Nephron[JOURNAL]
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200 papers
Metabolic Dysfunction-Associated Fatty Liver Disease in Advanced Chronic Kidney Disease: Impact on Patient Survival.
Garcia-Cantón C, Rivero Y, Bosch E … +10 more , Batista F, Gonzalez-Martin JM, González S, Guinea S, Tugores A, Aladro S, Afonso S, Fernandez S, Hernandez D, Boronat M
Nephron · 2025 · PMID 40414209 · Publisher ↗
INTRODUCTION: Metabolic dysfunction-associated fatty liver disease (MAFLD) is a prevalent liver condition commonly associated with obesity, metabolic syndrome, and type 2 diabetes mellitus. It has also been linked to an...
INTRODUCTION: Metabolic dysfunction-associated fatty liver disease (MAFLD) is a prevalent liver condition commonly associated with obesity, metabolic syndrome, and type 2 diabetes mellitus. It has also been linked to an increased risk of cardiovascular events and overall mortality. Recent studies have established pathophysiological connections between MAFLD and chronic kidney disease (CKD). This study aimed to determine the prevalence of MAFLD in patients with advanced chronic kidney disease (ACKD), identify associated factors, and evaluate its impact on patient survival. METHODS: A retrospective longitudinal cohort study was conducted with incident patients diagnosed with stage 4 or 5 CKD, not on dialysis, who initiated care for ACKD between 2011 and 2015. Clinical and laboratory data were collected, and the presence of MAFLD was estimated using the Fatty Liver Index (FLI). To assess the impact of FLI and other variables on survival, Kaplan-Meier univariate analysis and Cox regression multivariate analysis were performed, with follow-up through February 2024. RESULTS: Among 367 patients, 60.2% had diabetes, and 70.8% had an FLI ≥60. Age and diabetes mellitus were significant factors associated with a higher likelihood of FLI ≥60. FLI was identified as an independent risk factor for decreased survival in patients with diabetes, after adjusting for other variables (HR, 1.015; 95% CI 1.004-1.027; p = 0.009). However, in non-diabetic patients, FLI was not a significant predictor of lower survival in multivariate Cox regression analysis. CONCLUSIONS: MAFLD is highly prevalent in patients with ACKD, particularly among those with diabetes, for whom it may represent an independent risk factor for reduced survival. This association was not observed in non-diabetic ACKD patients. These results suggest the need to design preventive and treatment strategies for MAFLD in this population.
Perioperative Management of Atypical Hemolytic Uremic Syndrome in a Patient on Maintenance Eculizumab Therapy: A Case Report and Review of the Literature.
Mütiş Alan A, Dinçer MT, Kaykioğlu A … +5 more , Türk B, Nuhoğlu Kantarci E, Seyahi N, Trabulus S, Eşkazan AE
Nephron · 2025 · PMID 40414204 · Publisher ↗
INTRODUCTION: Atypical hemolytic uremic syndrome (aHUS) is a rare, complement-mediated disorder characterized by microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury. Eculizumab, a monoclonal anti...
INTRODUCTION: Atypical hemolytic uremic syndrome (aHUS) is a rare, complement-mediated disorder characterized by microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury. Eculizumab, a monoclonal antibody that inhibits complement component C5, is a cornerstone therapy for aHUS but increases the risk of infections, particularly from encapsulated organisms. Surgical procedures can also raise infection risks or exacerbate thrombotic microangiopathy. However, data on the perioperative management of patients with aHUS, particularly those receiving eculizumab, remain limited. CASE PRESENTATION: A 73-year-old male with a history of prostate cancer presented with acute kidney injury, thrombocytopenia, and hemolysis, leading to a diagnosis of aHUS. He was treated with eculizumab, which improved kidney function and eliminated the need for dialysis. Four months later, he developed abdominal pain and was found to have gallstones. The patient subsequently underwent a laparoscopic cholecystectomy while continuing maintenance eculizumab therapy. The procedure was performed without any complications, and the patient was discharged in stable condition. CONCLUSION: This case report details the successful perioperative management of a patient with aHUS on maintenance eculizumab undergoing cholecystectomy, highlighting the importance of careful management, including continued complement inhibition and infection prevention strategies. Our report emphasizes the need for individualized perioperative care to minimize risks in aHUS patients requiring surgery.
Association between Salivary pH and Estimated Glomerular Filtration Rate Status in a Community-Dwelling Population: A Cross-Sectional Study.
