In a patient with a failed kidney transplant who has returned to dialysis, how long should immunosuppression be continued and what are the recommended dosing regimens for mycophenolate sodium (Myfortic) and tacrolimus?

Management of Immunosuppression After Failed Kidney Transplant on Dialysis

Direct Recommendation

For patients with a failed kidney transplant who have returned to dialysis and are not candidates for retransplantation, discontinue mycophenolate sodium (Myfortic) immediately and taper tacrolimus to the lowest dose or off completely within 3-6 months, as continuing immunosuppression increases infection risk 3.4-fold and mortality risk 3.4-fold without providing meaningful benefit. 1, 2

---

Duration and Tapering Strategy Based on Retransplantation Status

If NOT a Candidate for Retransplantation (Anuric on Dialysis)

Stop mycophenolate sodium (Myfortic) first and immediately upon dialysis initiation, as anti-proliferative agents should be discontinued before other immunosuppressants when patients start dialysis. 1

Taper tacrolimus over 3-6 months to minimize or discontinue completely, using a personalized approach based on infection risk, residual renal function (if any), and individual patient factors. 1

Taper prednisone slowly to the minimal dose necessary over the first 6 months after graft failure, with timing of complete withdrawal based on individual patient needs. 1

If Candidate for Retransplantation with Long Waiting Time (Anuric on Dialysis)

Taper off all immunosuppressive medications or keep at absolute minimum levels, as the risks of infection and mortality outweigh benefits in anuric patients even awaiting retransplantation. 1

Establish baseline panel reactive antibody (PRA) value to monitor for development of donor-specific antibodies during the taper. 1

If Candidate for Retransplantation with Residual Renal Function (Not Yet on Dialysis)

Continue calcineurin inhibitor (tacrolimus) at therapeutic levels to maintain urine output and minimize risk of new donor-specific antibodies, as CNI is the main agent for this purpose. 1

Discontinue mycophenolate sodium as the first agent to reduce infection risk while preserving some immunosuppression. 1

---

Specific Dosing Recommendations

Mycophenolate Sodium (Myfortic)

• Discontinue immediately when dialysis begins (no tapering required for anti-proliferative agents). 1
• If continuation is absolutely necessary for residual function preservation: reduce by 50% initially (e.g., from 720 mg twice daily to 360 mg twice daily). 3

Tacrolimus

• Target low therapeutic trough levels (4-6 ng/mL range) during the taper period. 3
• Reduce dose by 25-50% every 2-4 weeks over 3-6 months until discontinued. 1
• Monitor levels closely if patient develops infections requiring antifungals (fluconazole inhibits CYP3A4 and raises tacrolimus levels). 4

Prednisone

• Taper slowly to 5 mg daily or less over 6 months. 1
• Do not abruptly discontinue to avoid adrenal insufficiency and potential graft intolerance syndrome. 1, 3

---

Critical Rationale: Mortality and Morbidity Data

Continuing immunosuppression after return to dialysis dramatically increases mortality (OR 3.4,95% CI 1.8-6.3), with deaths primarily from infectious disease (OR 2.8) and cardiovascular disease (OR 4.9). 2

Infection rates increase 3.4-fold (95% CI 2.5-4.5) in patients maintained on immunosuppression after dialysis initiation, with 88% experiencing documented infections in the first 6 months versus only 38% in those off immunosuppression. 1

Sepsis rates are highest in transplant patients returning to dialysis (19.7 events per 100 patient-years) compared to new dialysis patients (7.8 events) or recent transplant recipients (5.4 events). 1

The first week and first month after allograft failure carry mortality risks 13-fold and 7-fold higher, respectively, compared to transplant-naïve dialysis patients, making rapid immunosuppression reduction critical. 1

---

Monitoring During Taper

• Check tacrolimus trough levels weekly during dose reductions to ensure appropriate decline. 1
• Monitor for signs of graft intolerance syndrome (fever, pain over graft site, hematuria) which may develop during taper but does not mandate continuation of immunosuppression. 5, 2
• Assess for infection at every clinical encounter, as immunosuppressed dialysis patients have blunted inflammatory responses. 1
• Obtain PRA testing at baseline and periodically if retransplantation is planned, to detect development of donor-specific antibodies. 1

---

Common Pitfalls to Avoid

Do not continue full-dose immunosuppression "to preserve residual function" in anuric patients on dialysis—the infection and mortality risks far exceed any theoretical benefit. 1, 2

Do not maintain mycophenolate sodium at any dose once dialysis begins—it should be the first agent discontinued as it provides minimal benefit for preventing sensitization compared to CNI. 1

Do not taper too slowly out of fear of graft intolerance syndrome—symptomatic GIS occurs in a minority of patients and can be managed supportively; continued immunosuppression increases mortality without preventing GIS. 5, 2

Do not forget drug interactions during taper—if infections develop requiring azole antifungals, tacrolimus levels will rise significantly and require dose reduction. 4

Avoid abrupt cessation of all agents simultaneously—taper sequentially (mycophenolate first, then CNI, then steroids slowly) to minimize risk of severe graft intolerance syndrome. 1, 3