14 results on '"Gbadegesin, Rasheed A"'
Search Results
2. Contributors
- Author
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Abudayyeh, Ala, primary, Adrogué, Horacio J., additional, Allon, Michael, additional, Arif-Tiwari, Hina, additional, Barratt, Jonathan, additional, Berns, Jeffrey S., additional, Bjornstad, Petter, additional, Bomback, Andrew S., additional, Bowling, C. Barrett, additional, Braun, Daniela A., additional, Brewster, Ursula C., additional, Carson, John M., additional, Cattran, Daniel C., additional, Chandran, Sindhu, additional, Chapman, Arlene B., additional, Cherney, David, additional, Coca, Steven G., additional, Cohen, Debbie L., additional, Crawford, Brendan D., additional, Curhan, Gary C., additional, Dad, Taimur, additional, D'Agati, Vivette D., additional, Derebail, Vimal K., additional, De Vriese, An S., additional, de Zeeuw, Dick, additional, DuBose, Thomas D., additional, Emmett, Michael, additional, Evenepoel, Pieter, additional, Fairhead, Todd, additional, Falk, Ronald J., additional, Fervenza, Fernando C., additional, Finkel, Kevin W., additional, Födinger, Manuela, additional, Gbadegesin, Rasheed A., additional, Gehr, Todd W.B., additional, Gilbert, Scott J., additional, Gill, Jagbir S., additional, Gonwa, Thomas A., additional, Greenberg, Arthur, additional, Gregory, Martin C., additional, Herlitz, Leal, additional, Hildebrandt, Friedhelm, additional, Hladik, Gerald A., additional, Hladunewich, Michelle A., additional, Hoenig, Melanie P., additional, Hogan, Jonathan, additional, House, Andrew A., additional, Hutchison, Alastair J., additional, Ikizler, T. Alp, additional, Inker, Lesley A., additional, Ison, Michael G., additional, James, Matthew T., additional, Jennette, J. Charles, additional, Kain, Renate, additional, Kala, Jaya, additional, Kalantar-Zadeh, Kamyar, additional, Kalb, Bobby, additional, Kopp, Jeffrey B., additional, Knoll, Greg, additional, Kulkarni, Dhananjay P., additional, Lan, James, additional, Levey, Andrew S., additional, Lewis, Ed, additional, Linas, Stuart L., additional, Luciano, Randy L., additional, Lytvyn, Yuliya, additional, Macedo, Etienne, additional, Madias, Nicolaos E., additional, Martin, Diego R., additional, Matzke, Gary R., additional, Mehrotra, Rajnish, additional, Mehta, Ankit N., additional, Mehta, Ravindra L., additional, Meyers, Catherine M., additional, Misra, Madhukar, additional, Moe, Sharon M., additional, Nachman, Patrick H., additional, Nicolle, Lindsay E., additional, Nolin, Thomas D., additional, O'Hare, Ann M., additional, Pannu, Neesh, additional, Peixoto, Aldo J., additional, Perazella, Mark A., additional, Prochaska, Megan, additional, Provenzano, Laura Ferreira, additional, Quarles, L. Darryl, additional, Radhakrishnan, Jai, additional, Reddy, Bharathi, additional, Rizk, Dana V., additional, Ronco, Claudio, additional, Rosenberg, Avi Z., additional, Rosenblum, Norman D., additional, Sampson, Matthew G., additional, Sanders, Paul W., additional, Sarnak, Mark J., additional, Scheinman, Steven J., additional, Schnaper, H. William, additional, Schrauben, Sarah, additional, Semelka, Richard C., additional, Shirali, Anushree C., additional, Sica, Domenic A., additional, Sunder-Plassmann, Gere, additional, Sutherland, Richard W., additional, Szerlip, Harold M., additional, Kurella Tamura, Manjula, additional, Tangren, Jessica Sheehan, additional, Thurman, Joshua