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JOURNAL ARTICLE
Yask Gupta, David J Friedman, Michelle T McNulty, Atlas Khan, Brandon Lane, Chen Wang, Juntao Ke, Gina Jin, Benjamin Wooden, Andrea L Knob, Tze Y Lim, Gerald B Appel, Kinsie Huggins, Lili Liu, Adele Mitrotti, Megan C Stangl, Andrew Bomback, Rik Westland, Monica Bodria, Maddalena Marasa, Ning Shang, David J Cohen, Russell J Crew, William Morello, Pietro Canetta, Jai Radhakrishnan, Jeremiah Martino, Qingxue Liu, Wendy K Chung, Angelica Espinoza, Yuan Luo, Wei-Qi Wei, Qiping Feng, Chunhua Weng, Yilu Fang, Iftikhar J Kullo, Mohammadreza Naderian, Nita Limdi, Marguerite R Irvin, Hemant Tiwari, Sumit Mohan, Maya Rao, Geoffrey K Dube, Ninad S Chaudhary, Orlando M Gutiérrez, Suzanne E Judd, Mary Cushman, Leslie A Lange, Ethan M Lange, Daniel L Bivona, Miguel Verbitsky, Cheryl A Winkler, Jeffrey B Kopp, Dominick Santoriello, Ibrahim Batal, Sérgio Veloso Brant Pinheiro, Eduardo Araújo Oliveira, Ana Cristina Simoes E Silva, Isabella Pisani, Enrico Fiaccadori, Fangming Lin, Loreto Gesualdo, Antonio Amoroso, Gian Marco Ghiggeri, Vivette D D'Agati, Riccardo Magistroni, Eimear E Kenny, Ruth J F Loos, Giovanni Montini, Friedhelm Hildebrandt, Dirk S Paul, Slavé Petrovski, David B Goldstein, Matthias Kretzler, Rasheed Gbadegesin, Ali G Gharavi, Krzysztof Kiryluk, Matthew G Sampson, Martin R Pollak, Simone Sanna-Cherchi
African Americans have a significantly higher risk of developing chronic kidney disease, especially focal segmental glomerulosclerosis -, than European Americans. Two coding variants (G1 and G2) in the APOL1 gene play a major role in this disparity. While 13% of African Americans carry the high-risk recessive genotypes, only a fraction of these individuals develops FSGS or kidney failure, indicating the involvement of additional disease modifiers. Here, we show that the presence of the APOL1 p.N264K missense variant, when co-inherited with the G2 APOL1 risk allele, substantially reduces the penetrance of the G1G2 and G2G2 high-risk genotypes by rendering these genotypes low-risk...
November 30, 2023: Nature Communications
#2
Ibrahim Batal, Samih H Nasr, Surendra Dasari, Astrid Weins, Natalie Vena, Michael B Stokes, Krzysztof Kiryluk, Gerald B Appel
Fibronectin glomerulopathy is a rare inherited kidney disease, characterized by abnormal accumulation of fibronectin in the glomeruli. We report an exceptional case of recurrent fibronectin glomerulopathy first diagnosed in the kidney allograft. The presence of IgA staining in the native kidney biopsy and the reported family history of IgA nephropathy had led to initial pretransplant diagnosis of IgA nephropathy. At 4.5 years posttransplant, the patient presented with kidney insufficiency and minimal proteinuria...
March 2024: American Journal of Transplantation
#3
JOURNAL ARTICLE
Abir N Hassani, Luman Haris, Markus Appel, Tilo Seydel, Andreas M Stadler, Gerald R Kneller
We present an analysis of high-resolution quasi-elastic neutron scattering spectra of phosphoglycerate kinase which elucidates the influence of the enzymatic activity on the dynamics of the protein. We show that in the active state the inter-domain motions are amplified and the intra-domain asymptotic power-law relaxation ∝t-α is accelerated, with a reduced coefficient α. Employing an energy landscape picture of protein dynamics, this observation can be translated into a widening of the distribution of energy barriers separating conformational substates of the protein...
