Renal TGF-beta in HIV-associated kidney diseases.
Human immunodeficiency virus (HIV)-1 infection may be complicated by progressive renal glomerular disease, including focal segmental glomerulosclerosis (FSGS) and proliferative glomerulonephritis. We examined renal tissue from 71 patients, including biopsies and autopsies from patients in the presence and absence of HIV-1 infection. We assessed the extent of TGF-beta, interstitial fibrosis, and interstitial CD45-positive cellular infiltrate using immunohistochemistry. Extracellular TGF-beta 1/beta 3 was largely confined to the renal interstitium, with the highest scores in HIV-seropositive renal disease and crescentic nephritis. Among all biopsies, the TGF-beta 1/beta 3 score correlated with the fibrosis score (r = 0.79, P < 0.0001) and with the CD45 score (r = 0.60, P < 0.0001). Biopsies from HIV-infected patients, taken together, showed marginally more TGF-beta 1/beta 3 compared to biopsies from HIV-uninfected patients (P = 0.05); similarly, HIV-associated FSGS showed marginally more TGF-beta 1/beta 3 compared to FSGS biopsies obtained from HIV-uninfected patients (P = 0.05). Intracellular TGF-beta 1 and TGF-beta 3 were both expressed by renal tubular epithelial cells and in extraglomerular crescents, whereas TGF-beta 3 was also present within interstitial mononuclear cells and eosinophils, and, exclusively in HIV-infected patients, within glomerular cells. In conclusion, TGF-beta expression was increased in several progressive glomerular diseases, and was particularly but not uniquely elevated in HIV-associated renal diseases.
Bódi
I
I
Department of Medicine, George Washington University Medical Center, Washington, D.C. USA.
Kimmel
P L
PL
Abraham
A A
AA
Svetkey
L P
LP
Klotman
P E
PE
Kopp
J B
JB
D015658:HIV Infections / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D007668:Kidney / Q000737:chemistry*; D007674:Kidney Diseases / Q000378:metabolism*; D017493:Leukocyte Common Antigens / Q000032:analysis; D016212:Transforming Growth Factor beta / Q000032:analysis*
D016212:Transforming Growth Factor beta; D017493:Leukocyte Common Antigens