Multiple infusions of ex vivo-expanded regulatory T cells promote CD163+ myeloid cells and kidney allograft survival in non-lymphodepleted non-human primates
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. (Source: Kidney International)
Source: Kidney International - October 13, 2023 Category: Urology & Nephrology Authors: 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. Tags: basic research Source Type: research
Mayo Clinic consensus report on membranous nephropathy: proposal for a novel classification
Membranous nephropathy (MN) is a pattern of injury caused by autoantibodies binding to specific target antigens, with accumulation of immune complexes along the subepithelial region of glomerular basement membranes. The past 20 years have brought revolutionary advances in the understanding of MN, particularly via the discovery of novel target antigens and their respective autoantibodies. These discoveries have challenged the traditional classification of MN into primary and secondary forms. At least 14 target antigens have been identified, accounting for 80% –90% of cases of MN. (Source: Kidney International)
Source: Kidney International - October 5, 2023 Category: Urology & Nephrology Authors: Sanjeev Sethi, Laurence H. Beck, Richard J. Glassock, Mark Haas, An S. De Vriese, Tiffany N. Caza, Elion Hoxha, G érard Lambeau, Nicola M. Tomas, Benjamin Madden, Hanna Debiec, Vivette D. D’Agati, Mariam P. Alexander, Hatem Amer, Gerald B. Appel, Sean Tags: meeting report Source Type: research
An introduction to realist evaluation and synthesis for kidney research
Realist research describes a methodological approach which aims to explore how and why interventions work, for who, and under which circumstances. Rather than quantifying how well an intervention works under specific conditions, realist theory explores the function of interventions in detail, and specifically considers how the contexts in which interventional components are delivered influence the mechanisms that lead to outcomes. Realist methods can be applied to primary data (realist evaluation) or secondary data (realist synthesis). (Source: Kidney International)
Source: Kidney International - October 5, 2023 Category: Urology & Nephrology Authors: Dominic Taylor, Ailish Nimmo, Barnaby Hole, G.J. Melendez-Torres Tags: mini review Source Type: research
Evaluation of the stopping angiotensin converting enzyme inhibitor compared to angiotensin receptor blocker (STOP ACEi trial) in advanced and progressive chronic kidney disease.
In the STOP-ACEi trial, the outcome was similar whether or not renin –angiotensin system inhibitors (RASi) were discontinued. We now investigate whether the effect of withdrawing angiotensin converting enzyme inhibitors (ACEi) or angiotensin-receptor blockers (ARBs) differed. In this open label trial patients with estimated glomerular filtration rates (eGFR) under 30ml/min per 1.73 m2 and progressive chronic kidney disease (CKD) were randomized to stop or continue RASi. The primary outcome was eGFR at three years. (Source: Kidney International)
Source: Kidney International - September 29, 2023 Category: Urology & Nephrology Authors: Sunil Bhandari, Samir Mehta, Arif Khawaja, John G.F. Cleland, Natalie Ives, Paul Cockwell Tags: clinical trial Source Type: research
Hepatocyte nuclear factor 4 α mediated quinolinate phosphoribosylltransferase (QPRT) expression in the kidney facilitates resilience against acute kidney injury.
Nicotinamide adenine dinucleotide (NAD+) levels decline in experimental models of acute kidney injury (AKI). Attenuated enzymatic conversion of tryptophan to NAD+ in tubular epithelium may contribute to adverse cellular and physiological outcomes. Mechanisms underlying defense of tryptophan-dependent NAD+ production are incompletely understood. Here we show that regulation of a bottleneck enzyme in this pathway, quinolinate phosphoribosyltransferase (QPRT) may contribute to kidney resilience. Expression of QPRT declined in two unrelated models of AKI. (Source: Kidney International)
Source: Kidney International - September 29, 2023 Category: Urology & Nephrology Authors: Amanda J. Clark, Marie Christelle Saade, Vamsidhara Vemireddy, Kyle Q. Vu, Brenda Mendoza Flores, Valerie Etzrodt, Erin J. Ciampa, Huihui Huang, Ayumi Takakura, Kambiz Zandi-Nejad, Zsuzsanna K. Zsengell ér, Samir M. Parikh Tags: basic research Source Type: research
Drug discovery and therapeutic perspectives for proximal tubulopathies
The efficient reabsorption of essential nutrients by epithelial cells in the proximal tubule of the kidney is crucial for maintaining homeostasis. This process heavily relies on a complex ecosystem of vesicular trafficking pathways. At the center of this network, the lysosome plays a pivotal role in processing incoming molecules, sensing nutrient availability, sorting receptors and transporters, and balancing differentiation and proliferation in the tubular epithelial cells. Disruptions in these fundamental processes can lead to proximal tubulopathy − a condition characterized by the dysfunction of the tubular cells foll...
