Focal Segmental Glomerulosclerosis (FSGS) is a major cause of chronic kidney disease in childhood. This glomerulopaty is more frequent in minority populations, and often recurs in the transplanted kidney. Despite advances particulary in molecular genetics, the cause and optimal treatment of this condition remains poorly defined. Uncontrolled studies in adults with FSGS support the use of prolonged prednisone therapy. Preliminary data in children suggests that the calcineurin inhibitor tacrolimus may be efficacious in patients who have been refractory to other therapies. The purpose of this multicenter study is to compare the relative efficacy of tacrolimus with that of intensive prednisone therapy in preventing the progression of primary FSGS. This represents the first controlled evaluation of these two promising therapies in children with FSGS. We are proposing a randomized, open-label clinical trial in patients with nephrotic range proteinuria who fail to respond to 4 weeks of oral prednisone and who are found to have FSGS on renal biopsy. Patients will be assigned to receive daily prednisone (60 mg/m2) for 3 months followed by either alternate day prednisone (40 mg/m2) for the ensuing 15 months or tacrolimus plus low-dose alternate day (10 mg/m2) for 18 months. In addition, patients will receive optimal doses of losartan and atorvostatin to control proteinuria, hypertension, and hypelipidemia. The primary outcome indicators will be: complete or partial remission of proteinuria, preservation of glomerular filtration rate, and prevention of renal scarring. Secondary outcome indicators will include correlation of response with a novel histopathologic classification, assessed by a centrol core pathology group. The study design will incorporate collection and storage of potentially important biological samples at the direction of the Data Coordinating Center and the Steering Committee of the NIDDK. The Eastern Regional Group for the Study of Focal Segmental Glomerulosclerosis in Children will be comprised of 41 sites under the direction of the Regional Coordinating Center at Montefiore Medical Center of the Albert Einstein College of Medicine. This project is expected to: 1) improve the outcome of children with FSGS, and, 2) create a nationwide network of clinical investigators that will facilitate future basic and clinical research in the field of pediatric nephrology, in general, and FSGS, in particular.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project--Cooperative Agreements (U01)
Project #
5U01DK063549-06
Application #
7288373
Study Section
Special Emphasis Panel (ZDK1-GRB-2 (O3))
Program Officer
Moxey-Mims, Marva M
Project Start
2002-09-30
Project End
2009-08-31
Budget Start
2007-09-01
Budget End
2009-08-31
Support Year
6
Fiscal Year
2007
Total Cost
$388,400
Indirect Cost
Name
Montefiore Medical Center (Bronx, NY)
Department
Type
DUNS #
041581026
City
New York
State
NY
Country
United States
Zip Code
10467
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
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
Smith, Lorie B; Fadrowski, Jeffrey J; Howe, Chanelle J et al. (2010) Secondary hyperparathyroidism and anemia in children treated by hemodialysis. Am J Kidney Dis 55:326-34
Kumar, Juhi; Muntner, Paul; Kaskel, Frederick J et al. (2009) Prevalence and associations of 25-hydroxyvitamin D deficiency in US children: NHANES 2001-2004. Pediatrics 124:e362-70
Kumar, Juhi; Gordillo, Roberto; Kaskel, Frederick J et al. (2009) Increased prevalence of renal and urinary tract anomalies in children with congenital hypothyroidism. J Pediatr 154:263-6
Mahesh, Shefali; Del Rio, Marcela; Feuerstein, Dianne et al. (2008) Demographics and response to therapeutic plasma exchange in pediatric renal transplantation for focal glomerulosclerosis: a single center experience. Pediatr Transplant 12:682-8

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