Kidney360最新文献

{"title":"Comparative Analysis of Human Kidney Organoid and Tubuloid Models.","authors":"Ana B Nunez-Nescolarde, Leilani L Santos, Lingyun Kong, Elif Ekinci, Paddy Moore, Evdokia Dimitriadis, David J Nikolic-Paterson, Alexander N Combes","doi":"10.34067/KID.0000000834","DOIUrl":"https://doi.org/10.34067/KID.0000000834","url":null,"abstract":"<p><strong>Background: </strong>Epithelial kidney organoids (tubuloids) made from kidney biopsies, urine, or iPSC-derived kidney organoids offer new opportunities in experimental and clinical nephrology. Yet, we have limited knowledge of how tubuloid models differ from each other, from iPSC-derived kidney organoids and from the human kidney. New insight is required to guide model selection for studies in kidney physiology and disease.</p><p><strong>Methods: </strong>Tubuloids were generated from adult nephrectomy samples (adult tubuloids n=3), iPSC-derived kidney organoids (iTubuloids n=3), and for the first time, from human fetal kidneys (fetal tubuloids n=3). Kidney organoid and tubuloid models were compared to each other and to adult human kidney using bulk RNA sequencing. As a proof of principle study, the potential to investigate the tubular response to repeated hypoxic insults was examined in iTubuloids.</p><p><strong>Results: </strong>Expression signatures of proximal and distal tubules were stronger in adult kidneys than any organoid or tubuloid model. iPSC-derived kidney organoids expressed proximal tubule markers at higher levels than any tubuloid culture, despite adult tubuloids being derived from mature kidneys. Collecting duct signatures were enriched in adult and fetal tubuloids. Adult tubuloids showed stronger signatures of ageing and inflammation, while fetal tubuloids had enhanced ureteric tip progenitor signatures. Over 80 genes linked to inherited disorders were expressed in all tubuloid cultures, while a further 54 were expressed at higher levels in either adult, fetal or iTubuloids. iTubuloids subject to a single hypoxic injury effectively recovered by the end of the passage, while cultures exposed to hypoxia over three passages expressed markers of maladaptive repair.</p><p><strong>Conclusions: </strong>This study provides new transcriptome-wide reference data to aid in the selection and optimization of disease modelling for the human kidney. It defines common and unique opportunities to model inherited disorders in adult, fetal and iTubuloid models and illustrates new potential to model repetitive injury in long-lived tubuloid cultures.</p>","PeriodicalId":17882,"journal":{"name":"Kidney360","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144150968","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":"Association of Kidney Biopsy Needle Gauge with Post-Procedure Complications and Biopsy Adequacy.","authors":"MaryKate Staunton, Kanika Garg, Sagar Sadarangani, Amrita Makhijani, Kyra Shelton, Emma Koval, Cathleen Liang, Melissa Shaw, Candice Kent, F Perry Wilson, Chirag R Parikh, Mark A Perazella, Jeffrey Turner, Randy Luciano, Dennis G Moledina","doi":"10.34067/KID.0000000835","DOIUrl":"https://doi.org/10.34067/KID.0000000835","url":null,"abstract":"<p><strong>Background: </strong>While a larger needle gauge can provide additional kidney tissue for diagnosis, it might also predispose to greater complication risk. Here, we evaluate the safety and diagnostic adequacy of kidney biopsies in patients who underwent a biopsy with various needle sizes.</p><p><strong>Methods: </strong>We evaluated rates of biopsy-related complications and adequacy between participants who underwent biopsy with 16G vs 18G needles. We assessed safety using a composite outcome of blood transfusion, angiographic intervention, hemoglobin drop of at least 2 g/dl, or at least a medium sized hematoma after kidney biopsy. We defined adequacy as the number of glomeruli available for diagnosis.