Belatacept rescue for delayed kidney allograft function in a patient with previous combined heart-liver transplant
Bibliographic record
Abstract
To the Editor: There is scant literature on the use of belatacept for maintenance immunosuppression in patients with nonkidney solid organ transplants.1Kumar D LeCorchick S Gupta G Belatacept as an alternative to calcineurin inhibitors in patients with solid organ transplants.Frontiers Med. 2017; 4: 60Crossref Scopus (18) Google Scholar We report the case of a 61-year-old woman with transthyretin amyloidosis, chronic kidney disease stage 3B, and amyloid polyneuropathy with chronic hypotension, who initially underwent a simultaneous heart-liver transplant (SHLT). Her posttransplant course was complicated by hypotension, requiring prolonged vasopressors and then chronic use of midodrine. Her renal function deteriorated and she became hemodialysis dependent. Three years after her SHLT, she underwent a deceased donor kidney transplant. She was nonsensitized and had no donor-specific antibody at the time of this transplant. The donor was 60 years old, deceased after cardiac death with a kidney donor profile index of 90%, and a cold ischemia time of 22 hours and 54 minutes. Her preimplant biopsy showed no significant abnormalities. Induction therapy consisted of rabbit antithymocyte globulin 6 mg/kg followed by triple-drug immunosuppression including tacrolimus (target level 8-10 ng/mL), mycophenolate mofetil (MMF), and prednisone (tapered to 5 mg/d by 1-month posttransplant). Her postoperative course was again complicated by hypotension and delayed kidney graft function (DGF). A 3-week posttransplant kidney biopsy demonstrated severe acute tubular injury without rejection. These results were corroborated by the molecular microscope diagnostic system (MMDx, Alberta, Canada).2Halloran PF de Freitas DG Einecke G et al.The molecular phenotype of kidney transplants.Am J Transplant. 2010; 10: 2215-2222Abstract Full Text Full Text PDF PubMed Scopus (81) Google Scholar Despite tacrolimus target trough reduction (6-8 ng/mL), she had oliguric DGF for 2 months. Belatacept treatment was initiated as per our previous published protocol.3Gupta G Regmi A Kumar D et al.Safe conversion from tacrolimus to belatacept in high immunologic risk kidney transplant recipients with allograft dysfunction.Am J Transplant. 2015; 15: 2726-2731Abstract Full Text Full Text PDF PubMed Scopus (47) Google Scholar Given the presumed risk of early rejection, tacrolimus taper protocol was extended to 3 months (100% on Day 0, 75% on Day 14, 66% on Day 28, 50% on Day 42, and then off at Month 3). MMF was maintained at 1.5 g/d. Dialysis was discontinued at 6 weeks of postbelatacept conversion (Figure 1). Postconversion surveillance biopsies of all 3 allografts at differing time points including while completely off tacrolimus showed no evidence of rejection histologically and on MMDx. At 1-year post–kidney transplant, the patient continues to have adequate function of all 3 allografts, with no change in liver or cardiac function on serial testing since conversion. Here we describe the safe use of belatacept in a patient with a combined heart, liver, and kidney transplant. We hypothesized that the combined effect of chronic hypotension related to amyloid polyneuropathy and calcineurin inhibitor (CNI) use was the driving force behind our patient’s delayed graft function and thus planned to eliminate the CNI. We chose to avoid CNI minimization or switching to sirolimus due to the presumed higher risk of rejection with these approaches.4Karpe KM Talaulikar GS Walters GD Calcineurin inhibitor withdrawal or tapering for kidney transplant recipients.Cochrane Database Syst Rev. 2017; 7: Cd006750PubMed Google Scholar There are several possibilities about why we did not see acute rejection in our patient: (1) induction immunosuppression with a T cell–depleting agent5Ferguson R Grinyo J Vincenti F et al.Immunosuppression with belatacept-based, corticosteroid-avoiding regimens in de novo kidney transplant recipients.Am J Transplant. 2011; 11: 66-76Abstract Full Text Full Text PDF PubMed Scopus (143) Google Scholar; (2) slow CNI taper. This approach has been shown to be associated with a low risk of rejection in kidney transplant patients3Gupta G Regmi A Kumar D et al.Safe conversion from tacrolimus to belatacept in high immunologic risk kidney transplant recipients with allograft dysfunction.Am J Transplant. 2015; 15: 2726-2731Abstract Full Text Full Text PDF PubMed Scopus (47) Google Scholar; and (3) our patient was converted relatively late after SHLT. It is widely accepted that the risk of late rejection in adherent nonsensitized patients is low. This first case report, although limited in scope in terms of wide applicability, suggests cautious optimism favoring further studies examining the use of belatacept in non–kidney transplant patients. We thank and acknowledge the help of Mary Baldecchi, RN and Sarah Bersik, RN in coordinating care, testing, and shipping biopsy samples for analysis. The authors of this manuscript have conflicts of interest to disclose as described by the American Journal of Transplantation. Dr Gaurav Gupta has served on the Scientific Advisory Board of Bristol-Myers Squibb. The other authors have no conflicts of interest to disclose.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.008 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.002 |
| Open science | 0.002 | 0.001 |
| Research integrity | 0.005 | 0.005 |
| Insufficient payload (model declined to judge) | 0.003 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".