Donor-Specific Antibodies after Ceasing Immunosuppressive Therapy, with or without an Allograft Nephrectomy

Abstract

SummaryBackground and objectives Within the last few years, anti-human leukocyte antigen detection assays have significantly improved. This study asked, using the Luminex single-antigen assay, whether an allograft nephrectomy allowed donor-specific alloantibodies to appear that were not previously detected in the serum when the failed kidney was still in place.Design, setting, participants, & measurements After losing the kidney allograft and stopping immunosuppressive therapy, the proportions of donor-specific alloantibodies and nondonor-specific alloantibodies were compared in patients who had (n=48; group I) and had not (n=21; group II) undergone an allograft nephrectomy. Allograft nephrectomies were performed at 150 days after kidney allograft loss, and the time between allograft nephrectomy and last follow-up was 5386347 days.Results At kidney allograft loss, donor-specific alloantibodies were detected in three group II patients (14.2%) and six group I patients (12.5%). At last follow-up, donor-specific alloantibodies were detected in 11 patients (52.4%) without and 39 patients (81%) with an allograft nephrectomy (P=0.02). Anti-human leukocyte antigen class I donor-specific alloantibodies were positive in 23.8% of group II and 77% of group I patients (P,0.001); antihuman leukocyte antigen class II donor-specific alloantibodies were positive in 42.8% of group II and 62.5% of group I patients. Independent predictive factors for developing donor-specific alloantibodies after losing kidney allograft and stopping immunosuppressants were number of anti-human leukocyte antigen A/B mismatches at transplantation (zero versus one or more) and allograft nephrectomy.Conclusions The development of donor-specific alloantibodies was significantly greater in patients with a failed kidney who had undergone an allograft nephrectomy compared with those patients who had not undergone allograft nephrectomy.

Approach to the Highly Sensitized Kidney Transplant Candidate

“…This patient did not have an elevated PRA while receiving his maintenance immunosuppression but developed a high PRA after his immunosuppression was lowered. Weaning immunosuppression increases sensitization in many candidates (43,44), and the decision of whether to maintain a low dose of immunosuppression depends on the anticipated wait time to the next transplant, whether from a living or deceased donor. If the candidate has a living donor or the projected wait for a deceased donor is short so the candidate can be transplanted quickly, maintaining some immunosuppression to avoid sensitization should be considered.…”

Management of Patients with a Failed Kidney Transplant

“…Yapılmış bir çalışmada, graftını kaybeden hastalarda, graft kaybı sırasında bakılmış alloantikorları negatif hastaların yarısından fazlasının aylar-yıllar içerisinde sensitize oldukları gösterilmiştir. İmmunosüpresif tedavisi kesilen hastalarda graft nefrektomi ya da kan transfüzyonu olsun ya da olmasın de novo sınıf I ve sınıf II anti HLA antikorların geliştiği, immünosupresif tedavinin devam ettiği hastalarda ise antikorların gelişmediği gösterilmiştir (37). Yapılmış başka bir çalışma grafta kısa bir süre mağruziyetin bile immün sistemi tetikleyip antikor üretimine neden olabildiğini göstermiştir (38).…”

“…Ayrıca hasta sadece mTOR inhibitörü ve steroid kullanıyorsa, mTOR inhibitörü 4-6 hafta boyunca azaltılarak kesilmesi önerilmektedir (37)(38)(39).…”

“…Bazı olgularda graftın çıkarılması anti-HLA antikorların serum düzeylerinin artışına ve hastaların immünolojik açıdan daha duyarlı hale gelmesine neden olabilmektedir; bu durumun temel nedeni graftın antikorları emici etkisinin (sünger etkisi fenomeni) ortadan kalkmasıdır (44). Bir çalışmada graft nefrektomiden 5 gün kadar erken bir sürede de novo DSA oluştuğu gösterilmiştir (37) . Graft nefrektominin proinflamatuvar sitokinlerin ve HLA antikorlarının üretimini stimüle edebildiği ileri sürülmüştür (34).…”

Sequestration and Suppression of Anti-HLA Antibodies by a Failed Kidney Allograft

“…Systematically delineating the effects of transplant nephrectomy on circulating anti-HLA antibodies and clarifying mechanisms are important because the conclusions can impact clinical decisionmaking. The paper by Del Bello et al (10) in this issue of CJASN sheds new light on these issues.…”