Aoyama Y, Uchiyama C, Koike Y … +9 more , Hayashi K, Tokuda I, Sato H, Hirakawa A, Yamamoto Y, Kobayashi W, Ihara K, Murashita K, Nakaji S
Nephron · 2025 · PMID 40393448 · Publisher ↗
INTRODUCTION: Globally, chronic kidney disease (CKD) is a common condition associated with several complications and high mortality. Early detection and monitoring of CKD is important for prolonging healthy life expectan...
INTRODUCTION: Globally, chronic kidney disease (CKD) is a common condition associated with several complications and high mortality. Early detection and monitoring of CKD is important for prolonging healthy life expectancy. Salivary pH is reported to increase in patients with chronic renal failure; however, the association between salivary pH and the estimated glomerular filtration rate (eGFR) status, which is usually considered to assess kidney function in clinical settings, has not been adequately studied. Therefore, this study aimed to examine the association between salivary pH and eGFR through multivariate analysis. METHODS: We conducted a cross-sectional study using the data from a community-based cohort study conducted between 2017 and 2019 in Japan. We aimed to develop a prediction model to determine the eGFR status using salivary pH, instead of blood urea nitrogen (BUN), in combination with self-reported information (age, sex, body mass index, disease history, medication, and lifestyle) in 1,056 subjects (433 men and 623 women) who participated in the study in 2017. We first identified the logistic model including several explanatory variables in addition to BUN (BUN model) and also developed the logistic model that replaced BUN with salivary pH (pH model). We examined the predictive accuracy of the two developed models using the validation data of 298 subjects (116 men and 182 women) who participated in the study in 2019. RESULTS: BUN and salivary pH were significantly associated with the eGFR status (odds ratio [ORs]: 1.24, 95% confidence interval [CI]: 1.17-1.32, p < 0.001 for BUN; ORs: 0.96, 95% CI: 0.94-0.98, p < 0.001 for salivary pH, respectively). The developed pH model included age, kidney disease history, diabetes history, habitual medication for hypertension, habitual alcohol consumption status, and habitual exercise status in addition to salivary pH. The pH model showed accuracy comparable to that of the BUN model in determining the eGFR status (area under the curve for the pH and BUN models was 0.796 and 0.799, respectively; p = 0.933). CONCLUSION: This study clarified the association between salivary pH and the eGFR status.
Chronic Allograft Injury by Recurrent Crystalline Nephropathy of Adenine Phosphoribosyl Transferase Deficiency, Even after Early Initiation of Xanthine Oxidase Inhibitor.
Uesugi N, Miura Y, Nakafusa Y … +2 more , Ikeda N, Masutani K
Nephron · 2025 · PMID 40393441 · Publisher ↗
INTRODUCTION: Adenine phosphoribosyl transferase (APRT) deficiency is a rare genetic disorder of purine metabolism that results in excessive renal excretion of poorly soluble 2,8-dihydroxyadenine (DHA), leading to urolit...
INTRODUCTION: Adenine phosphoribosyl transferase (APRT) deficiency is a rare genetic disorder of purine metabolism that results in excessive renal excretion of poorly soluble 2,8-dihydroxyadenine (DHA), leading to urolithiasis, crystalline nephropathy, and renal failure. Recurrence after renal transplantation usually occurs in the early posttransplantation period and is sometimes the initial indication for the disease. Allograft survival is poor without adequate treatment with xanthine oxidase (XOR) inhibitors to reduce DHA levels. CASE PRESENTATION: A 49-year-old Japanese man with a history of recurrent renal stones presented with mild renal dysfunction 3 months after renal transplantation. Allograft biopsy revealed numerous brown crystals within the tubules and active interstitial inflammation. Febuxostat, a high-dose XOR inhibitor, was immediately prescribed. APRT deficiency was confirmed through urine metabolome analysis. The patient's renal function improved, and the febuxostat dose was subsequently reduced. One-year allograft biopsy demonstrated markedly reduced inflammation and crystals; however, an expanded scarred area with focal active inflammation and a few small crystals were observed. CONCLUSION: XOR inhibitors effectively reduce the crystals of recurrent APRT deficiency; however, they cannot prevent chronic injury. Diagnosing recurrent crystalline nephropathy and initiating XOR inhibitors as early as possible is essential for improving allograft survival.
What Is the Role of Sex Differences in Obesity-Associated Chronic Kidney Disease?
