Renal expression and urinary concentration of EGF and IL-6 in acutely dysfunctioning kidney transplanted patients

Nephrol Dial Transplant. 1997 Dec;12(12):2687-93. doi: 10.1093/ndt/12.12.2687.


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.

Design and method: 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).

Conclusion: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Adolescent
  • Adult
  • Cyclosporine / poisoning*
  • Epidermal Growth Factor / genetics
  • Epidermal Growth Factor / metabolism*
  • Epidermal Growth Factor / urine
  • Female
  • Gene Expression / physiology
  • Graft Rejection / metabolism*
  • Graft Rejection / urine
  • Humans
  • Immunosuppressive Agents / poisoning*
  • Interleukin-6 / genetics
  • Interleukin-6 / metabolism*
  • Interleukin-6 / urine
  • Kidney / drug effects
  • Kidney / metabolism*
  • Kidney / physiopathology
  • Male
  • Middle Aged


  • Immunosuppressive Agents
  • Interleukin-6
  • Epidermal Growth Factor
  • Cyclosporine