The Pharmaceutical Journal
Vol 271 No 7280 p834
20/27 December 2003

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New England Journal of Medicine abstract (more)

Kidney transplant patients need second phase of less toxic therapy

Transplanted kidneys may fail in the long term because of the effects of the drugs used to prevent acute rejection, a new study confirms. A two-stage treatment strategy should be adopted, suggest the authors of the study — first using powerful anti-rejection drugs to minimise immunologic injury and then switching to an alternative immunosuppressant that is not nephrotoxic.

The researchers, from the University of Sydney in Australia, regularly examined biopsies of transplanted kidneys over 15 years to find out why kidneys eventually succumb to chronic allograft nephropathy. They found two distinct phases of injury: an initial phase caused by ischaemic injury and, beyond one year, a phase characterised by microvascular and glomerular injury. They report that nephrotoxicity was almost universal at 10 years. This finding suggests that drugs used to prevent early rejection of kidney transplants — such as ciclosporin and tacrolimus — are not suitable as long-term immunosuppressants. “A two-stage treatment may be preferable, optimising therapy according to the individual risks during each period after transplantation,” they suggest (New England Journal of Medicine 2003:349:2326).

The National Institute for Clinical Excellence is expected to produce guidance on the use of immunosuppressant regimens in kidney transplantation in March 2004.