M., additional, Tonelli, Marcello, additional, Townsend, Raymond R., additional, Trachtman, Howard, additional, Turner, Jeffrey M., additional, Vardhan, Anand, additional, Verbalis, Joseph G., additional, Vincenti, Flavio G., additional, Vivarelli, Marina, additional, Voora, Raven, additional, Wadei, Hani M., additional, Warady, Bradley A., additional, Weidemann, Darcy K., additional, Weiner, Daniel E., additional, Whittier, William L., additional, Wilcox, Christopher S., additional, Wish, Jay B., additional, and Yeo, See Cheng, additional
- Published
- 2018
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3. Nephrotic Syndrome
- Author
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Gbadegesin, Rasheed, primary and Smoyer, William E., additional
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- 2008
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4. Contributors
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Alcon, Juan J., primary, Alexander, Stephen I., additional, Amaral, Joao Guilherme, additional, Amore, Alessandro, additional, Andreoli, Sharon Phillips, additional, Andrews, Walter S., additional, Aufricht, Christoph, additional, Avni, Fred E., additional, Bagga, Arvind, additional, Bakkaloglu, Aysin, additional, Batisky, Donald L., additional, Bauman, Mary, additional, Becker, Jan Ulrich, additional, Bergmann, Carsten, additional, Bettinelli, Alberto, additional, Bianchetti, Mario G., additional, Blowey, Douglas L., additional, Böckenhauer, Detlef, additional, Brophy, Patrick D., additional, Chand, Deepa H., additional, Cochat, Pierre, additional, Connolly, Bairbre, additional, Coppo, Rosanna, additional, Craig, Jonathan C., additional, Csaicsich, Dagmar, additional, Cuzzolin, Laura, additional, Dharnidharka, Vikas R., additional, Durkan, Anne M., additional, Eddy, Allison A., additional, Eggermann, Thomas, additional, Fanos, Vassilios, additional, Filler, Guido, additional, Fleming, Geoffrey M., additional, Furth, Susan L., additional, Gbadegesin, Rasheed, additional, Geary, Denis F., additional, Gerson, Arlene C., additional, Gipson, Debbie S., additional, Goldstein, Stuart L., additional, Gowrishankar, Manjula, additional, Graf, Nicole, additional, Greenbaum, Larry A., additional, Groothoff, Jaap W., additional, Gulati, Sanjeev, additional, Hadtstein, Charlotte, additional, Haffner, Dieter, additional, Hall, Michelle, additional, Harrison, Christine, additional, Hébert, Diane, additional, Hodson, Elisabeth M., additional, Hooper, Stephen, additional, Hoppe, Bernd, additional, Hothi, Daljit K., additional, Hoyer, Peter F., additional, Ingelfinger, Julie R., additional, Ismaili, Khalid, additional, Kashtan, Clifford E., additional, Kawasaki, Yukihiko, additional, Khoury, Antoine E., additional, Konrad, Martin, additional, Kumar, Alok, additional, Langlois, Valerie, additional, Lau, Perry Yew-Weng, additional, Leumann, Ernst, additional, Li, Xiaomei, additional, Licht, Christoph, additional, Lim, Ruth, additional, Lorenzo, Armando J., additional, Luckritz, Kera E., additional, Lurbe, Empar, additional, Mahan, John D., additional, Mak, Robert, additional, Marks, Stephen D., additional, Patricia Massicotte, M., additional, Mathews, Ranjiv, additional, Mattoo, Tej K., additional, Maxwell, Heather, additional, Mehls, Otto, additional, Melk, Anette, additional, Mengel, Michael, additional, Menon, Shina, additional, Milliner, Dawn