Kidney360最新文献

{"title":"A Metabolomics Approach to Identify Metabolites Associated with Uremic Symptoms in Patients Receiving Maintenance Hemodialysis.","authors":"Solaf Al Awadhi, Leslie Myint, Eliseo Guallar, Clary B Clish, Kendra E Wulczyn, Sahir Kalim, Ravi Thandhani, Dorry L Segev, Mara McAdams-DeMarco, Sharon M Moe, Ranjani N Moorthi, Jonathan Himmelfarb, Neil R Powe, Marcello Tonelli, Eugene P Rhee, Tariq Shafi","doi":"10.34067/KID.0000000838","DOIUrl":"https://doi.org/10.34067/KID.0000000838","url":null,"abstract":"<p><strong>Background: </strong>The specific toxins causing uremic symptoms (nausea, vomiting, pruritus, fatigue, difficulty concentrating and pain) in kidney failure remain unknown. We used untargeted metabolomics to identify plasma metabolites associated with uremic symptoms in patients receiving hemodialysis.</p><p><strong>Methods: </strong>We measured metabolites in plasma samples from Longitudinal US/Canada Incident Dialysis (LUCID) study participants at baseline (discovery; n=636) and year 1 (internal validation; n=260), and from Frailty Assessment in Renal Disease (FAIR) study participants (external validation; n=355). We used metabolite-wise linear models with empirical Bayesian inference to evaluate the association between metabolites and uremic symptoms' severity, adjusting for key covariates. We accounted for multiple testing using a false discovery rate (pFDR) for linear models and used two machine learning models to evaluate the association consistency. We defined association as significant if pFDR <0.1 and consistent if they had medium or high importance in both machine learning models.</p><p><strong>Results: </strong>Participants had a mean age of 63 years, with uremic symptom prevalence ranging from 44-83%. We identified 627 previously characterized (known) and 35,558 unknown metabolite peaks. No known metabolites were significantly and consistently associated with uremic symptoms' severity across all cohorts. Within cohorts, retinol was negatively associated with nausea/vomiting in LUCID at year 1, and indole-3-propionic acid was negatively associated with anorexia in FAIR. Several unknown metabolites were associated with symptoms (lowest pFDR, 0.0004), but none were consistent across cohorts.</p><p><strong>Conclusions: </strong>We identified metabolites associated with uremic symptom severity, though findings were inconsistent across cohorts. This study highlights the need for further research on uremic toxins and clinical outcomes.</p>","PeriodicalId":17882,"journal":{"name":"Kidney360","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145131248","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Residual Kidney Function and Response of Left Ventricular Mass to Intensive Hemodialysis: The Frequent Hemodialysis Network Trials.","authors":"Amin Tajerian, Tariq Shafi, Jason Zhang, Sobia Khan, Sandeep K Mallipattu, Andreas P Kalogeropoulos","doi":"10.34067/KID.0000000987","DOIUrl":"https://doi.org/10.34067/KID.0000000987","url":null,"abstract":"<p><strong>Background: </strong>Frequent (6 times/week) hemodialysis (HD) has been shown to reduce left ventricular mass (LVM) more than conventional (3 times/week) HD in patients with ESKD. Previous work suggested that the LVM benefits of frequent HD might be attenuated in the presence of residual kidney function (RKF). We hypothesized that patients without RKF would have greater LVM reduction with frequent HD compared to patients with RKF.</p><p><strong>Methods: </strong>We analyzed data from the Frequent Hemodialysis Network (FHN) Daily (in-center) and Nocturnal (home-based) Trials, which randomized patients with ESKD to either frequent or conventional HD over 12 months. RKF was evaluated through timed 24h urine collections, with anuria defined as urine output <100 mL/day. LVM was assessed via magnetic resonance imaging at baseline and 12 months. Combined trial data were analyzed using log-transformed LVM to evaluate the impact of RKF on LVM change.