October 14, 2023: Journal of Chemical Physics
#4
JOURNAL ARTICLE
Sanjeev Sethi, Laurence H Beck, Richard J Glassock, Mark Haas, An S De Vriese, Tiffany N Caza, Elion Hoxha, Gérard Lambeau, Nicola M Tomas, Benjamin Madden, Hanna Debiec, Vivette D D'Agati, Mariam P Alexander, Hatem Amer, Gerald B Appel, Sean J Barbour, Fernando Caravaca-Fontan, Daniel C Cattran, Marta Casal Moura, Domingos O D'Avila, Renato G Eick, Vesna D Garovic, Eddie L Greene, Loren P Herrera Hernandez, J Charles Jennette, John C Lieske, Glen S Markowitz, Karl A Nath, Samih H Nasr, Cynthia C Nast, Antonello Pani, Manuel Praga, Giuseppe Remuzzi, Helmut G Rennke, Piero Ruggenenti, Dario Roccatello, Maria Jose Soler, Ulrich Specks, Rolf A K Stahl, Raman Deep Singh, Jason D Theis, Jorge A Velosa, Jack F M Wetzels, Christopher G Winearls, Federico Yandian, Ladan Zand, Pierre Ronco, Fernando C Fervenza
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...
September 29, 2023: Mayo Clinic Proceedings
#5
JOURNAL ARTICLE
Sanjeev Sethi, Laurence H Beck, Richard J Glassock, Mark Haas, An S De Vriese, Tiffany N Caza, Elion Hoxha, Gérard Lambeau, Nicola M Tomas, Benjamin Madden, Hanna Debiec, Vivette D D'Agati, Mariam P Alexander, Hatem Amer, Gerald B Appel, Sean J Barbour, Fernando Caravaca-Fontan, Daniel C Cattran, Marta Casal Moura, Domingos O D'Avila, Renato G Eick, Vesna D Garovic, Eddie L Greene, Loren P Herrera Hernandez, J Charles Jennette, John C Lieske, Glen S Markowitz, Karl A Nath, Samih H Nasr, Cynthia C Nast, Antonello Pani, Manuel Praga, Giuseppe Remuzzi, Helmut G Rennke, Piero Ruggenenti, Dario Roccatello, Maria Jose Soler, Ulrich Specks, Rolf A K Stahl, Raman Deep Singh, Jason D Theis, Jorge A Velosa, Jack F M Wetzels, Christopher G Winearls, Federico Yandian, Ladan Zand, Pierre Ronco, Fernando C Fervenza
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...
December 2023: Kidney International
#6
JOURNAL ARTICLE
Birte Valentin, Benedikt Kamp, Jan Henke, Alexandra Ljimani, Elisabeth Appel, Gerald Antoch, Andrea Steuwe

Although iso-centric patient positioning is enormously important in CT, it is complicated in thoracoabdominal imaging by the varying dimensions of the body. Patient positioning can affect the appearance of the patient on the localizer. Positioned too close to the x-ray tube, a patient appears considerably more voluminous. The goal of this study is to assess the difference in radiation exposure of combined chest and abdomen CT scans between scans with prior 0°- and 180°-localizers in conjunction with patient positioning...
