Increased urinary excretion of transforming growth factor-beta(1) in renal transplant recipients during cytomegalovirus infection.
OBJECTIVE
Cytomegalovirus (CMV) is a suggested risk factor for chronic allograft nephropathy, and transforming growth factor-beta (TGF-beta) is a key fibrogenic molecule in this process. CMV has been shown to induce the expression of TGF-beta and several cytokines. We analyzed the impact of CMV on urinary excretion of TGF-beta, ICAM-1, TNF-alpha and correlated findings with biopsy histology.


METHODS
Urine samples from 46 renal transplant recipients were available for the study. Urine samples were taken when CMV infection was suspected, or for controlling of proteinuria or bacteriuria.


METHODS
CMV was diagnosed by antigenemia and viral cultures. Patients with previous CMV infection were excluded from the analysis. Urine samples were analyzed by ELISA-method to detect the levels of TNF-alpha, ICAM-1 and TGF-beta(1). Banff '97 criteria were used for scoring of protocol biopsies taken 6 months after transplantation.


RESULTS
At the time of the urine collection, 13/46 patients had CMV infection. Eight patients with no CMV infection were used as controls. TGF-beta(1) was significantly increased in the CMV group (samples taken mean 137+/-79 days post-transplantation) compared to controls (samples 139+/-64 days post-transplantation) (51.1+/-28.0 vs. 13.3+/-6.7 ng/mmol crea, p<0.001). No differences in the levels of other molecules were recorded. In the biopsies, interstitial fibrosis was significantly increased in the CMV group compared to controls.


CONCLUSIONS
Urinary excretion of TGF-beta(1) was increased in patients during CMV infection. This was associated with increased fibrosis in the biopsies.
Helanterä
Ilkka
I
Department of Virology, Helsinki University Central Hospital and University of Helsinki, Meilahti, FIN-00029 HUS, Helsinki, Finland. ilkka.helantera@helsinki.fi
Teppo
Anna-Maija
AM
Koskinen
Petri
P
Törnroth
Tom
T
Grönhagen-Riska
Carola
C
Lautenschlager
Irmeli
I
D000328:Adult; D003586:Cytomegalovirus Infections / Q000175:diagnosis / Q000209:etiology / Q000473:pathology / Q000652:urine*; D005260:Female; D005355:Fibrosis / Q000473:pathology; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000652:urine; D007674:Kidney Diseases / Q000150:complications / Q000473:pathology / Q000628:therapy / Q000652:urine / Q000821:virology; D016030:Kidney Transplantation / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D012307:Risk Factors; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000652:urine*; D014184:Transplantation, Homologous; D014409:Tumor Necrosis Factor-alpha / Q000652:urine
D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1