Sandino-Pérez J, González-García C, Hernández Velasco PJ … +2 more , Morales E, Sandino J
Nephron · 2025 · PMID 40349677 · Publisher ↗
BACKGROUND: Obesity is a well-established risk factor for chronic kidney disease (CKD), and its impact varies between sexes. Women generally have higher rates of obesity, which increases their susceptibility to CKD. Howe...
BACKGROUND: Obesity is a well-established risk factor for chronic kidney disease (CKD), and its impact varies between sexes. Women generally have higher rates of obesity, which increases their susceptibility to CKD. However, men tend to experience faster disease progression and a higher likelihood of death related to end-stage kidney disease. These differences may be driven by a combination of hormonal, metabolic, and physiological factors. SUMMARY: Sex-based differences play a crucial role in the development and progression of CKD related to obesity. While women are more frequently affected by obesity, men face a greater risk of severe disease outcomes. Approaches to managing obesity - including lifestyle changes, surgical interventions, and medications - may have differing effects and risk profiles in men and women. These disparities highlight the need for a gender-sensitive approach in both research and clinical practice. KEY MESSAGES: Obesity increases the risk of CKD, with notable differences between sexes in both prevalence and disease outcomes. Biological differences, such as hormonal and metabolic factors, contribute to sex-specific patterns in disease manifestation and treatment response. Weight loss strategies, pharmacological treatment effectiveness, and side effects may vary depending on sex. Incorporating a gender-based perspective into the diagnosis, treatment, and research of obesity-related CKD is essential for improving patient care and achieving equitable health outcomes.
Care Needs of Adults on Peritoneal Dialysis and Their Informal Caregiver: A Qualitative Study.
Aramini M, Luca CE, Bianchi M … +5 more , Bellasi A, Pezzoli G, Cippà P, Bonetti L, Bellasi A
Nephron · 2025 · PMID 40341291 · Full text
UNLABELLED: <p>Introduction: Peritoneal dialysis (PD) provides a sense of control, independence, freedom, and self-efficacy. However, it can also impact a patient's physical, psychological, and social well-being, affecti...
UNLABELLED: <p>Introduction: Peritoneal dialysis (PD) provides a sense of control, independence, freedom, and self-efficacy. However, it can also impact a patient's physical, psychological, and social well-being, affecting both patients and family members. This study aimed to investigate the experiences and needs of adults on PD and their informal caregivers to understand how a person-centred approach can improve the response to their needs. METHODS: This is a generic descriptive qualitative research study. Data were collected through semi-structured interviews, transcribed, and analysed using Braun and Clarke's thematic analysis and NVivo® software. The data of patients and caregivers were triangulated to better understand their needs. RESULTS: Twelve patients and four informal caregivers were interviewed. We identified five macro-themes: "living with kidney disease and PD and its needs," "preparation before initiating PD and its needs," "learning about PD and its needs," "impact of dialysis on the need of the patients and caregivers," and "experiences with the care team." The pre-dialysis period is crucial, with specific needs for information, education, shared decision-making, and support during the various psychological, physical, and organisational changes in treatment and the disease trajectory. Caregivers' roles are essential and should always be included in the care path. CONCLUSION: This study emphasises the importance of continuity in care for patients with their care team and how delicate and important the pre-dialysis phase is for informed and shared decision-making regarding kidney replacement treatment. This understanding can help ensure a more person-centred care approach. </p>.
Pathogenesis Mechanism of Ferroptosis and Pharmacotherapy in Kidney Diseases: A Review.
Li L, Zhang H, Tang J … +1 more , Zhang H
Nephron · 2025 · PMID 40273899 · Publisher ↗
BACKGROUND: Ferroptosis is a novel form of iron-dependent programmed cell death, characterized by lipid peroxidation and the accumulation of reactive oxygen species. Dysregulation of iron metabolism, lipid metabolism, or...
BACKGROUND: Ferroptosis is a novel form of iron-dependent programmed cell death, characterized by lipid peroxidation and the accumulation of reactive oxygen species. Dysregulation of iron metabolism, lipid metabolism, or the antioxidant system can trigger this process. Emerging evidence suggests that ferroptosis is implicated in the pathogenesis and progression of various kidney diseases. SUMMARY: This review explores the pathophysiological mechanisms of ferroptosis, focusing on its role in cellular damage and disease progression in kidney diseases. The roles of iron homeostasis, lipid peroxidation, and antioxidant defenses in ferroptosis are discussed. Studies have demonstrated that inhibiting ferroptosis can protect against kidney injury, highlighting its potential as a therapeutic target. Additionally, current findings on ferroptosis-targeted therapies, including preclinical studies and potential clinical applications, are summarized. KEY MESSAGES: Ferroptosis plays a critical role in the development and progression of kidney diseases. Understanding the mechanisms governing ferroptosis and its relationship with kidney pathology provides a foundation for novel diagnostic and therapeutic strategies. Further research is needed to identify specific molecular mechanisms and advance clinical trials to translate ferroptosis-targeted therapies into practice, paving the way for innovative therapeutic interventions in kidney diseases.
