Noninvasive Assessment of the Alloimmune Response in Kidney Transplantation

Adv Chronic Kidney Dis. 2021 Nov;28(6):548-560. doi: 10.1053/j.ackd.2021.08.002.


Transplantation remains the optimal mode of kidney replacement therapy, but unfortunately long-term graft survival after 1 year remains suboptimal. The main mechanism of chronic allograft injury is alloimmune, and current clinical monitoring of kidney transplants includes measuring serum creatinine, proteinuria, and immunosuppressive drug levels. The most important biomarker routinely monitored is human leukocyte antigen (HLA) donor-specific antibodies (DSAs) with the frequency based on underlying immunologic risk. HLA-DSA should be measured if there is graft dysfunction, immunosuppression minimization, or nonadherence. Antibody strength is semiquantitatively estimated as mean fluorescence intensity, with titration studies for equivocal cases and for following response to treatment. Determination of in vitro C1q or C3d positivity or HLA-DSA IgG subclass analysis remains of uncertain significance, but we do not recommend these for routine use. Current evidence does not support routine monitoring of non-HLA antibodies except anti-angiotensin II type 1 receptor antibodies when the phenotype is appropriate. The monitoring of both donor-derived cell-free DNA in blood or gene expression profiling of serum and/or urine may detect subclinical rejection, although mainly as a supplement and not as a replacement for biopsy. The optimal frequency and cost-effectiveness of using these noninvasive assays remain to be determined. We review the available literature and make recommendations.

Keywords: Antibody-mediated rejection; Donor-derived cell-free DNA; Donor-specific antibodies; Gene expression profiling; T-cell mediated rejection.

Publication types

  • Review

MeSH terms

  • Graft Rejection / diagnosis
  • Graft Survival
  • HLA Antigens
  • Humans
  • Kidney Transplantation*
  • Tissue Donors


  • HLA Antigens