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Journal of the American Society of Nephrology
Journal Prestige (SJR): 4.819  Citation Impact (citeScore): 7 Number of Followers: 39  Subscription journalISSN (Print) 1046-6673 - ISSN (Online) 1533-3450 Published by American Society of Nephrology  [2 journals]
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- Cover Image
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Authors: Xue; Rui; Yiu, Wai Han; Chan, Kam Wa; Lok, Sarah W.Y.; Zou, Yixin; Ma, Jingyuan; Li, Hongyu; Chan, Loretta Y.Y.; Huang, Xiao Ru; Lai, Kar Neng; Lan, Hui Yao; Tang, Sydney C.W.
Abstract:
No abstract available
PubDate: Thu, 01 Aug 2024 00:00:00 GMT-
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- Mendelian Randomization Unveils Drug Targets for IgA Nephropathy
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Authors: Khan; Atlas; Lim, Tze Y.; Sanna-Cherchi, Simone
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No abstract available
PubDate: Fri, 12 Jul 2024 00:00:00 GMT-
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- Does Our Classification System for CKD Serve the US Population Well'
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Authors: Kattah; Andrea G.; Rule, Andrew D.
Abstract: No abstract available
PubDate: Tue, 02 Jul 2024 00:00:00 GMT-
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- Can Kidney Care Be Sustainable'
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Authors: Piccoli; Giorgina Barbara; Cabiddu, Gianfranca
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No abstract available
PubDate: Tue, 02 Jul 2024 00:00:00 GMT-
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- Inflammasomes and Acute Kidney Injury
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Authors: Muruve; Daniel A.
Abstract: No abstract available
PubDate: Fri, 14 Jun 2024 00:00:00 GMT-
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- Lipolysis-Stimulated Lipoprotein Receptor in Proximal Tubule, BMP-SMAD
Signaling, and Kidney Disease-
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Authors: Jiang; Min; Wang, Xiangdong; Chen, Zhenni; Wang, Xin; An, Yanan; Ding, Lixia; Xu, Mengyuan; Fan, Baozhen; Jiao, Peng; Wang, Chao; Wang, Mingxia; Sun, Hui; Zhao, Shengtian; Gong, Yongfeng
Abstract:
Key Points We identify that lipolysis-stimulated lipoprotein receptor is highly enriched in the nucleus of mouse and human kidney.This study provides new insights into the role of lipolysis-stimulated lipoprotein receptor in kidney disease.Background Lipolysis-stimulated lipoprotein receptor (LSR) is a single-pass membrane protein that plays essential roles in tricellular tight junction organization in the epithelium and endothelium, but its function in kidney physiology and disease development remains unknown.Methods Conditional Lsr deletion mice were generated and analyzed to investigate the function of LSR in proximal tubule. Unilateral ischemia-reperfusion was used as an injury model to investigate the role of LSR in AKI and the progression to CKD. Detailed mechanistic analyses were conducted using whole-transcriptome RNA sequencing, immunofluorescence, dual-luciferase reporter gene assay, coimmunoprecipitation, RNA immunoprecipitation, and adeno-associated virus-mediated gene overexpression and knockdown.Results The nuclear localization of LSR was found in the kidney. Proximal tubule–specific Lsr knockout mice exhibited alleviated kidney damage and fibrosis compared with those in wild-type mice in response unilateral ischemia-reperfusion injury. Loss of LSR resulted in downregulation of Chrdl1 and activation of bone morphogenetic protein (BMP)-mothers against decapentaplegic homolog (SMAD) signaling in proximal tubules. Treatment with CHRDL1 counteracted the protective effect of LSR deletion in the unilaterally ischemic injured kidney. In addition, the systemic delivery of Chrdl1 short hairpin RNA attenuated injury-induced kidney fibrosis. LSR formed a complex with 14-3-3θ in the nucleus of proximal tubular cells, thereby reducing the interaction between human antigen R and 14-3-3θ, consequently leading to the translocation of unbound human antigen R to the cytoplasm. The absence of LSR promoted the association of 14-3-3θ with human antigen R, potentially resulting in decreased human antigen R levels in the cytoplasm. Reduced human antigen R levels impaired Chrdl1 mRNA stability, subsequently leading to the activation of BMP-SMAD signaling.Conclusions Deletion of LSR in proximal tubule deregulated Chrdl1 to activate BMP-SMAD signaling and ameliorated kidney disease.