Advances on Novel Biomarkers of Alloimmunity in Kidney Transplantation.
Carrera C, Kervella D, Crespo E … +2 more , Hafkamp F, Bestard O
Nephron · 2025 Apr · PMID 40267888 · Publisher ↗
Despite major advancements in transplant rejection physiopathology and the refinement of immunosuppressive therapies over the past decades, improvements in graft and patient survival remains limited. A potential explanat...
Despite major advancements in transplant rejection physiopathology and the refinement of immunosuppressive therapies over the past decades, improvements in graft and patient survival remains limited. A potential explanation is the insufficient implementation of biomarkers for individualized alloimmune risk stratification in clinical transplantation. Enormous efforts have focused in the last decades on developing sensitive and specific biomarkers to enable more personalized, non-invasive rejection diagnostics and informed treatment decisions in the transplant process. These biomarkers have distinct purposes; pre-transplantation, biomarkers aim to improve current donor-recipient immunological matching and rule out preformed anti-donor immune memory, whereas post-transplantation, their main aim focuses on identifying anti-donor alloimmune activation and on-going subclinical rejection in a non-invasive manner. This review summarizes the most advanced biomarkers and immune assays in the field, categorizing them by their diagnostic, prognostic, and predictive capabilities, and discusses their current validation status and integration into clinical trial designs aimed at improving transplant outcomes. Among them, we here highlight those assessing alloimmune susceptibility or activation, such as donor/recipient HLA molecular matching, donor (HLA/non-HLA)-specific antibodies (DSA), donor-reactive memory T and B cells, peripheral gene expression profiling (GEP) as well as some specific circulating immune cell phenotypes; and furthermore, we discuss those biomarkers diagnosing on-going subclinical graft injury, including donor-derived cell-free DNA (dd-cfDNA), and urinary chemokines or transcriptional biomarkers. Most importantly, these biomarkers are often complementary: some reflect ongoing alloimmune responses and may guide immunosuppression decisions, while others may provide early warnings of allograft injury prior to clinical manifestation. While some have progressed to advanced validation stages with strong diagnostic and prognostic value, others remain in early development. Rigorous interventional clinical trials are warranted to establish their clinical utility and define their role in transplant precision medicine to ultimately improve current clinical outcomes.
The Fabry Nephropathy in Patients with N215S Variant.
Mignani R, Berti GM, Vischini G … +6 more , Di Costanzo R, Ciurli F, Fabbrizio B, Pasquinelli G, La Manna G, Capelli I
Nephron · 2025 · PMID 40188808 · Publisher ↗
BACKGROUND: Fabry disease (FD) is a rare, X-linked lysosomal storage disorder that affects both males and females. It is caused by pathogenic variants in the gene that encodes the enzyme α-galactosidase A, GLA. The class...
BACKGROUND: Fabry disease (FD) is a rare, X-linked lysosomal storage disorder that affects both males and females. It is caused by pathogenic variants in the gene that encodes the enzyme α-galactosidase A, GLA. The classic form of the disease begins in childhood, presenting with a range of signs and symptoms that can lead to severe complications such as stroke, as well as cardiac and renal failure. In the late-onset form, the disease appears in adulthood, often with signs of cardiac involvement. SUMMARY: The N215S (p.Asn215Ser) missense mutation represents the most common late-onset variant in European countries. In these patients, cardiac involvement is usually more prominent than extracardiac signs and symptoms, which is why this form is often referred to as a cardiac variant. Renal involvement in the N215S variant has historically been considered infrequent and relatively mild, contributing little to the overall disease burden of late-onset FD, as it has not been thoroughly investigated. KEY MESSAGES: In this review, we examine Fabry nephropathy in patients with the late-onset N215S variant, providing an insight into the clinical and histopathologic aspects of renal involvement in these individuals.
Relapse Risk in Patients with Membranous Nephropathy after Inactivated COVID-19 Vaccination.