August 24, 2023: Journal of Radiological Protection: Official Journal of the Society for Radiological Protection
#7
Yask Gupta, David J Friedman, Michelle McNulty, Atlas Khan, Brandon Lane, Chen Wang, Juntao Ke, Gina Jin, Benjamin Wooden, Andrea L Knob, Tze Y Lim, Gerald B Appel, Kinsie Huggins, Lili Liu, Adele Mitrotti, Megan C Stangl, Andrew Bomback, Rik Westland, Monica Bodria, Maddalena Marasa, Ning Shang, David J Cohen, Russell J Crew, William Morello, Pietro Canetta, Jai Radhakrishnan, Jeremiah Martino, Qingxue Liu, Wendy K Chung, Angelica Espinoza, Yuan Luo, Wei-Qi Wei, Qiping Feng, Chunhua Weng, Yilu Fang, Iftikhar J Kullo, Mohammadreza Naderian, Nita Limdi, Marguerite R Irvin, Hemant Tiwari, Sumit Mohan, Maya Rao, Geoffrey Dube, Ninad S Chaudhary, Orlando M Gutiérrez, Suzanne E Judd, Mary Cushman, Leslie A Lange, Ethan M Lange, Daniel L Bivona, Miguel Verbitsky, Cheryl A Winkler, Jeffrey B Kopp, Dominick Santoriello, Ibrahim Batal, Sérgio Veloso Brant Pinheiro, Eduardo Araújo Oliveira, Ana Cristina Simoes E Silva, Isabella Pisani, Enrico Fiaccadori, Fangming Lin, Loreto Gesualdo, Antonio Amoroso, Gian Marco Ghiggeri, Vivette D D'Agati, Riccardo Magistroni, Eimear E Kenny, Ruth J F Loos, Giovanni Montini, Friedhelm Hildebrandt, Dirk S Paul, Slavé Petrovski, David B Goldstein, Matthias Kretzler, Rasheed Gbadegesin, Ali G Gharavi, Krzysztof Kiryluk, Matthew G Sampson, Martin R Pollak, Simone Sanna-Cherchi
Black Americans have a significantly higher risk of developing chronic kidney disease (CKD), especially focal segmental glomerulosclerosis (FSGS), than European Americans. Two coding variants (G1 and G2) in the APOL1 gene play a major role in this disparity. While 13% of Black Americans carry the high-risk recessive genotypes, only a fraction of these individuals develops FSGS or kidney failure, indicating the involvement of additional disease modifiers. Here, we show that the presence of the APOL1 p.N264K missense variant, when co-inherited with the G2 APOL1 risk allele, substantially reduces the penetrance of the G1G2 and G2G2 high-risk genotypes by rendering these genotypes low-risk...
August 4, 2023: medRxiv
#8
JOURNAL ARTICLE
Maddalena Marasa, Dina F Ahram, Atteeq U Rehman, Adele Mitrotti, Avinash Abhyankar, Namrata G Jain, Patricia L Weng, Stacy E Piva, Hilda E Fernandez, Natalie S Uy, Debanjana Chatterjee, Byum H Kil, Jordan G Nestor, Vanessa Felice, Dino Robinson, Dilys Whyte, Ali G Gharavi, Gerald B Appel, Jai Radhakrishnan, Dominick Santoriello, Andrew Bomback, Fangming Lin, Vivette D D'Agati, Vaidehi Jobanputra, Simone Sanna-Cherchi
INTRODUCTION: The diagnosis and management of proteinuric kidney diseases such as focal segmental glomerulosclerosis (FSGS) are challenging. Genetics holds the promise to improve clinical decision making for these diseases; however, it is often performed too late to enable timely clinical action and it is not implemented within routine outpatient nephrology visits. METHODS: We sought to test the implementation and feasibility of clinical rapid genome sequencing (GS) in guiding decision making in patients with proteinuric kidney disease in real-time and embedded in the outpatient nephrology setting...
August 2023: KI Reports
#9
JOURNAL ARTICLE
Sean J Barbour, Fernando C Fervenza, Dilshani Induruwage, Paul E Brenchley, Brad Rovin, Michelle A Hladunewich, Heather N Reich, Richard Lafayette, Nabeel Aslam, Gerald B Appel, Ladan Zand, Krzysztof Kiryluk, Lili Liu, Daniel C Cattran
BACKGROUND: The 2021 Kidney Disease Improving Global Outcomes (KDIGO) guidelines recommend following anti-phospholipase A2 receptor (PLA2R) antibody levels as a marker of treatment response in membranous nephropathy; however, the optimal timing to evaluate antibody levels and how to combine them with other clinical variables are currently unknown. METHODS: We used a cohort of 85 patients from the Membranous Nephropathy Trial Of Rituximab (MENTOR) with anti-PLA2R antibodies ≥14 RU/ml to identify risk factors for not experiencing proteinuria remission after 12 months of treatment with cyclosporine or rituximab...
