Basic fibroblast growth factor in HIV-associated hemolytic uremic syndrome.
Endothelial injury is the primary pathogenic event leading to the renal thrombotic microangiopathic lesions typical of the hemolytic uremic syndrome (HUS). Basic fibroblast growth factor (bFGF) is an angiogenic growth factor released by injured endothelial cells. In a previous study we have found a significant accumulation of bFGF in human immunodeficiency virus (HIV)-transgenic mice with renal disease. Here we investigated whether bFGF was accumulated in the circulation and kidneys of two children with HIV-associated HUS (HIV-HUS), and studied the mechanisms involved in this process. The plasma levels of bFGF in children with HIV-HUS (124+/-20 pg/ml) were increased compared with five children with HIV nephropathy (49+/-6 pg/ml) and twenty HIV-infected children without renal disease (26+/-4 pg/ml, P<0.001). Immunohistochemistry and receptor binding studies showed that bFGF was accumulated bound to heparan sulfate proteoglycans in renal glomeruli and interstitium surrounding renal tubules in HIV-HUS kidneys. Basic FGF stimulated the proliferation of mesangial and urinary renal tubular epithelial cells isolated from both patients. These findings support the hypothesis that bFGF and its low-affinity binding sites may play a relevant role in modulating the process of glomerular and renal tubular regeneration during the acute stages of HIV-HUS. A follow-up study in a larger sample population is required to confirm these results.
Ray
P E
PE
Center IV, Room R-211, Children's Research Institute, Children's National Medical Center, 111 Michigan Avenue N.W., Washington, DC 20010, USA, Pray@cnmc.org
Liu
X H
XH
Xu
L
L
Rakusan
T
T
D016263:AIDS-Associated Nephropathy / Q000097:blood* / Q000378:metabolism; D001667:Binding, Competitive; D002455:Cell Division; D002648:Child; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000097:blood* / Q000378:metabolism; D006463:Hemolytic-Uremic Syndrome / Q000097:blood* / Q000378:metabolism; D006801:Humans; D007118:Immunoassay; D007150:Immunohistochemistry; D007223:Infant; D007684:Kidney Tubules / Q000473:pathology; D008297:Male; D017468:Receptors, Fibroblast Growth Factor / Q000378:metabolism
D017468:Receptors, Fibroblast Growth Factor; D016222:Fibroblast Growth Factor 2