Question: Why do some dialysis patients with failed renal transplants remain on immunosuppressants?
This was a question asked by my hospitalist colleagues, when we were taking care of a patient who had recently started dialysis after a failed renal transplant.
Over the last few decades, renal transplant outcomes have significantly improved, but we still have a substantial number of patients who end up transitioning to dialysis as their renal allografts have failed. Most of these allografts are left in place as long as they are not causing any systemic inflammatory response or acute rejection. The idea is to avoid transplant nephrectomy in such patients with a lot of comorbidities and the dilemma is whether to withdraw immunosupressants.
Intuitively it may seem reasonable to withdraw immunosuppression as soon as possible to avoid its complications (like infection, cardiovascular complications or adverse effects of long-term steroid therapy). However, withdrawal of these agents may lead to acute rejection, requiring transplant nephrectomy. Symptoms resulting from rejection include graft tenderness, fever, hematuria, localized edema, and occasionally infection. Less fulminant rejection may present with unusual symptoms, such as weight loss, anemia, fatigue, gastrointestinal complaints, and neurologic disturbances. The other, although less common complication is the risk of secondary adrenal insufficiency. It has also been found that a longer taper of immunosuppression may preserve some residual renal function. Another argument is that removal of the graft leads to immunoreactivity and increased panel-reactive antibodies, which may not be desirable in patients for subsequent transplant. Hence, the most common current practice is to withdraw the anti-metabolite (cellcept or azothioprine), reduce the calcineurin inhibitor and prednisone dose; and then taper them slowly over 3 to 6 months.
A recent study (Ayus etal ) presents a contrarian view, suggesting that allograft nephrectomies should be done more routinely and that they have a 32% lower adjusted relative risk for all cause death than the current management strategies. This retrospective study has the potential of changing our current approach to failed renal allografts, but the benefits are yet to be proven in a randomized trial. So let us see which way evidence will take us in future!
Bottomline (for now):
1) Tranplant nephrectomies should be performed in patients who have evidence for systemic inflammatory response or acute rejection.
2) Immunosuppressive drugs should be tapered slowly (as tolerated )in patients with failed renal transplants.
