Yajas Shah, Hua Yang, Franco B Mueller, Carol Li, Shab E Gul Rahim, Elly Varma, Thalia Salinas, Darshana M Dadhania, Steven Salvatore, Surya V Seshan, Vijay K Sharma, Olivier Elemento, Manikkam Suthanthiran, Thangamani Muthukumar
Natural killer (NK) cells mediate spontaneous cell-mediated cytotoxicity and antibody-dependent cell-mediated cytotoxicity. This dual functionality could enable their participation in chronic active antibody-mediated rejection (CA-ABMR). Earlier microarray profiling studies have not subcategorized antibody-mediated rejection into CA-ABMR and active-ABMR, and the gene expression pattern of CA-ABMR has not been compared with that of T cell-mediated rejection (TCMR). To fill these gaps, we RNA sequenced human kidney allograft biopsies categorized as CA-ABMR, active-ABMR, TCMR, or No Rejection (NR)...
November 29, 2023: Kidney International
Marta Mariniello, Guglielmo Schiano, Ayumi Yoshifuji, Valentine Gillion, John Andrew Sayer, François Jouret, Yannick Le Meur, Emilie Cornec-Le Gall, Eric Gregory Olinger, Olivier Devuyst
No abstract text is available yet for this article.
November 26, 2023: Kidney International
Katya Loban, Elie Fadel, Peter Nugus, Antoine Przybylak-Brouillard, Heather Badenoch, Jorane-Tiana Robert, Ann Bugeja, Justin Gill, Marie-Chantal Fortin, Charo Rodriguez, Shaifali Sandal
No abstract text is available yet for this article.
November 24, 2023: Kidney International
Yuzhou Zhang, Bertha Martin, M Ashley Spies, Sarah M Roberts, Joel Nott, Renee X Goodfellow, Angela Fm Nelson, Samantha J Blain, Elena Redondo, Carla M Nester, Richard Jh Smith
Renin, an aspartate protease, regulates the renin-angiotensin system by cleaving its only known substrate angiotensinogen to angiotensin. Recent studies have suggested that renin may also cleave complement component C3 to activate complement or contribute to its dysregulation. Typically, C3 is cleaved by C3 convertase, a serine protease that uses the hydroxyl group of a serine residue as a nucleophile. Here, we provide seven lines of evidence to show that renin does not cleave C3. First, there is no association between renin plasma levels and C3 levels in patients with C3 Glomerulopathies (C3G) and atypical Hemolytic Uremic Syndrome (aHUS), implying that serum C3 consumption is not increased in the presence of high renin...
November 24, 2023: Kidney International
David Wimbury, Masahiro Muto, Jasraj S Bhachu, Katrin Scionti, Jeremy Brown, Karen Molyneux, Claudia Seikrit, Dita Maixnerová, Laura Pérez-Alós, Peter Garred, Jürgen Floege, Vladimír Tesař, Bengt Fellstrom, Rosanna Coppo, Jonathan Barratt
No abstract text is available yet for this article.
November 24, 2023: Kidney International
V A Luyckx, S Alasfar, D Bajpai, C E Atwater, J Knight, B Talbot, S Davies, A Niang
Healthcare on a global scale significantly contributes to carbon emissions, with high-income countries being the primary culprits. Within healthcare, dialysis plays a significant role as a major source of emissions. Low- and middle-income countries have a high burden of kidney disease, and are facing an increasing demand for dialysis. This reality presents multiple opportunities to plan for environmentally sustainable and quality kidney care. By placing a stronger emphasis on primary and secondary prevention of kidney disease and its progression, within the framework of universal health coverage, as well as empowering patients to enhance self-care, we can significantly reduce the need for costly and environmentally detrimental kidney replacement therapy...
