/1.73 m2, all p values >0.26). Telitacicept was well tolerated in the patients.</p><p><strong>Conclusions: </strong>This study indicates that telitacicept alone or on top of steroids therapy can significantly and safely reduce proteinuria in patients with IgAN. The long-term kidney protection still needs to be confirmed in large phase III trial.</p>","PeriodicalId":18998,"journal":{"name":"Nephron","volume":" ","pages":"1-10"},"PeriodicalIF":2.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142291732","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lipophagy and Mitophagy in Renal Pathophysiology.","authors":"Nicolas Dupont, Fabiola Terzi","doi":"10.1159/000540688","DOIUrl":"10.1159/000540688","url":null,"abstract":"<p><strong>Background: </strong>The lysosomal autophagic pathway plays a fundamental role in cellular and tissue homeostasis, and its deregulation is linked to human pathologies including kidney diseases. Autophagy can randomly degrade cytoplasmic components in a nonselective manner commonly referred to as bulk autophagy. In contrast, selective forms of autophagy specifically target cytoplasmic structures such as organelles and protein aggregates, thereby being important for cellular quality control and organelle homeostasis.</p><p><strong>Summary: </strong>Research during the past decades has begun to elucidate the role of selective autophagy in kidney physiology and kidney diseases.</p><p><strong>Key messages: </strong>In this review, we will summarize the knowledge on lipophagy and mitophagy, two forms of selective autophagy important in renal epithelium homeostasis, and discuss how their deregulations contribute to renal disease progression.</p>","PeriodicalId":18998,"journal":{"name":"Nephron","volume":" ","pages":"36-47"},"PeriodicalIF":2.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142056124","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of Serum Ferritin Levels with Short-Term Mortality Risk in Sepsis-Associated Acute Kidney Injury: A Retrospective Cohort Study.","authors":"Jie Sun, Ying Qi, Yan Wang, Wenxin Wang, Pengpeng Meng, Changjin Han, Bing Chen","doi":"10.1159/000542410","DOIUrl":"10.1159/000542410","url":null,"abstract":"<p><strong>Background: </strong>This study aimed to assess the prognostic significance of serum ferritin levels in sepsis-associated acute kidney injury (SA-AKI) and their correlation with short-term mortality. Despite the established predictive value of serum ferritin in various serious diseases, its specific prognostic relevance in SA-AKI remains unexplored. Therefore, this study seeks to fill this research gap by investigating the association between serum ferritin levels and short-term mortality in patients with SA-AKI.</p><p><strong>Methods: </strong>This retrospective cohort study utilized clinical data from the Medical Information Mart for Intensive Care-IV (MIMIC-IV) database, including all patients with SA-AKI admitted to the intensive care unit for the first time. The relationship between serum ferritin levels and 28-day mortality was explored using restricted cubic splines. Kaplan-Meier curves and Cox regression models were employed to evaluate the association between serum ferritin levels and mortality. Subgroup and sensitivity analyses were performed to verify the robustness of the results.</p><p><strong>Results: </strong>In this study, a total of 878 patients (486 males and 392 females) with a median age of 63.7 years were enrolled. The results indicated that increasing serum ferritin levels were linearly associated with a gradual increase in 28-day mortality rates. Specifically, patients in the highest quartile of serum ferritin had significantly higher 28-day mortality compared to those in the reference group (the first quartile of ferritin levels). After adjusting for various factors, the fully adjusted hazard ratio was 1.92 (95% CI: 1.24-2.96, p = 0.003).</p><p><strong>Conclusion: </strong>In patients with SA-AKI, higher serum ferritin levels are associated with an increased 28-day mortality rate.</p>","PeriodicalId":18998,"journal":{"name":"Nephron","volume":" ","pages":"185-196"},"PeriodicalIF":2.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142624121","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Multimethod International Mapping Exercise of Arts Interventions in Renal Units: The PAINT Project.","authors":"Trisha Forbes, Anna Wilson, Clare McKeaveney, Claire Carswell, Christopher Bailey, Jenny Baxley Lee, Mayleen Laico, Claire Meaney, Helen Noble","doi":"10.1159/000542878","DOIUrl":"10.1159/000542878","url":null,"abstract":"<p><strong>Introduction: </strong>Due to the chronic nature of kidney disease, the challenges of symptom burden, and reduced mortality and comorbidity, individuals living with the condition experience substantial anxiety and depression. Incorporating the arts into clinical practice is encouraged to promote and support mental health and well-being. The aim of the PAINT project was to undertake an international mapping exercise to identify the current provision of arts programmes in kidney centres for people living with kidney disease.</p><p><strong>Methods: </strong>A multimethod approach was employed, involving a cross-sectional online survey and semi-structured qualitative interviews, which employed qualitative description research design. Healthcare staff working in kidney centres or organisations providing arts activities to individuals living with kidney disease were recruited into the study.