October 1, 2023: Clinical Journal of the American Society of Nephrology: CJASN
#10
JOURNAL ARTICLE
Gail L Daumit, A Eden Evins, Corinne Cather, Arlene T Dalcin, Faith B Dickerson, Edgar R Miller, Lawrence J Appel, Gerald J Jerome, Una McCann, Daniel E Ford, Jeanne B Charleston, Deborah R Young, Joseph V Gennusa, Stacy Goldsholl, Courtney Cook, Tyler Fink, Nae-Yuh Wang
IMPORTANCE: Tobacco smoking drives markedly elevated cardiovascular disease risk and preventable death in persons with serious mental illness, and these risks are compounded by the high prevalence of overweight/obesity that smoking cessation can exacerbate. Guideline-concordant combined pharmacotherapy and behavioral smoking cessation treatment improves abstinence but is not routinely offered in community settings, particularly to those not seeking to quit smoking immediately. OBJECTIVE: To determine the effectiveness of an 18-month pharmacotherapy and behavioral smoking cessation intervention incorporating weight management and support for physical activity in adults with serious mental illness interested in quitting smoking within 1 or 6 months...
June 28, 2023: JAMA Psychiatry
#11
JOURNAL ARTICLE
Krzysztof Kiryluk, Elena Sanchez-Rodriguez, Xu-Jie Zhou, Francesca Zanoni, Lili Liu, Nikol Mladkova, Atlas Khan, Maddalena Marasa, Jun Y Zhang, Olivia Balderes, Simone Sanna-Cherchi, Andrew S Bomback, Pietro A Canetta, Gerald B Appel, Jai Radhakrishnan, Hernan Trimarchi, Ben Sprangers, Daniel C Cattran, Heather Reich, York Pei, Pietro Ravani, Kresimir Galesic, Dita Maixnerova, Vladimir Tesar, Benedicte Stengel, Marie Metzger, Guillaume Canaud, Nicolas Maillard, Francois Berthoux, Laureline Berthelot, Evangeline Pillebout, Renato Monteiro, Raoul Nelson, Robert J Wyatt, William Smoyer, John Mahan, Al-Akash Samhar, Guillermo Hidalgo, Alejandro Quiroga, Patricia Weng, Raji Sreedharan, David Selewski, Keefe Davis, Mahmoud Kallash, Tetyana L Vasylyeva, Michelle Rheault, Aftab Chishti, Daniel Ranch, Scott E Wenderfer, Dmitry Samsonov, Donna J Claes, Oleh Akchurin, Dimitrios Goumenos, Maria Stangou, Judit Nagy, Tibor Kovacs, Enrico Fiaccadori, Antonio Amoroso, Cristina Barlassina, Daniele Cusi, Lucia Del Vecchio, Giovanni Giorgio Battaglia, Monica Bodria, Emanuela Boer, Luisa Bono, Giuliano Boscutti, Gianluca Caridi, Francesca Lugani, GianMarco Ghiggeri, Rosanna Coppo, Licia Peruzzi, Vittoria Esposito, Ciro Esposito, Sandro Feriozzi, Rosaria Polci, Giovanni Frasca, Marco Galliani, Maurizio Garozzo, Adele Mitrotti, Loreto Gesualdo, Simona Granata, Gianluigi Zaza, Francesco Londrino, Riccardo Magistroni, Isabella Pisani, Andrea Magnano, Carmelita Marcantoni, Piergiorgio Messa, Renzo Mignani, Antonello Pani, Claudio Ponticelli, Dario Roccatello, Maurizio Salvadori, Erica Salvi, Domenico Santoro, Guido Gembillo, Silvana Savoldi, Donatella Spotti, Pasquale Zamboli, Claudia Izzi, Federico Alberici, Elisa Delbarba, Michał Florczak, Natalia Krata, Krzysztof Mucha, Leszek Pączek, Stanisław Niemczyk, Barbara Moszczuk, Malgorzata Pańczyk-Tomaszewska, Malgorzata Mizerska-Wasiak, Agnieszka