S., additional, Mitsnefes, Mark, additional, Neu, Alicia M., additional, Niaudet, Patrick, additional, Nissel, Richard, additional, Ermisch-Omran, Beate, additional, Omran, Heymut, additional, Ozen, Seza, additional, Perfumo, Francesco, additional, Phan, Veronique, additional, Pinsk, Maury, additional, Piscione, Tino D., additional, Querfeld, Uwe, additional, Ramage, Ian John, additional, Redon, Josep, additional, Robinson, Lisa A., additional, Robinson, Renee F., additional, Rosenblum, Norman D., additional, Salomon, Remi, additional, Sandhu, Gagandeep K., additional, Schaefer, Franz, additional, Schmitt, Claus P., additional, Schröder, Cornelis H., additional, Secker, Donna, additional, Sherali, Afroze Ramzan, additional, Sihoe, Jennifer Dart Yin, additional, Smoyer, William E., additional, Suzuki, Hitoshi, additional, Tasic, Velibor, additional, Tönshoff, Burkhard, additional, Traubici, Jeffrey, additional, Tullus, Kjell, additional, van't Hoff, William G., additional, Verghese, Priya S., additional, Verrina, Enrico Eugenio, additional, Vester, Udo, additional, Vohra, Sunita, additional, Waldegger, Siegfried, additional, Warady, Bradley A., additional, Waters, Aoife, additional, Webb, Nicholas J.A., additional, Weber, Stefanie, additional, Williams, Gabrielle, additional, Wong, Sik-Nin, additional, Wühl, Elke, additional, Yang, Li, additional, Yap, Hui-Kim, additional, Yeung, Chung-Kwong, additional, Yiu, Verna, additional, Zerres, Klaus, additional, and Zimmerhackl, Lothar Bernd, additional
- Published
- 2008
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5. The case for treatment of monogenic SRNS with calcineurin inhibitors.
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Lane BM and Gbadegesin RA
- Subjects
- Child, Humans, Immunosuppressive Agents therapeutic use, Immunosuppressive Agents pharmacology, Retrospective Studies, Biomarkers, Calcineurin Inhibitors adverse effects, Nephrotic Syndrome drug therapy, Nephrotic Syndrome genetics
- Abstract
Currently, no evidence-based guidelines exist for treatment of children with monogenic steroid-resistant nephrotic syndrome. A retrospective study on 141 patients from Malakasioti et al. revealed that 27.6% responded to calcineurin inhibitor (CNI) treatment, and 75% of responders maintained stable kidney function. Virtually all CNI nonresponders developed progressive loss of kidney function. This study emphasized roles for CNIs in patients with monogenic steroid-resistant nephrotic syndrome, and the need for future studies to identify CNI response biomarkers., (Copyright © 2023 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)
- Published
- 2023
- Full Text
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6. Longitudinal Changes in Health-Related Quality of Life in Primary Glomerular Disease: Results From the CureGN Study.
- Author
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Murphy SL, Mahan JD, Troost JP, Srivastava T, Kogon AJ, Cai Y, Davis TK, Fernandez H, Fornoni A, Gbadegesin RA, Herreshoff E, Canetta PA, Nachman PH, Reeve BB, Selewski DT, Sethna CB, Wang CS, Bartosh SM, Gipson DS, and Tuttle KR
- 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., (© 2020 Published by Elsevier, Inc., on behalf of the International Society of Nephrology.)
- Published
- 2020
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7. APOL1 Long-term Kidney Transplantation Outcomes Network (APOLLO): Design and Rationale.
