Nephron[JOURNAL]
Sun
200 papers
A Multimethod International Mapping Exercise of Arts Interventions in Renal Units: The PAINT Project.
Forbes T, Wilson A, McKeaveney C … +6 more , Carswell C, Bailey C, Baxley Lee J, Laico M, Meaney C, Noble H
Nephron · 2025 · PMID 39653028 · Full text
INTRODUCTION: 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. Inc...
INTRODUCTION: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
Sodium Retention in Liver Disease: Is ENaC Activation Independent of the Renin-Angiotensin-Aldosterone System a Therapeutic Target?
Batlle D, Rehman MZ, Brannon T … +1 more , Rosa R
Nephron · 2025 · PMID 39616997 · Full text
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Diosgenin Improves Lipid Metabolism in Diabetic Nephropathy via Regulation of miR-148b-3p/DNMT1/FOXO1 Axis.
Luo M, Hu Z, Yang J … +5 more , Yang J, Sheng W, Lin C, Li D, He Q
Nephron · 2025 · PMID 39602888 · Publisher ↗
BACKGROUND: The progression of diabetic nephropathy (DN) is closely associated with lipid accumulation. Diosgenin (Dio) plays a beneficial role in the lipid metabolism associated with multiple diseases. Thus, the mechani...
BACKGROUND: The progression of diabetic nephropathy (DN) is closely associated with lipid accumulation. Diosgenin (Dio) plays a beneficial role in the lipid metabolism associated with multiple diseases. Thus, the mechanism underlying Dio's function in DN associated with aberrant lipid accumulation warrants further investigation. METHODS: To model DN in vitro, HK-2 cells were treated with high glucose (HG) and palmitic acid. Cell viability was evaluated using MTT assay. The triglyceride (TG) content in HK-2 cells was measured using a commercial assay kit. The formation of lipid droplets in HK-2 cells was observed using Oil Red O staining. The expression levels of mRNA and protein were detected using RT-qPCR and Western blot, respectively. The DNA methylation of FOXO1 was assessed using MSP. The interaction between DNMT1 and the FOXO1 promoter was confirmed by ChIP assay. RESULTS: Dio treatment reduced TG levels and lipid droplet formation in HK-2 cells co-treated with HG and palmitic acid. Simultaneously, the levels of miR-148b-3p and FOXO1 were increased by Dio, while Dio decreased the expression levels of DNMT1 and SREBP-2. Meanwhile, miR-148b-3p can bind to DNMT1, which in turn inhibits the expression of FOXO1 by mediating the DNA methylation of FOXO1. In addition, FOXO1 negatively regulates the expression of SREBP-2 by interacting with the SREBP-2 promoter. MiR-148b-3p inhibition or silencing of FOXO1 abolished the inhibitory effect of Dio on TG production and lipid droplet formation. This effect was further exacerbated by the downregulation of DNMT1. FOXO1 overexpression may counteract the promotive effects of miR-148b-3p inhibitor on lipid accumulation. CONCLUSIONS: Dio treatment reduced TG production and lipid droplet formation in HK-2 cells during the progression of DN by modulating the miR-148b-3p/DNMT1/FOXO1/SREBP-2 axis. This finding provides new evidence supporting the therapeutic potential of Dio for DN.
Urine miR-340-5p Predicts the Adverse Prognosis of Sepsis-Associated Acute Kidney Injury and Regulates Renal Tubular Epithelial Cell Injury by Targeting KDM4C.
Pu M, Zhao H, Xu S … +3 more , Gu X, Feng Q, Huang P
Nephron · 2025 · PMID 39551047 · Publisher ↗
INTRODUCTION: Sepsis-associated acute kidney injury (SA-AKI) is a common complication of sepsis. miR-340-5p has been identified as an effective biomarker of various human diseases. As the downstream target, the involveme...
