Focal segmental glomerulosclerosis (FSGS) is the most common glomerular lesion leading to ESRD in Children. Approximately one-fifth of the steroid resistant patients with FSGS (SRFSGS) will respond to cyclospodne (CS). Those unresponsive patients will progress over a variable time interval to ESRD. The rate of progression is particularly severe in African-American and Hispanic children. To date no controlled trial with novel immunomodulatory agent(s) has demonstrated efficacy inducing a complete remission in SRFSGS patients who fail to respond to CS.
The Specific Aims of this proposal are to compare two regimens: (a) low-dose CS and sirolimus, and (b) intravenous methylprednisolone and cyclophosphamide in patients with SRFSGS who do not respond with a complete remission to a 16 week course of CS and low-dose prednisone in order to determine which regimen is more efficacious with fewer side-effects. An additional Specific Aim will attempt to predict progression in patients with SRFSGS by Sirius Red staining and by detecting fibrogenic cytokines in renal biopsy tissue at enrollment and 18 months after randomization. Additionally, 125I-iothalamate will be compared with Cystatin C as a measure of glomerular filtration rate (GFR) in order to determine if the latter is an acceptable """"""""gold standard"""""""" for serial measurement of GFR in patients with SRFSGS.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project--Cooperative Agreements (U01)
Project #
5U01DK063385-02
Application #
6666758
Study Section
Special Emphasis Panel (ZDK1-GRB-2 (O3))
Program Officer
Moxey-Mims, Marva M
Project Start
2002-09-30
Project End
2007-08-31
Budget Start
2003-09-01
Budget End
2004-08-31
Support Year
2
Fiscal Year
2003
Total Cost
$596,003
Indirect Cost
Name
State University New York Stony Brook
Department
Pediatrics
Type
Schools of Medicine
DUNS #
804878247
City
Stony Brook
State
NY
Country
United States
Zip Code
11794
Thurman, Joshua M; Wong, Maria; Renner, Brandon et al. (2015) Complement Activation in Patients with Focal Segmental Glomerulosclerosis. PLoS One 10:e0136558
D'Agati, Vivette D; Alster, Joan M; Jennette, J Charles et al. (2013) Association of histologic variants in FSGS clinical trial with presenting features and outcomes. Clin J Am Soc Nephrol 8:399-406
Hogg, Ronald J; Friedman, Aaron; Greene, Tom et al. (2013) Renal function and proteinuria after successful immunosuppressive therapies in patients with FSGS. Clin J Am Soc Nephrol 8:211-8
Ferris, Maria; Norwood, Victoria; Radeva, Milena et al. (2013) Patient recruitment into a multicenter randomized clinical trial for kidney disease: report of the focal segmental glomerulosclerosis clinical trial (FSGS CT). Clin Transl Sci 6:13-20
Wei, Changli; Trachtman, Howard; Li, Jing et al. (2012) Circulating suPAR in two cohorts of primary FSGS. J Am Soc Nephrol 23:2051-9
Gipson, Debbie S; Trachtman, Howard; Kaskel, Frederick J et al. (2011) Clinical trial of focal segmental glomerulosclerosis in children and young adults. Kidney Int 80:868-78
Gipson, Debbie S; Trachtman, Howard; Kaskel, Frederick J et al. (2011) Clinical trials treating focal segmental glomerulosclerosis should measure patient quality of life. Kidney Int 79:678-685