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1. 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, 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
medicine.medical_specialty, 030232 urology & nephrology, Disease, 030204 cardiovascular system & hematology, lcsh:RC870-923, Nephropathy, 03 medical and health sciences, 0302 clinical medicine, Focal segmental glomerulosclerosis, Quality of life, Membranous nephropathy, Clinical Research, Internal medicine, medicine, Minimal change disease, business.industry, lcsh:Diseases of the genitourinary system. Urology, medicine.disease, humanities, health-related quality of life, patient-reported outcomes, Nephrology, primary glomerular disease, Cohort, Anxiety, medicine.symptom, business, edema
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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2. 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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3. 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

4. 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

5. Design and process related MIM cap reliability improvement

Author

Justin Parke, Kathy Ha, Harold Hearne, Harlan Carl Cramer, and Randy Lewis

Subjects
Engineering, business.industry, Time-dependent gate oxide breakdown, Failure rate, Hardware_PERFORMANCEANDRELIABILITY, Dielectric, Condensed Matter Physics, Atomic and Molecular Physics, and Optics, Surfaces, Coatings and Films, Electronic, Optical and Magnetic Materials, law.invention, Nominal size, Capacitor, Reliability (semiconductor), Hardware_GENERAL, law, Control theory, Hardware_INTEGRATEDCIRCUITS, Electronic engineering, Electrical and Electronic Engineering, Safety, Risk, Reliability and Quality, business, Monolithic microwave integrated circuit, Voltage
Abstract

A root cause failure investigation was performed on anomalous (early) MIM capacitor failures on an HBT MMIC process. These failures were only observed on capacitors in the actual MMICs; process control monitor (PCM) capacitors were nominal. Multiple failure analysis techniques were employed to determine the most probable root cause of the early failures. The root cause was determined to be etching of the capacitor dielectric by a chemical used in the MMIC fabrication process, at a step after the capacitors themselves were fully built. It was determined that only CAD layouts with certain features were susceptible to the etching. These features were not present on the PCM capacitors. A design based corrective action was recommended to eliminate the failure mechanism. The effectiveness of the corrective actions was verified with several designed processing experiments. These experiments also demonstrated that the failure rate of the faulty parts increased with the time (even if the parts were not in operation). Finally, the experiments showed that the reliability of a nominal capacitor with a BCB layer on top was better than that of an identical capacitor without the BCB layer. Capacitor reliability model For the sake of completeness, the following discussion on ramped voltage TDDB testing of capacitors is included. In this work, ramped voltage data was not used to predict capacitor lifetimes, but it was used to quantitatively compare capacitor reliability by plotting percent cumulative failure versus failure voltage. Normally, destructive ramped voltage testing and the linear field model are employed in order to estimate the lifetime of capacitors. This method has been described in detail elsewhere for intrinsic capacitors (Cramer et al. [1] , [2] , [3] ). It is generally assumed that defects on or in the capacitor bottom plate or in dielectric itself causes a localized thinning of the dielectric which shortens the intrinsic lifetime of the capacitor, as illustrated in Fig. 2. Extrinsic capacitors require a refinement of the Nominal Thickness Method to the Effective Thickness Method. Typically, plots of percent cumulative failure versus failure voltage will be transformed into plots of percent cumulative failure versus lifetime via the above equations. The shapes of these two plots are nearly identical, only the values on the abscissa are changed from (linear) voltage to (logarithmic) lifetime. Since, in this work, the effort was directed at root cause determination of anomalous failures rather than predictions of expected lifetimes, the linear field model was never employed and the data was always plotted as a function of failure voltage.

Published
2015
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6. 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

7. Optimizing performance of Super-Lattice Castellated Field Effect Transistors

Author

Matthew R. King, Robert S. Howell, Eric J. Stewart, Karen Renaldo, Jeff Hartman, Bettina Nechay, Justin Parke, Shalini Gupta, Ishan Wathuthanthri, Harlan Carl Cramer, Megan Snook, H. George Henry, Pavel Borodulin, and Ron Freitag

Subjects
Materials science, business.industry, Transistor, PIN diode, Electrical engineering, Biasing, High-electron-mobility transistor, law.invention, RF switch, CMOS, law, Electronic engineering, Field-effect transistor, Electronics, business
Abstract

High performance RF switch components are vital for the successful implementation of a variety of system architectures, ranging from phased array radars and multi-function sensors to the wireless components of mobile phones and consumer electronics. FET based RF switches offer low power consumption, less demanding control biasing networks and fast switching capabilities compared to both PiN and RF MEMS technologies. However, many of these switch technologies, including those based on Si CMOS [1], GaAs pHEMT [2], or InP [3] and GaN HEMTs [4] have reported substantially higher insertion losses than the PiN diode and RF MEMS technologies. With this in mind, Northrop Grumman has recently introduced a novel field effect transistor structure called the Super-Lattice Castellated Field Effect Transistor, or SLCFET, that combines the advantages of FET-based switches with the performance of MEMS [5]. However, this is a new transistor structure that creates challenges for device design, especially with regard to managing electric fields for high breakdown voltage. This paper will discuss some of the challenges, tradeoffs, and techniques for optimizing the SLCFET device performance.

