Validation of noninvasive diagnosis of BK virus nephropathy and identification of prognostic biomarkers.
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.
Division of Nephrology and Hypertension, Department of Medicine, New York Presbyterian-Weill Cornell Medical Center, New York, NY, USA. dmd2001@med.cornell.edu
Darshana
D
Dadhania
Catherine
C
Snopkowski
Ruchuang
R
Ding
Thangamani
T
Muthukumar
Jun
J
Lee
Heejung
H
Bang
Vijay K
VK
Sharma
Surya
S
Seshan
Phyllis
P
August
Sandip
S
Kapur
Manikkam
M
Suthanthiran
D000328:Adult; D001739:BK Virus / Q000235:genetics / Q000302:isolation & purification*; D001706:Biopsy; D003404:Creatinine / Q000097:blood; D003430:Cross-Sectional Studies; D005260:Female; D005784:Gene Amplification; D006084:Graft Rejection / Q000175:diagnosis / Q000473:pathology / Q000652:urine / Q000821:virology; D006085:Graft Survival; D006801:Humans; D016030:Kidney Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction / Q000379:methods; D027601:Polyomavirus Infections / Q000175:diagnosis* / Q000453:epidemiology; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics / Q000652:urine; D012337:RNA, Ribosomal, 18S / Q000235:genetics / Q000652:urine; D012367:RNA, Viral / Q000235:genetics / Q000652:urine; D015203:Reproducibility of Results; D014184:Transplantation, Homologous; D014412:Tumor Virus Infections / Q000175:diagnosis* / Q000453:epidemiology
D012333:RNA, Messenger; D012337:RNA, Ribosomal, 18S; D012367:RNA, Viral; D003404:Creatinine