</p><p><strong>Results: </strong>Among 332 patients from both FHN trials (170 frequent, 162 conventional HD), 189 (57%) were anuric at baseline. Baseline LVM did not differ between anuric and non-anuric patients (log LVM: 4.90±0.32 vs 4.85±0.40; p=0.18). At 12 months, both anuric and non-anuric patients experienced similar LVM reductions with frequent HD (mean change in log LVM: -0.11±0.23 vs -0.08±0.23; p=0.44). No association was found between baseline urine volume and LVM response (rho= -0.002, p=0.98 for frequent; rho=0.003, p=0.97 for conventional HD). Changes in urine volume over 12 months did not correlate with LVM changes. In an exploratory analysis, LVM reduction correlated with urine volume decline in men (rho=0.23; p<0.01) but not in women (rho= -0.19; p= 0.10; pinteraction = 0.003).</p><p><strong>Conclusions: </strong>Both anuric and non-anuric patients experienced similar LVM reductions with frequent HD, and no association between urine output and LVM response was observed in the FHN trials. These data suggest that the response of LVM to frequent HD is independent of baseline residual kidney function.</p>","PeriodicalId":17882,"journal":{"name":"Kidney360","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145131197","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Saracatinib Delays the Progression of Renal Interstitial Fibrosis by Inhibiting the Wnt/β-Catenin Pathway.","authors":"Junjun Ma, Nan Jiao, Xingwei Liu, Xiao Lu","doi":"10.34067/KID.0000000972","DOIUrl":"https://doi.org/10.34067/KID.0000000972","url":null,"abstract":"<p><strong>Background: </strong>Renal interstitial fibrosis is a common pathological feature of CKD and is a critical determinant of disease progression. Recent studies have highlighted the significant role of the Wnt/β-catenin signaling pathway in the development of renal interstitial fibrosis, but the exact mechanisms remain unclear.</p><p><strong>Methods: </strong>Renal tissue samples from CKD patients with renal interstitial fibrosis who underwent renal biopsy at our center between January 2022 and December 2023 were selected for staining. Additionally, a rat model of renal interstitial fibrosis was established using unilateral ureteral obstruction (UUO). UUO rats were administered low- and high-dose doses of saracatinib via gavage for two weeks, followed by examination of changes in relevant indicators.</p><p><strong>Results: </strong>In this study, we showed that in the kidney tissues of both CKD patients and rats with renal interstitial fibrosis, there was a marked upregulation of the tyrosine 142 kinase Fyn, which accompanied the excessive activation of the Wnt/β-catenin pathway. Saracatinib was found to inhibit this pathway by binding to Fyn in kidney tissues, thereby blocking the phosphorylation of β-catenin at tyrosine 142. This inhibition 1) decreased the serum urea nitrogen and cystatin C levels, along with an increase in serum albumin and total protein concentration, 2) alleviated renal interstitial fibrosis in the unilateral ureteral obstruction rat model, resulting in an amelioration of the progression of renal interstitial fibrosis.</p><p><strong>Conclusions: </strong>This study suggests that saracatinib may be a novel therapeutic strategy for CKD treatment.</p>","PeriodicalId":17882,"journal":{"name":"Kidney360","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145125014","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Novel Human Distal Tubuloid-on-a-Chip Model for Investigating Sodium and Water Transport Mechanisms.","authors":"Murillo D L Bernardi, Emre Dilmen, Dorota Kurek, Henriette L Lanz, Jos Joore, Joost G Hoenderop, Maarten B Rookmaaker, Marianne C Verhaar","doi":"10.34067/KID.0000000992","DOIUrl":"https://doi.org/10.34067/KID.0000000992","url":null,"abstract":"<p><strong>Background: </strong>The distal nephron, which includes the thick ascending limb, distal convoluted tubule, connecting tubule, and collecting duct, is essential for the regulation of water and electrolyte balance. Injury or dysfunction of these segments contributes to significant kidney disease and systemic complications. Studying these regions directly in vivo is limited by the complexity of kidney architecture. Recently, three-dimensional cultures of human kidney tubule cells, called tubuloids, and microfluidic platforms that support dynamic flow have provided new opportunities to model kidney function in vitro.