November 24, 2023: Kidney International
Nora Fino, Ogechi M Adingwupu, Josef Coresh, Tom Greene, Ben Haaland, Michael G Shlipak, Veronica T Costa E Silva, Roberto Kalil, Ayse L Mindikoglu, Susan L Furth, Jesse C Seegmiller, Andrew S Levey, Lesley A Inker
Creatinine and cystatin-C are recommended for estimating glomerular filtration rate (eGFR) but accuracy is suboptimal. Here, using untargeted metabolomics data, we sought to identify candidate filtration markers for a new targeted assay using a novel approach based on their maximal joint association with measured GFR (mGFR) and with flexibility to consider their biological properties. We analyzed metabolites measured in seven diverse studies encompasing 2,851 participants on the Metabolon H4 platform that had Pearson correlations with log mGFR and used a stepwise approach to develop models to < -0...
November 23, 2023: Kidney International
Stefan Haug, Selvaraj Muthusamy, Yong Li, Galen Stewart, Xianwu Li, Martin Treppner, Anna Köttgen, Shreeram Akilesh
The kidney medulla is a specialized region with important homeostatic functions. It has been implicated in genetic and developmental disorders along with ischemic and drug-induced injuries. Despite its role in kidney function and disease, the medulla's baseline gene expression and epigenomic signatures have not been well described in the adult human kidney. Here we generated and analyzed gene expression (RNA-seq), chromatin accessibility (ATAC-seq), chromatin conformation (Hi-C) and spatial transcriptomic data from the adult human kidney cortex and medulla...
November 21, 2023: Kidney International
Valeryia Kuzmuk, Iwona Pranke, Ruth Rollason, Matthew Butler, Wen Y Ding, Matthew Beesley, Aoife M Waters, Richard J Coward, Richard Sessions, Jack Tuffin, Rebecca R Foster, Géraldine Mollet, Corinne Antignac, Aleksander Edelman, Gavin I Welsh, Moin A Saleem
Podocin is a key membrane scaffolding protein of the kidney podocyte essential for intact glomerular filtration. Mutations in NPHS2, the podocin-encoding gene, represent the commonest form of inherited nephrotic syndrome (NS), with early, intractable kidney failure. The most frequent podocin gene mutation in European children is R138Q, causing retention of the misfolded protein in the endoplasmic reticulum. Here, we provide evidence that podocin R138Q (but not wild-type podocin) complexes with the intermediate filament protein keratin 8 (K8) thereby preventing its correct trafficking to the plasma membrane...
November 21, 2023: Kidney International
Jeffrey A Beamish, Asha C Telang, Madison C McElliott, Anas Al-Suraimi, Mahboob Chowdhury, Jenna T Ference-Salo, Edgar A Otto, Rajasree Menon, Abdul Soofi, Joel M Weinberg, Sanjeevkumar R Patel, Gregory R Dressler
Acute kidney injury (AKI) is a common condition that lacks effective treatments. In part, this shortcoming is due to an incomplete understanding of the genetic mechanisms that control pathogenesis and recovery. Identifying the molecular and genetic regulators unique to nephron segments that dictate vulnerability to injury and regenerative potential could lead to new therapeutic targets to treat ischemic kidney injury. Pax2 and Pax8 are homologous transcription factors with overlapping functions that are critical for kidney development and are re-activated in AKI...
November 15, 2023: Kidney International
E Taber-Hight, A Gilmore, A N Friedman
Obesity is a leading risk factor for the development and progression of kidney disease and a major barrier to optimal management of patients with CKD. While in the past antiobesity drugs offered only modest weight loss efficacy in exchange for a variety of safety and tolerability risks, a wave of safer, more tolerable, and far more effective treatment options is transforming the management of obesity. This review evaluates current and future pharmacologic antiobesity therapy in adults through a kidney-oriented lens...
