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1. The Role of Glomerular Epithelial Injury in Kidney Function Decline in Patients With Diabetic Kidney Disease in the TRIDENT Cohort

Author

Matthew B. Palmer, Amin Abedini, Casey Jackson, Shira Blady, Shatakshee Chatterjee, Katie Marie Sullivan, Raymond R. Townsend, Jens Brodbeck, Salem Almaani, Anand Srivastava, Rupali Avasare, Michael J. Ross, Amy K. Mottl, Christos Argyropoulos, Jonathan Hogan, and Katalin Susztak

Subjects
diabetic kidney disease, end-stage kidney disease, glomerular epithelial injury, kidney function, pathological descriptors, Diseases of the genitourinary system. Urology, RC870-923
Abstract

Introduction: Although diabetic kidney disease (DKD) is responsible for more than half of all chronic and end-stage kidney disease (ESKD), the association of light (LM) and electron microscopic (EM) structural changes with clinical parameters and prognosis in DKD is incompletely understood. Methods: This is an interim analysis of 62 patients diagnosed with biopsy-confirmed DKD from the multicenter TRIDENT (Transformative Research in Diabetic Nephropathy) study. Twelve LM and 8 EM descriptors, representing changes in glomeruli, tubulointerstitium, and vasculature were analyzed for their relationship with clinical measures of renal function. Patients were followed every 6 months. Results: Multivariable linear regression analysis revealed that estimated glomerular filtration rate (eGFR) upon enrollment correlated the best with interstitial fibrosis. On the other hand, the rate of kidney function decline (eGFR slope) correlated the most with glomerular lesions including global glomerulosclerosis and mesangiolysis. Unbiased clustering analysis based on histopathologic data identified 3 subgroups. The first cluster, encompassing subjects with the mildest histologic lesions, had the most preserved kidney function. The second and third clusters had similar degrees of kidney dysfunction and structural damage, but differed in the degree of glomerular epithelial cell and podocyte injury (podocytopathy DKD subtype). Cox proportional hazard analysis showed that subjects in cluster 2 had the highest risk to reach ESKD (hazard ratio: 17.89; 95% confidence interval: 2.13–149.79). Glomerular epithelial hyperplasia and interstitial fibrosis were significant predictors of ESKD in the multivariate model. Conclusion: The study highlights the association between fibrosis and kidney function and identifies the role of glomerular epithelial changes and kidney function decline.

Published
2021
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2. Longitudinal Changes in Health-Related Quality of Life in Primary Glomerular Disease: Results From the CureGN Study

Author

Shannon L. Murphy, John D. Mahan, Jonathan P. Troost, Tarak Srivastava, Amy J. Kogon, Yi Cai, T. Keefe Davis, Hilda Fernandez, Alessia Fornoni, Rasheed A. Gbadegesin, Emily Herreshoff, Pietro A. Canetta, Patrick H. Nachman, Bryce B. Reeve, David T. Selewski, Christine B. Sethna, Chia-shi Wang, Sharon M. Bartosh, Debbie S. Gipson, Katherine R. Tuttle, Ali Gharavi, Wooin Ahn, Gerald B. Appel, Rupali S. Avasare, Revekka Babayev, Ibrahim Batal, Andrew S. Bomback, Eric Brown, Eric S. Campenot, Pietro Canetta, Brenda Chan, Vivette D. D’Agati, Bartosz Foroncewicz, Gian Marco Ghiggeri, William H. Hines, Namrata G. Jain, Krzysztof Kiryluk, Fangming Lin, Francesca Lugani, Maddalena Marasa, Glen Markowitz, Sumit Mohan, Krzysztof Mucha, Thomas L. Nickolas, Jai Radhakrishnan, Maya K. Rao, Renu Regunathan-Shenk, Simone Sanna-Cherchi, Dominick Santoriello, Michael B. Stokes, Natalie Yu, Anthony M. Valeri, Ronald Zviti, Larry A. Greenbaum, William E. Smoyer, Amira Al-Uzri, Isa Ashoor, Diego Aviles, Rossana Baracco, John Barcia, Sharon Bartosh, Craig Belsha, Michael C. Braun, Aftab Chishti, Donna Claes, Carl Cramer, Keefe Davis, Elif Erkan, Daniel Feig, Michael Freundlich, Melisha Hanna, Guillermo Hidalgo, Amrish Jain, Myda Khalid, Mahmoud Kallash, MD, Jerome C. Lane, John Mahan, Nisha Mathews, Carla Nester, Cynthia Pan, Hiren Patel, Adelaide Revell, Rajasree Sreedharan, Julia Steinke, Scott E. Wenderfer, Craig S. Wong, Ronald Falk, William Cook, Vimal Derebail, Agnes Fogo, Adil Gasim, Todd Gehr, Raymond Harris, Jason Kidd, Louis-Philippe Laurin, Will Pendergraft, Vincent Pichette, Thomas Brian Powell, Matthew B. Renfrow, Virginie Royal, Lawrence B. Holzman, Sharon Adler, Charles Alpers, Raed Bou Matar, Elizabeth Brown, Michael Choi, Katherine M. Dell, Ram Dukkipati, Fernando C. Fervenza, Crystal Gadegbeku, Patrick Gipson, Leah Hasely, Sangeeta Hingorani, Michelle A. Hladunewich, Jonathan Hogan, J. Ashley Jefferson, Kenar Jhaveri, Duncan B. Johnstone, Frederick Kaskel, Amy Kogan, Jeffrey Kopp, Kevin V. Lemley, Laura Malaga- Dieguez, Kevin Meyers, Alicia Neu, Michelle Marie O'Shaughnessy, John F. O’Toole, Rulan Parekh, Heather Reich, Kimberly Reidy, Helbert Rondon, Kamalanathan K. Sambandam, John R. Sedor, Jeffrey Schelling, John C. Sperati, Agnes Swiatecka-Urban, Howard Trachtman, Joseph Weisstuch, Olga Zhdanova, Brenda Gillespie, Matthias Kretzler, Bruce M. Robinson, Laura Mariani, Matthew Wladkowski, and Lisa M. Guay-Woodford

Subjects
edema, health-related quality of life, patient-reported outcomes, primary glomerular disease, Diseases of the genitourinary system. Urology, RC870-923
Abstract

Introduction: Prior cross-sectional studies suggest that health-related quality of life (HRQOL) worsens with more severe glomerular disease. This longitudinal analysis was conducted to assess changes in HRQOL with changing disease status. Methods: Cure Glomerulonephropathy (CureGN) is a cohort of patients with minimal change disease, focal segmental glomerulosclerosis, membranous nephropathy, IgA vasculitis, or IgA nephropathy. HRQOL was assessed at enrollment and follow-up visits 1 to 3 times annually for up to 5 years with the Patient-Reported Outcomes Measurement Information System (PROMIS). Global health, anxiety, and fatigue domains were measured in all; mobility was measured in children; and sleep-related impairment was measured in adults. Linear mixed effects models were used to evaluate HRQOL responsiveness to changes in disease status. Results: A total of 469 children and 1146 adults with PROMIS scores were included in the analysis. HRQOL improved over time in nearly all domains, though group-level changes were modest. Edema was most consistently associated with worse HRQOL across domains among children and adults. A greater number of symptoms also predicted worse HRQOL in all domains. Sex, age, obesity, and serum albumin were associated with some HRQOL domains. The estimated glomerular filtration rate (eGFR) was only associated with fatigue and adult physical health; proteinuria was not associated with any HRQOL domain in adjusted models. Conclusion: HRQOL measures were responsive to changes in disease activity, as indicated by edema. HRQOL over time was not predicted by laboratory-based markers of disease. Patient-reported edema and number of symptoms were the strongest predictors of HRQOL, highlighting the importance of the patient experience in glomerular disease. HRQOL outcomes inform understanding of the patient experience for children and adults with glomerular diseases.

Published
2020
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3. Sparsentan in patients with IgA nephropathy: a prespecified interim analysis from a randomised, double-blind, active-controlled clinical trial