INTRODUCTION: Sepsis-associated acute kidney injury (SA-AKI) is a common complication of sepsis. miR-340-5p has been identified as an effective biomarker of various human diseases. As the downstream target, the involvement of lysine (K)-specific demethylase 4C (KDM4C) in SA-AKI would help interpret the regulatory mechanism of miR-340-5p. The significance of miR-340-5p in the onset and progression of SA-AKI was evaluated to provide a potential therapeutic target for SA-AKI. METHODS: This study enrolled 64 healthy individuals (control) and 159 sepsis patients (92 SA-AKI and 67 non-AKI) and collected urine samples. The urine level of miR-340-5p was analyzed by PCR, and a series of statistical analyses were conducted to assess the clinical significance of miR-340-5p in the occurrence and development of SA-AKI. The injured renal tubular epithelial cells were established with LPS induction. The roles of miR-340-5p in cellular processes were evaluated. RESULTS: Increasing urine miR-340-5p discriminated SA-AKI patients from healthy individuals (AUC = 0.934) and non-AKI sepsis patients (AUC = 0.806) sensitively. Additionally, elevated miR-340-5p could predict the adverse prognosis (HR = 5.128, 95% CI = 1.259-20.892) and malignant development of SA-AKI patients. In vitro, lipopolysaccharide (LPS) also induced an increased level of miR-340-5p and significant cell injury in the renal tubular epithelial cell; silencing miR-340-5p could alleviate the suppressed proliferation, migration, and invasion caused by LPS. In mechanism, miR-340-5p negatively regulated KDM4C, which mediated the function of miR-340-5p. CONCLUSION: miR-340-5p served as a diagnostic and prognostic biomarker of SA-AKI and regulated renal tubular epithelial cell injury via modulating KDM4C.
Exploring the Critical Role of Tight Junction Proteins in Kidney Disease Pathogenesis.
Jayne D, Herbert C, Anquetil V … +1 more , Teixeira G
Nephron · 2025 · PMID 39532075 · Full text
BACKGROUND: Kidney disease poses a significant global health challenge, marked by a rapid decline in renal function due to a variety of causative factors. A crucial element in the pathophysiology of kidney disease is the...
BACKGROUND: Kidney disease poses a significant global health challenge, marked by a rapid decline in renal function due to a variety of causative factors. A crucial element in the pathophysiology of kidney disease is the dysregulation of epithelial cells, which are vital components of renal tissue architecture. The integrity and functionality of these cells are largely dependent on tight junctions (TJ) proteins, complex molecular structures that link adjacent epithelial cells. These TJ not only confer cellular polarity and maintain essential barrier functions but also regulate epithelial permeability. SUMMARY: TJ proteins are pivotal in their traditional role at cell junctions and in their non-junctional capacities. Recent research has shifted the perception of these proteins from mere structural elements to dynamic mediators of kidney disease, playing significant roles in various renal pathologies. This review explores the multifaceted roles of TJ proteins, focusing on their functions both within and external to the renal epithelial junctions. It highlights how these proteins contribute to mechanisms underlying kidney disease, emphasizing their impact on disease progression and outcomes. KEY MESSAGES: TJ proteins have emerged as significant players in the field of nephrology, not only for their structural role but also for their regulatory functions in disease pathology. Their dual roles in maintaining epithelial integrity and mediating pathological processes make them promising therapeutic targets for kidney disease. Understanding the intricate contributions of TJ proteins in kidney pathology offers potential for novel therapeutic strategies, aiming to modulate these proteins to halt or reverse the progression of kidney disease.
Association of Serum Ferritin Levels with Short-Term Mortality Risk in Sepsis-Associated Acute Kidney Injury: A Retrospective Cohort Study.
Sun J, Qi Y, Wang Y … +4 more , Wang W, Meng P, Han C, Chen B
Nephron · 2025 · PMID 39527922 · Publisher ↗
BACKGROUND: 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 predi...
BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSION: In patients with SA-AKI, higher serum ferritin levels are associated with an increased 28-day mortality rate.
Renal Endowment in Men and Women: Start from the Beginning.
Imberti B, Benigni A
Nephron · 2025 · PMID 39510055 · Full text
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...
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.
A Case of IgG4-Related Disease Manifesting as Extensive Abdominal Periarteritis and Membranous Nephropathy, Successfully Controlled with Low-Dose Steroid Therapy without Relapse or Complications.