November 3, 2023: Kidney International
Zhengzi Yi, Caixia Xi, Madhav C Menon, Paolo Cravedi, Fasika Tedla, Alan Soto, Zeguo Sun, Keyu Liu, Jason Zhang, Chengguo Wei, Man Chen, Wenlin Wang, Brandon Veremis, Monica Garcia-Barros, Abhishek Kumar, Danielle Haakinson, Rachel Brody, Evren U Azeloglu, Lorenzo Gallon, Philip O'Connell, Maarten Naesens, Ron Shapiro, Robert Colvin, Stephen Ward, Fadi Salem, Weijia Zhang
Lesion scores on procurement donor biopsies are commonly used to guide organ utilization for deceased-donor kidneys. However, frozen sections present challenges for histological scoring, leading to inter- and intra-observer variability and inappropriate discard. Therefore, we constructed deep-learning based models to recognize kidney tissue compartments in hematoxylin &eosin-stained sections from procurement needle biopsies performed nationwide in years 2011-2020. To do this, we extracted whole-slide abnormality features from 2431 kidneys and correlated with pathologists' scores and transplant outcomes...
November 3, 2023: Kidney International
Minho Eun, Donggun Kim, So-I Shin, Hyun Oh Yang, Kyoung-Dong Kim, Sin Young Choi, Sehoon Park, Kyung Chul Moon, Dong Ki Kim, Hajeong Lee, Jihwan Park
Diabetes is the leading cause of kidney disease that progresses to kidney failure. However, the key molecular and cellular pathways involved in diabetic kidney disease (DKD) pathogenesis are largely unknown. Here, we performed a comparative analysis of adult human kidneys by examining cell type-specific chromatin accessibility by single-nucleus ATAC-seq (snATAC-seq) and analyzing three-dimensional chromatin architecture via high-throughput chromosome conformation capture (Hi-C method) of paired samples. We mapped the cell type-specific and DKD-specific open chromatin landscape and found that genetic variants associated with kidney diseases were significantly enriched in the proximal tubule- (PT) and injured PT-specific open chromatin regions in samples from patients with DKD...
November 2, 2023: Kidney International
Laura Lucientes-Continente, Gema Fernández-Juárez, Bárbara Márquez-Tirado, Laura Jiménez-Villegas, Mercedes Acevedo, Teresa Cavero, Luís Sánchez Cámara, Juliana Draibe, Paula Anton-Pampols, Fernando Caravaca-Fontán, Manuel Praga, Javier Villacorta, Elena Goicoechea de Jorge
Activation of the alternative pathway (AP) of complement is involved in the pathogenesis of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), although the underlying molecular mechanisms are unclear. To gain insight into the role of the AP, common gene variants in CFH/CFHR1-5, CFB, C3 and MCP, and longitudinal determinations of plasma C3, C4, FH, FHR-1, FHR-2, FHR-5, FB, properdin and sC5b-9 levels were analyzed in a Spanish AAV cohort consisting of 102 patients; 54 with active AAV (active cohort) and 48 in remission not receiving immunosuppressants or dialysis therapy (remission cohort)...
November 1, 2023: Kidney International
Etienne Cavalier, Jordi Farré-Segura, Pierre Lukas, Anne-Sophie Gendebien, Stéphanie Peeters, Philippe Massonnet, Caroline Le Goff, Antoine Bouquegneau, Jean-Claude Souberbielle, Vincent Delatour, Pierre Delanaye
Precise determination of circulating parathyroid hormone (PTH) concentration is crucial to diagnose and manage various disease conditions, including the chronic kidney diseases-mineral and bone disorder. However, the lack of standardization in PTH assays is challenging for clinicians, potentially leading to medical errors because the different assays do not provide equivalent results and use different reference ranges. Here, we aimed to evaluate the impact of recalibrating PTH immunoassays by means of a recently developed LC-MS/MS method as the reference...