</p><p><strong>Results: </strong>Among 781 participants included in the analysis, 665 (85%) were performed using a 16G needle and 116 (15%) were performed using an 18G needle. We observed similar odds of complications in the 16G group as compared to the 18G group in univariable analysis (odds ratio, 1.56 (95% confidence interval, 0.81, 3.01)); however, there were higher odds of complications in the 16G group in both multivariable analysis adjusting for pre-biopsy bleeding risk factors (2.40 (1.16, 4.93)) and propensity score weighted analysis (2.92 (1.28, 6.67)). As compared to 18G needle, 16G biopsy needle was associated with more glomeruli obtained (13 [9,19] vs. (11 [6,15], P<0.001). The higher number of glomeruli in 16G group persisted after multivariable adjustment (5.06 (2.52, 7.59)) and propensity score weighted (4.39 (0.37, 8.42)) analyses.</p><p><strong>Conclusions: </strong>Participants with kidney biopsies performed with a 16G needle tended to sample more glomeruli and had similar complications on univariable analysis but higher complications when adjusting for pre-biopsy risk factors. This indicates that larger needle gauge provided more tissue for diagnosis, but clinicians appropriately avoided its use in those at higher risk of complications. Our findings suggest that use of a 16G needle improves diagnostic yield but carries a higher adjusted risk of complications, underscoring the importance of individualized needle gauge selection.</p>","PeriodicalId":17882,"journal":{"name":"Kidney360","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144128030","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":"Indoxyl Sulfate Contributes to Selenium Deficiency and Renal Ferroptosis by Decreasing the Expression of Selenium Transport Protein SEPP1.","authors":"Takehiro Nakano, Yutaka Kitazato, Takumu Ogawa, Kai Tokumaru, Yuhi Shintani, Takuma Yoshitake, Kohei Yasuno, Hitoshi Maeda, Motoko Tanaka, Kazutaka Matsushita, Toru Maruyama, Hiroshi Watanabe","doi":"10.34067/KID.0000000837","DOIUrl":"https://doi.org/10.34067/KID.0000000837","url":null,"abstract":"<p><strong>Background: </strong>The relationship between the progression of chronic kidney disease (CKD) and trace element deficiencies has attracted considerable attention. However, many aspects of trace element deficiency and the molecular mechanisms of CKD pathology remain unclear. Here, we hypothesized that uremic toxins are involved in trace element deficiencies, which contribute to the progression of CKD.</p><p><strong>Methods: </strong>Adenine-induced CKD mice were used for in vivo study. Cultured hepatocytes were used for in vitro study.</p><p><strong>Results: </strong>Seventeen trace elements in the plasma of CKD mice were measured using inductively coupled plasma mass spectrometry. Among these, selenium was identified as the trace element most significantly affected by the administration of AST-120, an oral spherical activated carbon. CKD mice displayed reduced levels of selenium in the plasma, which was restored after the administration of AST-120. In vivo and in vitro experiments showed the uremic toxin indoxyl sulfate (IS) decreased expression of the selenium transport protein SEPP1 in liver. IS suppressed SEPP1 expression through increased production of reactive oxygen species (ROS) via the OATP/AhR/NADPH oxidase pathway. Increased ROS led to the downregulation of transcription factors for SEPP1, such as AMPK/PGC1-α and miR-34a/HNF4α. Analysis of serum from hemodialysis patients also suggested that IS is involved in reducing serum SEPP1 levels and exacerbating selenium deficiency. Combination therapy with AST-120 and sodium selenite restored the supply of selenium to the kidneys and increased GPX4 expression, thereby exerting renoprotective effects via suppression of ferroptosis.</p><p><strong>Conclusions: </strong>This study highlights the key role IS plays in selenium deficiency and renal ferroptosis by suppressing hepatic SEPP1 expression. The findings suggest potential therapeutic strategies that target IS and selenium deficiency for the management of CKD.</p>","PeriodicalId":17882,"journal":{"name":"Kidney360","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144128033","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":"Deceased Donor Transplantation in Telangana State, India: Overcoming Challenges in a Low Resource Country.","authors":"Swarnalatha Guditi, Urmila Anandh","doi":"10.34067/KID.0000000832","DOIUrl":"https://doi.org/10.34067/KID.0000000832","url":null,"abstract":"","PeriodicalId":17882,"journal":{"name":"Kidney360","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144078776","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":"KRT in Remote Extreme Area: The Case of Easter