Renal expression and urinary concentration of EGF and IL-6 in acutely dysfunctioning kidney transplanted patients.
BACKGROUND
Despite marked improvements in the success of solid organ transplantation, a significant percentage of transplanted organs is lost due to recurrent episodes of acute cellular rejection. The mechanisms that govern allograft rejection likely include a complex regulatory network of multiple cytokines and growth factors.


METHODS
This study investigated the kidney gene (in situ hybridization) and protein (immunohistochemistry) expression and the urinary excretion rate of IL-6 and EGF in 29 renal transplant recipients: 16 with acute cellular rejection (AR) and 13 with acute tubular damage/cyclosporine toxicity (ATD).


RESULTS
AR patients displayed a 4-fold increase of renal IL-6 expression, which localized chiefly to proximal tubular cells and monocytes/macrophages, whereas EGF signal was extremely weak or even absent. In ATD patients, EGF expression was markedly reduced, while IL-6 specific signal was unchanged. In all the patients examined the renal expression of IL-6 and EGF strictly correlated with their urinary excretion rate (r:0.459, P:0.001). Thus, urinary IL-6/EGF ratio was markedly increased in the former group (> 20-fold at day 1), where it paralleled the modifications of plasma creatinine over time (r:0.603, P < 0.0001), and was only slightly increased in the latter group (< 3-fold).


CONCLUSIONS
Kidney transplanted patients with acute cellular rejection or acute tubular damage/CyA nephrotoxicity exhibit a distinctly different pattern of intragraft expression of IL-6 and EGF, which is closely reflected by their rate of urinary excretion.
Di Paolo
S
S
Institute of Nephrology, University of Bari, Italy.
Gesualdo
L
L
Stallone
G
G
Ranieri
E
E
Schena
F P
FP
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D016572:Cyclosporine / Q000506:poisoning*; D004815:Epidermal Growth Factor / Q000235:genetics / Q000378:metabolism* / Q000652:urine; D005260:Female; D015870:Gene Expression / Q000502:physiology; D006084:Graft Rejection / Q000378:metabolism* / Q000652:urine; D006801:Humans; D007166:Immunosuppressive Agents / Q000506:poisoning*; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism* / Q000652:urine; D007668:Kidney / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged
D007166:Immunosuppressive Agents; D015850:Interleukin-6; D004815:Epidermal Growth Factor; D016572:Cyclosporine