Author

Hiddo J L Heerspink, Jai Radhakrishnan, Charles E Alpers, Jonathan Barratt, Stewart Bieler, Ulysses Diva, Jula Inrig, Radko Komers, Alex Mercer, Irene L Noronha, Michelle N Rheault, William Rote, Brad Rovin, Howard Trachtman, Hernán Trimarchi, Muh Geot Wong, Vlado Perkovic, Eric Alarmartine, Dong Wan Chae, Lucia Del Vecchio, Jurgen Floege, Shang-Jyh Hwang, Bojan Jelakovic, Bart Maes, Robert Malecki, Marius Miglinas, Fernando Eduardo Barbosa Nolasco, Manual Praga, Kannaiyan Rabindranath, Mai Rosenberg, Sydney Chi Wai Tang, Vladmir Tesar, Bhadran Bose, Muralikrishna Gangadharan, Stephen McDonald, Chen Peh, Sadia Jahan, Chii Yeap, Philip Clayton, Georgina Irish, Nikhil Thyagarajan, Peter Hollett, Rathika Krishnasamy, Robert Carroll, Shilpanjali Jesudason, Susan Crail, Toby Coates, Jane Waugh, Euan Noble, Kumaradevan Mahadevan, Victoria Campbell, Tania Salehi, Wai Lim, Neil Boudville, Aron Chakera, Doris Chan, Anoushka Krishnan, Yusuf Eqbal, Alastair Gillies, Eswari Vilayur, Thida Maung Maung Myint, Nicholas Gray, Melissa Cheetham, Carol Pollock, Bruce Cooper, Amanda Mather, Sarah Roxburgh, Yvonne Shen, Stefanie Stangenberg, Amanda Siriwardana, Emma O'Lone, Susan Wan, Brendon Neuen, Jeffrey Tsun Kit Ha, Dana Kim, Lauren Heath, Arunima Jain, Elaine Phua, Yan Li, Martin Gallagher, Meg Jardine, Angus Ritchie, Mona Razavian, Celine Foote, Roger Wyndham, Shaundeep Sen, Zoltan Endre, Jonathan Erlich, Mangalee Fernando, Kenneth Yong, Grant Luxton, Sradha Kotwal, Simon Roger, Vidu Wijeratne, David Packham, Ian Fraser, Bert Vandewiele, Margo Laute, Wim Lemahieu, Sofie Jamar, Sara Ombelet, Gert Meeus, Marc Decupere, Olivier Schockaert, Peter Doubel, Liesbeth Viaene, Luc Radermacher, Catherine Masset, Martial Moonen, Eric Firre, Martina Milicevic, Xavier Warling, An Vanacker, Thomas Malfait, Ivan Durlen, Ivica Horvatic, Ana Savuk, Lana Gellineo, Sandra Karanovic, Zivka Dika, Djuro Plavljanic, Ivana Mikacic, Dubravka Trajbar Kentric, Dunja Barisic, Marija Stankovic, Karolina Majstorovic Barac, Ivan Kruljac, Drasko Pavlovic, Martin Drinkovic, Ingrid Prkacin, Jerko Barbic, Zvonimir Sitas, Dunja Vujcic, Ivan Rychlik, Anna Benesova, Klara Drinovska, Karolina Kratka, Dita Maixnerova, Madis Ilmoja, Kristin Unt, Kadri Lilienthal, Asta Auerbach, Liisi Leis, Julia Piel, Annika Adoberg, Kulli Kolvald, Kristi Veermae, Kadri Telling, Elviira Seppet, Jana Uhlinova, Philippe Zaoui, Pierre-Louis Carron, Ingrid Masson, Miriana Dinic, Damien Thibaudin, Christian Broyet, Nicolas Maillard, Hesham Mohey, Christophe Mariat, Guillaume Claisse, Eric Alamartine, Bertrand Dussol, Stephane Burtey, Noemie Chiche-Jourde, Jean-Emmanuel Serre, Guillaume Jeantet, Leila Chenine, Anne Blanchard, Stephane Roueff, Eric Thervet, David Fouassier, Alexandre Buffet, Marine Livrozet, Roxane Gaisset, Alexandre Karras, Anne-Elisabeth Heng, Cyril Garrouste, Carole Philipponnet, Clementine Nicolo, Alba Atenza, Camille Lanaret, Clarisse Greze, Valentin Mayet, Clement Dumond, Yahsou Delmas, Christian Combe, Claire Rigothier, Laure Burguet, Aurore Labat, Simon Mucha, Valérie de Précigout, Thomas Weinreich, Helmut Reichel, Diliana Draganova, Lothar Wolf, Bernd Hohenstein, Sven Heinrichs, Simone Kulka, Sebahat Sat, Lea Weiland, Thilo Krueger, Gunter Wolf, Christiane Kettner, Mandy Schlosser, Johann Konstantin Herfurth, Annegret Koch, Martin Busch, Stephan Christian Werth, Martin Nitschke, Figen Cakiroglu, Franziska Sarnow, Lisa Schulz, Stefan Weiner, Nikolaus Wirtz, Eric Koester, Marcus Moeller, Eleni Stamellou, Silja Sanden, Hans Schmidt-Guertler, Wanja Bernhardt, Margret Patecki, Georg Schlieper, Kevin Schulte, Annette Girardet, Ulrich Kunzendorf, Lorraine Pui Yuen Kwan, Maggie Ming Yee Mok, Gary Chi Wang Chan, Mingyao Ma, Davina Ngoi Wah Lie, Anthony Ting Pong Chan, Cheuk Chun Szeto, Kit Chung Jack Ng, Siu Fai Cheung, Tak Tai Andrew Yue, Ka Shun Samuel Fung, Hon Tang, Ka Fai Yim, Wai Ping Law, Yick Hei Wong, Chi Kwan Darwin Lam, Sze Ho Sunny Wong, Carmelita Marcantoni, Roberta Aliotta, Francesca Deodato, Gemma Patella, Nicolino Comi, Caterina Vita, Nazareno Carullo, Davide Bolignano, Michela Musolino, Matias Trillini, Norberto Perico, Giuseppe Remuzzi, Erica Daina, Luigi Biancone, Loredana Colla, Manuel Burdese, Chiara Cogno, Elena Boaglio, Isabella Abbasciano, Carlotta Federica Zizzi, Paolo Randone, Pietro Napodano, Anna Ricchiuto, Matthias Cassia, Simone Accarino, Mario Cozzolino, Rocco Baccaro, Stefano Costanzi, Federica Di Maio, Maria Arena, Federica Urciuolo, Sara Vigano, Andrea Cavalli, Monica Limardo, Monica Bordoli, Serena Ponti, Selena Longhi, Andrea Solazzo, Francesco Giaroni, Gabriele Donati, Massimo Torreggiani, Davide Catucci, Marco Colucci, Vittoria Esposito, Ciro Esposito, Loreto Gesualdo, Flavia Capaccio, Emma Diletta Stea, Carmen Sivo, Francesca Annese, Federica Papadia, Piergiorgio Messa, Mirco Belingheri, Patrizia Passerini, Silvia Malvica, Alvita Vickiene, Urte Zakauskiene, Egle Asakiene, Inga Arune Bumblyte', Asta Stankuviene, Lina Santockiene, Ashik Hayat, Allister Williams, Peter Sizeland, Eddie Tan, Gerald Waters, Lai Wan Chan, Andrew Henderson, Angus Turnbull, Andrew McNally, Annie Reynolds, Helen Pilmore, Ian Dittmer, Paul Manley, Elizabeth Stallworthy, Tze Goh, David Semple, Michael Collins, Elizabeth Curry, Jafar Ahmed, Thu Nguyen, Agata Winiarska, Justyna Zbrzezniak, Tomasz Stompor, Magdalena Krajewska, Hanna Augustyniak-Bartosik, Dorota Zielinska, Anna Jander, Malgorzata Stanczyk, Marcin Tkaczyk, Przemyslaw Miarka, Dariusz Aksamit, Piotr Jaskowski, Wladyslaw Sulowicz, Dominik Cieniawski, Julita Gontarek-Kacprzak, Elzbieta Felicjanczuk, Norbert Kwella, Bogna Kwella, Ewa Satora, João Carlos Fernandes, Ana Marta Gomes, Marina Reis, Daniela Lopes, Catarina Almeida, Helena Sá, Ana Carolina Figueiredo, Clara Pardinhas, Edgar Almeida, Mario Raimundo, Ana Cortesão Costa, Luis Pedro Falcao Goncalves, Sara Fernandes, Sónia Silva, Catarina Teixeira, Adriana Fernandes, Fernando Nolasco, Patricia Alves, Mario Gois, Nuno Fonseca, Ana Messias, Maria Menezes, Filipa Cardoso, Helena Sousa, Joana Marques, Rui Barata, Jose Antonio Lopes, Sofia Jorge, Joana Gameiro, Jose Nuno de Almeida Agapito Fonseca, Sara Goncalves, Ana Farinha, Patricia Valerio Santos, Ana Natario, Jose Carlos de Jesus Barreto, Catarina Abrantes, Elsa Sofia Quadrado Soares, Joana de Sousa Soares Felgueiras, Liliana Cunha, Lucia Parreira, Teresa Furtado, Alvaro Vaz, Kook-Hwan Oh, Hajeong Lee, Se Joong Kim, Jong Cheol Jeong, Yeong Hoon Kim, Yunmi Kim, Hyeong Cheon Park, Hoon Young Choi, Hyung Wook Kim, Moon Hyoung Lee, Songuk Yoon, Kyu-Beck Lee, YoungYoul Hyun, Tae-Hyun Yoo, Seung Hyeok Han, Jung Tak Park, Sunggyun Kim, Young Rim Song, Jwa-Kyung Kim, Hyung-seok Lee, Narae Joo, JungEun Lee, Hye Ryoun Jang, Junseok Jeon, Wookyung Chung, HyunHee Lee, Jae Hyun Chang, Ka Yeong Chun, Ji Yong Jung, Han Ro, Aejin Kim, Sang-Kyung Jo, Jihyun Yang, Myung-Gyu Kim, SeWon Oh, Caridad Martinez Villanueva, Ana Vilar Gimeno, Gustavo Andres Useche Bonilla, Esther Tamarit, Antonio Galan Serrano, Eduardo Verde Moreno, Jose Luño Fernandez, Maria Angeles Goicoechea Diezhandino, Ursula Verdalles Guzman, Ana Perez de Jose, Alberto Ortiz Arduan, María Vanessa Pérez Gómez, Catalina Martín Cleary, Raul Fernandez Prado, Elena Goma, Jose Ballarin, Montserrat Diaz Encarnacion, Iara Da Silva Santos, Helena Marco Rusinol, Monica Furlano, Carlos Arias, Clara Barrios, Eva Rodriguez Garcia, Adriana Sierra Ochoa, Belen Vizcaino Castillo, Jonay Pantoja Perez, Mercedes Gonzalez Moya, Mari Sargsyan, Emma Calatayud Aristoy, Ana Avila Bernabeu, Leticia Perez Lluna, Tamara Malek Marin, Maria Antonia Munar Vila, Ivon Maritza Bobadilla Rico, Natalia Allende Burgos, Eduardo Gutierrez Martinez, Elena Gutierrez Solis, Angel Sevillano, Evangelina Merida Herrero, Josep Miquel Blasco Pelicano, Lida Maria Rodas Marin, Luis F Quintana, Maria Antonieta Azancot Rivero, Natalia Ramos Terrades, Clara Garcia Carro, Irene Agraz Pamplona, Mercedes Salgueira Lazo, Francisco de la Prada Alvarez, Fabiola Alonso Garcia, Wenceslao Adrian Aguilera Morales, Salia Virxinia Pol Heres, Angel Forcen, Eduardo Parra Moncasi, Cristina Medrano Villarroya, Alejandro Soria Villen, Olga Gracia Garcia, Mercedes Velo Plaza, Maria Dolores Sánchez de la Nieta, Marta Calvo Arevalo, Antolina Moreno, Secundino Cigarran Guldris, Manuel Pereira de Vicente, Bang-Gee Hsu, Chih-Hsien Wang, Cheng-Hsu Chen, Tung-Min Yu, Ming-Ju Wu, Shang-Feng Tsai, Chia-Tien Hsu, Hsien-Fu Chiu, Kang-Ju Chou, Hua-Chang Fang, Po-Tsang Lee, Hsin-Yu Chen, Chien-Liang Chen, Chien-Wei Huang, Shih-Hsiang Ou, Tzung-Yo Ho, Chih-Yang Hsu, Ming-Shan Chang, Yen-Ling Chiu, Yu-Sen Peng, Kai-Hsiang Shu, Szu-Yu Pan, Shih-Ping Hsu, Ju-Yeh Yang, Mei-Fen Pai, Po-Yu Tseng, Hon-Yen Wu, Wan-Chuan Tsai, Kuei-Ting Tung, Hung-Yuan Chen, Hung-Chun Chen, Mei-Chuan Kuo, Daw-Yang Hwang, Yi-Wen Chiu, Chi-Chih Hung, Hung-Tien Kuo, Jer-Chia Tsai, Kieran McCafferty, Suzanne Forbes, Indranil Dasgupta, Mark Thomas, Amar Mahdi, Bamidele Ajayi, Paramit Chowdhury, Theodoros Kasimatis, Dimitrios Moutzouris, Caroline Dudreuilh, Rishi Pruthi, Nick Mansfield, Gabriel Doctor, Sapna Shah, Sui Kon, Priscilla Smith, Patrick Hamilton, Durga Kanigicherla, Omar Sherin Ibrahim Ragy, Bassam Alchi, Oliver Flossmann, Farid Ghalli, Sarah Lawman, Smeeta Sinha, Constantina Chrysochou, Chukwuma Chukwu, Aine Maire De Bhailis, Saif Al Chalabi, Amy Hudson, Arun Gopu, Olivia Wickens, Joshua Storrar, Mona Wahba, Nathan Lorde, Mohammad Rony, Sian Griffin, Farah Latif, Mohammad Ali, Louise DaSilva, Jonathan Ayling-Smith, Eamon Mahdi, Lisa Willcocks, Rachel Jones, Chee Kay Cheung, Haresh Selvaskandan, Dan Pugh, Matthew Sayer, Neeraj Dhaun, Fiona Chapman, Patrick Mark, Colin Geddes, Emily McQuarrie, Rajan Patel, Laurence Solomon, Arvind Ponnusamy, Adam Morris, Pedro Okoh, Lauren Floyd, Ajay Dhaygude, Janson Leung, Christopher Goldsmith, Bhavna Pandya, Didem Tez, Ashraf Mikhail, Karen Brown, Thomas Bucknall, Mark Lambie, Roderick Comunale, Donald Brandon, Stacy Martinez, Amanda Hall, Amy Henderson, Aaron Fearday, Nicole Douthit, Brian Snow, Arnold Silva, Cathylee Sly, Christopher Keller, Robert Davidson, Jerry Meng, Robert Haws, Siddhartha Kattamanchi, Javad Mojarrab, Unnikrishnan Pillai, Richard Lafayette, Michelle O'Shaughnessy, Fahameedah Kamal, Kshama Mehta, Bruce Baker, Mario Ruiz, Praveena Jyothinagaram, Usha Peri, William Paxton, James Tumlin, Kerri McGreal, Ellen McCarthy, Cassandra Kimber, Archana Gautam, Kassem Khalil, Viet Nguyen, Raffi Minasian, Dariush Arfaania, Sam Daneshvari, Michel Zakari, Artashes Patrikyan, Rouzbeh Afsari, Christine Ayvazyan, Faisal Fakih, Mark Lagatta, Alfred Rodriguez, Jorge Enrique Monroy Avella, Ramachandra Patak, Jigar Kadakia, Gerald Appel, Wooin Ahn, Bradley Nelson, Allyson Medina, Syeda Ahmad, Yonatan Peleg, Nisha Clement, Ian Chiu, Elizabeth Hendren, Andrew Bomback, Pietro Canetta, Bruce Spinowitz, Chaim Charytan, Nishita Parikh, Sheng Kuo, Ritesh Raichoudhury, Mirela Dobre, Lavinia Negrea, Aparna Padiyar, Arksarapuk Jittirat, Nishigandha Pradhan, Ranjit Dhelaria, Saravanan Balamuthusamy, Machaiah Madhrira, Thomas Powell, Howard Lifland, Asha Bailey, Sarah Ashley Ford Sightler, Meera Patel Suthar, Heather Green, Samir Parikh, Isabelle Ayoub, Salem Almaani, Gabriel Contreras, Alessia Fornoni, Yelena Drexler, Abdallah Geara, Brittany Sheridan, Gaia Coppock, Jonathan Hogan, Carlos Gonzalez, Shamik Bhadra, Pradip Chowdhury, Kay Kyaw, May Tan, Lathika Raakesh, Elder Mendoza, Veronica Viramontes, Asghar Chaudhry, Juan Carbonell, Rajdeep Gadh, Victor Fernandez, Mohamad Kassem, Radu Jacob, Karen Wilder, Britt Newsome, Kathryn Klamm, Irina Suyumova, Laura Ann Kooienga, Catherine Janko, Dana Rizk, Bruce Julian, Dawn Caster, Erika Perez, Gunjan Garg, Nayan Gowda, Suneel Udani, Sreedhar Mandayam, Biruh Workeneh, Ali Assefi, Barbara Greco, Michael Germain, Jusmin Patel, Sarah Quinn, James Sullivan, Jeffrey Glaze, Phillip Madonia, Kellyn McMahon, Harold Giles, Sharon Adler, and Tiane Dai