</p><p><strong>Methods: </strong>We developed a human distal tubuloid-on-a-chip model by integrating primary human tubuloid cells with the OrganoPlate® microfluidic culture system. Tubuloids were seeded to form three-dimensional tubular structures adjacent to a collagen type I matrix and exposed to alternating flow. Differentiation into a distal nephron phenotype was evaluated using quantitative polymerase chain reaction, immunohistochemistry, and barrier integrity assays. Functional sodium and water transport were investigated using radiolabeled sodium uptake, transepithelial resistance, dextran diffusion, and dome formation. Pharmacological studies were conducted using trimethoprim, an inhibitor of epithelial sodium channel activity.</p><p><strong>Results: </strong>Three-dimensional cultures under flow conditions showed increased expression of markers specific to distal nephron segments compared to conventional two-dimensional cultures. Immunostaining confirmed the formation of a highly polarized epithelium with apical and basolateral localization of key transport proteins. The tubules formed a leak-tight barrier, demonstrated by reduced dextran permeability and elevated transepithelial resistance. Radiolabeled assays revealed active sodium transport driven by apical epithelial sodium channels and basolateral sodium-potassium ATPase. Water transport accompanied sodium movement, indicated by dome formation beneath the epithelial layer. Exposure to trimethoprim reduced sodium uptake and dome formation, confirming functional responsiveness of the model.</p><p><strong>Conclusions: </strong>This distal tubuloid-on-a-chip system reproduces key structural and functional features of the human distal nephron. It enables the study of salt and water transport in primary human tubule cells under controlled microfluidic flow. The model provides a physiologically relevant and scalable platform for investigating kidney physiology, pathology, and pharmacological responses, with potential applications in drug discovery and toxicity testing.</p>","PeriodicalId":17882,"journal":{"name":"Kidney360","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145075495","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nrf2 Deficiency Enhances the Immunosuppressive Function of Monocytic Myeloid-derived Suppressor Cells in a PPARγ- Dependent Manner.","authors":"Yichen Jia, Jiawei Li, Tianying Yang, Ruimin Li, Guowei Tu, Yue Qiu, Xuepeng Zhang, Ruirui Sang, Yi Shi, Shihao Xu, Yin Celeste Cheuk, Jingjing Liu, Ruiming Rong, Yi Zhang","doi":"10.34067/KID.0000000947","DOIUrl":"https://doi.org/10.34067/KID.0000000947","url":null,"abstract":"<p><strong>Background: </strong>Myeloid-derived suppressor cells (MDSCs) comprise monocytic MDSCs (M-MDSCs) and granulocytic MDSCs (G-MDSCs), both of which are effective for controlling T cell responses. Although Nrf2 participates in the expansion of MDSCs and MDSC-mediated immunosuppression, the underlying mechanisms of Nrf2 in MDSC differentiation remain poorly understood.</p><p><strong>Methods: </strong>In this study, G-MDSCs or M-MDSCs were induced and sorted from the bone marrow (BM) of wild-type (WT) or Nrf2-/- mice using flow cytometry in vitro, with or without GW9662 treatment. Mouse models of tumorigenesis, acute kidney injury (AKI), and chronic kidney disease (CKD) were used to evaluate the immunosuppressive function of WT or Nrf2-/- M-MDSCs treated with or without GW9662. Histological analysis was performed to evaluate tumor angiogenesis or kidney injury. Immunohistochemical staining was used to evaluate lymphocyte infiltration in kidney. Masson's trichrome and Sirius red staining were performed to evaluate kidney fibrosis. Additionally, RNA sequencing (RNA-seq) was conducted to identify gene expression difference between WT and Nrf2-/- M-MDSCs, with real-time PCR or western blot used to validate key findings.</p><p><strong>Results: </strong>The immunosuppressive function of M-MDSCs generated from BM of Nrf2-/- mice and sorted from Nrf2-/- tumor-bearing mice was dramatically enhanced compared to the G-MDSC counterparts. Moreover, M-MDSCs with an Nrf2 deficiency could effectively ameliorate the inflammatory disorders in mice with AKI or CKD. Intriguingly, the efficacy of Nrf2-/- M-MDSCs could be attributed to increased expression of inducible nitric oxide synthase but decreased levels of arginase 1, indicating an unconventional mechanism of activation. Further mechanistic studies using RNA-seq and bioinformatics analyses identified an essential role of peroxisome proliferator-activated receptor-γ (PPARγ) in the differentiation and suppressive ability of Nrf2-/- M-MDSCs with which the effect could be markedly blocked with GW9662, a specific PPARγ inhibitor.