It has been requested that I do a post on the differences between early immunosuppressive agents and the ones that we currently use. One way to compare these differences in terms that most people are familiar with is likening the immunosuppressive agents to antibiotics. In the same way that separate classes of antibiotics disrupt bacteria multiplication through different mechanisms, these agents each intervene with specific functions of differing cells within the immune response. One of my earlier posts shows how several induction agents either prevented the antigen presenting cell from communicating with the T-cell or directly interfere with the response of the T-cell itself. Early exploration and differentiation of these agents was mainly focused on finding different mechanisms of action, searching for one which had the fewest number of collateral effects. Relating back to the my timeline of maintenance and induction agents, the main difference between earlier agents and ones that are used now lies in side effects (generally lesser with newer medication) and potency (how much it curbs immune response per a given dosage).
A higher strength agent is not, however, always the most desirable to use. One particular article which compares the the incidence of BK viremia (BK Virus presence in the bloodstream) and BK viruria (presence in the urine, which implies a strong presence in the kidney) of two different maintenance agents shows the risk of using the stronger agent. The study included 629 patients of various backgrounds who were randomly assigned a immunosuppressive regimen of either Tacrolimus (the most widely used and more powerful agent) or Cyclosporine (relatively weaker). Though the study did not go further and explore whether one drug has a higher rate of developing BK nephropathy (the actual damage to the kidney) it can be safely assumed that higher rates of viremia correlate with higher rates of nephropathy. The study showed significant difference in the rates of BK Viremia between the two agents.
So of the two to have, is viremia or viruria considered more of a problem- Or is one just a result of the other? Furthermore, if each of the two drugs poses a different benefit, is there some reason one cannot take, say, a fading-out of the Tacrolimus and a fading-in of the Cyclosporine, to get the initial positives of the Tacrolimus and the final positives of the Cyclosporine?
ReplyDeleteViremia and viruria are really two different ways of analyzing the same problem which is the total viral load within the body. As to the balancing of the two different agents, they have different half lives and as well as varying levels of absorption thus making it very difficult to work out a regimen without over or under-suppressing. Often times the patient is in charge of taking their own medication thus making complex regimens more likely to fail due to human error.
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