A proteomic atlas of kidney amyloidosis provides insights into disease pathogenesis
This study encompassed 2650 cases of amyloidosis due to light chain (AL), heavy chain (AH), leukocyte chemotactic factor-2-type (ALECT2), secondary (AA), fibrinogen (AFib), apo AIV (AApoAIV), apo CII (AApoCII) and 14 normal/disease controls. (Source: Kidney International)
Source: Kidney International - December 11, 2023 Category: Urology & Nephrology Authors: Charalampos Charalampous, Surendra Dasari, Ellen McPhail, Jason D. Theis, Julie A. Vrana, Angela Dispenzieri, Nelson Leung, Eli Muchtar, Morie Gertz, Marina Ramirez-Alvarado, Taxiarchis Kourelis Tags: Basic Research Source Type: research
Autosomal dominant ApoA4 mutations present as tubulointerstitial kidney disease with medullary amyloidosis.
Sporadic cases of apolipoprotein A-IV medullary amyloidosis have been reported. Here we describe five families found to have autosomal dominant medullary amyloidosis due to two different pathogenic APOA4 variants. A large family with autosomal dominant chronic kidney disease (CKD) and bland urinary sediment underwent whole genome sequencing with identification of a chr11:116692578 G>C (hg19) variant encoding the missense mutation p.L66V of the ApoA4 protein. We identified two other distantly related families from our registry with the same variant and two other distantly related families with a ch11:116693454 C>T (hg19) va...
Source: Kidney International - December 11, 2023 Category: Urology & Nephrology Authors: Tereza Kmochov á, Kendrah O. Kidd, Andrew Orr, Aleš Hnízda, Hana Hartmannová, Kateřina Hodaňová, Petr Vyleťal, Karolína Naušová, Vítězslav Brinsa, Helena Trešlová, Jana Sovová, Veronika Barešová, Klára Svojšová, Alena Vrbacká, Viktor Tags: clinical investigation Source Type: research
A proteomic atlas of kidney amyloidosis provides insights into disease pathogenesis.
This study encompassed 2650 cases of amyloidosis due to light chain (AL), heavy chain (AH), leukocyte chemotactic factor-2-type (ALECT2), secondary (AA), fibrinogen (AFib), apo AIV (AApoAIV), apo CII (AApoCII) and 14 normal/disease controls. (Source: Kidney International)
Source: Kidney International - December 11, 2023 Category: Urology & Nephrology Authors: Charalampous Charalampos, Dasari Surendra, McPhail Ellen, Theis D. Jason, Vrana A. Julie, Dispenzieri Angela, Leung Nelson, Muchtar Eli, Gertz Morie, Ramirez-Alvarado Marina, Kourelis Taxiarchis Tags: basic research Source Type: research
Glucagon-like peptide-1 receptor signaling modifies the extent of diabetic kidney disease through dampening the receptor for advanced glycation end products –induced inflammation
Glucagon like peptide-1 (GLP-1) is a hormone produced and released by cells of the gastrointestinal tract following meal ingestion. GLP-1 receptor agonists (GLP-1RA) exhibit kidney-protective actions through poorly understood mechanisms. Here we interrogated whether the receptor for advanced glycation end products (RAGE) plays a role in mediating the actions of GLP-1 on inflammation and diabetic kidney disease. Mice with deletion of the GLP-1 receptor displayed an abnormal kidney phenotype that was accelerated by diabetes and improved with co-deletion of RAGE in vivo. (Source: Kidney International)
Source: Kidney International - December 8, 2023 Category: Urology & Nephrology Authors: Karly C. Sourris, Yi Ding, Scott S. Maxwell, Annas Al-sharea, Phillip Kantharidis, Muthukumar Mohan, Carlos J. Rosado, Sally A. Penfold, Claus Haase, Yangsong Xu, Josephine M. Forbes, Simon Crawford, Georg Ramm, Brooke E. Harcourt, Karin Jandeleit-Dahm, A Tags: Basic Research Source Type: research
IL-22 is secreted by proximal tubule cells and regulates DNA damage response and cell death in acute kidney injury
Acute kidney injury (AKI) affects over 13 million people worldwide annually and is associated with a 4-fold increase in mortality. Our lab and others have shown that DNA damage response (DDR) governs the outcome of AKI in a bimodal manner. Activation of DDR sensor kinases protects against AKI, while hyperactivation of DDR effector proteins, such as p53, induces cell death and worsens AKI. The factors that trigger DDR to switch from pro-repair to pro-cell death remain to be resolved. Here we investigated the role of interleukin 22 (IL-22), an IL-10 family member whose receptor (IL-22RA1) is expressed on proximal tubule cell...
Source: Kidney International - December 4, 2023 Category: Urology & Nephrology Authors: Kensei Taguchi, Sho Sugahara, Bertha C. Elias, Navjot S. Pabla, Guillaume Canaud, Craig R. Brooks Tags: Basic Research Source Type: research
Transcriptomic signatures of chronic active antibody-mediated rejection deciphered by RNA sequencing of human kidney allografts.