Source: Kidney International - September 29, 2023 Category: Urology & Nephrology Authors: Svenja Keller, Zhiyong Chen, Anna Gaponova, Mikhail Korzinkin, Marine Berquez, Alessandro Luciani Tags: mini review Source Type: research
Mendelian randomization for nephrologists
Confounding is major limitation of observational studies. Mendelian randomization (MR) is a powerful study design that uses genetic variants as instrumental variables to enable examination of the causal effect of an exposure on an outcome in observational data. With the emergence of large-scale genome wide association studies in nephrology over the past decade, MR has become a popular method to establish causal inferences. However, MR is a complex and challenging methodology that requires careful consideration to ensure robust results. (Source: Kidney International)
Source: Kidney International - September 29, 2023 Category: Urology & Nephrology Authors: Ellen Dobrijevic, Anita van Zwieten, Krzsztof Kiryluk, Andrew J. Grant, Germaine Wong, Armando Teixeira-Pinto Tags: xyz of statistics Source Type: research
Glomerular-tubular crosstalk via cold shock Y-box binding protein-1 in the kidney
Glomerular-tubular crosstalk within the kidney has been proposed, but the paracrine signals enabling this remain largely unknown. The cold-shock protein Y-box binding protein 1 (YBX1) is known to regulate inflammation and kidney diseases but its role in podocytes remains undetermined. Therefore, we analyzed mice with podocyte specific Ybx1 deletion (Ybx1 ΔPod). Albuminuria was increased in unchallenged Ybx1ΔPod mice, which surprisingly was associated with reduced glomerular, but enhanced tubular damage. (Source: Kidney International)
Source: Kidney International - September 27, 2023 Category: Urology & Nephrology Authors: Rajiv Rana, Jayakumar Manoharan, Ahmed Elwakiel, Silke Zimmermann, Jonathan A. Lindquist, Dheerendra Gupta, Moh'd Mohanad Al-Dabet, Ihsan Gadi, J örg Fallmann, Kunal Singh, Anubhuti Gupta, Ronald Biemann, Sabine Brandt, Bekas Alo, Paul Kluge, Ravindra Ga Tags: Basic Research Source Type: research
A novel multi-ancestry proteome-wide Mendelian randomization study implicates extracellular proteins, tubular cells, and fibroblasts in estimated glomerular filtration rate regulation.
New treatments for chronic kidney disease are needed. Biomarkers that help or harm kidney cells are clues to new possible treatments. We need to find blood biomarkers that are not just markers of injury, but that actually impact the problem. We searched for genetic changes predictive of the concentration of more than 1000 biomarkers. We then compared how those same genetic changes impacted the risk for kidney disease. We found that the genetically altered amount of 22 different blood biomarkers changed kidney function. Some of these biomarkers were previously known, but many were not. Some were harmful, while others appear...
Source: Kidney International - September 27, 2023 Category: Urology & Nephrology Authors: Matthew B. Lanktree, Nicolas Perrot, Andrew Smyth, Michael Chong, Sukrit Narula, Meera Shanmuganathan, Zachary Kroezen, Philip Britz-Mckibbin, Mario Berger, Joan C. Krepinsky, Marie Pigeyre, Salim Yusuf, Guillaume Pare Tags: clinical investigation Source Type: research
Development of an automated estimation of foot process width using deep learning in kidney biopsies from patients with Fabry, minimal change, and diabetic kidney diseases.
Podocyte injury plays a key role in pathogenesis of many kidney diseases with increased podocyte foot process width (FPW), an important measure of podocyte injury. Unfortunately, there is no consensus on the best way to estimate FPW and unbiased stereology, the current gold standard, is time consuming and not widely available. To address this, we developed an automated FPW estimation technique using deep learning. A U-Net architecture variant model was trained to semantically segment the podocyte-glomerular basement membrane interface and filtration slits. (Source: Kidney International)
Source: Kidney International - September 27, 2023 Category: Urology & Nephrology Authors: David Smerkous, Michael Mauer, Camilla T øndel, Einar Svarstad, Marie-Claire Gubler, Robert G. Nelson, João-Paulo Oliveira, Forough Sargolzaeiaval, Behzad Najafian Tags: clinical investigation Source Type: research
Glomerular-tubular crosstalk via cold shock Y-box binding protein-1 in the kidney.