Matsumoto M, Yamamoto S, Yokoi H … +5 more , Koyasu S, Hara S, Tsuji T, Sachiko M, Yanagita M
Nephron · 2025 · PMID 39496248 · Full text
INTRODUCTION: IgG4-related disease (IgG4-RD) is an immune-mediated fibroinflammatory disease that can affect nearly every organ system, including blood vessels and the kidney. IgG4-related vascular lesions mainly involve...
INTRODUCTION: IgG4-related disease (IgG4-RD) is an immune-mediated fibroinflammatory disease that can affect nearly every organ system, including blood vessels and the kidney. IgG4-related vascular lesions mainly involve the aorta, and the dominant renal manifestation is tubulointerstitial nephritis (TIN). Here, we report a case of IgG4-RD demonstrating extensive abdominal periarteritis and membranous nephropathy (MN). CASE PRESENTATION: The patient was a 71-year-old man with peptic ulcer who developed nephrotic syndrome, with a low serum albumin level (1.8 g/dL), massive urinary protein (6.1 g/day), and high serum IgG4 level (435 mg/dL). Computed tomography images revealed soft tissue mass around the medium-sized abdominal arteries. Renal pathological findings showed MN and focal infiltration of numerous IgG4-positive cells in the interstitium. The findings of high serum IgG4 levels, periarteritis, and focal inflammation with rich IgG4-positive plasma cells led to the diagnosis of IgG4-RD. We chose low-dose steroid therapy to prevent the recurrence of the peptic ulcer and aneurysm formation in the affected arteries, which can occur with medium to high doses of prednisolone. We successfully controlled IgG4-related periarteritis and kidney disease without relapse or complications. CONCLUSION: The varied clinical manifestations of IgG4-RD sometimes make the diagnosis challenging. However, clinicians should diagnose IgG4-RD based on serological, radiological, and pathological evaluations because, without appropriate therapy, IgG4-RD can lead to irreversible organ failure caused by swelling, obstruction, or fibrosis of the organs.
Characteristics of Successful Percutaneous Transluminal Renal Angioplasty Cases with Severely Impaired Kidney Function Caused by Bilateral Atherosclerotic Stenosis: A Case Series.
Sugimoto H, Yamamoto S, Yanagita M
Nephron · 2025 · PMID 39496241 · Full text
INTRODUCTION: Previous randomized controlled trials have not demonstrated the benefits of renal artery stenting with respect to kidney function. However, these trials did not focus on patients with severely impaired kidn...
INTRODUCTION: Previous randomized controlled trials have not demonstrated the benefits of renal artery stenting with respect to kidney function. However, these trials did not focus on patients with severely impaired kidney function caused by severe bilateral stenosis. Therefore, the efficacy of stenting in such patients remains unclear. CASE PRESENTATION: We report 4 cases of successful percutaneous transluminal renal angioplasty (PTRA) with severely impaired kidney function with rapid decline caused by bilateral atherosclerotic stenosis. The catheterization before irreversible parenchymal damages was useful in improving kidney function dramatically in these cases of severe bilateral renal artery stenosis. Furthermore, we examined the clinical characteristics of the 4 cases to identify the potential predictors of PTRA effectiveness. Notably, bilateral renal artery >90% stenosis, elevated plasma renin activity, estimated glomerular filtration rate <15 mL/min/1.73 m2 with an accelerated decline within 6 months before PTRA (>50 mL/min/1.73 m2/6 months), and resistance index (RI) <0.7 were identified as common findings. CONCLUSION: PTRA should be considered a treatment strategy for patients with these features to preserve kidney function and avoid dialysis therapy. INTRODUCTION: Previous randomized controlled trials have not demonstrated the benefits of renal artery stenting with respect to kidney function. However, these trials did not focus on patients with severely impaired kidney function caused by severe bilateral stenosis. Therefore, the efficacy of stenting in such patients remains unclear. CASE PRESENTATION: We report 4 cases of successful percutaneous transluminal renal angioplasty (PTRA) with severely impaired kidney function with rapid decline caused by bilateral atherosclerotic stenosis. The catheterization before irreversible parenchymal damages was useful in improving kidney function dramatically in these cases of severe bilateral renal artery stenosis. Furthermore, we examined the clinical characteristics of the 4 cases to identify the potential predictors of PTRA effectiveness. Notably, bilateral renal artery >90% stenosis, elevated plasma renin activity, estimated glomerular filtration rate <15 mL/min/1.73 m2 with an accelerated decline within 6 months before PTRA (>50 mL/min/1.73 m2/6 months), and resistance index (RI) <0.7 were identified as common findings. CONCLUSION: PTRA should be considered a treatment strategy for patients with these features to preserve kidney function and avoid dialysis therapy.
