Abstract
ContextWe 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.ObjectiveTo 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.SettingAdult TSC participants were recruited from six clinical sites in the United States (comprehensive TSC clinics, 5; urology clinic, 1).PatientsThere were 28 TSC patients who completed all 24 months of the study and serum samples were available at 24 months from 18/28 patients.Main Outcome Measure(s)We compared the percent change in VEGF-D levels (baseline to 24 months) in patients from the two treatment subgroups.ResultsAt 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.Trial RegistrationClinical trials.gov NCT00126672.
Highlights
Vascular endothelial growth factors (VEGFs) are molecules that stimulate the development of vessels during embryogenesis and growth of new vessels in mature organisms after tissue injury, inflammation, infarct/ischemia, or during neoplastic vascularisation
Serum VEGF-D may be useful for monitoring response to treatment with sirolimus and kidney angiomyolipoma size in patients with tuberous sclerosis complex (TSC), but confirmation is needed
At 24 months, VEGF-D levels returned toward baseline in the OFF SIROLIMUS AFTER 12 MONTHS group (13% decrease compared with baseline), but not in the ON SIROLIMUS AFTER 12 MONTHS group (67% decrease compared with baseline)
Summary
Vascular endothelial growth factors (VEGFs) are molecules that stimulate the development of vessels during embryogenesis and growth of new vessels in mature organisms after tissue injury, inflammation, infarct/ischemia, or during neoplastic vascularisation. VEGF-D binds to VEGF receptors 2 and 3 (VEGFR2, VEGFR3), localized on endothelial cell membranes. Several groups have shown that serum VEGF-D levels are elevated in cohorts of sporadic pulmonary lymphangioleiomyomatosis (LAM) patients [2,3,4]. Sporadic LAM is an uncommon interstitial pulmonary disorder that can cause end stage lung disease in women [5]. Because VEGF-D testing may be a non-invasive alternative to lung biopsy for diagnosing LAM in women with cystic lung disease of unknown etiology [6], serum VEGF-D testing is available for clinical use (see http://www.thelamfoundation.org/, VEGF-D TEST, VEGF-D quantification sample submission form)
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