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. 2023 Oct 1;107(10):2271-2278.
doi: 10.1097/TP.0000000000004690. Epub 2023 Jun 16.

Performance and Advancement of the Kidney Solid Organ Response Test

Joshua Lee  1 , Mariel Barbachan E Silva  2 , Yi Bao  3 , Ryan Whitmarsh  1 , Sukanta Banerjee  1 , Jeannine O'Connor  1 , Jeffery Holbert  1 , Tiffany K Bratton  1 , Pilib Ó Broin  2 , Enver Akalin  3
Affiliations

Performance and Advancement of the Kidney Solid Organ Response Test

Joshua Lee et al. Transplantation. .

Abstract

Background: The kidney solid organ response test (kSORT) has been investigated for the prediction of acute rejection in kidney transplant recipients with conflicting results. We aimed to investigate if the kSORT assay score is associated with rejection or immune quiescence.

Methods: The blinded association between rejection and kSORT > 9 were investigated. Optimization of kSORT prediction was evaluated after unblinding to determine the optimal prediction cutoff value of kSORT score. Additionally, the predictive capability of the kSORT gene set was assessed using blinded normalized gene expression data from microarray (Affymetrix) and qPCR assays.

Results: Of the 95 blood samples analyzed, 18 patients had blood samples before transplant, 77 patients after transplant and 71 had clinically indicated biopsies of which 15 biopsies showed acute rejection and 16 showed chronic active antibody-mediated rejection. When 31 patients with rejection were compared to the remaining 64 patients, positive predictive value (PPV) was 54.29% and negative predictive value (NPV) was 75% when stratified using a kSORT score > 9, and PPV was 57.89% and NPV was 78.95% when stratified using a kSORT score > 5. Using the kSORT assay for detection of rejection showed an area under the curve value of 0.71. Microarray data improved prediction accuracy with PPV of 53% and NPV of 84% compared to qPCR results (PPV and NPV were 36% and 66%), respectively.

Conclusions: The kSORT assay has the potential to be used as a predictive tool for active rejection and/or immune quiescence, but additional studies will be useful in improving and refining the kSORT assay, in particular the prediction algorithm.

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Conflict of interest statement

J.L., T.K.B., and R.W. are employees of Immucor Inc., which owns the rights to kSORT. The other authors declare no conflicts of interest. E.A. received research grants from Immucor and CareDx and served on the advisory boards of Immucor, CareDx, and Transplant Genomics.

Figures

None
Graphical abstract
FIGURE 1.
FIGURE 1.
ROC curve for kSORT detection of biopsy-proven rejection with a cutoff of ≥9 as positive. The AUC is 0.71. AUC, area under the curve; kSORT, kidney solid organ response test; ROC, receiver operating characteristic.
See this image and copyright information in PMC

References

    1. Hariharan S, Israni AK, Danovitch G. Long-term survival after kidney transplantation. N Engl J Med. 2021;385:729–743. - PubMed
    1. Sellares J, de Freitas DG, Mengel M, et al. Understanding the causes of kidney transplant failure: the dominant role of antibody-mediated rejection and nonadherence. Am J Transplant. 2012;12:388–399. - PubMed
    1. Dhaun N, Bellamy CO, Cattran DC, et al. Utility of renal biopsy in the clinical management of renal disease. Kidney Int. 2014;85:1039–1048. - PubMed
    1. Bloom RD, Bromberg JS, Poggio ED, et al. ; Circulating Donor-Derived Cell-Free DNA in Blood for Diagnosing Active Rejection in Kidney Transplant Recipients (DART) Study Investigators. Cell-Free DNA and active rejection in kidney allografts. J Am Soc Nephrol. 2017;28:2221–2232. - PMC - PubMed
    1. Bu L, Gupta G, Pai A, et al. Clinical outcomes from the Assessing Donor-derived cell-free DNA Monitoring Insights of kidney Allografts with Longitudinal surveillance (ADMIRAL) study. Kidney Int. 2022;101:793–803. - PubMed

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