Perkowska-Ptasińska, Teresa Bączkowska, Magdalena Durlik, Krzysztof Pawlaczyk, Przemyslaw Sikora, Marcin Zaniew, Dorota Kaminska, Magdalena Krajewska, Izabella Kuzmiuk-Glembin, Zbigniew Heleniak, Barbara Bullo-Piontecka, Tomasz Liberek, Alicja Dębska-Slizien, Tomasz Hryszko, Anna Materna-Kiryluk, Monika Miklaszewska, Maria Szczepańska, Katarzyna Dyga, Edyta Machura, Katarzyna Siniewicz-Luzeńczyk, Monika Pawlak-Bratkowska, Marcin Tkaczyk, Dariusz Runowski, Norbert Kwella, Dorota Drożdż, Ireneusz Habura, Florian Kronenberg, Larisa Prikhodina, David van Heel, Bertrand Fontaine, Chris Cotsapas, Cisca Wijmenga, Andre Franke, Vito Annese, Peter K Gregersen, Sreeja Parameswaran, Matthew Weirauch, Leah Kottyan, John B Harley, Hitoshi Suzuki, Ichiei Narita, Shin Goto, Hajeong Lee, Dong Ki Kim, Yon Su Kim, Jin-Ho Park, BeLong Cho, Murim Choi, Ans Van Wijk, Ana Huerta, Elisabet Ars, Jose Ballarin, Sigrid Lundberg, Bruno Vogt, Laila-Yasmin Mani, Yasar Caliskan, Jonathan Barratt, Thilini Abeygunaratne, Philip A Kalra, Daniel P Gale, Ulf Panzer, Thomas Rauen, Jürgen Floege, Pascal Schlosser, Arif B Ekici, Kai-Uwe Eckardt, Nan Chen, Jingyuan Xie, Richard P Lifton, Ruth J F Loos, Eimear E Kenny, Iuliana Ionita-Laza, Anna Köttgen, Bruce A Julian, Jan Novak, Francesco Scolari, Hong Zhang, Ali G Gharavi
IgA nephropathy (IgAN) is a progressive form of kidney disease defined by glomerular deposition of IgA. Here we performed a genome-wide association study of 10,146 kidney-biopsy-diagnosed IgAN cases and 28,751 controls across 17 international cohorts. We defined 30 genome-wide significant risk loci explaining 11% of disease risk. A total of 16 loci were new, including TNFSF4/TNFSF18, REL, CD28, PF4V1, LY86, LYN, ANXA3, TNFSF8/TNFSF15, REEP3, ZMIZ1, OVOL1/RELA, ETS1, IGH, IRF8, TNFRSF13B and FCAR. The risk loci were enriched in gene orthologs causing abnormal IgA levels when genetically manipulated in mice...
July 2023: Nature Genetics
#12
JOURNAL ARTICLE
Lesley A Inker, Willem Collier, Tom Greene, Shiyuan Miao, Juhi Chaudhari, Gerald B Appel, Sunil V Badve, Fernando Caravaca-Fontán, Lucia Del Vecchio, Jürgen Floege, Marian Goicoechea, Benjamin Haaland, William G Herrington, Enyu Imai, Tazeen H Jafar, Julia B Lewis, Philip K T Li, Bart D Maes, Brendon L Neuen, Ronald D Perrone, Giuseppe Remuzzi, Francesco P Schena, Christoph Wanner, Jack F M Wetzels, Mark Woodward, Hiddo J L Heerspink
Glomerular filtration rate (GFR) decline is causally associated with kidney failure and is a candidate surrogate endpoint for clinical trials of chronic kidney disease (CKD) progression. Analyses across a diverse spectrum of interventions and populations is required for acceptance of GFR decline as an endpoint. In an analysis of individual participant data, for each of 66 studies (total of 186,312 participants), we estimated treatment effects on the total GFR slope, computed from baseline to 3 years, and chronic slope, starting at 3 months after randomization, and on the clinical endpoint (doubling of serum creatinine, GFR < 15 ml min-1 per 1...
