title: Similar trends in serum VEGF-D levels and kidney angiomyolipoma responses with longer duration sirolimus treatment in adults with tuberous sclerosis.
abstract: BACKGROUND
  We have previously shown that serum VEGF-D is elevated at baseline, correlates with kidney angiomyolipoma size at baseline and 12 months, and decreases with sirolimus treatment in adults with tuberous sclerosis complex (TSC). To further investigate the utility of serum VEGF-D for longer term monitoring of TSC kidney disease, we present VEGF-D level results with 24 month follow-up.
  
  
  OBJECTIVE
  To compare 24 month VEGF-D levels in two subgroups of sirolimus treated patients (OFF SIROLIMUS AFTER 12 MONTHS or ON SIROLIMUS AFTER 12 MONTHS). DESIGN AND INTERVENTION(S): Serum VEGF-D was measured in samples collected from subjects enrolled in a phase 2 multicenter trial evaluating sirolimus for the treatment of kidney angiomyolipomas associated with TSC or TSC/LAM. All participants were treated with sirolimus from 0-12 months. During months 12-24, sirolimus was discontinued in one subgroup. The other subgroup was treated with additional sirolimus.
  
  
  METHODS
  Adult TSC participants were recruited from six clinical sites in the United States (comprehensive TSC clinics, 5; urology clinic, 1).
  
  
  METHODS
  There were 28 TSC patients who completed all 24 months of the study and serum samples were available at 24 months from 18/28 patients.
  
  
  METHODS
  We compared the percent change in VEGF-D levels (baseline to 24 months) in patients from the two treatment subgroups.
  
  
  RESULTS
  At 24 months, VEGF-D levels decreased by 67% compared with baseline (to 787 ± 426 pg/ml) in the ON SIROLIMUS AFTER 12 MONTHS group versus a 13% decrease (to 2971 ± 4014 pg/ml) in the OFF SIROLIMUS AFTER 12 MONTHS group (p=0.013, Mann-Whitney test). A similar trend was observed in kidney angiomyolipoma size but not in pulmonary function tests. Conclusions Serum VEGF-D may be useful for monitoring response to treatment with sirolimus and kidney angiomyolipoma size in patients with TSC, but confirmation is needed.
  
  
  BACKGROUND
  Clinical trials.gov NCT00126672.
authors: Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.
authors: Izabela A
authors: IA
authors: Malinowska
authors: Nancy
authors: N
authors: Lee
authors: Vidhya
authors: V
authors: Kumar
authors: Elizabeth A
authors: EA
authors: Thiele
authors: David Neal
authors: DN
authors: Franz
authors: Stephen
authors: S
authors: Ashwal
authors: Arthur
authors: A
authors: Sagalowsky
authors: Francis J
authors: FJ
authors: Dimario
authors: Drew
authors: D
authors: Cutler
authors: Darcy
authors: D
authors: Krueger
authors: Susana
authors: S
authors: Camposano
authors: Jan
authors: J
authors: Paolini
authors: Sandra L
authors: SL
authors: Dabora
mesh_terms: D000328:Adult; D018207:Angiomyolipoma / Q000097:blood* / Q000188:drug therapy* / Q000473:pathology; D005260:Female; D006801:Humans; D007668:Kidney / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D007680:Kidney Neoplasms / Q000097:blood / Q000473:pathology; D008297:Male; D020123:Sirolimus / Q000494:pharmacology / Q000627:therapeutic use*; D013997:Time Factors; D014402:Tuberous Sclerosis / Q000097:blood* / Q000188:drug therapy* / Q000473:pathology; D042643:Vascular Endothelial Growth Factor D / Q000097:blood*
chemical_list: C579459:VEGFD protein, human; D042643:Vascular Endothelial Growth Factor D; D020123:Sirolimus