Being Thoughtful about Desensitization

Formica, Richard N.; Kulkarni, Sanjay

doi:10.2215/cjn.09000817

Cited by 2 publications

(1 citation statement)

References 10 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We and others have recently shown that patients with a calculated panel‐reactive antibody (cPRA) >99.9% continue to have a lower rate of transplantation despite having the highest priority in the current allocation system which suggests an ongoing need to develop desensitization therapies 2 . Certainly desensitization can be resource intensive and associated with morbidity, 5,6 but these risks must be weighed against the risk of remaining on dialysis because some patients simply do not have other options. HLA (human leukocyte antigen) incompatible transplantation has been associated with increased patient survival as compared to remaining on dialysis in large multicenter trials 7 .…”

Section: Introductionmentioning

confidence: 99%

Estimating alloantibody levels in highly sensitized renal allograft candidates: Using serial dilutions to demonstrate a treatment effect in clinical trials

Tambur

Schinstock

Maguire

et al. 2021

American Journal of Transplantation

View full text Add to dashboard Cite

Small reductions in calculated panel‐reactive antibody (cPRA) are associated with increased kidney transplantation in 100% cPRA patients. However, the high level of antibody in these patients is such that desensitization may reduce antibody but not cPRA, thus the cPRA change on undiluted serum with desensitization is an insensitive measure of effectiveness. We evaluated cPRA reduction, calculated per antibody titer, as a desensitization trial endpoint. To accomplish this, two serum samples from 20 kidney transplant candidates with cPRA ≥99.9% (100%) were obtained and serially diluted in triplicate to determine the titer of individual human leukocyte antigen (HLA) antibody specificities. CPRA was computed per dilution to identify the titer at which cPRA drops below 98%. Inter‐ and intra‐assay variability and changes overtime were determined. The dilution needed to reach a cPRA <98% was within 1 titer for replicates from the same sample, with 90% (36/40) concordance. This indicates that only changes >2 titers can be deemed clinically meaningful. The median (IQR) titer difference was 0 (0‐1) from baseline to follow‐up within 12 months. The cPRA per titer also risk‐stratified candidates for trial inclusion. In conclusion, determining the cPRA per titer is a reliable approach to simplify complex antibody data and an ideal endpoint for desensitization trials.

show abstract

Section: Introductionmentioning

confidence: 99%