Validation of a noninvasive prognostic signature for allograft failure following BK virus associated nephropathy.

TitleValidation of a noninvasive prognostic signature for allograft failure following BK virus associated nephropathy.
Publication TypeJournal Article
Year of Publication2021
AuthorsAbuhelaiqa E, Snopkowski C, Li C, Salvatore S, Lee JR, Muthukumar T, Lee JB, Hartono C, Ding R, Seshan SV, Suthanthiran M, Dadhania DM
JournalClin Transplant
Date Published2021 02
KeywordsAllografts, BK Virus, Graft Rejection, Humans, Kidney Diseases, Kidney Transplantation, Polyomavirus Infections, Prognosis, Tumor Virus Infections

Identifying kidney transplant recipients at risk for graft failure following BK virus nephropathy (BKVN) may allow personalization of therapy. We have reported that a noninvasive composite signature of urinary cell level of plasminogen activator inhibitor-1(PAI-1) mRNA and serum creatinine level, measured at the time of BKVN diagnosis, is prognostic of graft failure. In this investigation, we determined whether the composite signature is prognostic of graft failure in an independent cohort of 25 patients with BKVN. Of the 25 patients, 8 developed graft failure and 17 did not. We measured urinary cell levels of PAI-1 mRNA, 18S rRNA, and BKV VP1 mRNA at the time of BKVN diagnosis and evaluated clinical parameters including Banff pathology scores, acute rejection, and graft function. The area under the receiver operating characteristic curve for the noninvasive composite signature was 0.95 (P < .001) for prognosticating graft failure. The previously reported threshold of -0.858 predicted graft failure with a sensitivity of 75% and a specificity of 94%. Our current study validates the use of composite signature and the threshold of -0.858 to identify those at risk for graft failure following BKVN diagnosis, and supports future studies utilizing the composite signature score to personalize treatment of BKVN.

Alternate JournalClin Transplant
PubMed ID33349997
Grant ListR37 AI051652 / AI / NIAID NIH HHS / United States
Related Faculty: 
Steven P. Salvatore, M.D. Surya V. Seshan, M.D.

Pathology & Laboratory Medicine 1300 York Avenue New York, NY 10065 Phone: (212) 746-6464
Surgical Pathology: (212) 746-2700