</p><p><strong>Conclusions: </strong>Our findings elucidate an immunoregulatory mechanism of Nrf2 deficiency related to M-MDSC function and provides a foundation for the application of Nrf2-/- M-MDSCs in inflammatory diseases.</p>","PeriodicalId":17882,"journal":{"name":"Kidney360","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145075541","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nucleophosmin (NPM) Promotes Regulated Cell Death in Podocyte Injury.","authors":"Seiya Urae, Zhiyong Wang, Sudhir Kumar, Hui A Chen, Joel M Henderson, Laurence H Beck, Steven C Borkan","doi":"10.34067/KID.0000000996","DOIUrl":"https://doi.org/10.34067/KID.0000000996","url":null,"abstract":"<p><strong>Background: </strong>The mechanism of regulated podocyte death during glomerulopathy is unknown, limiting therapeutic interventions to protect this essential kidney cell. We hypothesize that cytosolic nucleophosmin (NPM) accumulation promotes Bax-mediated podocyte injury during experimental and clinical glomerulopathy.</p><p><strong>Methods: </strong>Cytosolic and total NPM were quantified in differentiated human podocytes subjected to mechanistically diverse stressors in vitro, in kidney tissue harvested from conditional, podocyte-specific integrin-linked kinase conditional knockout (ILK-cKO) mice, and in kidney tissue from patients with focal segmental glomerulosclerosis (FSGS), membranous nephropathy, or diabetic nephropathy using histologic and immunologic techniques. The effect of stress on NPM/Bax complex formation, mitochondrial Bax accumulation, and podocyte survival was assessed using an organelle-specific stain, NPM/Bax co-immunoprecipitation, and a colorimetric cell survival assay, respectively. To establish a potential role for NPM in regulated podocyte injury, NPM content was reduced and increased using molecular techniques, and the therapeutic effect of peptides designed to competitively inhibit NPM/Bax interaction was examined.</p><p><strong>Results: </strong>Cytosolic NPM accumulation increased after transient exposure to Adriamycin or hydrogen peroxide. Hydrogen peroxide increased cytosolic NPM/Bax complex formation and increased mitochondrial Bax accumulation, early hallmarks of regulated cell death. siRNA-mediated NPM suppression significantly increased human podocyte survival, whereas NPM over-expression significantly reduced podocyte survival after acute stress. A novel TP10-fused peptide reduced NPM/Bax interaction and significantly increased podocyte survival after stress. In contrast to 2-day-old pups, increased NPM expression and cytosolic NPM accumulation were detected in podocytes of 4-week-old ILK-KO mice, an early FSGS model, as well as in the glomeruli of kidney tissue harvested from patients with diverse forms of clinical glomerulopathy.</p><p><strong>Conclusions: </strong>Cytosolic NPM translocation accompanies experimental and clinical podocyte injury, promotes regulated podocyte death after stress, and is a promising target for protecting podocytes against glomerular injury.</p>","PeriodicalId":17882,"journal":{"name":"Kidney360","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145075501","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Thickening of Glomerular Basement Membrane is Associated with Long-Term Prognosis in Patients with IgA Nephropathy.","authors":"Fang Zhengying, Yang Mingxin, Wei Wenjie, Xu Jing, Du Wen, Chen Zijin, Ma Jun, Pan Xiaoxia, Wang Weiming, Ren Hong, Chen Nan, Ouyang Yan, Xie Jingyuan","doi":"10.34067/KID.0000000885","DOIUrl":"https://doi.org/10.34067/KID.0000000885","url":null,"abstract":"<p><strong>Background: </strong>Glomerular basement membrane (GBM) ultrastructural abnormalities are common in IgAN, however, few studies have focused on clinical significance and prognostic value of GBM ultrastructural changes in IgAN patients.</p><p><strong>Methods: </strong>A retrospective longitudinal cohort with 1006 biopsy-proven primary IgAN patients was collated. GBM thickness and texture of each case were assessed under transmission electron microscope. The primary end point was end stage renal disease (ESRD). Cox proportional hazards regression model was built to determine risk factors. Immunofluorescent staining was performed on patient kidney biopsy samples to validate the correlation between mesangial proliferation and abnormal GBM thickness. Twenty SNPs independently associated with IgAN in previous genome-wide association studies were genotyped in 617 patients and whole exome sequencing was performed in 56 patients to investigate potential variants underlying GBM ultrastructural changes.