Childhood nephrotic syndrome--current and future therapies.
The introduction of corticosteroids more than 50 years ago dramatically improved the prognosis of children with nephrotic syndrome. Corticosteroids remain the standard initial treatment for children with this disease, but a considerable proportion of patients do not respond and are therefore at risk of progressing to end-stage renal disease. Because of this risk, new therapeutic strategies are needed for steroid-resistant nephrotic syndrome. These strategies have historically focused on identifying effective alternative immunosuppressive agents, such as ciclosporin and tacrolimus, yet evidence now indicates that nephrotic syndrome results from podocyte dysfunction. Even conventional immunosuppressive agents, such as glucocorticoids and ciclosporin, directly affect podocyte structure and function, challenging the 'immune theory' of the pathogenesis of childhood nephrotic syndrome in which disease is caused by T cells. This Review summarizes the currently available treatments for childhood nephrotic syndrome, and discusses selected novel pathways in podocytes that could be targeted for the development of next-generation treatments for children with this syndrome.
Emory University, Atlanta, GA 30322, USA.
Larry A
LA
Greenbaum
Rainer
R
Benndorf
William E
WE
Smoyer
D000068879:Adalimumab; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use; D058846:Antibodies, Monoclonal, Murine-Derived / Q000627:therapeutic use; D018906:Antineoplastic Agents, Alkylating / Q000627:therapeutic use; D002648:Child; D003520:Cyclophosphamide / Q000627:therapeutic use; D016572:Cyclosporine / Q000627:therapeutic use; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D005690:Galactose / Q000627:therapeutic use; D005938:Glucocorticoids / Q000627:therapeutic use; D006706:Homeostasis; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D018793:Interleukin-13 / Q000037:antagonists & inhibitors; D047908:Intracellular Signaling Peptides and Proteins / Q000037:antagonists & inhibitors; D020935:MAP Kinase Signaling System / Q000187:drug effects; D009173:Mycophenolic Acid / Q000031:analogs & derivatives / Q000627:therapeutic use; D009404:Nephrotic Syndrome / Q000378:metabolism / Q000628:therapy*; D010956:Plasmapheresis; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors; D051880:Receptors, Notch / Q000502:physiology; D012263:Ribonucleosides / Q000627:therapeutic use; D000069283:Rituximab; D015398:Signal Transduction / Q000502:physiology; D016559:Tacrolimus / Q000627:therapeutic use; D045162:Thiazolidinediones / Q000627:therapeutic use; D056811:Unfolded Protein Response / Q000502:physiology; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors; D000099190:MAP-Kinase-Activated Kinase 2
D000068879:Adalimumab; D000893:Anti-Inflammatory Agents; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D058846:Antibodies, Monoclonal, Murine-Derived; D018906:Antineoplastic Agents, Alkylating; D003520:Cyclophosphamide; D016572:Cyclosporine; D004791:Enzyme Inhibitors; D005690:Galactose; D005938:Glucocorticoids; D007155:Immunologic Factors; D007166:Immunosuppressive Agents; D018793:Interleukin-13; D047908:Intracellular Signaling Peptides and Proteins; D009173:Mycophenolic Acid; D017346:Protein Serine-Threonine Kinases; D051880:Receptors, Notch; D012263:Ribonucleosides; D000069283:Rituximab; D016559:Tacrolimus; D045162:Thiazolidinediones; D048051:p38 Mitogen-Activated Protein Kinases; D000099190:MAP-Kinase-Activated Kinase 2; C010052:mizoribine; C561806:lebrikizumab