Subjects
General Medicine
Published
2023

4. Urinary Single-Cell Profiling Captures the Cellular Diversity of the Kidney

Author

Amin, Abedini, Yuan O, Zhu, Shatakshee, Chatterjee, Gabor, Halasz, Kishor, Devalaraja-Narashimha, Rojesh, Shrestha, Michael S, Balzer, Jihwan, Park, Tong, Zhou, Ziyuan, Ma, Katie Marie, Sullivan, Hailong, Hu, Xin, Sheng, Hongbo, Liu, Yi, Wei, Carine M, Boustany-Kari, Uptal, Patel, Salem, Almaani, Matthew, Palmer, Raymond, Townsend, Shira, Blady, Jonathan, Hogan, Lori, Morton, Katalin, Susztak, and Yan, Zhong

Subjects
Male, 0301 basic medicine, Nephrology, medicine.medical_specialty, Pathology, Cell type, Urinary system, Urinary Bladder, 030232 urology & nephrology, Urine, Biology, Kidney, Podocyte, Transcriptome, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Loop of Henle, DNA Barcoding, Taxonomic, Humans, RNA-Seq, Aged, Gene Library, Podocytes, General Medicine, Middle Aged, Basic Research, 030104 developmental biology, medicine.anatomical_structure, Female, Kidney Diseases, Single-Cell Analysis
Abstract

Background Microscopic analysis of urine sediment is probably the most commonly used diagnostic procedure in nephrology. The urinary cells, however, have not yet undergone careful unbiased characterization. Methods Single-cell transcriptomic analysis was performed on 17 urine samples obtained from five subjects at two different occasions, using both spot and 24-hour urine collection. A pooled urine sample from multiple healthy individuals served as a reference control. In total 23,082 cells were analyzed. Urinary cells were compared with human kidney and human bladder datasets to understand similarities and differences among the observed cell types. Results Almost all kidney cell types can be identified in urine, such as podocyte, proximal tubule, loop of Henle, and collecting duct, in addition to macrophages, lymphocytes, and bladder cells. The urinary cell-type composition was subject specific and reasonably stable using different collection methods and over time. Urinary cells clustered with kidney and bladder cells, such as urinary podocytes with kidney podocytes, and principal cells of the kidney and urine, indicating their similarities in gene expression. Conclusions A reference dataset for cells in human urine was generated. Single-cell transcriptomics enables detection and quantification of almost all types of cells in the kidney and urinary tract.

Published
2021
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5. Persistent Disease Activity in Patients With Long-Standing Glomerular Disease

Author

Elisa Delbarba, Maddalena Marasa, Pietro A. Canetta, Stacy E. Piva, Debanjana Chatterjee, Byum Hee Kil, Xueru Mu, Keisha L. Gibson, Michelle A. Hladunewich, Jonathan J. Hogan, Bruce A. Julian, Jason M. Kidd, Louis-Philippe Laurin, Patrick H. Nachman, Michelle N. Rheault, Dana V. Rizk, Neil S. Sanghani, Howard Trachtman, Scott E. Wenderfer, Ali G. Gharavi, Andrew S. Bomback, Wooin Ahn, Gerald B. Appel, Revekka Babayev, Ibrahim Batal, Eric Brown, Eric S. Campenot, Pietro Canetta, Brenda Chan, Vivette D. D’Agati, Hilda Fernandez, Bartosz Foroncewicz, Gian Marco Ghiggeri, William H. Hines, Namrata G. Jain, Krzysztof Kiryluk, Wai L. Lau, Fangming Lin, Francesca Lugani, Glen Markowitz, Sumit Mohan, Krzysztof Mucha, Thomas L. Nickolas, Stacy Piva, Jai Radhakrishnan, Maya K. Rao, Simone Sanna-Cherchi, Dominick Santoriello, Michael B. Stokes, Natalie Yu, Anthony M. Valeri, Ronald Zviti, Larry A. Greenbaum, William E. Smoyer, Amira Al-Uzri, Isa Ashoor, Diego Aviles, Rossana Baracco, John Barcia, Sharon Bartosh, Craig Belsha, Corinna Bowers, Michael C. Braun, Aftab Chishti, Donna Claes, Carl Cramer, Keefe Davis, Elif Erkan, Daniel Feig, Michael Freundlich, Rasheed Gbadegesin, Melisha Hanna, Guillermo Hidalgo, Tracy E. Hunley, Amrish Jain, Mahmoud Kallash, Myda Khalid, Jon B. Klein, Jerome C. Lane, John Mahan, Nisha Mathews, Carla Nester, Cynthia Pan, Larry Patterson, Hiren Patel, Adelaide Revell, Cynthia Silva, Rajasree Sreedharan, Tarak Srivastava, Julia Steinke, Katherine Twombley, Tetyana L. Vasylyeva, Donald J. Weaver, Craig S. Wong, Salem Almaani, Isabelle Ayoub, Milos Budisavljevic, Vimal Derebail, Huma Fatima, Ronald Falk, Agnes Fogo, Todd Gehr, Keisha Gibson, Dorey Glenn, Raymond Harris, Susan Hogan, Koyal Jain, J. Charles Jennette, Bruce Julian, Jason Kidd, H. Davis Massey, Amy Mottl, Patrick Nachman, Tibor Nadasdy, Jan Novak, Samir Parikh, Vincent Pichette, Caroline Poulton, Thomas Brian Powell, Matthew Renfrow, Dana Rizk, Brad Rovin, Virginie Royal, Manish Saha, Neil Sanghani, Sally Self, Sharon Adler, Charles Alpers, Raed Bou Matar, Elizabeth Brown, Daniel Cattran, Michael Choi, Katherine M. Dell, Ram Dukkipati, Fernando C. Fervenza, Alessia Fornoni, Crystal Gadegbeku, Patrick Gipson, Leah Hasely, Sangeeta Hingorani, Michelle Hladunewich, Jonathan Hogan, Lawrence B. Holzman, J. Ashley Jefferson, Kenar Jhaveri, Duncan B. Johnstone, Frederick Kaskel, Amy Kogan, Jeffrey Kopp, Richard Lafayette, Kevin V. Lemley, Laura Malaga-Dieguez, Kevin Meyers, Alicia Neu, Michelle Marie O’Shaughnessy, John F. O’Toole, Rulan Parekh, Heather Reich, Kimberly Reidy, Helbert Rondon, Kamalanathan K. Sambandam, John R. Sedor, David T. Selewski, Christine B. Sethna, Jeffrey Schelling, John C. Sperati, Agnes Swiatecka-Urban, Katherine R. Tuttle, Joseph Weisstuch, Suzanne Vento, Olga Zhdanova, Brenda Gillespie, Debbie S. Gipson, Peg Hill-Callahan, Margaret Helmuth, Emily Herreshoff, Matthias Kretzler, Chrysta Lienczewski, Sarah Mansfield, Laura Mariani, Cynthia C. Nast, Bruce M. Robinson, Jonathan Troost, Matthew Wladkowski, Jarcy Zee, Dawn Zinsser, and Lisa M. Guay-Woodford

Subjects
medicine.medical_specialty, glomerulonephropathy, glomerular disease, 030232 urology & nephrology, Disease, 030204 cardiovascular system & hematology, Nephropathy, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Focal segmental glomerulosclerosis, Membranous nephropathy, Clinical Research, Internal medicine, Biopsy, medicine, Minimal change disease, focal segmental glomerulosclerosis, Creatinine, medicine.diagnostic_test, business.industry, membranous nephropathy, IgA nephropathy, medicine.disease, minimal change disease, chemistry, Nephrology, Cohort, business
Abstract

