Nephrol Dial Transplant Vol. 19 No. 11 © ERA-EDTA 2004; all rights reserved
Preliminary Communication
Epithelial cell polarity and improved early outcomes in delayed graft function: a pilot study of polyclonal vs monoclonal antibodies
1 Department of Surgery, 2 Pathology and Laboratory Medicine, and 3 Medicine, University of Wisconsin-Madison, Madison, WI 53792, USA
Correspondence and offprint requests to: Bryan N. Becker, MD, UW Nephrology, 3034 Fish Hatchery Road, Suite B, Madison, WI 53713, USA. Email: bnb{at}medicine.wisc.edu
Background. Polyclonal antibody preparations contain antibodies that bind not only to molecules on circulating lymphocytes but also to other sites that bear similar antigens. We hypothesized that this extra-antibody effect would increase the number of intact tubular epithelial cells in organs at high risk for delayed graft function (DGF).
Methods. We used immunohistochemistry to examine serial biopsy samples (time 0 and 710 days after transplantation) in 18 kidney transplant recipients with DGF. These individuals received either polyclonal rabbit antithymocyte sera or a monoclonal humanized anti-CD25 antibody as induction immunosuppression. We also examined their early clinical course over 6 months.
Results. Individuals treated with the polyclonal preparation demonstrated greater preservation of kidney epithelial cell polarity manifested by more intense and more localized basolateral distribution of E-cadherin (P = 0.016), ß-catenin (P = 0.008) and Na-K ATPase (P = 0.02). These individuals were also more likely to maintain greater estimated glomerular filtration rates (eGFRs) at follow-up than patients treated with an anti-CD25 monoclonal antibody (6 month eGFR polyclonal: 55.5±7.12 ml/min vs monoclonal: 43.33±6.48 ml/min; P = 0.002).
Conclusion. Though a pilot study, these data suggest that a purified polyclonal antibody preparation may help conserve functional kidney mass during DGF with potential benefits on transplant function overall.
Keywords: antibody therapy; delayed graft function; epithelial polarity; kidney transplantation; transplant function