Island (Rapa Nui).","authors":"René Clavero, Carlos Schlack, Bernard Canaud","doi":"10.34067/KID.0000000833","DOIUrl":"https://doi.org/10.34067/KID.0000000833","url":null,"abstract":"","PeriodicalId":17882,"journal":{"name":"Kidney360","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144078782","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":"Protecting Individuals with Kidney Disease from Vaccine Preventable Infections.","authors":"Dorey A Glenn, Vimal K Derebail, Gia J Oh","doi":"10.34067/KID.0000000856","DOIUrl":"https://doi.org/10.34067/KID.0000000856","url":null,"abstract":"","PeriodicalId":17882,"journal":{"name":"Kidney360","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144078818","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":"The Rate of Procedures Required to Maintain Hemodialysis Vascular Access: A Data Linkage Analysis.","authors":"Katherine G Richards, Kevan R Polkinghorne, David O McGregor, Rachael C Walker, Curtis Walker, Jonathan A Williman, Suetonia C Green","doi":"10.34067/KID.0000000841","DOIUrl":"https://doi.org/10.34067/KID.0000000841","url":null,"abstract":"<p><strong>Background: </strong>Patients and clinicians prioritize the need for procedures to maintain hemodialysis vascular access as a core research outcome. The lack of procedural data in population datasets has limited certainty about the frequency of procedural events.</p><p><strong>Methods: </strong>This is a national linkage analysis of registry and administrative health data. We included all patients who started kidney replacement therapy between 2004 through 2021 in New Zealand, including data from two years prior to two years after hemodialysis commencement. The incidence rate of vascular access procedures per patient year was calculated and a multivariate flexible parametric model used to estimate associations with demographic and clinical variables.</p><p><strong>Results: </strong>In 7725 patients the average rate of vascular access procedures was 0.71 (95% CI 0.70-0.72) procedures per patient-year, median 2 (quartiles 1,3) procedures. The hazard of procedures associated with sex (adjusted hazard ratio (HR) female versus male 1.09; 95% CI 1.05, 1.13) and body mass index (HR 1.17; 95% CI 1.10, 1.24 BMI>35 kg/m2 versus 18.5-24.9). Patients in most recent treatment periods experienced lower procedural hazard (HR 0.77; 95% CI 0.73, 0.81 in 2017-2021 compared to 2002-2006), and the hazard varied among treating centers. Primary central venous catheter was associated with an increased procedural hazard (HR 1.34, 95% CI 1.28, 1.40) compared to primary arteriovenous fistula or graft.</p><p><strong>Conclusions: </strong>Half of adults underwent two or fewer hemodialysis vascular access procedures in the four-year period before and after hemodialysis commencement. Procedural rates differed by sex, body mass, treatment period and treatment center and were higher in adults with a primary central venous catheter.</p>","PeriodicalId":17882,"journal":{"name":"Kidney360","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144033609","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":"Association of Different Definitions of Erythropoiesis-Stimulating Agent Hyporesponsiveness with Major Adverse Cardiovascular Events: Insights From ASCEND-D.","authors":"Finnian R Mc Causland, Sushrut S Waikar, Brian Claggett, Gearoid M McMahon, Osvaldo M V Neto, Anjay Rastogi, Kearkiat Praditpornsilpa, Ricardo Correa-Rotter, Vijay Kher, Lucia Del Vecchio, Scott D Solomon, Ajay K Singh","doi":"10.34067/KID.0000000808","DOIUrl":"https://doi.org/10.34067/KID.0000000808","url":null,"abstract":"<p><strong>Background: </strong>Hyporesponsiveness to erythropoiesis-stimulating agents (ESAs) is a common clinical problem and is associated with major adverse cardiovascular events (MACE). Although several definitions have been proposed, data examining associations with MACE in clinical trials are limited.