Post-transplant maintenance immunosuppression

Typical maintenance immunosuppression is shown in Table 3. It is beyond the scope of this review to go into detail and the readers are referred to UpToDate ( for a current discussion of maintenance immunosuppression and some of the controversies such as calcineurin inhibitor (CNI) or steroid withdrawal or avoidance, or the use of mammalian targets of rapamycin (mTORs).

The typical immunosuppressive regimen at our center is induction with thymoglobulin 5mg/kg total body weight intravenously with the first dose 1 mg/kg begun intraoperatively followed by 2 mg/kg/d for two days. The dose is rounded to the nearest 25 mg and not adjusted for ideal body weight and there is no maximum dose.

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Tacrolimus is usually begun on post-operative day 1 or 2 even when DGF is present because delayed introduction and failure to obtain a therapeutic calcineurin inhibitor (CNI) level by post-operative day 7 is associated with more rejection and no decrease in the incidence or duration of DGF.6, 7 For tacrolimus, we target trough levels at 7-10 ng/mL for the first month and then 3-7 ng/mL thereafter.

For cyclosporine, we prefer to monitor peak (usually 90 minute levels), although the concentration at two hours post-dosing (C2) levels have been investigated and are interpretable. Because the “peak” might be missed, we rely on the trend of cyclosporine levels to inform us “how high can the patient get.” Our peak level targets are 800-1200 ng/mL for the first month and then 400-600 ng/mL thereafter. These targets were chosen based on literature showing that a level of 1000 ng/mL provides 90% calcineurin inhibition of lymphocytes and C2 levels of 400 prevent rejection and are associated with less nephrotoxicity in cardiac transplant recipients.8-10

Our team initiates enteric-coated mycophenolic acid (MPA) at 760 mg bid but decrease to 360 mg bid by post-operative day 5. We prefer MPA over MMF because the absorption of MMF requires hydrolysis of the mofetil ester, which requires an acid environment that is blocked by proton-pump inhibitors, medications commonly used for gastrointestinal prophylaxis.6,11

This “reduced dose” of MPA is used because the pivotal trials leading to the approval of MMF and MPA were performed with cyclosporine, which inhibits the absorption of MMF and MPA by 30%-50%.12 We prefer enteric coated mycophenolic acid (MPA) to MMF because we use proton pump inhibitors (PPIs) to control gastrointestinal symptoms. These agents reduce the exposure of MMF but not MPA.13 Methylprednisolone 
7 mg/kg is used intraoperatively and then prednisone 1 mg/kg is administered to a maximum of 80 mg prior to administration of rATG on post-operative days 1 and 2. Prednisone is then administered at 20 mg per day during the first week and tapered by 5 mg/week to 5 mg/day by week 4-5 where it is maintained.

The ELITE-Symphony trial, which compared cyclosporine, tacrolimus, and rapamycin showed that the best overall maintenance regimen is one using relative low-dose tacrolimus, mycophenolate, and low-dose steroids.14 We have a low threshold to replace mycophenolate with azathioprine for any indication based on the MYSS and MYSS follow-up trials, which showed that there was no difference in rejection or patient or graft survival, but GFR was better long term with azathioprine compared with MMF even if steroids were withdrawn.15,16

The current literature and available immunosuppression regimens do not support steroid avoidance. In a randomized, double-blind, placebo-controlled trial with five year follow up of early corticosteroid withdrawal compared with low-dose continuation there were no major differences in corticosteroid-related side effects but an almost doubling of the acute and chronic rejection rates in the group with early corticosteroid withdrawal.17

Post-transplant clinic visits

Post-transplant monitoring visits are not routine. Routine visits or laboratory work ups are not billable. Thus, we typically state in the chief complaint, “The patient returned today for continued care of his renal transplant (diagnostic code V42.0), immunosuppressive management (diagnostic codes V58.69 and V58.44), and related medical problems.” The Kidney Disease: Improving Global Outcomes (KDIGO) guidelines do not specify how often kidney transplant recipients should be seen by a physician.18

Historically, patients were seen after discharge twice a week for the first month, monthly for six months, and then every three to four months thereafter. This is no longer necessary or feasible. With the widespread use of induction agents, particularly anti-lymphocyte depleting therapy, and improved maintenance immunosuppression, acute rejection rates in the first three months are relatively uncommon and the incidence of acute rejection is 5%-15% nationally in the first year. Kidney volumes and improved success have led to overcrowded clinics and overworked staff.

At our center, patients see the surgeons at two weeks after transplant and the transplant nephrologists at two to four weeks post-transplant and then at six weeks and every three months thereafter up to one year. Then we see patients every three months for the next two years. Patients are asked to coordinate visits with their primary nephrologist and primary care physician so that they are seen every three to six months.

Regular clinic visits give clinicians the opportunity to assess signs and symptoms that may dictate a change in immunosuppressive management beyond what might have been suggested from laboratory monitoring. Such signs and symptoms may be uncontrolled hypertension, insomnia and tremors (tacrolimus), rage disorder or warts (prednisone), or gastrointestinal complications (MMF, MPA, tacrolimus). The yearly clinic visit to the transplant center provides an opportunity to update patients on developments in transplantation and to verify data to satisfy UNOS requirements for reporting. 

Because of this infrequent face-to-face contact, our team is unable to accommodate patients adequately. Therefore, we rely on care from informed primary nephrologists and primary care physicians. We ask that the patient be the intermediary and inform the transplant center if there has been any addition, deletion, or change in any medication so that we can check for interactions and side effects. We also rely on frequent post-transplant monitoring labs.