Title | Validation of noninvasive diagnosis of BK virus nephropathy and identification of prognostic biomarkers. |
Publication Type | Journal Article |
Year of Publication | 2010 |
Authors | Dadhania D, Snopkowski C, Ding R, Muthukumar T, Lee J, Bang H, Sharma VK, Seshan S, August P, Kapur S, Suthanthiran M |
Journal | Transplantation |
Volume | 90 |
Issue | 2 |
Pagination | 189-97 |
Date Published | 2010 Jul 27 |
ISSN | 1534-6080 |
Keywords | Adult, Biopsy, BK Virus, Creatinine, Cross-Sectional Studies, Female, Gene Amplification, Graft Rejection, Graft Survival, Humans, Kidney Transplantation, Male, Middle Aged, Polymerase Chain Reaction, Polyomavirus Infections, Prognosis, Reproducibility of Results, RNA, Messenger, RNA, Ribosomal, 18S, RNA, Viral, Transplantation, Homologous, Tumor Virus Infections |
Abstract | BACKGROUND: BK virus nephropathy (BKVN) may cause renal allograft dysfunction and failure. The gold standard test is kidney biopsy, which is invasive and costly. A noninvasive, accurate biomarker for diagnosis of BKVN and prognostication of allograft function after BKVN infection may improve allograft survival. METHODS: We tested the diagnostic accuracy of our previously reported cutoff value of 6.5x10(5) BKV viral capsid protein 1 (VP-1) mRNA/ng RNA in urinary cells (Ding et al., Transplantation 2002; 74: 987) using an independent cohort (n=89). We also examined whether urinary cell mRNA profiles obtained at the time of BKVN diagnosis identified patients at risk of subsequent decline in graft function. RESULTS: BKVN was accurately diagnosed (sensitivity of 100% and specificity of 97%) using our previously reported cutoff value. Levels of granzyme B (GB) mRNA (P=0.002) and proteinase inhibitor (PI)-9 mRNA (P=0.01) in urinary cells were higher in BKVN patients with a subsequent decline in renal function (n=8) compared with patients with stable function (n=10), and were positively associated (GB, P=0.01; PI-9, P=0.04) with rise in serum creatinine from the time of BKVN diagnosis to 12 months after diagnosis. GB levels in the BKVN patients with a decline in renal function were similar to those in the acute rejection group (n=11, P>0.05), but higher than the normal biopsy group (n=36, P<0.001); levels in BKVN patients with stable function were lower than those in the acute rejection group (P<0.01) and not significantly different from the normal biopsy group (P>0.05). CONCLUSIONS: Noninvasive diagnosis of BKVN and prognostication of renal allograft function after BKVN diagnosis are feasible by measurement of transcripts for BKV viral capsid protein 1 (VP-1), GB, and PI-9 in urine. |
DOI | 10.1097/TP.0b013e3181e2a932 |
Alternate Journal | Transplantation |
PubMed ID | 20526237 |
PubMed Central ID | PMC2989149 |
Grant List | R01 AI060706-03 / AI / NIAID NIH HHS / United States R01 AI060706-01 / AI / NIAID NIH HHS / United States R01 AI060706 / AI / NIAID NIH HHS / United States UL1 RR024996 / RR / NCRR NIH HHS / United States UL1 RR024996-01 / RR / NCRR NIH HHS / United States UL1 RR024996-03 / RR / NCRR NIH HHS / United States UL1 RR024996-02 / RR / NCRR NIH HHS / United States R01 AI060706-05 / AI / NIAID NIH HHS / United States R01 AI060706-02 / AI / NIAID NIH HHS / United States R37 AI051652 / AI / NIAID NIH HHS / United States ULI RR024996 / RR / NCRR NIH HHS / United States R37AI51652 / AI / NIAID NIH HHS / United States R01 AI060706-04 / AI / NIAID NIH HHS / United States R37 AI051652-06 / AI / NIAID NIH HHS / United States R01AI60706 / AI / NIAID NIH HHS / United States |
Related Faculty:
Surya V. Seshan, M.D.