</p><p><strong>Results: </strong>One hundred and nineteen participants from 29 countries responded to the survey, with 39 of the respondents reporting arts activities in their renal unit. There was a wide range of respondents in terms of role, and the types of arts activities included visual arts activities, music, literature/creative writing, film, movement/dance, and craft. Individuals with chronic kidney disease who had taken part in arts activities were mostly adults (64%), and most were undergoing haemodialysis (82%). Sixteen respondents participated in the semi-structured interviews and encouraged the adoption of arts activities for people living with kidney disease. Three themes were identified: enhanced well-being and positive outcomes for individuals living with kidney disease; staff engagement and enthusiasm; and barriers to participation.</p><p><strong>Conclusions: </strong>This overview of arts activities being offered globally to people living with kidney disease and experiences of renal healthcare staff who provide activities in their units are encouraging in terms of arts in healthcare. These practitioners have observed the benefits of this person-centred arts approach in action, predominantly in terms of the positive impact on the well-being of individuals with kidney disease and improved relationships with staff in dialysis units. Further attention and funding should be focused on arts activities within renal centres.</p>","PeriodicalId":18998,"journal":{"name":"Nephron","volume":" ","pages":"288-301"},"PeriodicalIF":2.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12101804/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142801718","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Systems Biology and Novel Biomarkers for the Early Detection of Diabetic Kidney Disease.","authors":"Priscila Villalvazo, Carlos Villavicencio, Marina Gonzalez de Rivera, Beatriz Fernandez-Fernandez, Alberto Ortiz","doi":"10.1159/000540307","DOIUrl":"10.1159/000540307","url":null,"abstract":"<p><p>Diabetic kidney disease is the most common driver of chronic kidney disease (CKD)-associated mortality and kidney replacement therapy. Despite recent therapeutic advances (sodium glucose co-transporter 2 [SGLT2] inhibitors, finerenone), the residual kidney and mortality risk remains high for patients already diagnosed of having CKD (i.e., estimated glomerular filtration rate <60 mL/min/1.73 m2 or urinary albumin:creatinine ratio >30 mg/g). The challenge for the near future is to identify patients at higher risk of developing CKD to initiate therapy before CKD develops (primary prevention of CKD) and to identify patients with CKD and high risk of progression or death, in order to intensify therapy. We now discuss recent advances in biomarkers that may contribute to the identification of such high-risk individuals for clinical trials of novel primary prevention or treatment approaches for CKD. The most advanced biomarker from a clinical development point of view is the urinary peptidomics classifier CKD273, that integrates prognostic information from 273 urinary peptides and identifies high-risk individuals before CKD develops.</p>","PeriodicalId":18998,"journal":{"name":"Nephron","volume":" ","pages":"29-35"},"PeriodicalIF":2.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141792891","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lysinuric Protein Intolerance: Not Only a Disorder for Pediatric Nephrologists - Case Report.","authors":"Miriam Rigoldi, Caterina Mele, Matteo Breno, Marina Noris, Amantia Imeraj, Sara Gamba, Arrigo Schieppati, Erica Daina","doi":"10.1159/000541363","DOIUrl":"10.1159/000541363","url":null,"abstract":"<p><strong>Introduction: </strong>Lysinuric protein intolerance (LPI) is a multisystemic inborn error of metabolism with a variable clinical expressivity that usually begins in childhood with growth failure and gastroenterological/neurological problems related to the altered urea cycle and, later, with complications involving the renal, pulmonary, and immunohematological systems.</p><p><strong>Case report: </strong>We present the case of a 40-year-old woman suffering from chronic kidney disease in the context of a LPI, whose diagnosis was challenging because the signs of the disease were always blurred and the patient never manifested critical episodes typical of this multisystemic disease. In addition to renal disease, splenomegaly, thrombocytopenia, elevated lactate dehydrogenase (LDH), hyperferritinemia, and hypertriglyceridemia were also present. A thorough investigation of the patient's food preferences revealed her spontaneous aversion to protein-containing foods and excessive drowsiness during the occurrence of infectious episodes or on the rare occasions of excessive protein intake, although without ever coming to medical attention. These nuanced signs led us to suspect an impairment of the urea cycle and ultimately allowed us to narrow down the diagnosis to LPI through biochemical and genetic investigations.</p><p><strong>Conclusion: </strong>Nephrologists should consider LPI in the differential diagnosis, whenever a patient presents with mixed proteinuria, tubular dysfunction, and/or chronic kidney disease of unknown origin. In these circumstances, we suggest looking for other signs such as growth failure, signs and symptoms ascribed to urea-cycle impairment, pulmonary involvement, hepatosplenomegaly, and laboratory alterations such as pancytopenia, hyperferritinemia, lipid abnormalities, and elevated LDH.</p>","PeriodicalId":18998,"journal":{"name":"Nephron","volume":" ","pages":"116-124"},"PeriodicalIF":2.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142291734","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}