- Author
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Freedman BI, Moxey-Mims MM, Alexander AA, Astor BC, Birdwell KA, Bowden DW, Bowen G, Bromberg J, Craven TE, Dadhania DM, Divers J, Doshi MD, Eidbo E, Fornoni A, Gautreaux MD, Gbadegesin RA, Gee PO, Guerra G, Hsu CY, Iltis AS, Jefferson N, Julian BA, Klassen DK, Koty PP, Langefeld CD, Lentine KL, Ma L, Mannon RB, Menon MC, Mohan S, Moore JB, Murphy B, Newell KA, Odim J, Ortigosa-Goggins M, Palmer ND, Park M, Parsa A, Pastan SO, Poggio ED, Rajapakse N, Reeves-Daniel AM, Rosas SE, Russell LP, Sawinski D, Smith SC, Spainhour M, Stratta RJ, Weir MR, Reboussin DM, Kimmel PL, and Brennan DC
- Abstract
Introduction: Much of the higher risk for end-stage kidney disease (ESKD) in African American individuals relates to ancestry-specific variation in the apolipoprotein L1 gene ( APOL1 ). Relative to kidneys from European American deceased-donors, kidneys from African American deceased-donors have shorter allograft survival and African American living-kidney donors more often develop ESKD. The National Institutes of Health (NIH)-sponsored APOL1 Long-term Kidney Transplantation Outcomes Network (APOLLO) is prospectively assessing kidney allograft survival from donors with recent African ancestry based on donor and recipient APOL1 genotypes., Methods: APOLLO will evaluate outcomes from 2614 deceased kidney donor-recipient pairs, as well as additional living-kidney donor-recipient pairs and unpaired deceased-donor kidneys., Results: The United Network for Organ Sharing (UNOS), Association of Organ Procurement Organizations, American Society of Transplantation, American Society for Histocompatibility and Immunogenetics, and nearly all U.S. kidney transplant programs, organ procurement organizations (OPOs), and histocompatibility laboratories are participating in this observational study. APOLLO employs a central institutional review board (cIRB) and maintains voluntary partnerships with OPOs and histocompatibility laboratories. A Community Advisory Council composed of African American individuals with a personal or family history of kidney disease has advised the NIH Project Office and Steering Committee since inception. UNOS is providing data for outcome analyses., Conclusion: This article describes unique aspects of the protocol, design, and performance of APOLLO. Results will guide use of APOL1 genotypic data to improve the assessment of quality in deceased-donor kidneys and could increase numbers of transplanted kidneys, reduce rates of discard, and improve the safety of living-kidney donation., (© 2019 International Society of Nephrology. Published by Elsevier Inc.)
- Published
- 2019
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8. Aberrant IgM on T cells: biomarker or pathogenic factor in childhood nephrotic syndrome?
- Author
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Chambers ET and Gbadegesin RA
- Subjects
- Biomarkers, Child, Humans, Immunoglobulin M, Recurrence, T-Lymphocytes, Nephrotic Syndrome
- Abstract
Although the pathogenesis of steroid-sensitive nephrotic syndrome (SSNS) remains elusive, multiple epidemiologic, clinical, and experimental studies converge on the common theme of immune dysregulation. Initially, T-cell adaptive immunity was solely emphasized; however, the role of humoral immunity in nephrotic syndrome has gained recognition. The study by Colucci and colleagues provides preliminary evidence that production of deglycosylated IgM that is unable to regulate T-cell function in the presence or absence of corticosteroid may be responsible for a steroid-dependence course in SSNS. This study provides invaluable insights into the mechanistic roles of both T-cell and B-cell responses in the pathogenesis and clinical course of SSNS., (Copyright © 2019 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)
- Published
- 2019
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9. Health-related quality of life in glomerular disease.
- Author
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Canetta PA, Troost JP, Mahoney S, Kogon AJ, Carlozzi N, Bartosh SM, Cai Y, Davis TK, Fernandez H, Fornoni A, Gbadegesin RA, Herreshoff E, Mahan JD, Nachman PH, Selewski DT, Sethna CB, Srivastava T, Tuttle KR, Wang CS, Falk RJ, Gharavi AG, Gillespie BW, Greenbaum LA, Holzman LB, Kretzler M, Robinson BM, Smoyer WE, Guay-Woodford LM, Reeve B, and Gipson DS
- Subjects
- Adolescent, Adult, Aged, Child, Edema psychology, Female, Glomerulonephritis psychology, Humans, Longitudinal Studies, Male, Middle Aged, Self Report statistics & numerical data, Edema etiology, Glomerulonephritis complications, Quality of Life
- 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., (Copyright © 2019 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)
- Published
- 2019
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10. Clinical Characteristics and Treatment Patterns of Children and Adults With IgA Nephropathy or IgA Vasculitis: Findings From the CureGN Study.
