Use of immunosuppressants is essential for successful organ transplantation. In general 3 types of regimens are used depending upon the stage of transplantation.
IMMUNOSUPPRESSION IN ORGAN TRANSPLANTATION
Use of immunosuppressants is essential for successful organ
transplantation. In general 3 types of regimens are used depending upon the
stage of transplantation.
Induction Regimen: This is given in the perioperative period: starting just before the
transplant to about 2–12 weeks after it. Accelerated rejection develops in the
first week, while acute rejections are most likely from 2–12 weeks. The most
common regimens include triple therapy cyclosporine + prednisolone +
azathioprine (with or without muromonab CD3/ATG), but 2 drug and single drug
regimens are also used. Many experts do not give cyclosporine preoperatively, and
try to dealy its induction as far as possible to avoid nephrotoxicity,
particularly in renal transplantation. If no rejection develops, the doses are
gradually reduced after 2 weeks and this phase merges imperceptably with
maintenance phase.
Maintenance
Regimen: This is given for prolonged periods, may be lifelong. Triple
drug regimen is favoured because each component is needed in lower
doses—reduces toxicity and cost. Cyclosporine is the most costly and its
nephrotoxicity is often the limiting factor. Long-term steroid therapy has its
own problems. The component which produces toxicity in a given patient is
curtailed or dropped. Two drug and one drug regimens are also used, but are
associated with more episodes of acute rejection. After 1 year, cyclosporine is
generally dropped, but its continuation is associated with fewer acute rejections.
In case of intolerance to the first line drugs cyclosporine, azathioprine and
prednisolone, the second line drugs like cyclophosphamide, MMF, chlorambucil
are substituted.
Anti-Rejection
Regimen: This is given to suppress an episode of acute rejection. Steroid
pulse therapy (methylprednisolone 0.5–1 g i.v. daily for 3–5 days) is effective
in majority of cases. In case of no response, muromonab CD3/ATG is given as rescue
therapy or the antibodies are combined with steroids. Tacrolimus, MMF have also
been used in rescue therapy of steroid resistant rejection. If the maintenance
regimen had not included cyclosporine, its addition can treat acute rejection,
but can be damaging to the transplanted kidney.
Adverse Effects The two general
untoward effects of immunosuppressant
therapy are:
·
Increased risk of bacterial, fungal, viral
(especially CMV) as well as opportunistic infections.
·
Development of lymphomas and related malignancies
after a long latency.
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