PubDate: Wed, 29 May 2024 00:00:00 GMT-
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- Evolution of Biologically Related Living Kidney Donation in the United
States from 1988 to 2022-
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Authors: Al Ammary; Fawaz; Adeyemo, Simeon; Lentine, Krista L.; Muzaale, Abimereki D.
Abstract:
No abstract available
PubDate: Wed, 29 May 2024 00:00:00 GMT-
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- Correction: Sex Differences in Age-Related Loss of Kidney Function
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Abstract:
No abstract available
PubDate: Tue, 21 May 2024 00:00:00 GMT-
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- Climate Change, Kidney Health, and Environmentally Sustainable Kidney
Care: A Multinational Survey of Health Care Professionals-
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Authors: Sandal; Shaifali; Ethier, Isabelle; Onu, Ugochi; Fung, Winston; Bajpai, Divya; Bilchut, Workagegnehu Hailu; Bagasha, Peace; De Chiara, Letizia; Hafiz, Ehab; Smyth, Brendan; Kelly, Dearbhla; Pippias, Maria; Jha, Vivekanand
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Key Points A multinational survey of health care professionals on the kidney health impacts of climate change and the environmental burden of kidney care was conducted.Most participants reported knowledge gaps and high level of concern on these interconnected issues.Only a minority report personal or organizational initiatives in environmentally sustainable kidney care; this did not vary by country income level.Background Given the threat of climate change to kidney health and the significant environmental effect of kidney care, calls are increasing for health care professionals and organizations to champion climate advocacy and environmentally sustainable kidney care. Yet, little is known about their engagement, and existing literature is primarily emerging from high-income countries.Methods We conducted a cross-sectional survey to understand the knowledge, attitude, and practice of health care professionals on the interconnectedness of climate change and kidney health; to identify personal and organizational initiatives in sustainable kidney care and strategies to increase their engagement; and to compare responses by their country's income level as classified by the World Bank.Results Participants (n=972) represented 108 countries, with 64% from lower- or middle-income countries. Ninety-eight percent believed that climate change is happening, yet
PubDate: Mon, 20 May 2024 00:00:00 GMT-
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- Pharmacokinetic Issue May Influence the Perceived Cardiac Risk Posed by
Ondansetron in Patients Undergoing Chronic Hemodialysis-
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Authors: Hung; Kuo-Chin; Chao, Chia-Ter
Abstract: No abstract available
PubDate: Mon, 20 May 2024 00:00:00 GMT-
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- Authors' Reply: Pharmacokinetic Issue May Influence the Perceived Cardiac
Risk Posed by Ondansetron in Patients Undergoing Chronic Hemodialysis-
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Authors: Ismail; Sherin; Funk, Michele Jonsson; Flythe, Jennifer E.