Introduction Glomerular diseases are characterized by variable disease activity over many years. We aimed to analyze the relationship between clinical disease activity and duration of glomerular disease. Methods Disease activity in adults with chronic minimal change disease, focal segmental glomerulosclerosis, membranous nephropathy, and IgA nephropathy (IgAN; first diagnostic biopsy >5 years before enrollment; Of Longstanding Disease [OLD] cohort, n = 256) followed at Columbia University Medical Center (CUMC), was compared with disease activity of an internal and external cohort of patients with first diagnostic biopsy, Graphical abstract

Published
2020
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6. Plasma metabolite profiles, cellular cholesterol efflux, and non-traditional cardiovascular risk in patients with CKD

Author

Xu Shi, Robert E. Gerszten, Maria Hamm de Miguel, Olle Melander, Alan R. Tall, Joanne Hsieh, Renu Regunathan-Shenk, Yuan Zhang, Jonathan Hogan, Annie J. Febus, Eric Lai, Jessica R. Singer, Rafael Lantigua, Martin Magnusson, Nan Wang, Anjali Ganda, Andrew J. Murphy, Nora Bijl, Serge Cremers, Farah N. Hussain, Ying Wang, Linda Vernocchi, Rupali S. Avasare, Bibhas Chakraborty, Laurent Yvan-Charvet, and Kristie M. Gordon

Subjects
Male, 0301 basic medicine, medicine.medical_specialty, Disease, 030204 cardiovascular system & hematology, Pharmacology, Monocytes, Article, Cell Line, Cytokine Receptor Common beta Subunit, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Risk Factors, Carnitine, Internal medicine, medicine, Humans, Diabetic Nephropathies, Renal Insufficiency, Chronic, Molecular Biology, Aged, Kidney, biology, Cholesterol, Biological Transport, Middle Aged, medicine.disease, 030104 developmental biology, medicine.anatomical_structure, Endocrinology, ABCG1, chemistry, Cardiovascular Diseases, ABCA1, Metabolome, biology.protein, Female, lipids (amino acids, peptides, and proteins), Efflux, Animal studies, Cardiology and Cardiovascular Medicine, ATP Binding Cassette Transporter 1, Follow-Up Studies, Kidney disease
Abstract

Patients with chronic kidney disease (CKD) experience high rates of atherosclerotic cardiovascular disease and death that are not fully explained by traditional risk factors. In animal studies, defective cellular cholesterol efflux pathways which are mediated by the ATP binding cassette transporters ABCA1 and ABCG1 are associated with accelerated atherosclerosis. We hypothesized that cholesterol efflux in humans would vary in terms of cellular components, with potential implications for cardiovascular disease.We recruited 120 CKD patients (eGFR30mL/min/1.73mThere was a strong positive correlation between cell-surface IL-3Rβ levels and monocyte counts in CKD (P0.001). ABCA1 mRNA was reduced in CKD vs. control monocytes (P0.05), across various etiologies of CKD. Cholesterol efflux to apolipoprotein A1 was impaired in monocytes from CKD patients with diabetic nephropathy (P0.05), but we found no evidence for a circulating HDL-mediated defect in cholesterol efflux in CKD. Profiling of plasma metabolites showed that medium-chain acylcarnitines were both independently associated with lower levels of cholesterol transporter mRNA in CKD monocytes at baseline (P0.05), and with cardiovascular events in CKD patients after median 2.6years of follow-up.Cholesterol efflux in humans varies in terms of cellular components. We report a cellular defect in ABCA1-mediated cholesterol efflux in monocytes from CKD patients with diabetic nephropathy. Unlike several traditional risk factors for atherosclerotic cardiovascular disease, plasma metabolites inversely associated with endogenous cholesterol transporters predicted cardiovascular events in CKD patients. (Funded by the National Institute of Diabetes and Digestive and Kidney DiseasesK23DK097288 and others.).

Published
2017
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7. Paraneoplastic glomerular diseases

Author

Jai Radhakrishnan and Jonathan Hogan

Subjects
Kidney, Pathology, medicine.medical_specialty, medicine.diagnostic_test, urogenital system, business.industry, Monoclonal immunoglobulin, Urine, urologic and male genital diseases, medicine.disease, medicine.anatomical_structure, Membranous nephropathy, Biopsy, medicine, Monoclonal protein, business, Glomerular diseases, B cell
Abstract

Paraneoplastic glomerular diseases are caused by proteins and other molecules that are produced by, or in response to tumors. The paraprotein-associated glomerular diseases are well-characterized paraneoplastic syndromes, because evidence can be provided for the site of production (clonal plasma or B cell), the tumor product (circulating monoclonal immunoglobulin in the blood or urine) and end-organ damage (kidney biopsy showing involvement by the monoclonal protein). Other paraneoplastic glomerular diseases exist, such as cancer-associated membranous nephropathy and some podocytopathies. In this chapter, we review the paraneoplastic glomerular diseases.

Published
2020
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8. Rationale and design of the Transformative Research in Diabetic Nephropathy (TRIDENT) Study

Author

Raymond R. Townsend, Paolo Guarnieri, Christos Argyropoulos, Shira Blady, Carine M. Boustany-Kari, Kishor Devalaraja-Narashimha, Lori Morton, Amy K. Mottl, Uptal Patel, Matthew Palmer, Michael J. Ross, Lea Sarov-Blat, Kathryn Steinbugler, Katalin Susztak, Randy Luciano, Michael Ross, Pietro Canetta, Krik Campbell, Jonathan Hogan, Amy Mottl, Oliver Lenz, Harold Szerlip, Shweta Bansal, Chip Brosius, Jeffery Schelling, Salem Almaani, Matthias Kretzler, Tamara Isakova, Rupali Avasare, and Richard Lafayette

Subjects
Adult, Aged, 80 and over, Male, Pathology, medicine.medical_specialty, Adolescent, business.industry, Biopsy, Kidney Glomerulus, Middle Aged, medicine.disease, Diabetic nephropathy, Observational Studies as Topic, Young Adult, Nephrology, Research Design, Glomerulus, Medicine, Humans, Diabetic Nephropathies, Female, Prospective Studies, business, Aged, Glomerular Filtration Rate
Published
2019

10. CureGN Study Rationale, Design, and Methods: Establishing a Large Prospective Observational Study of Glomerular Disease

Author

Laura H. Mariani, Andrew S. Bomback, Pietro A. Canetta, Michael F. Flessner, Margaret Helmuth, Michelle A. Hladunewich, Jonathan J. Hogan, Krzysztof Kiryluk, Patrick H. Nachman, Cynthia C. Nast, Michelle N. Rheault, Dana V. Rizk, Howard Trachtman, Scott E. Wenderfer, Corinna Bowers, Peg Hill-Callahan, Maddalena Marasa, Caroline J. Poulton, Adelaide Revell, Suzanne Vento, Laura Barisoni, Dan Cattran, Vivette D’Agati, J. Charles Jennette, Jon B. Klein, Louis-Philippe Laurin, Katherine Twombley, Ronald J. Falk, Ali G. Gharavi, Brenda W. Gillespie, Debbie S. Gipson, Larry A. Greenbaum, Lawrence B. Holzman, Matthias Kretzler, Bruce Robinson, William E. Smoyer, Lisa M. Guay-Woodford, Wooin Ahn, Gerald B. Appel, Revekka Babayev, Ibrahim Batal, Eric Brown, Eric S. Campenot, Pietro Canetta, Lucrezia Carlassara, Brenda Chan, Debanjana Chatterjee, Vivette D. D’Agati, Elisa Delbarba, Samriti Dogra, Hilda Fernandez, Bartosz Foroncewicz, Gian Marco Ghiggeri, William H. Hines, S. Ali Husain, Namrata G. Jain, Pascale Khairallah, Byum Hee Kil, Anushya Jeyabalan, Wai L. Lau, Fangming Lin, Francesca Lugani, Glen Markowitz, Sumit Mohan, Xueru Mu, Krzysztof Mucha, Thomas L. Nickolas, Stacy Piva, Jai Radhakrishnan, Maya K. Rao, Renu Regunathan-Shenk, Simone Sanna-Cherchi, Dominick Santoriello, Shayan Shirazian, Michael B. Stokes, Natalie Yu, Anthony M. Valeri, Ronald Zviti, Amira Al-Uzri, Josephine Ambruzs, Isa Ashoor, Diego Aviles, Rossana Baracco, John Barcia, Sharon Bartosh, Craig Belsha, Michael C. Braun, Yi Cai, Vladimir Chernitskiy, Aftab Chishti, Donna Claes, Kira Clark, Carl Cramer, Keefe Davis, Amy Dutcher, Elif Erkan, Daniel Feig, Michael Freundlich, Joseph Gaut, Rasheed Gbadegesin, Melisha Hanna, Guillermo Hidalgo, David Hooper, Tracy E. Hunley, Amrish Jain, Mahmoud Kallash, Margo Kamel, Myda Khalid, Theresa Kump, Jerome C. Lane, Helen Liapis, John Mahan, Nisha Mathews, Carla Nester, Cynthia Pan, Larry Patterson, Hiren Patel, Alice Raad, Cynthia Silva, Rajasree Sreedharan, Tarak Srivastava, Julia Steinke, Susan Sumner, Tetyana L. Vasylyeva, Chia-shi Wang, Donald J. Weaver, Craig S. Wong, Hong Yin, Anand Achanti, Salem Almaani, Isabelle Ayoub, Milos Budisavljevic, Maggie D'Angelo, Vimal Derebail, Huma Fatima, Ronald Falk, Agnes Fogo, Keisha Gibson, Dorey Glenn, Susan Hogan, Koyal Jain, Bruce Julian, Jason Kidd, H. Davis Massey, Amy Mottl, Shannon Murphy, Tibor Nadasdy, Jan Novak, Samir Parikh, Caroline Poulton, Thomas Brian Powell, Bryce Reeve, Matthew Renfrow, Monica Reynolds, Dana Rizk, Brad Rovin, Virginie Royal, Manish Saha, Neil Sanghani, Sally Self, Sharon Adler, Nada Alachkar, Charles Alpers, Raed Bou Matar, Carmen Avila-Casado, Serena Bagnasco, Emily Brede, Elizabeth Brown, Daniel Cattran, Michael Choi, Gabriel Contreras, Katherine M. Dell, Darren Dewalt, Michelle Denburg, Ram Dukkipati, Fernando C. Fervenza, Alessia Fornoni, Crystal Gadegbeku, Patrick Gipson, Anny Gonzalez-Zea, Leah Hasely, Elizabeth Hendren, Sangeeta Hingorani, Michelle Hladunewich, Jonathan Hogan, Jean Hou, J. Ashley Jefferson, Kenar Jhaveri, Duncan B. Johnstone, Frederick Kaskel, Amy Kogan, Jeffrey Kopp, Richard Lafayette, Kevin V. Lemley, Laura Malaga-Dieguez, Kevin Meyers, Alicia Neu, Michelle Marie O'Shaughnessy, John F. O’Toole, Andrea Oliverio, Matthew Palmer, Rulan Parekh, Renee Pitter, Heather Reich, Kimberly Reidy, Helbert Rondon, Kamalanathan K. Sambandam, Matthew Sampson, John R. Sedor, David T. Selewski, Christine B. Sethna, Jeffrey Schelling, John C. Sperati, Agnes Swiatecka-Urban, Katherine R. Tuttle, Meryl Waldman, Joseph Weisstuch, Roger Wiggins, David Williams, Cheryl Winkler, Eric Young, Olga Zhdanova, Charlotte Beil, Richard Eikstadt, Brenda Gillespie, John Graff, Stephen Hewitt, Emily Herreshoff, Chrysta Lienczewski, Sarah Mansfield, Laura Mariani, Keith McCullough, Nicholas Moore, Bruce M. Robinson, Melissa Sexton, Jonathan Troost, Matthew Wladkowski, Jarcy Zee, and Dawn Zinsser