Advances in Molecular Imaging of Kidney Diseases.
Klinkhammer BM, Ay I, Caravan P … +2 more , Caroli A, Boor P
Nephron · 2025 · PMID 39496240 · Publisher ↗
BACKGROUND: Diagnosing and monitoring kidney diseases traditionally rely on blood and urine analyses and invasive procedures such as kidney biopsies, the latter offering limited possibilities for longitudinal monitoring...
BACKGROUND: Diagnosing and monitoring kidney diseases traditionally rely on blood and urine analyses and invasive procedures such as kidney biopsies, the latter offering limited possibilities for longitudinal monitoring and a comprehensive understanding of disease dynamics. Current noninvasive methods lack specificity in capturing intrarenal molecular processes, hindering patient stratification and patient monitoring in clinical practice and clinical trials. SUMMARY: Molecular imaging enables noninvasive and quantitative assessment of physiological and pathological molecular processes. By using specific molecular probes and imaging technologies, e.g., magnetic resonance imaging, positron emission tomography, single-photon emission computed tomography, or ultrasound, molecular imaging allows the detection and longitudinal monitoring of disease activity with spatial and temporal resolution of different kidney diseases and disease-specific pathways. Several approaches have already shown promising results in kidneys and exploratory clinical studies, and validation is needed before implementation in clinical practice. KEY MESSAGES: Molecular imaging offers a noninvasive assessment of intrarenal molecular processes, overcoming the limitations of current diagnostic methods. It has the potential to serve as companion diagnostics, not only in clinical trials, aiding in patient stratification and treatment response assessment. By guiding therapeutic interventions, molecular imaging might contribute to the development of targeted therapies for kidney diseases.
Phenotypic Discordance among Siblings with Autosomal Recessive Polycystic Kidney Disease: Case Report and Review of the Literature.
Henein M, Russo F, Sentell ZT … +2 more , Goupil R, Kitzler TM
Nephron · 2024 · PMID 39467534 · Full text
Missense variants in the PKHD1 gene are associated with the full spectrum of autosomal recessive polycystic kidney disease severity and exhibit variable expressivity. The study of clinical expressivity is limited by the...
Missense variants in the PKHD1 gene are associated with the full spectrum of autosomal recessive polycystic kidney disease severity and exhibit variable expressivity. The study of clinical expressivity is limited by the extensive allelic heterogeneity within the PKHD1 gene, which encodes a 4074-amino-acid protein. We report the case of adult siblings with biallelic missense PKHD1 variants, c.4870C>T (p.Arg1624Trp) and c.8206T>G (p.Trp2736Gly), who presented with discordant phenotypes. Patient A developed progressive chronic kidney disease and Caroli syndrome in childhood requiring combined liver and kidney transplantation, while patient B remains minimally affected in the fourth decade of life with normal kidney function and signs of medullary sponge kidney on imaging. We review previously reported cases of phenotypic discordance among siblings and suggest that genotypes composed of at least one hypomorphic missense variant are more likely to lead to phenotypic discordance.
Sex Differences in Kidney Health and Disease.
Harvey BJ, Alvarez de la Rosa D
Nephron · 2025 · PMID 39406203 · Publisher ↗
BACKGROUND: Sex differences exist in kidney physiology and disease which are underpinned by the biological actions of the sex hormones estrogen, progesterone and testosterone. In this review, we present an up-to-date dis...