Published
2015
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8. The Super-Lattice Castellated Field Effect Transistor (SLCFET): A novel high performance Transistor topology ideal for RF switching

Author

Parrish Ralston, Karen Renaldo, Shalini Gupta, Ron Freitag, Eric J. Stewart, H. George Henry, Justin Parke, Bettina Nechay, Matthew R. King, R. Chris Clarke, Harlan Carl Cramer, Ishan Wathuthanthri, Megan Snook, Robert S. Howell, and Jeffrey Hartman

Subjects
Materials science, business.industry, Heterostructure-emitter bipolar transistor, Transistor, Multiple-emitter transistor, High-electron-mobility transistor, law.invention, RF switch, law, Optical transistor, Optoelectronics, Field-effect transistor, business, Static induction transistor
Abstract

NGES reports the development of a novel transistor structure based on a GaN super-lattice channel with a 3D gate, named the SLCFET (Super-Lattice Castellated Field Effect Transistor). Transistor measurements provided median values of I MAX >2.7 A/mm, V PINCH = −8V, with R ON =0.41 Ω-mm and C OFF =0.19 pF/mm, for an RF switch FOM of F CO =2.1 THz.

Published
2014
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9. Low Loss, High Performance 1-18 GHz SPDT Based on the Novel Super-Lattice Castellated Field Effect Transistor (SLCFET)

Author

Jeff Hartman, Bettina Nechay, Justin Parke, Karen Renaldo, Harlan Carl Cramer, Eric J. Stewart, Robert S. Howell, Parrish Ralston, Megan Snook, Shalini Gupta, Matthew R. King, Ishan Wathuthanthri, H. George Henry, Pavel Borodulin, and Ron Freitag

Subjects
RF switch, Materials science, business.industry, Broadband, dBm, Return loss, Electrical engineering, Insertion loss, Linearity, Optoelectronics, Field-effect transistor, Radio frequency, business
Abstract

A low loss, high isolation, broadband RF switch has been developed using a novel type of field effect transistor structure that exploits the use of a super-lattice structure in combination with a three dimensional, castellated gate to achieve excellent RF switch performance. Using an AlGaN/GaN super-lattice epitaxial layer, this Super-Lattice Castellated Field Effect Transistor (SLCFET) was used to build 1-18 GHz SPDT RF switches. Measured insertion loss of the SPDT at 10 GHz was -0.4 dB, with -35 dB of isolation and -23 dB of return loss, along with a measured linearity OIP3 value 62 dBm and a P0.1dB of 34 dBm.

Published
2014
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10. Optimization and shape control of GaN nanopillars fabricated by inductively coupled plasma etching

Author

Geetha S. Aluri, Sean McLaughlin, Harlan Carl Cramer, Albert V. Davydov, Abhishek Motayed, Dipak Paramanik, Sergiy Krylyuk, Matthew R. King, Shalini Gupta, and Babak Nikoobakht

Subjects
Plasma etching, Materials science, business.industry, Nanotechnology, Gallium nitride, Substrate (electronics), chemistry.chemical_compound, chemistry, Etching (microfabrication), Optoelectronics, Dry etching, Reactive-ion etching, Inductively coupled plasma, business, Nanopillar
Abstract

We report the systematic etching profile of GaN nano pillar structures using inductively coupled plasma (ICP) etching techniques. We were able to control the side wall angle, sh ape and dimension of such nanoscale structures by carefully selecting the etching parameters. We present the effects of variations of the etch parameters, such as ICP power, RF power, chamber pressure, and substrate temperature on the etch characteristics, such as etch rate, sidewall angle, anisotropy, mask erosion, and surface rou ghness. Utilizing such methods, we dem onstrated the fabrication of nanoscale structures with designed shapes and dimensions over large area. Nanocolumns with diameter of 120 nm and height of 1.6 µm with sidewall angle of 86° (90° represent a vertical si dewall) were fabricated. Nanocon es with tip diameter of 30 nm and height of 1.6 Pm with sidewall angle of 70° were demonstrated. The structures produced by such top-down method could potentially be used in light-emitting diodes, laser diodes, photodetectors, vertical transistors, field-emitters, and photovoltaic devices. Keywords: GaN nano pillars, ICP plasma etching, LED

Published
2012
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