Subjects
Adult, Male, medicine.medical_specialty, Henoch-Schonlein purpura, Adolescent, 030232 urology & nephrology, Disease, Glomerulonephritis, Membranous, Risk Assessment, Severity of Illness Index, Article, Nephropathy, Diagnosis, Differential, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Focal segmental glomerulosclerosis, Glomerulonephritis, Sex Factors, Membranous nephropathy, Internal medicine, medicine, Humans, Minimal change disease, 030212 general & internal medicine, Prospective Studies, Prospective cohort study, Child, Academic Medical Centers, business.industry, Glomerulosclerosis, Focal Segmental, Nephrosis, Lipoid, Biopsy, Needle, Age Factors, Glomerulonephritis, IGA, Middle Aged, medicine.disease, Prognosis, Immunohistochemistry, Survival Analysis, Nephrology, Multivariate Analysis, Disease Progression, Linear Models, Kidney Failure, Chronic, Female, business, Kidney disease
Abstract

Rationale & Objectives Glomerular diseases, including minimal change disease, focal segmental glomerulosclerosis, membranous nephropathy, and immunoglobulin A (IgA) nephropathy, share clinical presentations, yet result from multiple biological mechanisms. Challenges to identifying underlying mechanisms, biomarkers, and new therapies include the rarity of each diagnosis and slow progression, often requiring decades to measure the effectiveness of interventions to prevent end-stage kidney disease (ESKD) or death. Study Design Multicenter prospective cohort study. Setting & Participants Cure Glomerulonephropathy (CureGN) will enroll 2,400 children and adults with minimal change disease, focal segmental glomerulosclerosis, membranous nephropathy, or IgA nephropathy (including IgA vasculitis) and a first diagnostic kidney biopsy within 5 years. Patients with ESKD and those with secondary causes of glomerular disease are excluded. Exposures Clinical data, including medical history, medications, family history, and patient-reported outcomes, are obtained, along with a digital archive of kidney biopsy images and blood and urine specimens at study visits aligned with clinical care 1 to 4 times per year. Outcomes Patients are followed up for changes in estimated glomerular filtration rate, disease activity, ESKD, and death and for nonrenal complications of disease and treatment, including infection, malignancy, cardiovascular, and thromboembolic events. Analytical Approach The study design supports multiple longitudinal analyses leveraging the diverse data domains of CureGN and its ancillary program. At 2,400 patients and an average of 2 years' initial follow-up, CureGN has 80% power to detect an HR of 1.4 to 1.9 for proteinuria remission and a mean difference of 2.1 to 3.0mL/min/1.73m2 in estimated glomerular filtration rate per year. Limitations Current follow-up can only detect large differences in ESKD and death outcomes. Conclusions Study infrastructure will support a broad range of scientific approaches to identify mechanistically distinct subgroups, identify accurate biomarkers of disease activity and progression, delineate disease-specific treatment targets, and inform future therapeutic trials. CureGN is expected to be among the largest prospective studies of children and adults with glomerular disease, with a broad goal to lessen disease burden and improve outcomes.

Published
2018

11. Clinical Characteristics and Treatment Patterns of Children and Adults With IgA Nephropathy or IgA Vasculitis: Findings From the CureGN Study

Author

David T. Selewski, Josephine M. Ambruzs, Gerald B. Appel, Andrew S. Bomback, Raed Bou Matar, Yi Cai, Daniel C. Cattran, Aftab S. Chishti, Vivette D. D'Agati, Cynthia J. D'Alessandri-Silva, Rasheed A. Gbadegesin, Jonathan J. Hogan, Sandra Iragorri, J. Charles Jennette, Bruce A. Julian, Myda Khalid, Richard A. Lafayette, Helen Liapis, Francesca Lugani, Sarah A. Mansfield, Sherene Mason, Patrick H. Nachman, Cynthia C. Nast, Carla M. Nester, Damien G. Noone, Jan Novak, Michelle M. O'Shaughnessy, Heather N. Reich, Michelle N. Rheault, Dana V. Rizk, Manish K. Saha, Neil S. Sanghani, C. John Sperati, Rajasree Sreedharan, Tarak Srivastava, Agnieszka Swiatecka-Urban, Katherine Twombley, Tetyana L. Vasylyeva, Donald J. Weaver, Hong Yin, Jarcy Zee, Ronald J. Falk, Ali G. Gharavi, Brenda W. Gillespie, Debbie S. Gipson, Larry A. Greenbaum, Lawrence B. Holzman, Matthias Kretzler, Bruce M. Robinson, William E. Smoyer, Michael Flessner, Lisa M. Guay-Woodford, Krzysztof Kiryluk, Ali Gharavi, Wooin Ahn, Rupali S. Avasare, Revekka Babayev, Ibrahim Batal, Eric Brown, Eric S. Campenot, Pietro Canetta, Brenda Chan, Vivette D. D’Agati, Hilda Fernandez, Bartosz Foroncewicz, Gian Marco Ghiggeri, William H. Hines, Namrata G. Jain, Fangming Lin, Maddalena Marasa, Glen Markowitz, Sumit Mohan, Krzysztof Mucha, Thomas L. Nickolas, Jai Radhakrishnan, Maya K. Rao, Renu Regunathan-Shenk, Simone Sanna-Cherchi, Dominick Santoriello, Michael B. Stokes, Natalie Yu, Anthony M. Valeri, Ronald Zviti, Amira Al-Uzri, Isa Ashoor, Diego Aviles, Rossana Baracco, John Barcia, Sharon Bartosh, Craig Belsha, Michael C. Braun, Aftab Chishti, Donna Claes, Carl Cramer, Keefe Davis, Elif Erkan, Daniel Feig, Michael Freundlich, Melisha Hanna, Guillermo Hidalgo, Amrish Jain, Mahmoud Kallash, Jerome C. Lane, John Mahan, Nisha Mathews, Carla Nester, Cynthia Pan, Hiren Patel, Adelaide Revell, Julia Steinke, Scott E. Wenderfer, Craig S. Wong, Ronald Falk, William Cook, Vimal Derebail, Agnes Fogo, Adil Gasim, Todd Gehr, Raymond Harris, Jason Kidd, Louis-Philippe Laurin, Will Pendergraft, Vincent Pichette, Thomas Brian Powell, Matthew B. Renfrow, Virginie Royal, Sharon Adler, Charles Alpers, Elizabeth Brown, Daniel Cattran, Michael Choi, Katherine M. Dell, Ram Dukkipati, Fernando C. Fervenza, Alessia Fornoni, Crystal Gadegbeku, Patrick Gipson, Leah Hasely, Sangeeta Hingorani, Michelle A. Hladunewich, Jonathan Hogan, J. Ashley Jefferson, Kenar Jhaveri, Duncan B. Johnstone, Frederick Kaskel, Amy Kogan, Jeffrey Kopp, Kevin V. Lemley, Laura Malaga- Dieguez, Kevin Meyers, Alicia Neu, Michelle Marie O’Shaughnessy, John F. O’Toole, Rulan Parekh, Heather Reich, Kimberly Reidy, Helbert Rondon, Kamalanathan K. Sambandam, John R. Sedor, Christine B. Sethna, Jeffrey Schelling, Agnes Swiatecka-Urban, Howard Trachtman, Katherine R. Tuttle, Joseph Weisstuch, Olga Zhdanova, Brenda Gillespie, Laura Barisoni, Sarah Mansfield, Laura Mariani, and Matthew Wladkowski

Subjects
medicine.medical_specialty, 030232 urology & nephrology, Disease, 030204 cardiovascular system & hematology, urologic and male genital diseases, Nephropathy, 03 medical and health sciences, 0302 clinical medicine, Focal segmental glomerulosclerosis, Membranous nephropathy, Clinical Research, Internal medicine, IgA nephropathy (IgAN), Biopsy, medicine, Minimal change disease, medicine.diagnostic_test, business.industry, IgA vasculitis (IgAV), medicine.disease, 3. Good health, IgA vasculitis, Nephrology, Cohort, business, glomerulonephritis, Henoch-Schönlein purpura (HSP)
Abstract

Introduction The Cure Glomerulonephropathy Network (CureGN) is a 66-center longitudinal observational study of patients with biopsy-confirmed minimal change disease, focal segmental glomerulosclerosis, membranous nephropathy, or IgA nephropathy (IgAN), including IgA vasculitis (IgAV). This study describes the clinical characteristics and treatment patterns in the IgA cohort, including comparisons between IgAN versus IgAV and adult versus pediatric patients. Methods Patients with a diagnostic kidney biopsy within 5 years of screening were eligible to join CureGN. This is a descriptive analysis of clinical and treatment data collected at the time of enrollment. Results A total of 667 patients (506 IgAN, 161 IgAV) constitute the IgAN/IgAV cohort (382 adults, 285 children). At biopsy, those with IgAV were younger (13.0 years vs. 29.6 years, P < 0.001), more frequently white (89.7% vs. 78.9%, P = 0.003), had a higher estimated glomerular filtration rate (103.5 vs. 70.6 ml/min per 1.73 m2, P < 0.001), and lower serum albumin (3.4 vs. 3.8 g/dl, P < 0.001) than those with IgAN. Adult and pediatric individuals with IgAV were more likely than those with IgAN to have been treated with immunosuppressive therapy at or prior to enrollment (79.5% vs. 54.0%, P < 0.001). Conclusion This report highlights clinical differences between IgAV and IgAN and between children and adults with these diagnoses. We identified differences in treatment with immunosuppressive therapies by disease type. This description of baseline characteristics will serve as a foundation for future CureGN studies.