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). (Source: Kidney International)
Source: Kidney International - November 29, 2023 Category: Urology & Nephrology Authors: 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 Tags: clinical investigation Source Type: research
Uromodulin Processing in DNAJB11-kidney Disease
Autosomal dominant polycystic kidney disease (ADPKD) and autosomal dominant tubulointerstitial kidney disease (ADTKD) are among the most frequent monogenic disorders causing chronic kidney disease (CKD). The main genes associated with ADPKD are PKD1 and PKD2 encoding membrane and primary cilia proteins, polycystin-1 and polycystin-2, which are involved in multiple pathways regulating tubular cell differentiation. Recently, genes coding for proteins involved in the endoplasmic reticulum (ER) have been associated with rare, atypical forms of ADPKD. (Source: Kidney International)
Source: Kidney International - November 25, 2023 Category: Urology & Nephrology Authors: Marta Mariniello, Guglielmo Schiano, Ayumi Yoshifuji, Valentine Gillion, John Andrew Sayer, Fran çois Jouret, Genkyst Study Group, Yannick Le Meur, Emilie Cornec-Le Gall, Eric Gregory Olinger, Olivier Devuyst Tags: research letter Source Type: research
Living kidney donors ’ health care needs, experiences, and perspectives across their entire donation trajectory: a semistructured, in-depth interview study
Living kidney donors (LKDs) are an indispensable source of organs even in countries with robust deceased donor programs. In some regions, they are the only possible therapeutic option for patients with kidney failure.1 Improving their care and experiences and addressing their needs across the entire donation trajectory are critical to their long-term health and well-being. (Source: Kidney International)
Source: Kidney International - November 24, 2023 Category: Urology & Nephrology Authors: 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 Tags: Policy Forum Source Type: research
Targeted-release budesonide modifies key pathogenic biomarkers in immunoglobulin A nephropathy: Insights from the NEFIGAN trial
Nefecon is the first approved treatment for patients with IgA nephropathy (IgAN) at high risk of progression to kidney failure (accelerated approval: US Food and Drug Administration [FDA]; conditional approval: European Medicines Agency [EMA]).1-3 Nefecon delivers budesonide, in a targeted formulation, to the gut-associated lymphoid tissue (GALT) of the ileum directly addressing immune dysregulation within this Peyer ’s patches (PP)-rich area of the GALT and downregulating the local production of the polymeric poorly O-galactosylated form of immunoglobulin (Ig)A1 or galactose-deficient IgA1 (Gd-IgA1) and generation of pa...
Source: Kidney International - November 24, 2023 Category: Urology & Nephrology Authors: David Wimbury, Masahiro Muto, Jasraj S. Bhachu, Katrin Scionti, Jeremy Brown, Karen Molyneux, Claudia Seikrit, Dita Maixnerov á, Laura Pérez-Alós, Peter Garred, Jürgen Floege, Vladimír Tesař, Bengt Fellstrom, Rosanna Coppo, Jonathan Barratt Tags: research letter Source Type: research
Living kidney donors ’ healthcare needs, experiences and perspectives across their entire donation trajectory: a semi-structured, in-depth interview study
Living kidney donors (LKDs) are an indispensable source of organs even in countries with robust deceased donor programs. In some regions, they are the only possible therapeutic option for patients with kidney failure.1 Improving their care and experiences and addressing their needs across the entire donation trajectory is critical to their long-term health and well-being. (Source: Kidney International)
Source: Kidney International - November 24, 2023 Category: Urology & Nephrology Authors: 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 Tags: policy forum Source Type: research
Providing environmentally sustainable nephrology care: focus in Low- and Middle-Income Countries
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 pati...
Source: Kidney International - November 24, 2023 Category: Urology & Nephrology Authors: V.A. Luyckx, S. Alasfar, D. Bajpai, C.E. Atwater, J. Knight, B. Talbot, S. Davies, A. Niang Tags: mini review Source Type: research
Renin and renin blockade have no role in complement activity
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 Uremi...
Source: Kidney International - November 24, 2023 Category: Urology & Nephrology Authors: 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 Tags: basic research Source Type: research
Evaluation of novel candidate filtration markers from a global metabolomic discovery for glomerular filtration rate estimation.
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 (Source: Kidney International)
Source: Kidney International - November 23, 2023 Category: Urology & Nephrology Authors: 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 Tags: clinical investigation Source Type: research
Multi-omic analysis of human kidney tissue identified medulla-specific gene expression patterns
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 cort ex and medulla. (Source: Kidney International)
Source: Kidney International - November 21, 2023 Category: Urology & Nephrology Authors: Stefan Haug, Selvaraj Muthusamy, Yong Li, Galen Stewart, Xianwu Li, Martin Treppner, Anna K öttgen, Shreeram Akilesh Tags: Basic Research Source Type: research
Multi-omic analysis of human kidney tissue identified medulla-specific gene expression patterns.
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 cort ex and medulla. (Source: Kidney International)
Source: Kidney International - November 21, 2023 Category: Urology & Nephrology Authors: Stefan Haug, Selvaraj Muthusamy, Yong Li, Galen Stewart, Xianwu Li, Martin Treppner, Anna K öttgen, Shreeram Akilesh Tags: basic research Source Type: research