Abstract: No abstract available
PubDate: Mon, 20 May 2024 00:00:00 GMT-
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- Individualized Risk of CKD Progression among US Adults
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Authors: Tio; Maria Clarissa; Butler, Javed; Zhu, Xiaoqian; Obi, Yoshitsugu; Yen, Timothy E.; Kalantar-Zadeh, Kamyar; Streja, Elani; Dossabhoy, Neville R.; Hall, Michael E.; Shafi, Tariq
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Key Points A total of 8.42 million US adults have high CKD progression risk, and 4.77 million of them have eGFR>60 ml/min per 1.73 m2.An individual's absolute risk of CKD progression is important in the diagnosis and prognostication of CKD.Background CKD is currently defined using GFR or albuminuria. This is on the basis of the relative risk of mortality and kidney outcomes compared with a healthy population and does not consider an individual's absolute risk of CKD progression.Methods Using National Health and Nutrition Examination Survey data from 1999 to 2020, we characterized the individual-level absolute 3-year risk of ≥40% decline in eGFR (ml/min per 1.73 m2) or kidney failure (3-year risk) among US adults. We categorized the 3-year risk and considered ≥5% as high risk.Results Among 199.81 million US adults, 8.42 million (4%) had a 3-year risk ≥5%, including 1.04 million adults without CKD (eGFR ≥60 and albuminuria
PubDate: Wed, 15 May 2024 00:00:00 GMT-
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- Clinical Trials for Kidney Disease in the Era of Personalized Medicine
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Authors: Heerspink; Hiddo J.L.; Kretzler, Matthias
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No abstract available
PubDate: Thu, 09 May 2024 00:00:00 GMT-
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- Defining, Understanding, and Addressing Postdialysis Fatigue: Takeaways
from a Scientific Workshop Hosted by the National Institutes of Health-
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Authors: Reddy; Yuvaram N.V.; O'Hare, Ann M.; Edwards, Dawn; Hall, Rasheeda
Abstract:
No abstract available
PubDate: Thu, 09 May 2024 00:00:00 GMT-
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- Complement Terminal Pathway Activation and Intrarenal Immune Response in
C3 Glomerulopathy-
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Authors: Meuleman; Marie-Sophie; Petitprez, Florent; Pickering, Matthew C.; Le Quintrec, Moglie; Artero, Mikel Rezola; Duval, Anna; Rabant, Marion; Gilmore, Alyssa; Boyer, Olivia; Hogan, Julien; Servais, Aude; Provot, François; Gnemmi, Vivianne; Eloudzeri, Maeva; Grunenwald, Anne; Buob, David; Boffa, Jean-Jacques; Moktefi, Anissa; Audard, Vincent; Goujon, Jean-Michel; Bridoux, Frank; Thervet, Eric; Karras, Alexandre; Roumenina, Lubka T.; Frémeaux Bacchi, Véronique; Duong Van Huyen, Jean-Paul; Chauvet, Sophie
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Key Points We evidenced terminal pathway activation (C5b-9 deposits) in most of the glomeruli on kidney biopsy of C3 glomerulopathy.The amount of C5b-9 deposits correlated with disease prognosis in C3 glomerulopathy.Increased terminal pathway activation was found predominantly in a subgroup exhibiting an immuno-fibroblastic signature.Background C3 glomerulopathy is a rare disease resulting from an overactivation of the complement alternative pathway. Although there is also evidence of terminal pathway activation, its occurrence and consequences on the disease have been poorly studied.Methods We retrospectively studied a cohort of 42 patients diagnosed with C3 glomerulopathy. We performed centralized extensive characterization of histological parameters. Kidney C5b-9 staining was performed as a marker of terminal pathway activation; intrarenal immune response was characterized through transcriptomic analysis.Results Eighty-eight percent of biopsies showed C5b-9 deposits in glomeruli. Biopsies were grouped according to the amount of C5b-9 deposits (no or low n=15/42, 36%; intermediate n=15/42, 36%; and high n=12/42, 28%). Patients with high C5b-9 deposits significantly differed from the two other groups of patients and were characterized by a significant higher histological chronicity score (P = 0.005) and lower outcome-free survival (P = 0.001). In multivariable analysis, higher glomerular C5b-9 remained associated with poor kidney prognosis after adjustment. One third of the 847 studied immune genes were upregulated in C3 glomerulopathy biopsies compared with controls. Unsupervised clustering on differentially expressed genes identified a group of kidney biopsies enriched in high glomerular C5b-9 with high immune and fibroblastic signature and showed high chronicity scores on histological examination.Conclusions In a cohort of patients with C3 glomerulopathy, intrarenal terminal pathway activation was associated with specific histological phenotype and disease prognosis.