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Selewski DT, Ambruzs JM, Appel GB, Bomback AS, Matar RB, Cai Y, Cattran DC, Chishti AS, D'Agati VD, D'Alessandri-Silva CJ, Gbadegesin RA, Hogan JJ, Iragorri S, Jennette JC, Julian BA, Khalid M, Lafayette RA, Liapis H, Lugani F, Mansfield SA, Mason S, Nachman PH, Nast CC, Nester CM, Noone DG, Novak J, O'Shaughnessy MM, Reich HN, Rheault MN, Rizk DV, Saha MK, Sanghani NS, Sperati CJ, Sreedharan R, Srivastava T, Swiatecka-Urban A, Twombley K, Vasylyeva TL, Weaver DJ, Yin H, Zee J, Falk RJ, Gharavi AG, Gillespie BW, Gipson DS, Greenbaum LA, Holzman LB, Kretzler M, Robinson BM, Smoyer WE, Flessner M, Guay-Woodford LM, and Kiryluk K
- 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 m
2 , 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
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11. The author replies.
- Author
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Gbadegesin RA
- Subjects
- Female, Humans, Male, Autoantigens genetics, Collagen Type IV genetics, Glomerulosclerosis, Focal Segmental genetics
- Published
- 2015
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12. Rare hereditary COL4A3/COL4A4 variants may be mistaken for familial focal segmental glomerulosclerosis.
- Author
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Malone AF, Phelan PJ, Hall G, Cetincelik U, Homstad A, Alonso AS, Jiang R, Lindsey TB, Wu G, Sparks MA, Smith SR, Webb NJ, Kalra PA, Adeyemo AA, Shaw AS, Conlon PJ, Jennette JC, Howell DN, Winn MP, and Gbadegesin RA
- Subjects
- Adolescent, Adult, Child, DNA Mutational Analysis, Exome, Female, Genetic Testing, Genotype, Glomerular Basement Membrane ultrastructure, Glomerulosclerosis, Focal Segmental complications, Glomerulosclerosis, Focal Segmental pathology, Hearing Loss genetics, Hematuria etiology, Humans, Male, Middle Aged, Mutation, Missense, Phenotype, Podocytes ultrastructure, Proteinuria etiology, Young Adult, Autoantigens genetics, Collagen Type IV genetics, Glomerulosclerosis, Focal Segmental genetics
- Abstract
Focal segmental glomerulosclerosis (FSGS) is a histological lesion with many causes, including inherited genetic defects, with significant proteinuria being the predominant clinical finding at presentation. Mutations in COL4A3 and COL4A4 are known to cause Alport syndrome (AS), thin basement membrane nephropathy, and to result in pathognomonic glomerular basement membrane (GBM) findings. Secondary FSGS is known to develop in classic AS at later stages of the disease. Here, we present seven families with rare or novel variants in COL4A3 or COL4A4 (six with single and one with two heterozygous variants) from a cohort of 70 families with a diagnosis of hereditary FSGS. The predominant clinical finding at diagnosis was proteinuria associated with hematuria. In all seven families, there were individuals with nephrotic-range proteinuria with histologic features of FSGS by light microscopy. In one family, electron microscopy showed thin GBM, but four other families had variable findings inconsistent with classical Alport nephritis. There was no recurrence of disease after kidney transplantation. Families with COL4A3 and COL4A4 variants that segregated with disease represent 10% of our cohort. Thus, COL4A3 and COL4A4 variants should be considered in the interpretation of next-generation sequencing data from such patients. Furthermore, this study illustrates the power of molecular genetic diagnostics in the clarification of renal phenotypes.
- Published
- 2014
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13. Inverted formin 2 mutations with variable expression in patients with sporadic and hereditary focal and segmental glomerulosclerosis.
