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Steroid-resistant kidney transplant rejection: diagnosis and treatment
1Division of Nephrology, Kantonsspital, Aarau, Switzerland. bock@ksa.ch
Abstract:
Decreases in transplant function may be attributable to a variety of conditions, including prerenal and postrenal failure, cyclosporin A (CsA) toxicity, polyoma nephritis, recurrent glomerulonephritis, and rejection. The diagnosis of rejection should therefore be made on the basis of a transplant biopsy of adequate size, before the initiation of any therapy. Pulse steroid treatment (three to five 0.25- to 1.0-g pulses of methylprednisolone, administered intravenously) is the usual first-line therapy and has a 60 to 70% success rate, although orally administered prednisone (0.25 g) may be just as efficacious. Even if reverted, any rejection should trigger an at least temporary increase in basal immunosuppression, consisting of an increase in CsA or tacrolimus target levels, the addition of steroids or an increase in their dosage, the addition of mycophenolate mofetil, or a switch from CsA to tacrolimus. The addition of rapamycin or its RAD derivative may fulfill the same purpose. Steroid resistance should not be assumed before the fifth day of pulse steroid treatment, although histologic features of vascular rejection may indicate the need for more aggressive treatment earlier. Steroid-resistant rejection is traditionally treated with poly- or monoclonal antilymphocytic antibodies, with success rates of 60 to 70%. Their potential benefit must be carefully balanced against the risks of infection and lymphoma. More recently, mycophenolate mofetil has been successfully used to treat steroid-resistant rejection, but only of the interstitial (cellular) type. Switching from CsA to tacrolimus for treating recurrent or antibody-resistant rejection is successful in approximately 60% of cases. Plasmapheresis and intravenously administered Ig have been used in some desperate cases, with surprising success. Because none of the available drugs has a significantly better profile of therapeutic versus adverse effects, the possible benefits of continued rejection therapy must be continuously balanced with the potential for serious, sometimes fatal, side effects.
Insights
Diagnosing transplant rejection requires a biopsy. First-line treatment involves pulse steroids, with options for managing steroid-resistant cases and adjusting immunosuppression to balance efficacy and serious side effects.
Area of Science:
- Nephrology
- Transplantation Immunology
- Pharmacology
Background:
- Decreased transplant function can stem from various causes, including prerenal/postrenal failure, drug toxicity (cyclosporine A), polyoma nephritis, recurrent glomerulonephritis, and rejection.
- Accurate diagnosis of rejection is critical and should be confirmed by a transplant biopsy before initiating treatment.
Purpose of the Study:
- To review current diagnostic criteria and therapeutic strategies for managing kidney transplant rejection.
- To outline first-line and alternative treatments for acute rejection, including steroid-sensitive and steroid-resistant forms.
- To emphasize the importance of adjusting immunosuppression and balancing treatment benefits against potential adverse effects.
Main Methods:
- Review of existing literature on transplant rejection diagnosis and management.
- Analysis of therapeutic approaches including pulse steroid therapy, adjustments to basal immunosuppression, and treatments for steroid-resistant rejection.
- Discussion of alternative therapies like antilymphocytic antibodies, mycophenolate mofetil, and newer agents.
Main Results:
- Pulse steroid therapy (methylprednisolone) is the primary treatment for rejection, with a 60-70% success rate.
- Steroid-resistant rejection can be treated with antilymphocytic antibodies or mycophenolate mofetil (for interstitial type), yielding similar success rates.
- Switching from cyclosporine A to tacrolimus is effective in about 60% of recurrent or antibody-resistant rejection cases.
Conclusions:
- Prompt diagnosis via biopsy is essential for effective transplant rejection management.
- Treatment strategies involve initial pulse steroids, with subsequent adjustments to immunosuppression or alternative therapies for resistant cases.
- Balancing the benefits of rejection therapy against significant potential side effects is crucial for patient outcomes.