PubDate: Mon, 06 May 2024 00:00:00 GMT-
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- Single-Cell Transcriptional Signatures of Glomerular Disease in Transgenic
Mice with APOL1 Variants-
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Authors: Yoshida; Teruhiko; Latt, Khun Zaw; Santo, Briana A.; Shrivastav, Shashi; Zhao, Yongmei; Fenaroli, Paride; Chung, Joon-Yong; Hewitt, Stephen M.; Tutino, Vincent M.; Sarder, Pinaki; Rosenberg, Avi Z.; Winkler, Cheryl A.; Kopp, Jeffrey B.
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Key Points Apolipoprotein L1 (APOL1)-G1 induced kidney disease in the two APOL1 transgenic mouse models, HIV-associated nephropathy and IFN-γ administration.Glomerular single-nuclear RNA-sequencing identified genes differentially expressed among mice with APOL1-G1 and G0 variants at single-cell resolution.Background Apolipoprotein L1 (APOL1) high-risk variants contribute to kidney disease among individuals with African ancestry. We sought to describe cell-specific APOL1 variant–induced pathways using two mouse models.Methods We characterized bacterial artificial chromosome/APOL1 transgenic mice crossed with HIV-associated nephropathy (HIVAN) Tg26 mice and bacterial artificial chromosome/APOL1 transgenic mice given IFN-γ.Results Both mouse models showed more severe glomerular disease in APOL1-G1 compared with APOL1-G0 mice. Synergistic podocyte-damaging pathways activated by APOL1-G1 and by the HIV transgene were identified by glomerular bulk RNA sequencing (RNA-seq) of HIVAN model. Single-nuclear RNA-seq revealed podocyte-specific patterns of differentially expressed genes as a function of APOL1 alleles. Shared activated pathways, for example, mammalian target of rapamycin, and differentially expressed genes, for example, Ccn2, in podocytes in both models suggest novel markers of APOL1-associated kidney disease. HIVAN mouse-model podocyte single-nuclear RNA-seq data showed similarity to human focal segmental glomerulosclerosis glomerular RNA-seq data. Differential effects of the APOL1-G1 variant on the eukaryotic initiation factor 2 pathway highlighted differences between the two models.Conclusions These findings in two mouse models demonstrated both shared and distinct cell type–specific transcriptomic signatures induced by APOL1 variants. These findings suggest novel therapeutic opportunities for APOL1 glomerulopathies.
PubDate: Mon, 06 May 2024 00:00:00 GMT-
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- The Role of Genetic Testing in Adult CKD
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Authors: Knoers; Nine V.A.M.; van Eerde, Albertien M.
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Mounting evidence indicates that monogenic disorders are the underlying cause in a significant proportion of patients with CKD. In recent years, the diagnostic yield of genetic testing in these patients has increased significantly as a result of revolutionary developments in genetic sequencing techniques and sequencing data analysis. Identification of disease-causing genetic variant(s) in patients with CKD may facilitate prognostication and personalized management, including nephroprotection and decisions around kidney transplantation, and is crucial for genetic counseling and reproductive family planning. A genetic diagnosis in a patient with CKD allows for screening of at-risk family members, which is also important for determining their eligibility as kidney transplant donors. Despite evidence for clinical utility, increased availability, and data supporting the cost-effectiveness of genetic testing in CKD, especially when applied early in the diagnostic process, many nephrologists do not use genetic testing to its full potential because of multiple perceived barriers. Our aim in this article was to empower nephrologists to (further) implement genetic testing as a diagnostic means in their clinical practice, on the basis of the most recent insights and exemplified by patient vignettes. We stress why genetic testing is of significant clinical benefit to many patients with CKD, provide recommendations for which patients to test and which test(s) to order, give guidance about interpretation of genetic testing results, and highlight the necessity for and essential components of pretest and post-test genetic counseling.