Published
2018

12. Health-related quality of life in glomerular disease

Author

Pietro A. Canetta, Jonathan P. Troost, Shannon Mahoney, Amy J. Kogon, Noelle Carlozzi, Sharon M. Bartosh, Yi Cai, T. Keefe Davis, Hilda Fernandez, Alessia Fornoni, Rasheed A. Gbadegesin, Emily Herreshoff, John D. Mahan, Patrick H. Nachman, David T. Selewski, Christine B. Sethna, Tarak Srivastava, Katherine R. Tuttle, Chia-shi Wang, Ronald J. Falk, Ali G. Gharavi, Brenda W. Gillespie, Larry A. Greenbaum, Lawrence B. Holzman, Matthias Kretzler, Bruce M. Robinson, William E. Smoyer, Lisa M. Guay-Woodford, Bryce Reeve, Debbie S. Gipson, Wooin Ahn, Gerald B. Appel, Revekka Babayev, Ibrahim Batal, Andrew S. Bomback, Eric Brown, Eric S. Campenot, Pietro Canetta, Lucrezia Carlassara, Brenda Chan, Debanjana Chatterjee, Vivette D. D’Agati, Elisa Delbarba, Samriti Dogra, Bartosz Foroncewicz, Gian Marco Ghiggeri, William H. Hines, S. Ali Husain, Namrata G. Jain, Pascale Khairallah, Byum Hee Kil, Krzysztof Kiryluk, Anushya Jeyabalan, Wai L. Lau, Fangming Lin, Francesca Lugani, Maddalena Marasa, Glen Markowitz, Sumit Mohan, Xueru Mu, Krzysztof Mucha, Thomas L. Nickolas, Stacy Piva, Jai Radhakrishnan, Maya K. Rao, Regunathan-Shenk Renu, Simone Sanna-Cherchi, Dominick Santoriello, Shayan Shirazian, Michael B. Stokes, Natalie Uy, Anthony M. Valeri, Amira Al-Uzri, Josephine Ambruzs, Isa Ashoor, Diego Aviles, Rossana Baracco, John Barcia, Sharon Bartosh, Craig Belsha, Corinna Bowers, Michael C. Braun, Vladimir Chernitskiy, Aftab Chishti, Donna Claes, Kira Clark, Carl Cramer, Keefe Davis, Elif Erkan, Daniel Feig, Michael Freundlich, Joseph Gaut, Rasheed Gbadegesin, Melisha Hanna, Guillermo Hidalgo, David Hooper, Tracy E. Hunley, Amrish Jain, Mahmoud Kallash, Margo Kamel, Myda Khalid, Jon B. Klein, Theresa Kump, Jerome C. Lane, Helen Liapis, John Mahan, Carla Nester, Cynthia Pan, Larry Patterson, Hiren Patel, Alice Raad, Adelaide Revell, Michelle N. Rheault, Cynthia Silva, Rajasree Sreedharan, Julia Steinke, Susan Sumner, Katherine Twombley, Scott E. Wenderfer, Tetyana L. Vasylyeva, Donald J. Weaver, Craig S. Wong, Hong Yin, Anand Achanti, Salem Almaani, Isabelle Ayoub, Milos Budisavljevic, Maggie D’Angelo, Huma Fatima, Ronald Falk, Agnes Fogo, Keisha Gibson, Dorey Glenn, Susan Hogan, J. Charles Jennette, Bruce Julian, Jason Kidd, Louis-Philippe Laurin, H. Davis Massey, Amy Mottl, Shannon Murphy, Patrick Nachman, Tibor Nadasdy, Jan Novak, Samir Parikh, Caroline Poulton, Thomas Brian Powell, Matthew Renfrow, Monica Reynolds, Dana Rizk, Brad Rovin, Virginie Royal, Neil Sanghani, Sally Self, Sharon Adler, Nada Alachkar, Charles Alpers, Raed Bou Matar, Carmen Avila-Casado, Serena Bagnasco, Emily Brede, Elizabeth Brown, Daniel Cattran, Michael Choi, Katherine M. Dell, Darren Dewalt, Michelle Denburg, Ram Dukkipati, Fernando C. Fervenza, Crystal Gadegbeku, Patrick Gipson, Anny Gonzalez-Zea, Leah Hasely, Elizabeth Hendren, Sangeeta Hingorani, Michelle Hladunewich, Jonathan Hogan, Jean Hou, J. Ashley Jefferson, Kenar Jhaveri, Duncan B. Johnstone, Frederick Kaskel, Amy Kogan, Jeffrey Kopp, Richard Lafayette, Kevin V. Lemley, Laura Malaga-Dieguez, Kevin Meyers, Alicia Neu, Michelle Marie O'Shaughnessy, John F. O’Toole, Andrea Oliverio, Matthew Palmer, Rulan Parekh, Renee Pitter, Heather Reich, Kimberly Reidy, Helbert Rondon, Kamalanathan K. Sambandam, Matthew Sampson, John R. Sedor, Jeffrey Schelling, John C. Sperati, Agnes Swiatecka-Urban, Howard Trachtman, Meryl Waldman, Joseph Weisstuch, Roger Wiggins, David Williams, Cheryl Winkler, Suzanne Vento, Eric Young, Olga Zhdanova, Laura Barisoni, Charlotte Beil, Richard Eikstadt, Brenda Gillespie, John Graff, Stephen Hewitt, Peg Hill-Callahan, Margaret Helmuth, Chrysta Lienczewski, Sarah Mansfield, Laura Mariani, Keith McCullough, Nicholas Moore, Cynthia C. Nast, Melissa Sexton, Jonathan Troost, Matthew Wladkowski, Jarcy Zee, and Dawn Zinsser

Subjects
0301 basic medicine, Adult, Male, medicine.medical_specialty, Adolescent, 030232 urology & nephrology, Renal function, Article, Nephropathy, 03 medical and health sciences, 0302 clinical medicine, Focal segmental glomerulosclerosis, Glomerulonephritis, Membranous nephropathy, Quality of life, Internal medicine, medicine, Edema, Humans, Minimal change disease, Longitudinal Studies, Child, Aged, business.industry, Middle Aged, medicine.disease, Obesity, humanities, 030104 developmental biology, Nephrology, Quality of Life, Anxiety, Female, Self Report, medicine.symptom, business
Abstract

There is scant literature describing the effect of glomerular disease on health-related quality of life (HRQOL). The Cure Glomerulonephropathy study (CureGN) is an international longitudinal cohort study of children and adults with four primary glomerular diseases (minimal change disease, focal segmental glomerulosclerosis, membranous nephropathy, and IgA nephropathy). HRQOL is systematically assessed using items from the Patient-Reported Outcomes Measurement Informative System (PROMIS). We assessed the relationship between HRQOL and demographic and clinical variables in 478 children and 1115 adults at the time of enrollment into CureGN. Domains measured by PROMIS items included global assessments of health, mobility, anxiety, fatigue, and sleep impairment, as well as a derived composite measure incorporating all measured domains. Multivariable models were created that explained 7 to 32% of variance in HRQOL. Patient-reported edema consistently had the strongest and most robust association with each measured domain of HRQOL in multivariable analysis (adjusted β [95% CI] for composite PROMIS score in children, -5.2 [-7.1 to -3.4]; for composite PROMIS score in adults, -6.1 [-7.4 to -4.9]). Female sex, weight (particularly obesity), and estimated glomerular filtration rate were also associated with some, but not all, domains of HRQOL. Primary diagnosis, disease duration, and exposure to immunosuppression were not associated with HRQOL after adjustment. Sensitivity analyses and interaction testing demonstrated no significant association between disease duration or immunosuppression and any measured domain of HRQOL. Thus, patient-reported edema has a consistent negative association with HRQOL in patients with primary glomerular diseases, with substantially greater impact than other demographic and clinical variables.

Published
2018

13. Investigating the Presence of Circadian Rhythms in Colon Regeneration

Author

Nari, Jonathan Hogan

Abstract

Little is known about the regenerative response in the colon as directed by the circadian clock. The latter is an evolutionary molecular oscillator which generates periodic 24-hour (circadian) rhythms in division and that is synchronized with daily external cues, such as photoperiod and temperature variations. This is troubling, since improper intestinal stem cell proliferation is 20 times more likely to lead to cancer in the human large intestine than in the human small intestine. We propose to characterize the circadian rhythm in colon regeneration of wild type mice following Dextran Sulfate Sodium (DSS)-induced colitis to create damage conditions in the large intestine, and we hypothesize that the damaged colon will still have circadian rhythms. Ten-micron sections of three wild type mouse intestine samples treated with DSS have been gathered at six different time points. These sections have been stained using antibody to pHH3, which labels cells undergoing mitosis, and DAPI, which labels the nuclei of all living cells. Fluorescence microscopy quantification is now being used to assess the number of dividing cells to the total number of cells in 10-20 crypts for the proximal and distal regions of the small intestine and the colon of each sample. Undamaged intestinal tissue should, and so far, has shown to have low pHH3 staining throughout, indicating undamaged intestinal tissue has a lower rate of regeneration. Damaged intestinal tissue should display more pHH3 staining. Quantification of the ratio of pHH3-stained cells to the total number DAPI-stained cells at 6 different time points that show repetitive 24-hour patterns will determine the presence of circadian rhythm mediation. Knowledge of circadian rhythms of the colon in damaged and undamaged conditions will supplement our understanding of regeneration of the intestine as a whole, allowing for improved timing of treatments of gastrointestinal disorders.

Published
2018

15. Contributors

Author

Ala Abudayyeh, Horacio J. Adrogué, Michael Allon, Hina Arif-Tiwari, Jonathan Barratt, Jeffrey S. Berns, Petter Bjornstad, Andrew S. Bomback, C. Barrett Bowling, Daniela A. Braun, Ursula C. Brewster, John M. Carson, Daniel C. Cattran, Sindhu Chandran, Arlene B. Chapman, David Cherney, Steven G. Coca, Debbie L. Cohen, Brendan D. Crawford, Gary C. Curhan, Taimur Dad, Vivette D. D'Agati, Vimal K. Derebail, An S. De Vriese, Dick de Zeeuw, Thomas D. DuBose, Michael Emmett, Pieter Evenepoel, Todd Fairhead, Ronald J. Falk, Fernando C. Fervenza, Kevin W. Finkel, Manuela Födinger, Rasheed A. Gbadegesin, Todd W.B. Gehr, Scott J. Gilbert, Jagbir S. Gill, Thomas A. Gonwa, Arthur Greenberg, Martin C. Gregory, Leal Herlitz, Friedhelm Hildebrandt, Gerald A. Hladik, Michelle A. Hladunewich, Melanie P. Hoenig, Jonathan Hogan, Andrew A. House, Alastair J. Hutchison, T. Alp Ikizler, Lesley A. Inker, Michael G. Ison, Matthew T. James, J. Charles Jennette, Renate Kain, Jaya Kala, Kamyar Kalantar-Zadeh, Bobby Kalb, Jeffrey B. Kopp, Greg Knoll, Dhananjay P. Kulkarni, James Lan, Andrew S. Levey, Ed Lewis, Stuart L. Linas, Randy L. Luciano, Yuliya Lytvyn, Etienne Macedo, Nicolaos E. Madias, Diego R. Martin, Gary R. Matzke, Rajnish Mehrotra, Ankit N. Mehta, Ravindra L. Mehta, Catherine M. Meyers, Madhukar Misra, Sharon M. Moe, Patrick H. Nachman, Lindsay E. Nicolle, Thomas D. Nolin, Ann M. O'Hare, Neesh Pannu, Aldo J. Peixoto, Mark A. Perazella, Megan Prochaska, Laura Ferreira Provenzano, L. Darryl Quarles, Jai Radhakrishnan, Bharathi Reddy, Dana V. Rizk, Claudio Ronco, Avi Z. Rosenberg, Norman D. Rosenblum, Matthew G. Sampson, Paul W. Sanders, Mark J. Sarnak, Steven J. Scheinman, H. William Schnaper, Sarah Schrauben, Richard C. Semelka, Anushree C. Shirali, Domenic A. Sica, Gere Sunder-Plassmann, Richard W. Sutherland, Harold M. Szerlip, Manjula Kurella Tamura, Jessica Sheehan Tangren, Joshua M. Thurman, Marcello Tonelli, Raymond R. Townsend, Howard Trachtman, Jeffrey M. Turner, Anand Vardhan, Joseph G. Verbalis, Flavio G. Vincenti, Marina Vivarelli, Raven Voora, Hani M. Wadei, Bradley A. Warady, Darcy K. Weidemann, Daniel E. Weiner, William L. Whittier, Christopher S. Wilcox, Jay B. Wish, and See Cheng Yeo