July 2023: Nature Medicine
#13
JOURNAL ARTICLE
Dina F Ahram, Tze Y Lim, Juntao Ke, Gina Jin, Miguel Verbitsky, Monica Bodria, Byum Hee Kil, Debanjana Chatterjee, Stacy E Piva, Maddalena Marasa, Jun Y Zhang, Enrico Cocchi, Gianluca Caridi, Zoran Gucev, Vladimir J Lozanovski, Isabella Pisani, Claudia Izzi, Gianfranco Savoldi, Barbara Gnutti, Valentina P Capone, William Morello, Stefano Guarino, Pasquale Esposito, Sarah Lambert, Jai Radhakrishnan, Gerald B Appel, Natalie S Uy, Maya K Rao, Pietro A Canetta, Andrew S Bomback, Jordan G Nestor, Thomas Hays, David J Cohen, Carolina Finale Na, Joanna A E van Wijk, Claudio La Scola, Olga Baraldi, Francesco Tondolo, Dacia Di Renzo, Anna Jamry-Dziurla, Alessandro Pezzutto, Valeria Manca, Adele Mitrotti, Domenico Santoro, Giovanni Conti, Marida Martino, Mario Giordano, Loreto Gesualdo, Lada Zibar, Giuseppe Masnata, Mario Bonomini, Daniele Alberti, Gaetano La Manna, Yasar Caliskan, Andrea Ranghino, Pierluigi Marzuillo, Krzysztof Kiryluk, Grażyna Krzemień, Monika Miklaszewska, Fangming Lin, Giovanni Montini, Francesco Scolari, Enrico Fiaccadori, Adela Arapović, Marijan Saraga, James McKiernan, Shumyle Alam, Marcin Zaniew, Maria Szczepańska, Agnieszka Szmigielska, Przemysław Sikora, Dorota Drożdż, Malgorzata Mizerska-Wasiak, Shrikant Mane, Richard P Lifton, Velibor Tasic, Anna Latos-Bielenska, Ali G Gharavi, Gian Marco Ghiggeri, Anna Materna-Kiryluk, Rik Westland, Simone Sanna-Cherchi
BACKGROUND: Congenital obstructive uropathy (COU) is a common cause of developmental defects of the urinary tract, with heterogeneous clinical presentation and outcome. Genetic analysis has the potential to elucidate the underlying diagnosis and help risk stratification. METHODS: We performed a comprehensive genomic screen of 733 independent COU cases, which consisted of individuals with ureteropelvic junction obstruction (UPJO; n=321), ureterovesical junction obstruction/congenital megaureter (UVJO; n=178), and congenital hydronephrosis not otherwise specified (COU-NOS; n=234)...
March 30, 2023: Journal of the American Society of Nephrology: JASN
#14
JOURNAL ARTICLE
Hiddo J L Heerspink, Lesley A Inker, Hocine Tighiouart, Willem H Collier, Benjamin Haaland, Jiyu Luo, Gerald B Appel, Tak Mao Chan, Raymond O Estacio, Fernando Fervenza, Jürgen Floege, Enyu Imai, Tazeen H Jafar, Julia B Lewis, Philip Kam-Tao Li, Francesco Locatelli, Bart D Maes, Annalisa Perna, Ronald D Perrone, Manuel Praga, Francesco P Schena, Christoph Wanner, Di Xie, Tom Greene
SIGNIFICANCE STATEMENT: Changes in albuminuria and GFR slope are individually used as surrogate end points in clinical trials of CKD progression, and studies have demonstrated that each is associated with treatment effects on clinical end points. In this study, the authors sought to develop a conceptual framework that combines both surrogate end points to better predict treatment effects on clinical end points in Phase 2 trials. The results demonstrate that information from the combined treatment effects on albuminuria and GFR slope improves the prediction of treatment effects on the clinical end point for Phase 2 trials with sample sizes between 100 and 200 patients and duration of follow-up ranging from 1 to 2 years...