Zhang H, Chen R, Xu M … +8 more , Huang X, Zhao W, Zhou J, Zhang M, Xu Y, Shang D, Xie Q, Hao CM
Nephron · 2025 · PMID 40174580 · Publisher ↗
BACKGROUND: Although there have been reports of relapse or worsening of membranous nephropathy after receiving vaccines against coronavirus disease 2019 (COVID-19), the causal relationship or association between them has...
BACKGROUND: Although there have been reports of relapse or worsening of membranous nephropathy after receiving vaccines against coronavirus disease 2019 (COVID-19), the causal relationship or association between them has not been established. This study aimed to investigate the occurrence of relapse or worsening of membranous nephropathy following inactivated COVID-19 vaccination. METHODS: Patients who had been diagnosed with membranous nephropathy before receiving their first dose of vaccination, or before March 1, 2021, for unvaccinated patients, were included in the study. All patients were monitored at the Membranous Nephropathy Clinic of Huashan Hospital, Fudan University. The reasons for not receiving vaccines were investigated. The impact of COVID-19 vaccination on membranous nephropathy was assessed by comparing the relapse or worsening of membranous nephropathy within 12 months in vaccinated and unvaccinated patients with proteinuria <3.5 g/d. The baseline variables were balanced using cardinality matching. RESULTS: A total of 353 patients with membranous nephropathy were included in the study, with 186 (53%) having received inactivated COVID-19 vaccines. Among the 167 unvaccinated participants, 114 (68%) expressed concerns about the possibility of disease relapse, and 47 (28%) were worried about the vaccine's efficacy due to their immunosuppressive therapy. Of the 239 participants with proteinuria <3.5 g/d, 152 were vaccinated, and 16 (11%) experienced a relapse or worsening of the disease during the follow-up period, which was similar to the 14 (16%) observed in the unvaccinated group. Following cardinality matching, there was no difference in the rate of relapse or worsening between the two groups, with 10 (13%) in the vaccinated group and 11 (15%) in the unvaccinated group (hazard ratio 0.98, 95% confidence interval 0.42-2.33). CONCLUSION: Getting the inactivated COVID-19 vaccine may not increase risk of relapse or worsening in patients with membranous nephropathy.
Can-SOLVE CKD: Reflections on Successes, Challenges, and Future Opportunities in Patient-Oriented Kidney Research.
Talson MD, Hampson M, Loverock K … +9 more , Desjarlais A, Jones J, Pollock G, Woods C, Atkinson T, Manns BJ, James MT, Scholey JW, Levin A
Nephron · 2025 · PMID 40168956 · Publisher ↗
Abstract loading — click title to view on PubMed.
Further Clinical and Biochemical Phenotype of GLA p.A143T: A Fabry Disease Newborn Screening Experience.
Paltzer A, Paltzer AM, Quadri AM … +4 more , Rasmussen C, Schiffmann R, Charrow J, Prada CE
Nephron · 2025 · PMID 40159218 · Publisher ↗
BACKGROUND: In 2015, Illinois added Fabry disease to the newborn screening (NBS) panel, and numerous individuals who have the controversial p.A143T GLA variant were identified. Ann & Robert H. Lurie Children's Hospital o...
BACKGROUND: In 2015, Illinois added Fabry disease to the newborn screening (NBS) panel, and numerous individuals who have the controversial p.A143T GLA variant were identified. Ann & Robert H. Lurie Children's Hospital of Chicago identified 80 individuals with this variant. SUMMARY: Of the 80 individuals, 34/80 were identified by NBS, 2/80 were identified by gene panel testing, and 44/80 were identified by cascade testing. These individuals were from 36 families and ranged in age from 7 months to 71 years. Most individuals identified by NBS were male (90.9%) and 35.96% had the p.A143T variant. All newborns with known pathogenic or likely pathogenic variants in GLA had enzyme leukocyte activities below 20% of the percentage of mean of normal. This threshold could serve as a guideline for determining risk of symptom development for p.A143T and other variants of unknown significance. No person with p.A143T had significant lyso-GL3 elevation in this cohort. KEY MESSAGES: These data suggest the variant impacts enzyme levels, but its effect on health outcomes remains unclear. We further characterize clinical and biochemical data on individuals with the p.A143T GLA variant to help provide guidance on its clinical significance.
Dapagliflozin Treatment Attenuates the Interaction between the Renal Sodium Chloride Co-Transporter and Ezrin in Hypertensive Diabetic db/db Mice.