Published
2018
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16. The Treatment of Idiopathic Focal Segmental Glomerulosclerosis in Adults

Author

Jai Radhakrishnan and Jonathan Hogan

Subjects
Adult, medicine.medical_specialty, Pathology, Nephrotic Syndrome, medicine.medical_treatment, Renal function, Angiotensin-Converting Enzyme Inhibitors, Angiotensin II Type 2 Receptor Blockers, Disease, urologic and male genital diseases, Gastroenterology, Focal segmental glomerulosclerosis, Internal medicine, medicine, Humans, Glucocorticoids, Kidney, Proteinuria, Glomerulosclerosis, Focal Segmental, urogenital system, business.industry, Immunosuppression, Mycophenolic Acid, medicine.disease, female genital diseases and pregnancy complications, Treatment Outcome, medicine.anatomical_structure, Nephrology, Hypertension, medicine.symptom, business, Nephrotic syndrome, Immunosuppressive Agents, Kidney disease
Abstract

Focal segmental glomerulosclerosis (FSGS) is the histologic end point of many disease processes that affect the kidney. Clinically, adults with FSGS present with proteinuria that may be accompanied by the nephrotic syndrome. Once identifiable (secondary) causes are excluded, the diagnosis of idiopathic FSGS, a challenging glomerular disease to understand and manage, is made. On the basis of mostly retrospective data, first-line treatment for idiopathic FSGS patients with nephrotic-range proteinuria is a prolonged course of corticosteroids. However, steroid resistance is common and portends an increased risk of long-term decline in kidney function and end-stage kidney disease in these patients compared with responders. Multiple other immunosuppression regimens have been used in steroid-resistant FSGS, some of which have been studied in randomized controlled trials. Here, we review the data on the treatment for idiopathic FSGS in adults.

Published
2014
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17. Is Newer Safer? Adverse Events Associated with First-Line Therapies for ANCA-Associated Vasculitis and Lupus Nephritis

Author

Rupali S. Avasare, Jonathan Hogan, and Jai Radhakrishnan

Subjects
medicine.medical_specialty, Cyclophosphamide, Epidemiology, Lupus nephritis, Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis, Azathioprine, Critical Care and Intensive Care Medicine, Mycophenolic acid, Antibodies, Monoclonal, Murine-Derived, medicine, Humans, Immunologic Factors, Intensive care medicine, Adverse effect, Randomized Controlled Trials as Topic, Transplantation, business.industry, Mycophenolic Acid, medicine.disease, Lupus Nephritis, In-Depth Review, Regimen, Nephrology, Immunology, Rituximab, business, Vasculitis, Immunosuppressive Agents, medicine.drug
Abstract

Clinical outcomes in ANCA-associated vasculitis (AAV) and lupus nephritis have improved greatly with treatment regimens containing high-dose glucocorticoids and cyclophosphamide. However, with the use of these medications come significant adverse events, most notably infections, cytopenias, malignancies, and reproductive abnormalities. Multiple recent randomized controlled trials in AAV and lupus nephritis have compared cyclophosphamide-based regimens with agents such as rituximab, mycophenolate mofetil, and azathioprine, with the hope of providing better clinical outcomes with improved safety profiles. Although some of these newer regimens are now considered first-line treatments of these diseases, their adverse event profiles have been disappointingly similar to those of cyclophosphamide-based protocols. Physicians and patients should consider the adverse event profiles generated by these trials in the context of their extensive use in other patient populations, as well as available measures to prevent such events, when choosing the ideal regimen for an individual patient.

Published
2014
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18. Rituximab treatment for fibrillary glomerulonephritis

Author

Michaela D. Restivo, Jai Radhakrishnan, Jonathan Hogan, Gerald B. Appel, Leal Herlitz, Andrew S. Bomback, and Pietro A. Canetta

Subjects
Adult, Male, Nephrology, medicine.medical_specialty, medicine.medical_treatment, Urology, Renal function, Antineoplastic Agents, Antibodies, Monoclonal, Murine-Derived, chemistry.chemical_compound, Glomerulonephritis, Internal medicine, medicine, Humans, Adverse effect, Aged, Retrospective Studies, Transplantation, Creatinine, Proteinuria, business.industry, Fibrillary Glomerulonephritis, Immunosuppression, Middle Aged, chemistry, Microfibrils, Disease Progression, Female, Rituximab, medicine.symptom, business, Follow-Up Studies, Glomerular Filtration Rate, medicine.drug
Abstract

Background Approximately 50% of patients with fibrillary glomerulonephritis (GN) progress to end-stage renal disease (ESRD) within 2 years of diagnosis, and no standard therapy exists. The data on rituximab therapy for fibrillary GN are limited and have inconsistent outcomes. Here, we report the largest case series to date using rituximab for fibrillary GN. Methods Retrospective chart reviews were conducted on 12 patients with fibrillary GN who were treated with rituximab (1 g i.v. × 2 doses or 375 mg/m(2) × 4 doses) at the Center for Glomerular Diseases at Columbia University Medical Center. Non-progression of disease was defined as stable/improved serum creatinine (SCr) with a minimum of 1 year of follow-up. Results The median SCr was 2.1 (range 0.7-2.7) mg/dL, median estimated glomerular filtration rate (eGFR) 39 (range 21-98) mL/min/1.73 m(2) and median proteinuria 4497 (range 210-7542) mg/day at the time of rituximab initiation. Four patients had received immunosuppression before rituximab, and nine received immunosuppression after rituximab, with four receiving a second rituximab course. Four of 12 patients were non-progressors, 3 of 12 had progressive renal dysfunction without reaching ESRD, and 5 patients reached ESRD. The median follow-up for patients who did not reach ESRD was 38 (range 14-76) months after rituximab treatment. Non-progressors had lower SCr values, higher eGFRs and shorter median duration from diagnosis to treatment than progressors. No serious adverse events were noted. Conclusions Rituximab therapy was associated with non-progression of renal disease in 4 of 12 patients. At the time of treatment, these non-progressors had better renal function and shorter time from diagnosis to treatment than progressors.

Published
2014
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19. Diagnostic Tests and Treatment Options in Glomerular Disease: 2014 Update

Author

Prince Mohan, Gerald B. Appel, and Jonathan Hogan

Subjects
medicine.medical_specialty, Pathology, medicine.medical_treatment, Antibodies, Monoclonal, Humanized, Glomerulonephritis, Membranous, Antibodies, Monoclonal, Murine-Derived, Glomerulonephritis, Focal segmental glomerulosclerosis, Membranous nephropathy, Biopsy, Humans, Immunologic Factors, Medicine, Intensive care medicine, Glucocorticoids, Randomized Controlled Trials as Topic, Kidney, medicine.diagnostic_test, Glomerulosclerosis, Focal Segmental, urogenital system, business.industry, Gold standard, Glomerulonephritis, IGA, Immunosuppression, Complement C3, Mycophenolic Acid, medicine.disease, Pathophysiology, Blockade, medicine.anatomical_structure, Nephrology, Rituximab, business, Immunosuppressive Agents
Abstract

Glomerular diseases historically have been challenging disorders to comprehend and treat for patients and physicians alike. Kidney biopsy is the gold standard of diagnosis, but the link between pathophysiology and the histologic representation of kidney injury has remained elusive in many of these diseases. As a result, treatment of glomerular disease usually involves therapies that are not specific to disease pathogenesis, such as blockade of the renin-angiotensin-aldosterone system and various immunosuppression regimens. Recent research has resulted in greater insight into some glomerular diseases, leading to the hope that new diagnostic tests and treatments targeting disease-specific mechanisms are on the horizon. We review recent progress on the understanding, diagnosis, and treatment of 4 glomerular diseases: immunoglobulin A nephropathy, focal segmental glomerulosclerosis, the C3 glomerulopathies, and idiopathic membranous nephropathy.

Published
2014
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20. Treatment of Idiopathic FSGS with Adrenocorticotropic Hormone Gel

Author

Gerald B. Appel, Jonathan Hogan, Kshama R. Mehta, Pietro A. Canetta, Maya K. Rao, Richard A. Lafayette, Andrew S. Bomback, and Jai Radhakrishnan

Subjects
Adult, Male, medicine.medical_specialty, Nephrotic Syndrome, Time Factors, Epidemiology, Injections, Subcutaneous, medicine.medical_treatment, Adrenocorticotropic hormone, Critical Care and Intensive Care Medicine, Gastroenterology, California, Drug Administration Schedule, Adrenocorticotropic Hormone, Membranous nephropathy, Recurrence, Diabetes mellitus, Internal medicine, medicine, Humans, Prospective Studies, Adverse effect, Prospective cohort study, Retrospective Studies, Academic Medical Centers, Transplantation, Proteinuria, Glomerulosclerosis, Focal Segmental, business.industry, Remission Induction, Immunosuppression, Original Articles, Middle Aged, medicine.disease, Surgery, Treatment Outcome, Nephrology, Female, New York City, medicine.symptom, business, Gels, Nephrotic syndrome
Abstract

Summary Background and objectives Adrenocorticotropic hormone (ACTH) has shown efficacy as primary and secondary therapy for nephrotic syndrome due to membranous nephropathy. The data on using ACTH to treat idiopathic FSGS are limited. This report describes our experience using ACTH for nephrotic syndrome due to idiopathic FSGS in the United States. Design, setting, participants, & measurements Twenty-four patients with nephrotic syndrome from idiopathic FSGS were treated with ACTH gel at two academic medical centers between 2009 and 2012, either as part of investigator-initiated pilot studies (n=16) or by prescription for treatment-resistant FSGS (n=8). The primary outcome was remission of proteinuria. The median dose of ACTH was 80 units injected subcutaneously twice weekly. Treatment durations were not uniform. Results Twenty-two patients had received immunosuppression (mean, 2.2 medications) before ACTH therapy. Six patients had steroid-dependent and 15 had steroid-resistant FSGS. At the time of ACTH initiation, the medianserumcreatinine(interquartilerange)was2.0(1.1–2.7)mg/dl,estimatedGFRwas36(28–78)ml/minper 1.73 m 2 , and urine protein-to-creatinine ratio was 4595 (2200–8020) mg/g. At the end of ACTH therapy, 7 of 24 patients (29%) experienced remission (n=2 complete remissions, n=5 partial remissions). All remitters had steroid-resistant (n=5) or steroid-dependent (n=2) FSGS. Two responders relapsed during the follow-up period (mean 6 SD, 70631 weeks). Adverse events occurred in 21 of 24 patients, including one episode of new-onset diabetes that resolved after stopping ACTH and two episodes of AKI. Conclusions Response to ACTH treatment among steroid-resistant or steroid-dependent patients with FSGS is low, but ACTH gel may be a viable treatment option for some patients with resistant nephrotic syndrome due to idiopathic FSGS. Further research is necessary to determine which patients will respond to therapy. Clin J Am Soc Nephrol 8: 2072–2081, 2013. doi: 10.2215/CJN.02840313