June 1, 2023: Journal of the American Society of Nephrology: JASN
#15
JOURNAL ARTICLE
Willem Collier, Lesley A Inker, Benjamin Haaland, Gerald B Appel, Sunil V Badve, Fernando Caravaca-Fontán, John Chalmers, Jürgen Floege, Marian Goicoechea, Enyu Imai, Tazeen H Jafar, Julia B Lewis, Philip K T Li, Francesco Locatelli, Bart D Maes, Brendon L Neuen, Ronald D Perrone, Giuseppe Remuzzi, Francesco P Schena, Christoph Wanner, Hiddo J L Heerspink, Tom Greene
BACKGROUND: The GFR slope has been evaluated as a surrogate end point for kidney failure in meta-analyses on a broad collection of randomized controlled trials (RCTs) in CKD. These analyses evaluate how accurately a treatment effect on GFR slope predicts a treatment effect on kidney failure. We sought to determine whether severity of CKD in the patient population modifies the performance of GFR slope. METHODS: We performed Bayesian meta-regression analyses on 66 CKD RCTs to evaluate associations between effects on GFR slope (the chronic slope and the total slope over 3 years, expressed as mean differences in ml/min per 1...
February 1, 2023: Clinical Journal of the American Society of Nephrology: CJASN
#16
JOURNAL ARTICLE
John H Klich, Catherine M Kasse, Joseph L Mann, Yaoqi Huang, Andrea I d'Aquino, Abigail K Grosskopf, Julie Baillet, Gerald G Fuller, Eric A Appel
Monoclonal antibodies are a staple in modern pharmacotherapy. Unfortunately, these biopharmaceuticals are limited by their tendency to aggregate in formulation, resulting in poor stability and often requiring low concentration drug formulations. Moreover, existing excipients designed to stabilize these formulations are often limited by their toxicity and tendency to form particles such as micelles. Here, we demonstrate the ability of a simple "drop-in", amphiphilic copolymer excipient to enhance the stability of high concentration formulations of clinically-relevant monoclonal antibodies without altering their pharmacokinetics or injectability...
January 2023: Advanced Therapeutics
#17
REVIEW
Fadi Fakhouri, Nora Schwotzer, Gianfranca Cabiddu, Jonathan Barratt, Hélène Legardeur, Vesna Garovic, Alejandra Orozco-Guillen, Jack Wetzels, Eric Daugas, Gabriella Moroni, Marina Noris, Vincent Audard, Manuel Praga, Elisa Llurba, Grégoire Wuerzner, Rossella Attini, David Desseauve, Elena Zakharova, Claudio Luders, Kate Wiles, Filomena Leone, Shilpanjali Jesudason, Nathalie Costedoat-Chalumeau, Andrea Kattah, Virgilia Soto-Abraham, Alexandre Karras, Jai Prakash, Liz Lightstone, Pierre Ronco, Claudio Ponticelli, Gerald Appel, Giuseppe Remuzzi, Vassilis Tsatsaris, Giorgina Barbara Piccoli
Our understanding of the various aspects of pregnancy in women with kidney diseases has significantly improved in the last decades. Nevertheless, little is known about specific kidney diseases. Glomerular diseases are not only a frequent cause of chronic kidney disease in young women, but combine many challenges in pregnancy: immunologic diseases, hypertension, proteinuria, and kidney tissue damage. An international working group undertook the review of available current literature and elicited expert opinions on glomerular diseases in pregnancy with the aim to provide pragmatic information for nephrologists according to the present state-of-the-art knowledge...