Gholam MF, Alli AA
Nephron · 2025 Mar · PMID 40122032 · Publisher ↗
INTRODUCTION: Ezrin is a protein that links the actin cytoskeleton to membrane proteins. The sodium chloride cotransporter (NCC) plays a key role in regulating total body electrolyte homeostasis and systemic blood pressu...
INTRODUCTION: Ezrin is a protein that links the actin cytoskeleton to membrane proteins. The sodium chloride cotransporter (NCC) plays a key role in regulating total body electrolyte homeostasis and systemic blood pressure. Dapagliflozin, an SGLT2 inhibitor, is used to manage type 2 diabetes mellitus. We hypothesize dapagliflozin reduces sodium reabsorption and blood pressure by inhibiting the interaction between NCC and ezrin in the distal convoluted tubules of salt-loaded hypertensive mice. METHODS: Male diabetic db/db mice were salt loaded to induce hypertension and then given dapagliflozin or vehicle by oral gavage. The mice were subject to metabolic cage experiments and blood pressure was assessed using the tail-cuff method to study the impact of dapagliflozin compared to the vehicle. Protein expression of NCC and ezrin was evaluated using immunohistochemistry and Western blotting. RESULTS: Treatment with dapagliflozin lowered systolic blood pressure, raised urine sodium excretion, and lowered urinary potassium excretion. A decrease in phospho-NCC and ezrin proteins was observed in db/db mice treated with dapagliflozin. There was less co-localization of ezrin and phosphorylated NCC in dapagliflozin treated mice. CONCLUSION: Collectively, we demonstrate that dapagliflozin reduces sodium retention and blood pressure via decreasing the density of renal NCC at the luminal membrane and the interaction between NCC and the actin cytoskeleton.
Sodium-Glucose Cotransporter-2 Inhibitors and Uric Acid.
Sanchez-Lozada LG, Lanaspa MA, Rodriguez-Iturbe B … +3 more , Brown JM, Madero M, Johnson RJ
Nephron · 2025 · PMID 40122030 · Publisher ↗
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Correlation between Plasma Aldosterone Concentrations and Simple Renal Cyst in Hypertensive Patients.
Ma H, Cai X, Song S … +12 more , Zhu Q, Hu J, Shen D, Yang W, Zhang Y, Ma R, Zhou P, Zhang D, Luo Q, Hong J, Li N, Li N
Nephron · 2025 · PMID 40122023 · Publisher ↗
BACKGROUND: Previous studies have linked primary aldosteronism to simple renal cysts (SRCs), but the relationship between plasma aldosterone concentration (PAC) and SRC remains unclear. This study aimed to investigate th...
BACKGROUND: Previous studies have linked primary aldosteronism to simple renal cysts (SRCs), but the relationship between plasma aldosterone concentration (PAC) and SRC remains unclear. This study aimed to investigate the association between PAC and SRC in hypertensive patients. METHODS: A total of 30,135 hypertensive patients who visited our hospital from January 2014 to December 2023 were included. Logistic regression analyses were conducted to explore the relationship between PAC and SRC, while restricted cubic splines (RCS) assessed the dose-response relationship. SRC were further categorized by size (≥2 cm) and number ≥2). Subgroup analyses were performed to evaluate PAC effects across different conditions. RESULTS: Multivariate logistic regression showed a positive association between PAC levels (per 5-ng/dL increase) and SRC (OR: 1.20, 95% CI: 1.17-1.23) after adjusting for confounders. Compared to the lowest PAC quartile (Q1), the Q2, Q3, and Q4 groups had progressively higher risks of SRC, with ORs of 1.03 (95% CI: 0.95-1.12), 1.25 (95% CI: 1.15-1.35), and 1.65 (95% CI: 1.52-1.78), respectively. Combining Q3 and Q4 (PAC ≥14.92) yielded an OR of 1.41 compared to Q1 and Q2 (<14.92). Similar trends were observed for SRC size ≥2 cm and number ≥2. RCS analysis confirmed a linear dose-response relationship between PAC and SRC risk. Subgroup and sensitivity analyses consistently supported these findings. CONCLUSIONS: Elevated PAC levels have been linked to an increased risk of SRC in hypertensive patients. Regulating PAC levels may help mitigate SRC formation; however, further prospective studies are required to confirm this causal relationship.
Lysosomal Storage-Independent Fabry Disease Variants with α-Galactosidase A Misprocessing-Induced ER Stress and the Unfolded Protein Response.
