[Low-toxicity immunosuppressive therapy in renal transplant]

Renal allograft loss in the long term may be due to the death of a patient with a functioning graft or to chronic allograft nephropathy. One of the most important factors in the development of chronic allograft nephropathy is drug nephrotoxicity. The term nephrotoxicity comprises two distinct forms of renal injury: acute and chronic. Immunosuppressive drugs, and in particular calcineurin inhibitors, have a variety of side effects including nephrotoxicity. The nephrotoxicity associated with calcineurin inhibitors is well known; this association has also been described for the newer agents.

We reviewed a large number of recent studies that attempted to reduce the toxicity of immunosuppressive regimens.

A number of low-toxicity protocols have been developed. Encouraging results have been obtained with regimens that reduce or eliminate nephrotoxicity-inducing calcineurin inhibitors and with regimens that reduce or eliminate steroids, which are responsible for many diseases that may lead to the death of the patient, even with a functioning graft.

All immunosuppressive drugs may be nephrotoxic, even if they act through different mechanisms. Combining different drugs at low dosage would therefore seem the best solution. It is not yet clear which regimens will be the most effective from the point of view of maximizing patient and graft survival, minimizing rejection, and minimizing adverse events.