Browsing by Author "Gipson, Debbie S."

Now showing 1 - 3 of 3
  • Thumbnail Image
    Item
    Clinical Characteristics and Treatment Patterns of Children and Adults With IgA Nephropathy or IgA Vasculitis: Findings From the CureGN Study
    (Elsevier, 2018-08-03) Selewski, David T.; Ambruzs, Josephine M.; Appel, Gerald B.; Bomback, Andrew S.; Matar, Raed Bou; Cai, Yi; Cattran, Daniel C.; Chishti, Aftab S.; D’Agati, Vivette D.; D’Alessandri-Silva, Cynthia J.; Gbadegesin, Rasheed A.; Hogan, Jonathan J.; Iragorri, Sandra; Jennette, J. Charles; Julian, Bruce A.; Khalid, Myda; Lafayette, Richard A.; Liapis, Helen; Lugani, Francesca; Mansfield, Sarah A.; Mason, Sherene; Nachman, Patrick H.; Nast, Cynthia C.; Nester, Carla M.; Noone, Damien G.; Novak, Jan; O’Shaughnessy, Michelle M.; Reich, Heather N.; Rheault, Michelle N.; Rizk, Dana V.; Saha, Manish K.; Sanghani, Neil S.; Sperati, C. John; Sreedharan, Rajasree; Srivastava, Tarak; Swiatecka-Urban, Agnieszka; Twombley, Katherine; Vasylyeva, Tetyana L.; Weaver, Donald J.; Yin, Hong; Zee, Jarcy; Falk, Ronald J.; Gharavi, Ali G.; Gillespie, Brenda W.; Gipson, Debbie S.; Greenbaum, Larry A.; Holzman, Lawrence B.; Kretzler, Matthias; Robinson, Bruce M.; Smoyer, William E.; Flessner, Michael; Guay-Woodford, Lisa M.; Kiryluk, Krzysztof; CureGN Consortium; Pediatrics, School of Medicine
    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.
  • Thumbnail Image
    Item
    Scaffold protein SH3BP2 signalosome is pivotal for immune activation in nephrotic syndrome
    (American Society for Clinical Investigation, 2024-02-08) Srivastava, Tarak; Garola, Robert E.; Zhou, Jianping; Boinpelly, Varun C.; Rezaiekhaligh, Mohammad H.; Joshi, Trupti; Jiang, Yuexu; Ebadi, Diba; Sharma, Siddarth; Sethna, Christine; Staggs, Vincent S.; Sharma, Ram; Gipson, Debbie S.; Hao, Wei; Wang, Yujie; Mariani, Laura H.; Hodgin, Jeffrey B.; Rottapel, Robert; Yoshitaka, Teruhito; Ueki, Yasuyoshi; Sharma, Mukut; Biomedical and Applied Sciences, School of Dentistry
    Despite clinical use of immunosuppressive agents, the immunopathogenesis of minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS) remains unclear. Src homology 3-binding protein 2 (SH3BP2), a scaffold protein, forms an immune signaling complex (signalosome) with 17 other proteins, including phospholipase Cγ2 (PLCγ2) and Rho-guanine nucleotide exchange factor VAV2 (VAV2). Bioinformatic analysis of human glomerular transcriptome (Nephrotic Syndrome Study Network cohort) revealed upregulated SH3BP2 in MCD and FSGS. The SH3BP2 signalosome score and downstream MyD88, TRIF, and NFATc1 were significantly upregulated in MCD and FSGS. Immune pathway activation scores for Toll-like receptors, cytokine-cytokine receptor, and NOD-like receptors were increased in FSGS. Lower SH3BP2 signalosome score was associated with MCD, higher estimated glomerular filtration rate, and remission. Further work using Sh3bp2KI/KI transgenic mice with a gain-in-function mutation showed ~6-fold and ~25-fold increases in albuminuria at 4 and 12 weeks, respectively. Decreased serum albumin and unchanged serum creatinine were observed at 12 weeks. Sh3bp2KI/KI kidney morphology appeared normal except for increased mesangial cellularity and patchy foot process fusion without electron-dense deposits. SH3BP2 co-immunoprecipitated with PLCγ2 and VAV2 in human podocytes, underscoring the importance of SH3BP2 in immune activation. SH3BP2 and its binding partners may determine the immune activation pathways resulting in podocyte injury leading to loss of the glomerular filtration barrier.
  • Thumbnail Image
    Item
    Treatment Patterns Among Adults and Children With Membranous Nephropathy in the Cure Glomerulonephropathy Network (CureGN)
    (Elsevier, 2019-12) O’Shaughnessy, Michelle M.; Troost, Jonathan P.; Bomback, Andrew S.; Hladunewich, Michelle A.; Ashoor, Isa F.; Gibson, Keisha L.; Matar, Raed Bou; Selewski, David T.; Srivastava, Tarak; Rheault, Michelle N.; Al-Uzri, Amira; Kogon, Amy J.; Khalid, Myda; Vento, Suzanne; Sanghani, Neil S.; Gillespie, Brenda W.; Gipson, Debbie S.; Wang, Chia-shi; Parsa, Afshin; Guay-Woodford, Lisa; Laurin, Louis-Philippe; Pediatrics, School of Medicine
    Introduction The 2012 Kidney Disease: Improving Global Outcomes (KDIGO) Clinical Practice Guidelines for Glomerulonephritis recommend that patients with membranous nephropathy (MN) at risk for progression receive immunosuppressive therapy (IST), usually after 6 months of observation. A cyclophosphamide (CYC) or calcineurin inhibitor (CNI)–based regimen is recommended as first-line IST. However, the extent to which KDIGO recommendations are adopted in practice remains largely unknown. Methods We evaluated prescribing practice among patients with primary MN (diagnosed 2010–2018) enrolled in the Cure Glomerulonephropathy Network (CureGN) cohort study. We also evaluated the availability of testing for phospholipase A2 receptor (PLA2R) in the contemporary era. Results Among 361 patients (324 adults and 37 children) with MN who were IST-naïve at biopsy and had at least 6 months of follow-up, 55% of adults and 58% of children initiated IST <6 months after biopsy. Of these, 1 in 5 had no indication for (i.e., urine protein-to-creatinine ratio [uPCR] <4 g/g) or an apparent contraindication to (i.e., an estimated glomerular filtration rate [eGFR] <30 ml/min per 1.73 m2) IST. As first-line IST, half of treated patients received either CYC (16% of adults; 0% of children) or a CNI (40% and 46%, respectively), whereas 1 in 5 received corticosteroid monotherapy (20% and 27%, respectively) and 1 in 6 rituximab (15% and 15%, respectively). More than 80% of surveyed centers had access to PLA2R testing. Conclusion These findings suggest that providers are not aware of, or lack confidence in, current KDIGO guidelines for MN. Treatment patterns observed in this cohort might critically inform the drafting of planned updates to KDIGO guidelines.