Živná M, Živná M, Lenders M … +1 more , Kmoch S
Nephron · 2025 · PMID 40112790 · Full text
<p>Background: Clinical findings in Fabry disease have classically been attributed to loss-of-function variants in the GLA gene that result in α-galactosidase A deficiency, intracellular accumulation of globotriaosylcera...
<p>Background: Clinical findings in Fabry disease have classically been attributed to loss-of-function variants in the GLA gene that result in α-galactosidase A deficiency, intracellular accumulation of globotriaosylceramides and clinical manifestations. However, over time, increasing number of patients have been identified with GLA variants causing either non-classic Fabry disease or having unclear clinical effects. Summary: Searching for additional etiologic and lysosomal storage-independent factors, investigators have recently identified that certain missense GLA variants not only affect enzymatic activity, but also encode for misfolded α-galactosidase A that itself induces chronic endoplasmic reticulum stress and the unfolded protein response. Thus, Fabry disease pathogenesis may be caused by decreased enzymatic activity as well as cellular toxicity from accumulation of the misfolded α-galactosidase A protein, with the contribution of each factor determined by the type of the genetic variant and host factors. Key Messages: Defective proteostasis and misfolding of certain missense α-galactosidase A variants induce chronic endoplasmic reticulum stress and the unfolded protein response that may contribute to intra-familial and inter-familial variation in disease penetrance and clinical expressivity. Pharmacologic modulation of defective proteostasis may have therapeutic implications in Fabry disease. </p>.
The Cost and Outcomes of Using Multidisciplinary Care Program in the Care of Adult Patients with Advanced Chronic Kidney Disease.
Kwek JL, Ang LC, Lim LWW … +7 more , Teo SH, Lim CC, Xin X, Ng LC, Foo MWY, Tan CS, Choo JCJ
Nephron · 2025 · PMID 40107249 · Publisher ↗
OBJECTIVE: The aim of the study was to compare the direct healthcare cost and outcomes of a multidisciplinary care (MDC) program versus usual care for patients with advanced chronic kidney disease (CKD) in Singapore. MET...
OBJECTIVE: The aim of the study was to compare the direct healthcare cost and outcomes of a multidisciplinary care (MDC) program versus usual care for patients with advanced chronic kidney disease (CKD) in Singapore. METHODS: A retrospective study of patients with an estimated glomerular filtration rate (eGFR) less than 20 mL/min/1.73 m2, attending the MDC program or the usual care clinic in a tertiary hospital from 2016 to 2019. The usual care group was matched to the MDC group using propensity score matching based on age, gender, baseline eGFR, and diabetes mellitus. The primary outcome was the rate of emergent long-term kidney replacement therapy (KRT) initiation and the direct healthcare cost incurred from eGFR for less than 20 mL/min/1.73 m2 for the initiation of long-term KRT. RESULTS: There were 280 patients in each group. The MDC group had a lower rate of emergent KRT initiation than the usual care group (33.3 vs. 55.7 events per 100 patient-year, p = 0.003), shorter length of hospitalization stay (8.0 vs. 16.5 days per year, p = 0.004), lower number of emergency department visits (0.7 vs. 1.2 visits per year, p = 0.005), and higher number of renal clinic visits (14.5 vs. 13.0 visits per year, p = 0.009). The healthcare cost was lower in the MDC group than in the usual care group (SGD USD 18,408.83 (USD 13,664.51) vs. SGD USD 28,734.43 (USD 21,329.00) per patient-year, p = 0.016). CONCLUSION: The MDC program for patients with advanced CKD in Singapore was associated with lower rate of emergent KRT initiation, shorter hospitalization stay, lower number of emergency department visit, and lower healthcare cost.
Unraveling the Molecular Nexus between Ankylosing Spondylitis and IgA Nephropathy: Insights from Mendelian Randomization and Bioinformatics Analysis.
Shao N, Tan K, Chen P … +1 more , Luo Q
Nephron · 2025 · PMID 40073855 · Publisher ↗
INTRODUCTION: Renal complications are frequently observed in patients with ankylosing spondylitis (AS), with IgA nephropathy (IgAN) being a particularly significant concern. Although anecdotal evidence suggests a potenti...