October 31, 2023: Kidney International
Wesley N Hayes, Emma Laing, Rosemary Brown, Laura Silsby, Laura Smith, Helen Thomas, Fotini Kaloyirou, Rupa Sharma, James Griffiths, Helen Hume-Smith, Stephen D Marks, Nicos Kessaris, Martin Christian, Jan Dudley, Mohan Shenoy, Michal Malina, Mordi Muorah, Nicholas Ware, Pallavi Yadav, Ben Reynolds, William Bryant, Anastassia Spiridou, Jo Wray, Mark J Peters
Acute electrolyte and acid-base imbalance is experienced by many children following kidney transplant. This is partly because doctors give very large volumes of artificial fluids to keep the new kidney working. When severe, fluid imbalance can lead to seizures, cerebral edema and death. In this pragmatic, open-label, randomized controlled trial, we randomly assigned (1:1) pediatric kidney transplant recipients to Plasma-Lyte-148 or standard of care perioperative intravenous fluids (predominantly 0.45% sodium chloride and 0...
October 30, 2023: Kidney International
Xiaoxue Li, Aiting Liu, Chen Xie, Yanlian Chen, Kuan Zeng, Changming Xie, Zhengzhipeng Zhang, Pei Luo, Hui Huang
Arterial calcification is a hallmark of vascular pathology in the elderly and in individuals with chronic kidney disease (CKD). Vascular smooth muscle cells (VSMCs), after attaining a senescent phenotype, are implicated in the calcifying process. However, the underlying mechanism remains to be elucidated. Here, we reveal an aberrant upregulation of transcriptional factor GATA6 in the calcified aortas of humans, mice with CKD and mice subjected to vitamin D3 injection. Knockdown of GATA6, via recombinant adeno-associated virus carrying GATA6 shRNA, inhibited the development of arterial calcification in mice with CKD...
October 30, 2023: Kidney International
Hong Zhang, Dana V Rizk, Vlado Perkovic, Bart Maes, Naoki Kashihara, Brad Rovin, Hernán Trimarchi, Ben Sprangers, Matthias Meier, Dmitrij Kollins, Olympia Papachristofi, Julie Milojevic, Guido Junge, Prasanna Kumar Nidamarthy, Alan Charney, Jonathan Barratt
Targeting the alternative complement pathway is an attractive therapeutic strategy given its role in the pathogenesis of immunoglobulin A nephropathy (IgAN). Iptacopan (LNP023) is an oral, proximal alternative complement inhibitor that specifically binds to Factor B. Our randomized, double-blind, parallel-group adaptive Phase 2 study (NCT03373461) enrolled patients with biopsy-confirmed IgAN (within previous three years) with estimated glomerular filtration rates of 30 mL/min/1.73 m2 and over and urine protein 0...
October 30, 2023: Kidney International
John S Gill, Steven J Chadban, John S Gill
Declining rates of peri-transplant cardiovascular death, an increasing burden of pre-transplant tests and concerns over the effectiveness of screening candidates for coronary artery disease have led many transplant programs to de-escalate screening protocols. Recent KDIGO and American Heart Association scientific statements and guidelines neatly summarize current evidence, but also identify areas of need. Here, we argue that key questions should be addressed by adequately powered clinical trials before our long-held screening paradigms are completely re-written...
October 30, 2023: Kidney International
Kazuki Sasaki, Masahiko Kubo, Yu-Chao Wang, Lien Lu, Veronica Vujevich, Michelle A Wood-Trageser, Kayla Golnoski, Andrew Lesniak, Vikraman Gunabushanam, Armando Ganoza, Martin J Wijkstrom, Abhinav Humar, Anthony J Demetris, Angus W Thomson, Mohamed B Ezzelarab
Clinical verification of adoptively transferred regulatory T cell (Treg) efficacy in transplantation remains challenging. Here, we examined the influence of autologous ex vivo-expanded polyclonal Tregs on kidney graft survival in a clinically relevant non-human primate model. Peripheral blood Tregs were isolated and expanded using artificial antigen presenting cells. Immunosuppression was comprised of tapered tacrolimus and CTLA4 immunoglobulin, in five animals each without or with Treg infusions. Escalating Treg doses were administered 6, 10, 13, 16, 20, 23, 27 and 30 days after transplant...
October 14, 2023: Kidney International
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