BACKGROUND: Sex differences exist in kidney physiology and disease which are underpinned by the biological actions of the sex hormones estrogen, progesterone and testosterone. In this review, we present an up-to-date discussion of the hormonal and molecular signalling pathways implicated in sex differences in kidney health and disease. SUMMARY: Estrogen and progesterone have protective effects on renal blood flow, glomerular filtration rate and nephron ion and water reabsorptive processes, whereas testosterone tends to compromise these functions. The biological effects of estrogen appear to be the most important in reinforcing kidney function and protecting against kidney diseases in females. The actions of estrogen are myriad but all tend to bolster kidney physiology to maintain a steady-state and adaptable extracellular fluid volume (ECFV) and blood pressure. Estrogen safeguards ECFV homeostasis by stimulating renal epithelial sodium channel (ENaC) and water channel (AQP2) expression and transport function. Renal maintenance of ECFV within narrow physiological limits is a first-line of defense against hypertension and lowers the risk of cardiovascular disease in women. The estrogenic and XX chromosome basis for a female advantage are evident in a wide range of kidney diseases including acute kidney injury, chronic kidney disease, end-stage kidney disease, diabetic kidney disease, and polycystic kidney disease. The molecular mechanisms involve estrogen regulation of nephron ion and water transport, genetic immunogenic responses, activation of the protective arm of the renin angiotensin-aldosterone system and XX chromosome reinforcement of immune responses. Kidney disease can also predispose patients to cancer and women are protected in renal cancer with lower incidence, morbidity, and mortality than age-matched men with the disease. KEY MESSAGES: This review underscores the importance of incorporating sex-specific considerations into clinical practice and basic research to bridge the gap in understanding and addressing biological sex disparities in kidney disease and renal cancer.
Demand Analysis of Self-Management Mobile Health Applications for Middle-Aged and Older Patients with Chronic Kidney Disease Based on the Kano Model.
Yan Y, Liu M, Duan DF … +3 more , Yan LJ, Li L, Ma DY
Nephron · 2025 · PMID 39396506 · Publisher ↗
INTRODUCTION: Middle-aged and older individuals often face significant challenges in adopting digital health solutions, leading to a digital divide that hinders their ability to benefit from mobile health (mHealth) inter...
INTRODUCTION: Middle-aged and older individuals often face significant challenges in adopting digital health solutions, leading to a digital divide that hinders their ability to benefit from mobile health (mHealth) interventions. This study aimed to investigate the specific requirements of middle-aged and older patients with chronic kidney disease (CKD) for self-management through mobile health applications (mHealth apps), using the Kano model. METHODS: A multicenter cross-sectional survey was conducted from April to September 2023 in five hospitals across Sichuan, Shandong, Guangdong, and Shaanxi provinces in China. The Kano model was employed to analyze participants' preferences regarding mHealth apps for self-management. RESULTS: Out of 359 participants (57.1% men, predominantly aged 45-54), the study identified essential and desirable features for mHealth apps. Essential attributes include comprehensive CKD information and robust privacy protection. Key to enhancing user satisfaction is features like symptom and medication management, access to medical insurance information, and app interface simplicity. Additional attractive features for increasing app appeal include diet management, exercise guidance, and customizable text size. CONCLUSION: This study identifies critical mHealth app features for self-management in middle-aged and older CKD patients, emphasizing the importance of user-centric design. The findings provide valuable insights for app developers to create tailored solutions that cater to the specific needs of this demographic, potentially enhancing their self-management capabilities.
Myths, Realities, and Pathways Forward: A Patient's Thoughts on Person-Centred Care.
Wang B
Nephron · 2025 · PMID 39396505 · Publisher ↗
Abstract loading — click title to view on PubMed.
NF-κB/miR-455-5p/SOCS3 Axis Aggravates Sepsis-Induced Acute Kidney Injury through Promoting Renal Inflammation.