</p><p><strong>Results: </strong>Of 1006 patients, 52% were female, and the mean age was 37.3±12.3 years old. Among all patients, 80 (8%) had abnormal thickness of GBM including 29 (3%) thickening of GBM and 51 (5%) thinning of GBM. Abnormal GBM texture was found in 25 (2%) patients. During a mean follow-up time of 46.4 months, 91 (9%) patients progressed to ESRD. By Cox regression analyses, we demonstrated that thickening of GBM at biopsy increased the risk of ESRD before (HR, 3.64, 95%CI, 1.47-7.55) and after adjusted by Oxford Scoring (HR, 2.92, 95%CI, 1.12-6.48) or international risk-prediction tool in IgA nephropathy (HR, 3.51, 95%CI, 1.41-7.29). Relevance analyses showed GBM thickening was positively correlated to mesangial hyperplasia and proliferation, but not genetic variants in IgAN patients.</p><p><strong>Conclusions: </strong>Thickening of GBM correlated with mesangial hyperplasia and proliferation was associated with ESRD in IgAN patients, demonstrating the potential of incorporating ultrastructural changes into the pathological evaluation system of IgAN.</p>","PeriodicalId":17882,"journal":{"name":"Kidney360","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145075506","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Complexity and Health Care Utilization in Infant ESKD.","authors":"Ashna R Pudupakkam, Michael C Braun, Catherine Joseph, Poyyapakkam R Srivaths, Sarah J Swartz, Shweta S Shah","doi":"10.34067/KID.0000000959","DOIUrl":"https://doi.org/10.34067/KID.0000000959","url":null,"abstract":"<p><strong>Background: </strong>Dialysis in neonates with ESKD is often associated with multiple comorbidities and the need for more intensified dialysis regimens. With recent advances in prenatal interventions and infant specific KRT, survival of neonates with ESKD has improved over the last decade. Little is known however about the impact on the health care system of improved survival in this population. Our primary aim was to investigate healthcare utilization in infants with ESKD.</p><p><strong>Methods: </strong>We conducted a retrospective review of infants with ESKD started on KRT during their initial neonatal admission at Texas Children's Hospital (TCH) from 2011 to 2022. The primary inclusion criteria were patients who initiated chronic dialysis in the Neonatal Intensive Care Unit (NICU) at TCH and survival to discharge. Data abstracted included patient demographics, number of hospitalizations and length of stays (LOS), comorbidities, pediatric sub-specialist care, and gross hospital charges related to the initial hospitalization, dialytic care, and care post-discharge up to the age of 2 years.</p><p><strong>Results: </strong>19 patients initiated dialysis in the NICU and were discharged on chronic dialysis: 68% were male, 79% had a gestational age ≥ 37 weeks, and 90% had a birth weight ≥2500 g. The average LOS for the initial hospitalization was 200 days (standard deviation of 48 days) with an average of 8 subspecialty consults. There were on average 5 admissions prior to age 2 years and 15 average outpatient visits per patient. The median cost of care for the initial hospitalization was $1.2 million with dialysis accounting for 16% of the total cost. The median aggregate cost of care post-discharge until age 2 years was $467,607.</p><p><strong>Conclusions: </strong>Infant ESKD is associated with significant healthcare utilization including hospitalizations, on-going non-nephrology sub-specialty care, and significant financial expenditures. Further investigation of healthcare utilization in this patient population can help guide the appropriate allocation of resources to support care delivery.