- Author
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Gbadegesin RA, Lavin PJ, Hall G, Bartkowiak B, Homstad A, Jiang R, Wu G, Byrd A, Lynn K, Wolfish N, Ottati C, Stevens P, Howell D, Conlon P, and Winn MP
- Subjects
- Adolescent, Adult, Aged, Amino Acid Sequence, Amino Acid Substitution, Child, Child, Preschool, Exons, Female, Formins, Genes, Dominant, Genes, Recessive, Genetic Testing, Glomerulosclerosis, Focal Segmental pathology, Humans, Infant, Male, Microfilament Proteins chemistry, Middle Aged, Models, Molecular, Molecular Sequence Data, Mutant Proteins chemistry, Mutant Proteins genetics, Mutation, Missense, Protein Structure, Tertiary, Sequence Homology, Amino Acid, Young Adult, Glomerulosclerosis, Focal Segmental genetics, Microfilament Proteins genetics, Mutation
- Abstract
Focal and segmental glomerulosclerosis (FSGS) is a major cause of end-stage kidney disease. Recent advances in molecular genetics show that defects in the podocyte play a major role in its pathogenesis and mutations in inverted formin 2 (INF2) cause autosomal dominant FSGS. In order to delineate the role of INF2 mutations in familial and sporadic FSGS, we sought to identify variants in a large cohort of patients with FSGS. A secondary objective was to define an approach for genetic screening in families with autosomal dominant disease. A total of 248 individuals were identified with FSGS, of whom 31 had idiopathic disease. The remaining patients clustered into 64 families encompassing 15 from autosomal recessive and 49 from autosomal dominant kindreds. There were missense mutations in 8 of the 49 families with autosomal dominant disease. Three of the detected variants were novel and all mutations were confined to exon 4 of INF2, a regulatory region responsible for 90% of all changes reported in FSGS due to INF2 mutations. Thus, in our series, INF2 mutations were responsible for 16% of all cases of autosomal dominant FSGS, with these mutations clustered in exon 4. Hence, screening for these mutations may represent a rapid, non-invasive and cost-effective method for the diagnosis of autosomal dominant FSGS.
- Published
- 2012
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14. Role of TGF-beta1 in renal parenchymal scarring following childhood urinary tract infection.
- Author
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Cotton SA, Gbadegesin RA, Williams S, Brenchley PE, and Webb NJ
- Subjects
- Child, Child, Preschool, Cicatrix immunology, Cicatrix pathology, Female, Fibrosis, Gene Frequency, Genotype, Humans, In Vitro Techniques, Infant, Kidney immunology, Leukocytes, Mononuclear immunology, Male, Polymorphism, Restriction Fragment Length, Transforming Growth Factor beta1, Urinary Tract Infections pathology, Kidney pathology, Transforming Growth Factor beta genetics, Transforming Growth Factor beta immunology, Urinary Tract Infections genetics, Urinary Tract Infections immunology
- Abstract
Background: Significant variability exists in the outcome of renal parenchymal inflammation following urinary tract infection (UTI) in childhood as some children experience renal parenchymal scarring (RPS) while others do not scar. Since TGF-beta1 is pro-fibrotic, we examined the role of this cytokine in RPS following UTI., Methods: Five polymorphisms of the TGF-beta1 gene were investigated as well as the relationship between these polymorphisms and TGF-beta1 production by peripheral blood mononuclear cells (PBMC) in vitro. DNA was isolated from 91 children shown to have developed RPS, 43 children with no evidence of scarring (NS) following UTI, and 171 healthy controls. Genotyping was performed by restriction fragment length polymorphism (RFLP). PBMC were isolated from a subgroup of 24 patients from the total population. Cells were stimulated with LPS + PMA + PHA and then TGF-beta1 production was determined by ELISA., Results: Comparing the NS with the RPS group, there was an increase in the -800 GA genotypes (18.6 vs. 7.4%, P=0.05; chi2) and the Leu10-->Pro CT (62.8 vs. 41.5%, P=0.021), and a decrease in the -509 TT genotype (0.0 vs. 8.5%, P=0.049). PBMC TGF-beta1 production was higher in those patients with the -800 GG compared to those with a GA genotype stimulation index [stimulated/unstimulated TGF-beta1 levels were 1.54 interquartile range (IQR) 1.42 to 1.75 vs. 1.19, IQR 0.94 to 1.51, P=0.031]., Conclusions: There is an association between the TGF-beta1 -800 GA, -509 TT and Leu10-->Pro CT genotypes and the presence or absence of RPS. The low TGF-beta1 producer status of the -800 GA genotype may protect against the development of a pro-fibrotic pathology.
- Published
- 2002
- Full Text
- View/download PDF
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