Validation of noninvasive diagnosis of BK virus nephropathy and identification of prognostic biomarkers

Darshana Dadhania, Catherine Snopkowski, Ruchuang Ding, Thangamani Muthukumar, Jun Lee, Heejung Bang, Vijay K. Sharma, Surya Seshan, Phyllis August, Sandip Kapur, Manikkam Suthanthiran

Research output: Contribution to journalArticle

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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 6.5×10 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.

Original languageEnglish
Pages (from-to)189-197
Number of pages9
JournalTransplantation
Volume90
Issue number2
DOIs
Publication statusPublished - 27 Jul 2010
Externally publishedYes

Fingerprint

BK Virus
Biomarkers
Granzymes
Allografts
Kidney
Messenger RNA
Capsid Proteins
Viral Proteins
Biopsy
Cell Transplantation
Virus Diseases
Creatinine
Peptide Hydrolases
Urine
RNA

Keywords

  • Biomarkers
  • BKV
  • Gene expression
  • Kidney

ASJC Scopus subject areas

  • Transplantation

Cite this

Validation of noninvasive diagnosis of BK virus nephropathy and identification of prognostic biomarkers. / Dadhania, Darshana; Snopkowski, Catherine; Ding, Ruchuang; Muthukumar, Thangamani; Lee, Jun; Bang, Heejung; Sharma, Vijay K.; Seshan, Surya; August, Phyllis; Kapur, Sandip; Suthanthiran, Manikkam.

In: Transplantation, Vol. 90, No. 2, 27.07.2010, p. 189-197.

Research output: Contribution to journalArticle

Dadhania, D, Snopkowski, C, Ding, R, Muthukumar, T, Lee, J, Bang, H, Sharma, VK, Seshan, S, August, P, Kapur, S & Suthanthiran, M 2010, 'Validation of noninvasive diagnosis of BK virus nephropathy and identification of prognostic biomarkers', Transplantation, vol. 90, no. 2, pp. 189-197. https://doi.org/10.1097/TP.0b013e3181e2a932
Dadhania, Darshana ; Snopkowski, Catherine ; Ding, Ruchuang ; Muthukumar, Thangamani ; Lee, Jun ; Bang, Heejung ; Sharma, Vijay K. ; Seshan, Surya ; August, Phyllis ; Kapur, Sandip ; Suthanthiran, Manikkam. / Validation of noninvasive diagnosis of BK virus nephropathy and identification of prognostic biomarkers. In: Transplantation. 2010 ; Vol. 90, No. 2. pp. 189-197.
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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 6.5×10 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.",
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AU - Snopkowski, Catherine

AU - Ding, Ruchuang

AU - Muthukumar, Thangamani

AU - Lee, Jun

AU - Bang, Heejung

AU - Sharma, Vijay K.

AU - Seshan, Surya

AU - August, Phyllis

AU - Kapur, Sandip

AU - Suthanthiran, Manikkam

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N2 - 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 6.5×10 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.

AB - 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 6.5×10 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.

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