PubDate: Mon, 06 May 2024 00:00:00 GMT-
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- Long Non-coding RNA NEAT1, NOD-Like Receptor Family Protein 3
Inflammasome, and Acute Kidney Injury-
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Authors: Xue; Rui; Yiu, Wai Han; Chan, Kam Wa; Lok, Sarah W.Y.; Zou, Yixin; Ma, Jingyuan; Li, Hongyu; Chan, Loretta Y.Y.; Huang, Xiao Ru; Lai, Kar Neng; Lan, Hui Yao; Tang, Sydney C.W.
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Key Points Long non-coding RNA (lncRNA) nuclear-enriched abundant transcript 1 (NEAT1) was upregulated in human and murine AKI. It returned to baseline after recovery in humans. Its knockdown preserved kidney function in animals.In vitro, LPS upregulated NEAT1 by TLR4/NF-κB signaling and caused its translocation into the cytoplasm where it activated nucleotide oligomerization domain-like receptor family protein 3 by binding receptor of activated protein C kinase 1.Background AKI is common in hospitalized patients and is associated with high mortality. Inflammation plays a key role in the pathophysiology of AKI. Long non-coding RNAs (lncRNAs) are increasingly recognized as regulators of the inflammatory and immune response, but its role in AKI remains unclear.Methods We explored the role of lncRNA nuclear-enriched abundant transcript 1 (NEAT1) in (1) a cross-sectional and longitudinal cohort of AKI in humans, (2) three murine models of septic and aseptic AKI, and (3) cultured C1.1 mouse kidney tubular cells.Results In humans, hospitalized patients with AKI (N=66) demonstrated significantly higher lncRNA NEAT1 levels in urinary sediment cells and buffy coat versus control participants (N=152) from a primary care clinic; among six kidney transplant recipients, NEAT1 levels were the highest immediately after transplant surgery, followed by a prompt decline to normal levels in parallel with recovery of kidney function. In mice with AKI induced by sepsis (by LPS injection or cecal ligation and puncture) and renal ischemia-reperfusion, kidney tubular Neat1 was increased versus sham-operated mice. Knockdown of Neat1 in the kidney using short hairpin RNA preserved kidney function and suppressed overexpression of the AKI biomarker neutrophil gelatinase-associated lipocalin, leukocyte infiltration, and both intrarenal and systemic inflammatory cytokines IL-6, CCL-2, and IL-1β. In LPS-treated C1.1 cells, Neat1 was overexpressed by TLR4/NF-κB signaling and translocated from the cell nucleus into the cytoplasm where it promoted activation of nucleotide oligomerization domain-like receptor family protein 3 inflammasomes by binding with the scaffold protein receptor of activated protein C kinase 1. Silencing Neat1 ameliorated LPS-induced cell inflammation, whereas its overexpression upregulated IL-6 and CCL-2 expression even without LPS stimulation.Conclusions Our findings demonstrate a pathogenic role of NEAT1 induction in human and mice during AKI with alleviation of kidney injury in three experimental models of septic and aseptic AKI after knockdown of Neat1. LPS/TLR4-induced Neat1 overexpression in tubular epithelial cells increased the inflammatory response by binding with the scaffold protein, receptor of activated protein C kinase 1, to activate nucleotide oligomerization domain-like receptor family protein 3 inflammasomes.