</p><p><strong>Methods: </strong>ASCEND-D (NCT02879305), a large event-driven cardiovascular outcomes trial, randomized 2,964 patients receiving maintenance dialysis to either daprodustat or conventional ESAs. All patients received an ESA for at least 6 weeks before randomization and were managed with dosing algorithms for iron and randomized treatment. Three definitions of ESA hyporesponsiveness were prespecified: 1) HypoR1: an erythropoietin resistance index (ERI) ≥2U/kg/wk/g/L or prior ESA dose/estimated dry weight ≥450 U/kg/wk; 2) HypoR2: ERI ≥1.5U/kg/wk/g/L; 3) HypoR3: baseline ESA dose (U/week) in top 20th percentile. Adjusted Cox regression models were fit to examine the association of each definition with the adjudicated MACE composite (death, non-fatal myocardial infarction, non-fatal stroke).</p><p><strong>Results: </strong>Baseline ESA hyporesponsiveness was present in 12%, 20%, and 20% of patients according to definitions HypoR1, HypoR2, and HypoR3, respectively. Compared to those without hyporesponsiveness, all definitions were associated with a higher risk of the composite MACE outcome: adjusted hazard ratio [HR] 1.32 (95%CI 1.04, 1.68) for HypoR1; HR 1.33; 95%CI 1.08, 1.63) for HypoR2; HR 1.36 (95%CI 1.12, 1.66) for HypoR3. There was no evidence for effect modification by randomized treatment (P-interaction >0.40 for all).</p><p><strong>Conclusions: </strong>Baseline ESA hyporesponsiveness is a potent predictor of MACE among patients receiving maintenance dialysis in ASCEND-D. All pre-specified definitions were similarly associated with a higher risk of MACE.</p>","PeriodicalId":17882,"journal":{"name":"Kidney360","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143989482","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":"Packed Red Blood Cell and Whole Blood Perfusates during Ex-Vivo Normothermic Perfusion for Assessment of High-Risk Donor Kidneys.","authors":"Armin Ahmadi, Heiko Yang, Kuang-Yu Jen, Sili Fan, Ivonne Palma, Junichiro Sageshima, Naeem Goussous, Baback Roshanravan, Richard V Perez","doi":"10.34067/KID.0000000815","DOIUrl":"https://doi.org/10.34067/KID.0000000815","url":null,"abstract":"<p><strong>Background: </strong>Ex-vivo normothermic perfusion (EVNP) with a blood based perfusate has the potential to both assess viability of and repair high-risk organs prior to transplantation. The optimal perfusate is yet to be established.</p><p><strong>Methods: </strong>We assessed hemodynamic, functional, and metabolic changes of eight paired high-risk human kidneys perfused with either a leukocyte-depleted packed red blood cell (PRBC) or a whole blood (WB) perfusate during a three-hour EVNP.</p><p><strong>Results: </strong>After a mean cold ischemia time (CIT) of 54 hours, all kidneys showed high renal blood flow (RBF) through perfusion. Renal resistance (RR) increased for both groups during the first hour and then decreased to similar terminal values. The kidneys perfused with PRBC had 55 ml/min greater RBF (95% CI of 21 to 89; P=0.004) and higher total urine output (UO) (145 vs 25 ml, P= 0.002) compared to the WB group. Urinary acute kidney biomarkers of NGAL and KIM-1 were also significantly lower (mean differences of 281 and 2.1 ng/ml respectively; P<0.01) in the PRBC perfused kidneys. Compared to PRBC, within group tissue metabolic profiling revealed a similar (23% vs 18%) but a more pronounced alteration involving (branched chain) amino acid and mitochondrial energy metabolism in the WB group. Similarly, lipid profile temporal changes showed WB group were highlighted by elevation of plasma membrane and structure lipids including glycerolipids, sphingolipids, and steroids. The PRBC group had minimal temporal tissue lipid profile changes.</p><p><strong>Conclusions: </strong>Compared to WB, PRBC perfusion is superior in mitigating post-ischemia damage and facilitating function and metabolic recovery of high-risk kidneys subjected to long CITs during a three-hour EVNP.</p>","PeriodicalId":17882,"journal":{"name":"Kidney360","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144017523","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":"Tubule-Specific Compensatory Responses to Cpt1a Deletion in Aged Mice.","authors":"Steven D Funk, Justin T Kern, Olga M Viquez, Elizabeth Sulvaran-Guel, Jeffrey R Koenitzer, Kyle C Feola, Jacob S Blum, Roy Zent, Benjamin D Humphreys, Sarah C Huen, Leslie S Gewin","doi":"10.34067/KID.0000000746","DOIUrl":"10.34067/KID.0000000746","url":null,"abstract":"","PeriodicalId":17882,"journal":{"name":"Kidney360","volume":" ","pages":"707-719"},"PeriodicalIF":3.2,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143730702","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}