Emerging drugs for treatment of focal segmental glomerulosclerosis

被引:18
作者
Trachtman, Howard [1 ]
机构
[1] NYU Langone Hlth, Dept Pediat, Div Nephrol, New York, NY 10016 USA
关键词
Glomerulosclerosis; FSGS; biomarker profiling; targeted therapy; precision medicine; CHRONIC KIDNEY-DISEASE; CLINICAL-TRIALS; BARDOXOLONE; MECHANISMS; PODOCYTES; DESIGN; FSGS; CHALLENGES; ABATACEPT; ANTIBODY;
D O I
10.1080/14728214.2020.1803276
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Background Glomerulosclerosis represents the final stage of glomerular injury during the course of kidney disease and can result from a primary disturbance in disorders like focal segmental glomerulosclerosis or a secondary response to tubulointerstitial disease. Overall, primary focal glomerulosclerosis (FSGS), the focus of this review, accounts for 10-20% of patients of all ages who progress to end stage kidney disease. There are no FDA approved therapeutic options that effectively prevent or delay the onset of kidney failure. Areas covered Current immunosuppressive therapy and conservative management including inhibitors of the renin-angiotensin-aldosterone axis and sodium-glucose cotransporter are reviewed. FSGS is now recognized to represent a heterogeneous entity with multiple underlying disease mechanisms. Therefore, novel approaches targeting the podocyte cytoskeleton, immunological, inflammatory, hemodynamic and metabolic pathways are highlighted Expert opinion A number of factors are driving the development of drugs to treat focal segmental glomerulosclerosis in particular and glomerulosclerosis in general including growing awareness of the burden of chronic kidney disease, improved scientific understanding of the mechanism of injury, and the development of noninvasive profiles to identify subgroups of patients with discrete mechanisms of glomerular injury.
引用
收藏
页码:367 / 375
页数:9
相关论文
共 66 条
[21]   Phase I Trial of Rosiglitazone in FSGS: I. Report of the FONT Study Group [J].
Joy, Melanie S. ;
Gipson, Debbie S. ;
Dike, Mary ;
Powell, Leslie ;
Thompson, Amber ;
Vento, Suzanne ;
Eddy, Allison ;
Fogo, Agnes B. ;
Kopp, Jeffrey B. ;
Cattran, Daniel ;
Trachtman, Howard .
CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY, 2009, 4 (01) :39-47
[22]   A novel dual PPAR-γ agonist/sEH inhibitor treats diabetic complications in a rat model of type 2 diabetes [J].
Khan, Md Abdul Hye ;
Kolb, Lauren ;
Skibba, Melissa ;
Hartmann, Markus ;
Blocher, Ren ;
Proschak, Ewgenij ;
Imig, John D. .
DIABETOLOGIA, 2018, 61 (10) :2235-2246
[23]   Understanding the Rewards of Successful Drug Development - Thinking Inside the Box [J].
Khullar, Dhruv ;
Ohn, Jennifer A. ;
Trusheim, Mark ;
Bach, Peter B. .
NEW ENGLAND JOURNAL OF MEDICINE, 2020, 382 (05) :473-480
[24]   Focal Segmental Glomerulosclerosis and Chronic Kidney Disease in Pediatric Patients [J].
Kiffel, Jeremy ;
Rahimzada, Yael ;
Trachtman, Howard .
ADVANCES IN CHRONIC KIDNEY DISEASE, 2011, 18 (05) :332-338
[25]   B cell-derived IL-4 acts on podocytes to induce proteinuria and foot process effacement [J].
Kim, Alfred H. J. ;
Chung, Jun-Jae ;
Akilesh, Shreeram ;
Koziell, Ania ;
Jain, Sanjay ;
Hodgin, Jeffrey B. ;
Miller, Mark J. ;
Stappenbeck, Thaddeus S. ;
Miner, Jeffrey H. ;
Shaw, Andrey S. .
JCI INSIGHT, 2017, 2 (21)
[26]  
Komers R, 2016, AM J PHYSL REGUL INT, V310, pR87
[27]   Renal p38 MAP kinase activity in experimental diabetes [J].
Komers, Radko ;
Lindsley, Jessie N. ;
Oyama, Terry T. ;
Cohen, David M. ;
Anderson, Sharon .
LABORATORY INVESTIGATION, 2007, 87 (06) :548-558
[28]   Study Design of the Phase 3 Sparsentan Versus Irbesartan (DUPLEX) Study in Patients With Focal Segmental Glomerulosclerosis [J].
Komers, Radko ;
Diva, Ulysses ;
Inrig, Jula K. ;
Loewen, Andrea ;
Trachtman, Howard ;
Rote, William E. .
KIDNEY INTERNATIONAL REPORTS, 2020, 5 (04) :494-502
[29]   Change in Albuminuria and GFR as End Points for Clinical Trials in Early Stages of CKD: A Scientific Workshop Sponsored by the National Kidney Foundation in Collaboration With the US Food and Drug Administration and European Medicines Agency [J].
Levey, Andrew S. ;
Gansevoort, Ron T. ;
Coresh, Josef ;
Inker, Lesley A. ;
Heerspink, Hiddo L. ;
Grams, Morgan E. ;
Greene, Tom ;
Tighiouart, Hocine ;
Matsushita, Kunihiro ;
Ballew, Shoshana H. ;
Sang, Yingying ;
Vonesh, Edward ;
Ying, Jian ;
Manley, Tom ;
de Zeeuw, Dick ;
Eckardt, Kai-Uwe ;
Levin, Adeera ;
Perkovic, Vlado ;
Zhang, Luxia ;
Willis, Kerry .
AMERICAN JOURNAL OF KIDNEY DISEASES, 2020, 75 (01) :84-104
[30]   ASK1 contributes to fibrosis and dysfunction in mode of kidney disease [J].
Liles, John T. ;
Corkey, Britton K. ;
Nolte, Gregory T. ;
Budas, Grant R. ;
Lansdon, Eric B. ;
Hinojosa-Kirschenbaum, Ford ;
Badal, Shawn S. ;
Lee, Michael ;
Schultz, Brian E. ;
Wise, Sarah ;
Pendem, Swetha ;
Graupe, Michael ;
Castonguay, Laurie ;
Koch, Keith A. ;
Wong, Melanie H. ;
Papalia, Giuseppe A. ;
French, Dorothy M. ;
Sullivan, Theodore ;
Huntzicker, Erik G. ;
Ma, Frank Y. ;
Nikolic-Paterson, David J. ;
Altuhaifi, Tareq ;
Yang, Haichun ;
Fogo, Agnes B. ;
Breckenridge, David G. .
JOURNAL OF CLINICAL INVESTIGATION, 2018, 128 (10) :4485-4500