Yan M, Zhang N, Quan L … +6 more , Bin W, Xi J, Dou C, Liu Z, Gui Y, Yin LH
Nephron · 2025 · PMID 39378861 · Publisher ↗
INTRODUCTION: Sepsis is the leading contributor to acute kidney injury (AKI), responsible for 45-70% of AKI occurrences. Despite this, septic AKI is a highly multifactorial and complex condition, and our grasp of its pat...
INTRODUCTION: Sepsis is the leading contributor to acute kidney injury (AKI), responsible for 45-70% of AKI occurrences. Despite this, septic AKI is a highly multifactorial and complex condition, and our grasp of its pathogenesis is still not fully developed. Consequently, there remains a significant gap in effective diagnostic and therapeutic strategies for septic AKI. METHODS: In the in vitro experiments, BUMPT cells were exposed to lipopolysaccharides (LPS). In vivo experiments involved inducing sepsis in mice through administration of LPS injections. Additionally, in certain experiments, either a miR-455-5p mimic or an anti-miR-455-5p LAN was administered to the mice via injections into the tail vein. The mice were then sacrificed 24 h following LPS administration for subsequent analysis. RESULTS: We observed a significant elevation in miR-455-5p levels within renal tubular cells following LPS-induced septic AKI. Our investigation revealed that NF-κB plays a crucial role in the upregulation of miR-455-5p. Inhibition of NF-κB using TPCA-1 prevented the rise in miR-455-5p levels in BUMPT cells (mouse proximal tubular cells from Boston University) cultured in vitro. Chromatin immunoprecipitation assays confirmed that NF-κB directly interacts with the promoter region of the miR-455-5p gene in response to LPS treatment. Functionally, introducing miR-455-5p mimics intensified cell apoptosis, kidney damage, and the production of inflammatory cytokines, while silencing miR-455-5p had protective effects in septic mice. Notably, administering anti-miR-455-5p enhanced SOCS3 expression, whereas miR-455-5p mimics reduced SOCS3 levels following LPS exposure. Furthermore, our luciferase reporter assays demonstrated that SOCS3 is a direct target of miR-455-5p. CONCLUSION: This study indicates an NF-κB/miR-455-5p/SOCS3 axis which can exacerbate kidney damage by enhancing renal inflammation. This process highlights potential therapeutic targets for managing septic AKI.
An Outbreak of Shiga Toxin-Positive Enteroaggregative Escherichia coli O104:H4 Related Hemolytic Uremic Syndrome in Turkey: A Multicenter Study.
Havan M, Gurbanov A, Özkan E … +16 more , Uçmak H, Kahveci F, Öztürk Z, Çakıcı EK, Uyar E, Emeksiz S, Temel Ö, Bozan G, Halıcıoğlu HT, Çakmaklı HF, Yılmaz S, Levent B, Özdemir H, Karahan ZC, Özçakar ZB, Kendirli T
Nephron · 2025 · PMID 39378856 · Publisher ↗
INTRODUCTION: Serious outbreaks of Shiga toxin-producing Escherichia coli-associated hemolytic uremic syndrome (STEC-HUS) have been reported globally. In 2011, Germany experienced a significant outbreak of HUS caused by...
INTRODUCTION: Serious outbreaks of Shiga toxin-producing Escherichia coli-associated hemolytic uremic syndrome (STEC-HUS) have been reported globally. In 2011, Germany experienced a significant outbreak of HUS caused by enteroaggregative E. coli (EAEC) O104:H4 strain. Since then, no other outbreaks of this strain have been reported. This study aims to evaluate pediatric patients affected by the second documented worldwide outbreak of STEC-HUS (EAEC O104:H4 serotype) contaminating local drinking water. METHODS: Medical records of patients hospitalized in five pediatric intensive care units (PICUs) diagnosed with STEC-HUS between July and September 2022 were evaluated retrospectively. RESULTS: Eighteen patients (14 girls and 4 boys) were enrolled in the study. The median age was 7.4 (Interquartile range [IQR] 1.3-17) years. Abdominal pain was the most common symptom (100%). The mean duration between symptom onset and development of STEC-HUS was 3 days (IQ 1-9). EAEC O104:H4 serotype was detected in the stool samples of 8 patients. Neurological involvement was observed in 3 patients, cardiac involvement in 2 patients, and both in 1 patient. Two patients required respiratory support and dialysis was performed in 16 (88.8%) patients. Plasmapheresis was administered to 2 patients, and eculizumab was given to four. No mortality was reported during follow-up; the mean durations of PICU and hospital stays were 11.3 and 31.6 days, respectively. CONCLUSION: Outbreaks of HUS can have serious impacts on both mortality and morbidity. However, timely diagnosis and implementation of appropriate supportive care, including dialysis, respiratory support, and medical treatment for eligible patients, can lead to favorable outcomes.