February 2023: Kidney International
#18
JOURNAL ARTICLE
Laura H Mariani, Sean Eddy, Fadhl M AlAkwaa, Phillip J McCown, Jennifer L Harder, Viji Nair, Felix Eichinger, Sebastian Martini, Adebowale D Ademola, Vincent Boima, Heather N Reich, Jamal El Saghir, Bradley Godfrey, Wenjun Ju, Emily C Tanner, Virginia Vega-Warner, Noel L Wys, Sharon G Adler, Gerald B Appel, Ambarish Athavale, Meredith A Atkinson, Serena M Bagnasco, Laura Barisoni, Elizabeth Brown, Daniel C Cattran, Gaia M Coppock, Katherine M Dell, Vimal K Derebail, Fernando C Fervenza, Alessia Fornoni, Crystal A Gadegbeku, Keisha L Gibson, Laurence A Greenbaum, Sangeeta R Hingorani, Michelle A Hladunewich, Jeffrey B Hodgin, Marie C Hogan, Lawrence B Holzman, J Ashley Jefferson, Frederick J Kaskel, Jeffrey B Kopp, Richard A Lafayette, Kevin V Lemley, John C Lieske, Jen-Jar Lin, Rajarasee Menon, Kevin E Meyers, Patrick H Nachman, Cynthia C Nast, Michelle M O'Shaughnessy, Edgar A Otto, Kimberly J Reidy, Kamalanathan K Sambandam, John R Sedor, Christine B Sethna, Pamela Singer, Tarak Srivastava, Cheryl L Tran, Katherine R Tuttle, Suzanne M Vento, Chia-Shi Wang, Akinlolu O Ojo, Dwomoa Adu, Debbie S Gipson, Howard Trachtman, Matthias Kretzler
The diagnosis of nephrotic syndrome relies on clinical presentation and descriptive patterns of injury on kidney biopsies, but not specific to underlying pathobiology. Consequently, there are variable rates of progression and response to therapy within diagnoses. Here, an unbiased transcriptomic-driven approach was used to identify molecular pathways which are shared by subgroups of patients with either minimal change disease (MCD) or focal segmental glomerulosclerosis (FSGS). Kidney tissue transcriptomic profile-based clustering identified three patient subgroups with shared molecular signatures across independent, North American, European, and African cohorts...
March 2023: Kidney International
#19
RANDOMIZED CONTROLLED TRIAL
Carla Nester, Gerald B Appel, Andrew S Bomback, Koenraad Peter Bouman, H Terence Cook, Erica Daina, Bradley P Dixon, Kara Rice, Nader Najafian, James Hui, Steven D Podos, Craig B Langman, Liz Lightstone, Samir V Parikh, Matthew C Pickering, C John Sperati, Howard Trachtman, James Tumlin, Aiko Pj de Vries, Jack F M Wetzels, Giuseppe Remuzzi
INTRODUCTION: C3 glomerulopathy (C3G) is an ultrarare, chronic and progressive nephropathy mediated by dysregulation of the alternative pathway of complement (AP), with poor prognosis and limited treatment options. Targeted inhibition of proximal AP through factor D (FD) blockade represents a rational treatment approach. We present two phase 2 proof-of-concept clinical studies of the orally active FD inhibitor danicopan in patients with C3G and immune complex-mediated membranoproliferative glomerulonephritis (IC-MPGN) (NCT03369236 and NCT03459443)...
2022: American Journal of Nephrology
#20
RANDOMIZED CONTROLLED TRIAL
Bradley A Warady, Pablo E Pergola, Rajiv Agarwal, Sharon Andreoli, Gerald B Appel, Sripal Bangalore, Geoffrey A Block, Arlene B Chapman, Melanie P Chin, Keisha L Gibson, Angie Goldsberry, Kazumoto Iijima, Lesley A Inker, Clifford E Kashtan, Bertrand Knebelmann, Laura H Mariani, Colin J Meyer, Kandai Nozu, Megan O'Grady, Michelle N Rheault, Arnold L Silva, Peter Stenvinkel, Roser Torra, Glenn M Chertow
BACKGROUND AND OBJECTIVES: Alport syndrome is an inherited disease characterized by progressive loss of kidney function. We aimed to evaluate the safety and efficacy of bardoxolone methyl in patients with Alport syndrome. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We randomly assigned patients with Alport syndrome, ages 12-70 years and eGFR 30-90 ml/min per 1.73 m2 , to bardoxolone methyl ( n =77) or placebo ( n =80). Primary efficacy end points were change from baseline in eGFR at weeks 48 and 100...
December 2022: Clinical Journal of the American Society of Nephrology: CJASN
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