</p>","PeriodicalId":17882,"journal":{"name":"Kidney360","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145023557","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Associations of Biomarkers of Kidney Tubule Health with Retinal Microvascular Signs: The Multi-Ethnic Study of Atherosclerosis (MESA).","authors":"Armin Ahmadi, Hassan Gorji, Sanskrita Shashikant, Ronit Katz, Alfons J H M Houben, Robert N Weinreb, Matthew Allison, Stacy M Meuer, Barbara E Klein, Mary Frances Cotch, Orlando M Gutierrez, Mark J Sarnak, Michael Shlipak, Joachim H Ix, Rakesh Malhotra","doi":"10.34067/KID.0000000970","DOIUrl":"https://doi.org/10.34067/KID.0000000970","url":null,"abstract":"<p><strong>Background: </strong>CKD is strongly associated with cardiovascular disease (CVD), yet the etiology responsible for this link remains elusive. Novel blood and urine biomarkers reflecting kidney tubule dysfunction and injury may provide novel insights to mechanisms linking the kidney to CVD.</p><p><strong>Methods: </strong>In 470 participants of the Multi-Ethnic Study of Atherosclerosis (MESA) without type 2 diabetes, CVD or CKD, we measured six plasma (kidney injury molecule-1 [KIM-1], monocyte chemoattractant protein-1 [MCP-1], soluble urokinase plasminogen activator receptor [suPAR], tumor necrosis factor receptor [TNFR] 1 and 2, and anti-chitinase-3-like protein 1 [YKL-40]) and six urinary (alpha 1 microglobulin [A-1M], epidermal growth factor [EGF], KIM-1, MCP-1, YKL-40 and uromodulin [UMOD]) kidney tubule health biomarkers. To assess microvascular health, we used retinal microvascular measurements assessed from fundus photography: central retinal arteriolar and venular equivalents (CRAE and CRVE, respectively). Multivariable linear regression evaluated associations of tubule biomarkers and kidney function with CRAE and CRVE.</p><p><strong>Results: </strong>The mean participant age was 60 ± 10 years with 52% female. The racial/ethnic distribution was 46% White, 24% African American, 18% Hispanic, and 11% Chinese. The mean eGFR was 92.1 ± 13.3 mL/min/1.73m2, and the median urine ACR was 4.7 mg/g (IQR 3.0, 9.4). Higher plasma KIM-1 (β -5.14, 95% confidence interval [95% CI], -9.84 to -0.45), and urine KIM-1 (β -5.68, 95% CI, -10.15 to -1.22) concentrations were individually associated with narrower CRAE, while plasma suPAR concentrations were individually associated with wider CRAE (β 9.15, 95% CI, 0.89 to 17.4) and CRVE (β 21.49, 95% CI, 9.39 to 33.59). There were no significant associations between the remaining tubule health biomarkers and CRAE or CRVE, nor were there associations between eGFR or urine ACR with CRAE and CRVE.</p><p><strong>Conclusions: </strong>In this study of community-living individuals without CKD, diabetes, or CVD, selected kidney tubule health markers are associated with retinal microvascular changes. These findings suggest that kidney tubules biomarkers may reflect or contribute to systemic microvascular dysfunction, above and beyond glomerular damage. Tubular biomarkers may help elucidate the shared microvascular mechanisms linking CKD and CVD.</p>","PeriodicalId":17882,"journal":{"name":"Kidney360","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145000893","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nephrology in Nepal: How it Started and Where We Are.","authors":"Deepak Sharma, Taranath Sharma, Jie Tang","doi":"10.34067/KID.0000000991","DOIUrl":"10.34067/KID.0000000991","url":null,"abstract":"<p><p>Nepal has made significant strides in nephrology, progressing from no dialysis services to offering comprehensive kidney care, including dialysis and transplantation. The journey began in the 1980s with the establishment of the first nephrology unit at Bir Hospital and has since grown to encompass over 60 dialysis centers and multiple transplant facilities. Government initiatives, such as financial subsidies and health insurance schemes, have increased accessibility, yet disparities persist due to workforce shortages, uneven infrastructure distribution, and inconsistent quality control in dialysis services. Pre-dialysis care remains underdeveloped, and challenges in adopting peritoneal dialysis persist due to socioeconomic and logistical barriers. The kidney transplant program, primarily reliant on living donors, has shown steady growth. Critical care nephrology and interventional services are gradually emerging. To advance, addressing workforce shortages, improving care quality, and expanding equitable access through strategic investments and global partnerships are essential.</p>","PeriodicalId":17882,"journal":{"name":"Kidney360","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144959360","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}