Brenner's Unforgettable Legacy: Transforming Medicine and Renal Science for Generations.
Remuzzi G, Warnock D
Nephron · 2024 · PMID 39369687 · Publisher ↗
Abstract loading — click title to view on PubMed.
Urinary Complement C3 and Vitamin D-Binding Protein Predict Adverse Outcomes in Patients with Acute Kidney Injury after Cardiac Surgery.
Holthoff JH, Alge JL, Arthur JM … +5 more , Ayub F, Bin Homam W, Janech MG, Ravula S, Karakala N
Nephron · 2025 · PMID 39348806 · Publisher ↗
INTRODUCTION: Acute kidney injury (AKI) is associated with adverse outcomes, including death and dialysis. The goal of this study was to identify prognostic biomarkers of AKI that could be used across multiple phenotypes...
INTRODUCTION: Acute kidney injury (AKI) is associated with adverse outcomes, including death and dialysis. The goal of this study was to identify prognostic biomarkers of AKI that could be used across multiple phenotypes of AKI and across different species. METHODS: Liquid chromatography/tandem mass spectrometry analysis of urine samples from three species (human, rat, and mouse) and four etiologies of AKI identified five potential biomarkers, of which two were validated, complement C3 and vitamin D-binding protein, in a cohort of 157 patients that developed AKI following cardiothoracic surgery. We studied the relationship between the biomarker's concentration in the urine and the development of a composite primary endpoint (stage 3 AKI within 10 days or death within 30 days). RESULTS: Of the 153 patients who developed AKI following cardiovascular surgery, 17 met the combined primary outcome. The median concentration of urine complement C3 adjusted to urine creatinine had the best predictive value and was significantly higher in the primary outcome group than in the controls. Similarly, the median concentration of vitamin D-binding protein was higher in the primary outcome group. CONCLUSIONS: The studies provide proof in principle that cross-species discovery analyses could be a valuable tool for identifying novel prognostic biomarkers in AKI. Urine complement C3 and vitamin D-binding protein could be promising early predictors of adverse outcomes in patients who develop AKI after cardiac surgery.
Adoption of CKD-EPI (2021) for Glomerular Filtration Rate Estimation: Implications for UK Practice.
Roy R, Raman M, Dark PM … +2 more , Kalra PA, Green D
Nephron · 2025 · PMID 39342928 · Full text
INTRODUCTION: Recommendations to move to a race-free estimating equation for glomerular filtration rate (GFR) have gained increasing prominence since 2021. We wished to determine the impact of any future adoption upon th...
