Kidney Transplant Rejection and Immunosuppression
On this page
Direct answer
Kidney transplant rejection is immune injury to the graft, classified by timing and mechanism as hyperacute, acute or chronic. Hyperacute rejection occurs within minutes to hours because of preformed antibodies and is irreversible. Acute rejection develops in the early months and usually responds to steroids or antibody-directed therapy, while chronic rejection evolves over months to years. Maintenance immunosuppression combines a calcineurin inhibitor, an antimetabolite and a corticosteroid.
What you must remember
- Hyperacute rejection: minutes to hours after reperfusion, from preformed anti-donor antibodies, causing graft thrombosis and irreversible loss.
- Acute cellular rejection: T-cell mediated, typically in the early months, with tubulitis and interstitial inflammation on biopsy.
- Acute antibody-mediated rejection: donor-specific antibodies with C4d positivity in peritubular capillaries.
- Chronic rejection: interstitial fibrosis and tubular atrophy, transplant glomerulopathy and chronic antibody-mediated injury.
- Acute treatment: pulse methylprednisolone for cellular rejection, and IVIG, plasma exchange or rituximab for resistant antibody-mediated rejection.
- Triple maintenance: tacrolimus, mycophenolate mofetil and prednisolone is a commonly used first-line regimen.
- Induction: basiliximab for most standard-risk recipients and antithymocyte globulin for those at high immunological risk.
- Prophylaxis: cotrimoxazole against Pneumocystis in the early post-transplant period, and valganciclovir for CMV in selected recipients.
From suspected rejection to treatment
A recipient two months after transplant has a rising creatinine, a low tacrolimus level and a tender graft. Rejection is only one possibility, so the work-up starts with the simplest causes and moves to biopsy. The steps below set out how each step guides the next.
- Recognise the signal: a rise in serum creatinine, fever, graft tenderness or falling urine output after transplant prompts evaluation.
- Check drug levels and imaging: measure tacrolimus trough levels for under-dosing or non-adherence, and use Doppler ultrasound to exclude obstruction or vascular problems.
- Biopsy the graft: classify rejection by Banff criteria, with C4d staining to identify antibody-mediated rejection.
- Treat acute cellular rejection: give pulse intravenous methylprednisolone and adjust the maintenance regimen.
- Treat antibody-mediated rejection: use IVIG, plasma exchange or rituximab, aimed at the donor-specific antibodies.
- Review maintenance: balance rejection against infection, malignancy and calcineurin nephrotoxicity when adjusting the regimen.
A creatinine rise does not automatically mean rejection, and the biopsy is the decisive test. Treatment is then tailored to the mechanism, since antibody-mediated rejection needs a different approach from cellular rejection.
Where the exam tests transplant rejection
Examiners test whether you match the rejection type with the correct drug and avoid the wrong label.
- Trap: labelling every creatinine rise as rejection Correct: exclude obstruction, calcineurin nephrotoxicity and BK virus nephropathy before diagnosing rejection.
- Trap: treating hyperacute rejection with steroids Correct: it is irreversible, so prevention through ABO matching and crossmatch is the key.
- Trap: prescribing two calcineurin inhibitors together Correct: only one calcineurin inhibitor is used, with tacrolimus preferred in most regimens and cyclosporine as the alternative.
Frequently asked questions
What is the main difference between hyperacute and acute kidney graft rejection?
Hyperacute rejection occurs within minutes to hours because of preformed antibodies and is irreversible. Acute rejection develops in the early months, often responds to steroids or antibody-directed therapy, and is treated while the graft can still be saved.
What is the typical maintenance immunosuppression after kidney transplant?
The commonly used maintenance regimen after kidney transplant is tacrolimus, mycophenolate mofetil and prednisolone, a triple therapy. Tacrolimus levels are monitored closely, because low levels increase rejection and high levels increase nephrotoxicity.
What does C4d staining indicate in a kidney transplant biopsy?
C4d staining in peritubular capillaries indicates antibody-mediated injury, because complement is activated by donor-specific antibodies. It is a key Banff feature used to diagnose antibody-mediated rejection in a kidney allograft.
Why is cotrimoxazole given after kidney transplant?
Cotrimoxazole is given to prevent Pneumocystis jirovecii pneumonia in kidney transplant recipients during the early post-transplant period. It is a standard prophylactic measure against this opportunistic infection.