Glomerular-tubular crosstalk within the kidney has been proposed, but the paracrine signals enabling this remain largely unknown. The cold-shock protein Y-box binding protein 1 (YBX1) is known to regulate inflammation and kidney diseases but its role in podocytes remains undetermined. Therefore, we analyzed mice with podocyte specific Ybx1 deletion (Ybx1 ΔPod). Albuminuria was increased in unchallenged Ybx1ΔPod mice, which surprisingly was associated with reduced glomerular, but enhanced tubular damage. (Source: Kidney International)
Source: Kidney International - September 27, 2023 Category: Urology & Nephrology Authors: Rajiv Rana, Jayakumar Manoharan, Ahmed Elwakiel, Silke Zimmermann, Jonathan A. Lindquist, Dheerendra Gupta, Moh'd Mohanad Al-Dabet, Ihsan Gadi, J örg Fallmann, Kunal Singh, Anubhuti Gupta, Ronald Biemann, Sabine Brandt, Bekas Alo, Paul Kluge, Ravindra Ga Tags: basic research Source Type: research
Advanced optical imaging reveals preferred spatial orientation of podocyte processes along the axis of glomerular capillaries
Mammalian kidneys filter enormous volumes of water and small solutes, a filtration driven by the hydrostatic pressure in glomerular capillaries, which is considerably higher than in most other tissues. Interdigitating cellular processes of podocytes form the slits for fluid filtration connected by the membrane-like slit diaphragm cell junction containing a mechanosensitive ion channel complex and allow filtration while counteracting hydrostatic pressure. Several previous publications speculated that podocyte processes may display a preferable orientation on glomerular capillaries instead of a random distribution. (Source: ...
Source: Kidney International - September 27, 2023 Category: Urology & Nephrology Authors: David Unnersj ö-Jess, Amer Ramdedovic, Linus Butt, Ingo Plagmann, Martin Höhne, Agnes Hackl, Hjalmar Brismar, Hans Blom, Bernhard Schermer, Thomas Benzing Tags: technical notes Source Type: research
The spectrum of glomerular and vascular kidney pathology associated with myeloproliferative neoplasms.
A high prevalence of chronic kidney disease (CKD) occurs in patients with myeloproliferative neoplasms (MPN). However, MPN-related glomerulopathy (MPN-RG) may not account for the entirety of CKD risk in this population. The systemic vasculopathy encountered in these patients raises the hypothesis that vascular nephrosclerosis may be a common pattern of injury in patients with MPN and with CKD. In an exhaustive, retrospective, multicenter study of MPN kidney biopsies in four different pathology departments, we now describe glomerular and vascular lesions and establish clinicopathologic correlations. (Source: Kidney International)
Source: Kidney International - September 26, 2023 Category: Urology & Nephrology Authors: Thibaut d ’Izarny-Gargas, Pierre Isnard, Idris Boudhabhay, David Buob, Anissa Moktefi, Charel Linster, Aurélie Hummel, Emmanuel Esteve, Vincent Audard, Hélène Lazareth, Nadine Maroun, Alexandre Hertig, Clément Gosset, Charlotte Jouzel, Sarah Permal, Tags: clinical investigation Source Type: research
Cryofibrinogen-associated membranoproliferative glomerulonephritis
A 74-year-old man, with a history of diabetes mellitus and prostatic cancer, visited the emergency department with generalized edema and weakness for 1 week. At admission, the serum creatinine level was 3.9 mg/dl (up from a baseline creatinine of 1.2 mg/dl 6 months earlier), and urinalysis revealed microscopic hematuria and nephrotic-range proteinuria (5.15 g/d in 24 hours ’ urine). The C3 level was decreased (64 mg/dl). There was no evidence of monoclonal gammopathy. Kidney biopsy revealed basement membrane thickening, mesangial matrix prominence, and lobular accentuation of glomerular tufts with diffuse endocapillary h...
Source: Kidney International - September 20, 2023 Category: Urology & Nephrology Authors: Minah Kim, Sung Sun Kim, Hoon-In Choi, Hong Sang Choi, Eun Hui Bae, Seong Kwon Ma, Soo Wan Kim, Chang Seong Kim Tags: Nephrology Image Source Type: research
Intussusception as a complication of idiopathic nephrotic syndrome
A 19-year-old male patient presented with abdominal pain associated with a relapse of minimal change disease (serum creatinine: 90 μmol/l; albumin: 1.6 g/dl; proteinuria: 7.8 g/g). A right iliac fossa ileo–ileal intussusception was found on the computed tomography (CT) scan (Figure 1). The pain subsided with administration of paracetamol but recurred 2 days later. A second CT scan showed 2 other right lumbar jejuno–jejuna l intussusceptions, and 1 upper-left-quadrant ileo–ileal intussusception, but the right iliac fossa ileo–ileal intussusception was no longer visible (Figure 2). (Source: Kidney International)
Source: Kidney International - September 20, 2023 Category: Urology & Nephrology Authors: Fanny Dreant, Benedicte Sautenet, Christelle Barbet, Jean-Michel Halimi Tags: Nephrology Image Source Type: research