Published
2013
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21. Update on the treatment of lupus nephritis

Author

Gerald B. Appel and Jonathan Hogan

Subjects
medicine.medical_specialty, business.industry, Treatment regimen, Patient demographics, Lupus nephritis, Azathioprine, medicine.disease, Lupus Nephritis, Response to treatment, law.invention, Patient population, Treatment Outcome, Randomized controlled trial, Nephrology, law, Internal Medicine, Humans, Medicine, Drug Therapy, Combination, business, Intensive care medicine, Adverse effect, Immunosuppressive Agents, medicine.drug
Abstract

PURPOSE OF REVIEW Lupus nephritis occurs in as many as half of patients presenting with systemic lupus erythematosus and is a major predictor of morbidity and mortality in this patient population. Prior to the last decade, the treatment of lupus nephritis was largely limited to corticosteroids, high-dose alkylating agents, and azathioprine, and this therapy was broadly prescribed regardless of patient demographics, clinical presentation, or prior toxicities. RECENT FINDINGS Over the last decade, new immunomodulatory agents have emerged as effective induction and maintenance therapies in lupus nephritis. With these options, physicians are able to individualize the treatment regimens in an attempt to maximize clinical benefit and minimize adverse events. Moreover, the influence of patient demographics on disease severity and response to treatment has come to the forefront. SUMMARY Here, we review the recent progress made in the therapy of lupus nephritis with a focus on the randomized controlled trials which have demonstrated the efficacy of these new treatment regimens.

Published
2013
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22. Should mycophenolate mofetil replace cyclophosphamide as first-line therapy for severe lupus nephritis?

Author

Jai Radhakrishnan, Michael H. Schwenk, and Jonathan Hogan

Subjects
medicine.medical_specialty, Cyclophosphamide, Cost-Benefit Analysis, glomerular disease, Lupus nephritis, macromolecular substances, Mycophenolate, Severity of Illness Index, Gastroenterology, Drug Costs, Maintenance therapy, Risk Factors, Internal medicine, Severity of illness, medicine, Humans, Adverse effect, lupus nephritis, business.industry, Glomerulonephritis, Mycophenolic Acid, medicine.disease, Clinical trial, Treatment Outcome, Nephrology, Immunology, business, Immunosuppressive Agents, glomerulonephritis, medicine.drug
Abstract

Available treatments for severe (class III, IV, and V) lupus nephritis (LN) have expanded greatly over the last 40 years. In the 1970s and 1980s, cyclophosphamide (CYC), in combination with glucocorticoids, gained favor as induction and maintenance therapy for severe LN. However, the adverse event profile of CYC led to the search for other medications for severe LN. Beginning in the late 1990 s, mycophenolate mofetil (MMF) was introduced as induction and maintenance therapy for severe LN. This review discusses the clinical trial results, pharmacology, cost-effectiveness, and adverse effect profiles of CYC compared to MMF for induction and maintenance therapy for severe LN. The authors conclude that MMF should be considered first-line induction and maintenance treatment therapy for severe LN, although CYC may have a place under specific clinical and economic circumstances.

Published
2012
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23. The Assessment and Importance of Hypertension in the Dental Setting

Author

Jai Radhakrishnan and Jonathan Hogan

Subjects
medicine.medical_specialty, Medication use, High prevalence, business.industry, MEDLINE, Disease, stomatognathic diseases, Blood pressure, Risk Factors, Dental Care for Chronically Ill, Hypertension, Prevalence, medicine, Humans, Mass Screening, In patient, Hypertension diagnosis, Intensive care medicine, business, General Dentistry, Antihypertensive Agents, Mass screening
Abstract

Many patients with hypertension have uncontrolled disease. The dental visit presents a unique opportunity to screen patients for undiagnosed and undertreated hypertension, which may lead to improved monitoring and treatment. Although there are no clinical studies, it is generally recommended that nonemergent procedures be avoided in patients with a blood pressure of greater than 180/110 mm Hg. Because of the high prevalence of disease and medication use for hypertension, dentists should be aware of the oral side effects of antihypertensive medications as well as the cardiovascular effects of medications commonly used during dental visits.

Published
2012
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24. Chronic Diverticulitis: Clinical, Radiographic, and Pathologic Findings

Author

Stephen E. Rubesin, Marc S. Levine, Igor Laufer, Alicia A. Levin, Emma E. Furth, Jonathan Hogan, and Laura Sheiman

Subjects
Adult, Male, medicine.medical_specialty, Abdominal pain, Iohexol, medicine.medical_treatment, Radiography, Contrast Media, Enema, Diatrizoate, chemistry.chemical_compound, medicine, Humans, Fluoroscopy, Radiology, Nuclear Medicine and imaging, Diverticulitis, Aged, Diatrizoate Meglumine, Barium enema, Aged, 80 and over, medicine.diagnostic_test, business.industry, Sigmoid colon, General Medicine, Middle Aged, medicine.disease, digestive system diseases, Intestinal Diseases, Barium sulfate, medicine.anatomical_structure, chemistry, Chronic Disease, Female, Radiology, Barium Sulfate, medicine.symptom, Tomography, X-Ray Computed, business
Abstract

OBJECTIVE. The purpose of our study is to present a series of 14 patients with chronic diverticulitis on barium enema examinations and to correlate the radiographic findings with the clinical and pathologic findings in these patients.CONCLUSION. Chronic diverticulitis is a distinct pathologic entity characterized by the frequent development of chronic obstructive symptoms and abdominal pain rather than the classic clinical findings of acute sigmoid diverticulitis. Barium enema examinations usually reveal a relatively long segment of circumferential narrowing in the sigmoid colon with a spiculated contour and tapered margins, sometimes associated with retrograde obstruction. Our experience suggests that chronic diverticulitis can often be diagnosed on the basis of the characteristic clinical and radiographic findings in these patients.

Published
2008
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25. Minimal Change Disease

Author

Jonathan Hogan, Jai Radhakrishnan, and Howard Trachtman

Subjects
medicine.medical_specialty, business.industry, Internal medicine, Cardiology, Medicine, Minimal change disease, business, medicine.disease
Published
2014
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26. Minimal Change Disease in Adults

Author

Jai Radhakrishnan and Jonathan Hogan

Subjects
business.industry, nutritional and metabolic diseases, Bioinformatics, medicine.disease, Idiopathic Nephrotic Syndrome, eye diseases, Pathophysiology, Podocyte, Pathogenesis, medicine.anatomical_structure, Etiology, Medicine, Minimal change disease, business, Nephrotic syndrome, Glucocorticoid, medicine.drug
Abstract

Minimal change disease (MCD) is the etiology of the nephrotic syndrome in the majority of children and up to one-fourth of adults with this condition. The pathophysiology of MCD is poorly understood, but recent studies suggest the roles of regulatory T-cell dysfunction and specific podocyte proteins in its pathogenesis. Oral glucocorticoids are considered first-line therapy for adult MCD and lead to remission in over 80 % of cases. Most patients experience relapse, and some develop glucocorticoid dependence or resistance with further treatment. Here we review the pathophysiology, clinical presentation, and treatment of MCD in adults.

Published
2013
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27. The treatment of minimal change disease in adults

Author

Jai Radhakrishnan and Jonathan Hogan

Subjects
Adult, Pediatrics, medicine.medical_specialty, Alkylating Agents, Calcineurin Inhibitors, Drug Resistance, law.invention, Randomized controlled trial, law, Adrenal Cortex Hormones, Recurrence, medicine, Humans, Minimal change disease, business.industry, Nephrosis, Lipoid, nutritional and metabolic diseases, General Medicine, medicine.disease, eye diseases, Nephrology, Etiology, Observational study, Controlled Clinical Trials as Topic, business, Nephrotic syndrome, Immunosuppressive Agents
Abstract

Minimal change disease (MCD) is the etiology of 10%-25% of cases of nephrotic syndrome in adults. The mainstay of treatment for adult MCD, oral glucocorticoids, is based on two randomized controlled trials and extensive observational data in adults, and this treatment leads to remission in over 80% of cases. Relapses are common, and some patients become steroid-resistant (SR), steroid-dependent (SD), or frequently relapsing (FR). The data guiding the treatment of these patients are limited. Here, we review MCD in adults with particular focus on the evidence for immunosuppressive therapy in these patients.

Published
2013

28. Design of an External Combustion Engine and its Application in a Free Piston Compressor

Author

Jonathan Hogan Webb

Subjects
Valve timing, Reciprocating compressor, Materials science, Applied Mathematics, General Mathematics, External combustion engine, Mechanical engineering, Four-stroke engine, law.invention, Piston, Internal combustion engine, law, Ionic liquid piston compressor, Combustion chamber
Abstract

The design of a free piston compressor and an analysis on integrating an external combustion engine into the compressor design are presented in this article. A free piston compressor is a device which converts chemical energy to work on a volume of air through the kinetic energy of an inertia driven piston, which is not rigidly attached to a ground. An external combustion engine serves as in intermediate chamber which transfers combustion gases to a device to perform some work. The following discusses the design and experiments on an external combustion engine, with a focus on eliminating an injection holding force on a free piston compressor’s elastomeric membranes. The efficiency of the external combustion engine to transfer energy without significant losses due to heat, dead volume, air/fuel mixtures, and actuated valve speed are also presented.

Published
2007
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29. Hydroxyl Tagging Velocimetry and Methods of Dynamic Image Analysis

Author

Jonathan Hogan Webb

Subjects
Spatial correlation, Computer science, business.industry, Applied Mathematics, General Mathematics, Acoustics, Airflow, Velocimetry, symbols.namesake, Software, Mach number, symbols, Scramjet, Supersonic speed, business, Hydroxyl tagging velocimetry, Simulation
Abstract

This article presents the method of analyzing a mach 2 flow of air through a scramjet and over a cavity using hydroxyl tagging velocimetry (HTV). This method is of particular use in supersonic engines, where, fuel is ignited by a flame protected from airflow by a cavity. Emphasis of the experiment discussed is placed on the image analysis portion of the HTV experiments. The current software used to analyze laser intersections, created by Michigan State University, is user-intensive and inefficient because of the large number of inputs needed to produce a result. The conceptual method behind this imaging software is explained along with the mathematical algorithms related to the spatial correlation technique. The spatial correlation technique offers a way to determine the distance that an object has moved from one photograph to another. This work focuses on improvements to the dynamic analysis of images to expand the applicability of current software tools. The failures and successes of each method are explained.

Published
2006
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