PubDate: Tue, 30 Apr 2024 00:00:00 GMT-
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- Circulating Proteins and IgA Nephropathy: A Multiancestry Proteome-Wide
Mendelian Randomization Study-
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Authors: Tang; Chen; Chen, Pei; Xu, Lin-Lin; Lv, Ji-Cheng; Shi, Su-Fang; Zhou, Xu-Jie; Liu, Li-Jun; Zhang, Hong
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Key Points A multiancestry proteome-wide Mendelian randomization analysis was conducted for IgA nephropathy.The findings from the study would help prioritize new drug targets and drug-repurposing opportunities.Background The therapeutic options for IgA nephropathy are rapidly evolving, but early diagnosis and targeted treatment remain challenging. We aimed to identify circulating plasma proteins associated with IgA nephropathy by proteome-wide Mendelian randomization studies across multiple ancestry populations.Methods In this study, we applied Mendelian randomization and colocalization analyses to estimate the putative causal effects of 2615 proteins on IgA nephropathy in Europeans and 235 proteins in East Asians. Following two-stage network Mendelian randomization, multitrait colocalization analysis and protein-altering variant annotation were performed to strengthen the reliability of the results. A protein–protein interaction network was constructed to investigate the interactions between the identified proteins and the targets of existing medications.Results Putative causal effects of 184 and 13 protein–disease pairs in European and East Asian ancestries were identified, respectively. Two protein–disease pairs showed shared causal effects across them (CFHR1 and FCRL2). Supported by the evidence from colocalization analysis, potential therapeutic targets were prioritized and four drug-repurposing opportunities were suggested. The protein–protein interaction network further provided strong evidence for existing medications and pathways that are known to be therapeutically important.Conclusions Our study identified a number of circulating proteins associated with IgA nephropathy and prioritized several potential drug targets that require further investigation.
PubDate: Tue, 30 Apr 2024 00:00:00 GMT-
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- American Society of Nephrology Efforts to Address Challenges Highlighted
in Recent Joint Global Consensus Statement Issued with European Renal
Association and International Society of Nephrology-
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Authors: Murray; Ryan; Roy-Chaudhury, Prabir; Parikh, Samir
Abstract: No abstract available
PubDate: Tue, 30 Apr 2024 00:00:00 GMT-
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- The Carbon Footprint of Peritoneal Dialysis in Australia
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Authors: McAlister; Scott; Talbot, Ben; Knight, John; Blair, Susan; McGain, Forbes; McDonald, Stephen; Nelson, Craig; Knight, Richard; Barraclough, Katherine A.
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Key Points Automated peritoneal dialysis (APD) had a higher carbon impact than continuous ambulatory peritoneal dialysis (CAPD).This was due to higher emissions from the manufacture and disposal of APD consumables, and their higher weight, meaning greater transport emissions.Polyvinyl chloride recycling can partially mitigate peritoneal dialysis–associated emissions.Background As climate change escalates with increasing health impacts, health care must address its carbon footprint. The first critical step is understanding the sources and extent of emissions from commonly utilized clinical care pathways.Methods We used attributional process-based life-cycle analysis to quantify CO2 equivalent emissions associated with the delivery of Baxter’s HomeChoice automated peritoneal dialysis (APD) and continuous ambulatory peritoneal dialysis (CAPD) in Australia.Results The annual per-patient carbon emissions attributable to the manufacture and disposal of peritoneal dialysis (PD) fluids and consumables were 1992 kg CO2 equivalent emissions for APD and 1245 kg CO2 equivalent emissions for CAPD. Transport impacts varied depending on the distance between the site of manufacture of PD fluids and consumables and the state of origin of the patient. Therefore, the total impact of providing PD also differed by Australian state, ranging from 2350 to 4503 kg CO2 equivalent emissions for APD and from 1455 to 2716 kg CO2 equivalent emissions for CAPD. Recycling of polyvinyl chloride (PVC) could reduce emissions by up to 14% for APD and 30% for CAPD depending on the distance between the site of PVC waste generation and the recycling center.Conclusions This study demonstrated higher per-patient carbon emissions from APD compared with CAPD, owing to both higher fluid and consumable requirements and the consequent higher transport impacts. PVC recycling can partially mitigate PD-associated carbon emissions.
PubDate: Fri, 26 Apr 2024 00:00:00 GMT-
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- An Innovation Ecosystem: The Center for Dialysis Innovation (CDI)
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Authors: Himmelfarb; Jonathan; Ratner, Buddy D.
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No abstract available
PubDate: Mon, 08 Apr 2024 00:00:00 GMT-
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