Some Studies Suggest Antirejection Drugs Not Always Needed to Protect Kidney Graft

Abstract

RESEARCHERS ARE EXPLORING THE tantalizing prospect of identifying patients with kidney transplants who do not need to continue to take antirejection medicines to preserve their donated organ. At the very least, this line of research might enable physicians to recognize those patients with renal allografts who could take less immunosuppressive medicine, reducing the risks of infection and cancer associated with such drugs. Such hopes were raised by researchers in the United States and Europe who identified biological signatures of a small minority of patients who had stopped taking antirejection medicines for a variety of reasons, such as adverse effects or cost, yet still preserved their allograft function. The researchers found that renal allograft tolerance was strongly associated with a distinct pattern of genes expressed by B lymphocytes (B cells). If more rigorous studies replicate these findings, it might be possible to design drug-weaning protocols for certain patients with a favorable B cell signature. In the US-based study, researchers enrolled 25 patients who had stable graft function despite receiving no immunosuppression for at least 1 year and as long as 32 years and compared them with persons who maintained stable graft function while receiving immunosuppression therapy and with nontransplanted controls. In tolerant patients, the B cell signature was associated with upregulation of CD20 messenger RNA in urine sediment cells and elevated numbers of peripheral blood-naive and transitional B cells compared with the other cohorts (Newell KA et al. J Clin Invest. 2010; 120[6]:1836-1847). The European-based researchers studied 24 renal transplant recipients and compared them with individuals with stable graft function while receiving immunosuppression therapy, those with biopsy-proven and immunologically driven chronic rejection, and nontransplanted controls. Compared with the other cohorts, the tolerant patients displayed, among a variety of factors, an expansion of peripheral blood