INTRODUCTION: Recommendations to move to a race-free estimating equation for glomerular filtration rate (GFR) have gained increasing prominence since 2021. We wished to determine the impact of any future adoption upon the chronic kidney disease (CKD) patient population of a large teaching hospital, with a population breakdown largely similar to that of England as a whole. METHODS: We compared four estimating equations (Modification of Diet in Renal Disease [MDRD], CKD-EPI [2009], CKD-EPI [2021], and European Kidney Function Consortium [EKFC]) using the Bland-Altman method. Bias and precision were calculated (in both figures and percentages) for all patients with CKD and specific subgroups determined by age, ethnic group, CKD stage, and sex. CKD stage was assessed using all four equations. RESULTS: All equations studied had a positive bias in South Asian patients and a negative bias in black patients compared to CKD-EPI (2021). Similarly, there was a positive bias in white patients across all equations studied. Comparing CKD-EPI (2009) and EKFC, this positive bias increased as patients aged; the opposite was seen with MDRD. Between 10% and 28% of patients in our dataset changed their CKD staging depending upon the estimating equation used. DISCUSSION: Our work confirms previous findings that the MDRD equation overestimates estimated GFR (eGFR) in South Asians and underestimates eGFR in blacks. The alternative equations also demonstrated similar bias. This may, in part, explain the health inequalities seen in ethnic minority patients in the UK. Applying our findings to the UK CKD population as a whole would result in anywhere from 260,000 to 730,000 patients having their CKD stage reclassified, which in turn will impact secondary care services. INTRODUCTION: Recommendations to move to a race-free estimating equation for glomerular filtration rate (GFR) have gained increasing prominence since 2021. We wished to determine the impact of any future adoption upon the chronic kidney disease (CKD) patient population of a large teaching hospital, with a population breakdown largely similar to that of England as a whole. METHODS: We compared four estimating equations (Modification of Diet in Renal Disease [MDRD], CKD-EPI [2009], CKD-EPI [2021], and European Kidney Function Consortium [EKFC]) using the Bland-Altman method. Bias and precision were calculated (in both figures and percentages) for all patients with CKD and specific subgroups determined by age, ethnic group, CKD stage, and sex. CKD stage was assessed using all four equations. RESULTS: All equations studied had a positive bias in South Asian patients and a negative bias in black patients compared to CKD-EPI (2021). Similarly, there was a positive bias in white patients across all equations studied. Comparing CKD-EPI (2009) and EKFC, this positive bias increased as patients aged; the opposite was seen with MDRD. Between 10% and 28% of patients in our dataset changed their CKD staging depending upon the estimating equation used. DISCUSSION: Our work confirms previous findings that the MDRD equation overestimates estimated GFR (eGFR) in South Asians and underestimates eGFR in blacks. The alternative equations also demonstrated similar bias. This may, in part, explain the health inequalities seen in ethnic minority patients in the UK. Applying our findings to the UK CKD population as a whole would result in anywhere from 260,000 to 730,000 patients having their CKD stage reclassified, which in turn will impact secondary care services.
Immediate-Release versus Extended-Release Tacrolimus: Comparing Blood Pressure Control in Kidney Transplant Recipients - A Retrospective Cohort Study.
Yang CW, Velez JCQ, Cohen DL
Nephron · 2025 · PMID 39307127 · Full text
BACKGROUND: Hypertension (HTN) is a common side effect of tacrolimus (Tac), the first-line antirejection medication for kidney transplant recipients. The impact of immediate-release tacrolimus (Tac IR) dosed twice daily...
BACKGROUND: Hypertension (HTN) is a common side effect of tacrolimus (Tac), the first-line antirejection medication for kidney transplant recipients. The impact of immediate-release tacrolimus (Tac IR) dosed twice daily versus extended-release tacrolimus (Tac ER) dosed once daily on long-term blood pressure control in kidney transplant recipients remains understudied. This study aims to compare the use of Tac IR versus Tac ER in kidney transplant recipients and evaluate the effects of the different formulations on systolic blood pressure (SBP), diastolic blood pressure (DBP), and HTN crisis. METHODS: This retrospective cohort study at a single institution collected baseline characteristics, time-varying exposure to Tac IR versus Tac ER, SBP, DBP, HTN crisis, and confounders at each posttransplant visit. A marginal structural linear mixed-effects model was employed to analyze the longitudinal blood pressure control in kidney transplant recipients receiving Tac IR and Tac ER. RESULTS: The final analysis included 654 patients, with mean ages of 52.0 years for Tac IR and 50.3 years for Tac ER. Males constituted 56.7% in Tac IR and 55.0% in Tac ER. Notably, the black population had 2.44 times higher odds of receiving Tac ER after adjusting for the rest of the baseline characteristics. No difference was found between longitudinal SBP (p = 0.386, 95% CI: -1.00, 2.57) or DBP (p = 0.797, 95% CI: -1.38, 1.06). CONCLUSION: Our study indicates that posttransplant patients taking Tac ER exhibit no difference in chronic SBP and DBP controls compared to Tac IR.
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