INTRODUCTION: Renal complications are frequently observed in patients with ankylosing spondylitis (AS), with IgA nephropathy (IgAN) being a particularly significant concern. Although anecdotal evidence suggests a potential association between AS and IgAN, robust epidemiological data remain limited. Previous studies have reported varying prevalence rates of IgAN among AS patients, but these studies are often constrained by small sample sizes and inconsistent methodologies. Establishing a causal relationship between AS and IgAN through conventional observational studies has proven challenging due to confounding factors and reverse causality. Mendelian randomization (MR) offers a promising alternative, utilizing genetic variants to explore causal relationships. This study employs MR combined with bioinformatics analysis to investigate the molecular link between AS and IgAN, aiming to identify potential therapeutic targets. METHODS: Two publicly available datasets were utilized: a genome-wide association study (GWAS) of AS (dataset ID: ebi-a-GCST005529) with 9,069 AS cases and 13,578 controls, and IgAN data from the FinnGen project, which included 653 cases and 411,528 controls. Instrumental variables were selected based on stringent criteria. MR analysis was conducted using the inverse variance weighted, weighted median, and MR-Egger methods to assess the causal relationship between AS and IgAN. Reverse MR analysis and sensitivity analysis were conducted to validate the findings. Bioinformatics analysis involved acquiring gene expression data from the GEO database and identifying differentially expressed genes (DEGs) using the limma package. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, protein-protein interaction (PPI) network construction, and hub gene identification were performed to elucidate the biological functions involved. RESULTS: A total of 24 independent single-nucleotide polymorphisms (SNPs) associated with AS were identified through stringent SNP selection. MR analysis revealed a protective causal relationship between AS and IgAN (odds ratio = 0.552, 95% confidence interval, 0.339-0.900; p = 0.017). Analysis of DEGs identified 332 DEGs for IgAN and 5,521 DEGs for AS, with 59 common DEGs shared between the two diseases. Functional enrichment analysis highlighted significant changes in biological processes, cellular components, molecular functions, and KEGG pathways. PPI network analysis identified eight hub genes, including CX3CR1, which links AS and IgAN. External validation confirmed CX3CR1 as a crucial gene associated with both diseases. CONCLUSION: This study provides evidence of a protective causal relationship between AS and IgAN using MR analysis. Furthermore, bioinformatics analysis identifies CX3CR1 as a key gene, suggesting its role in mediating the protective link between AS and IgAN. These findings provide valuable insights into the molecular mechanisms underlying the connection between the two diseases and propose CX3CR1 as a potential therapeutic target for IgAN.
Comments regarding "Adoption of CKD-EPI (2021) for Glomerular Filtration Rate Estimation: Implications for UK Practice".
Williams PT
Nephron · 2025 · PMID 40068669 · Publisher ↗
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When Proteins Go Berserk: The Unfolded Protein Response and ER Stress.
Dvela-Levitt M, Meiseles D, Arbeli N … +1 more , Dvela-Levitt M
Nephron · 2025 · PMID 40037304 · Full text
BACKGROUND: The cellular proteostasis machinery is essential for maintaining protein homeostasis by employing quality control systems that identify, sequester, and eliminate damaged or misfolded proteins. However, the ac...
BACKGROUND: The cellular proteostasis machinery is essential for maintaining protein homeostasis by employing quality control systems that identify, sequester, and eliminate damaged or misfolded proteins. However, the accumulation of misfolded proteins can overwhelm these protective mechanisms, disrupting proteostasis. This phenomenon is a hallmark of numerous pathologies, including a variety of genetic disorders. In the secretory pathway, the buildup of misfolded proteins triggers endoplasmic reticulum (ER) stress, which activates the unfolded protein response (UPR). The UPR serves as an adaptive mechanism, aiming to alleviate stress and restore cellular homeostasis. However, if ER stress is prolonged or severe, the UPR may fail to restore balance and apoptosis is induced. SUMMARY: This review introduces the intricate signaling pathways activated by the three UPR transmembrane sensors: protein-kinase R-like endoplasmic reticulum kinase (PERK), inositol requiring enzyme 1 (IRE1), and activating transcription factor 6 (ATF6). We briefly present the roles of the distinct transcriptional programs activated by each sensor in modulating the cellular response to protein stress and in determining cell fate. We discuss how genetic variants and environmental factors contribute to the heterogeneity observed in protein misfolding diseases. Finally, we critically evaluate select therapeutic strategies, specifically protein stabilization, trafficking modulation, and UPR sensor targeting approaches. KEY MESSAGES: This review introduces the potential consequences of protein misfolding, which may not only impair protein function but can also lead to toxic protein accumulation and stress induction. Using Fabry disease as a compelling example, we suggest that future therapeutic intervention may require nuanced, combination approaches that address both loss and gain of protein function.
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