Sustained BK viruria as an early marker for the development of BKV-associated nephropathy: analysis of 4128 urine and serum samples.
BACKGROUND
BKV reactivation plays the causative role in the development of BKV-associated nephropathy (BKVAN). Because of the lack of effective therapy, early diagnosis of BKV reactivation is paramount for the prevention of BKVAN. Resting in uroepithelial cells, BKV is excreted first in urine before it can be detected in plasma. The present study analyzed predictive value of BK viruria for the development of BK viremia and its possible advantage for the early BKVAN prediction.


METHODS
Total of 4128 urine and serum samples obtained from renal transplant patients were analyzed for BKV positivity by real-time polymerase chain reaction in 433 patients in cross-sectional and in 233 patients in longitudinal manner, respectively. The prospective longitudinal analysis included seven measurements during the first posttransplant year.


RESULTS
A total of 7% and 19% patients were positive for BKV in serum and urine, respectively. Sustained BK viruria showed sensitivity of 100% and specificity of 94% for BK viremia and was associated with significantly higher level of BK load than the patients with transient viruria (P<0.01). Interestingly, BK viremia was preceded by BK viruria: the peak of viral load and number of positive patients appeared during the third and fifth posttransplant month for urine and serum, respectively. BKVAN diagnosed in 21.4% of patient with persistent BK viruria appeared 5 and 11 weeks after BKV reactivation in serum and urine, respectively, was detected.


CONCLUSIONS
Sustained BK viruria is a reliable marker allowing an early identification of patients at high risk of BKVAN development and therefore assure precocious therapeutic interventions.
Babel
Nina
N
Department of Nephrology, Charité University Medicine Berlin, Campus Virchow Clinic, Berlin, Germany. nina.babel@charite.de
Fendt
Juliane
J
Karaivanov
Stoyan
S
Bold
Gantuja
G
Arnold
Steffen
S
Sefrin
Anett
A
Lieske
Evelyn
E
Hoffzimmer
Martin
M
Dziubianau
Mikalai
M
Bethke
Nicole
N
Meisel
Christian
C
Grütz
Gerald
G
Reinke
Petra
P
D000328:Adult; D001739:BK Virus / Q000235:genetics / Q000302:isolation & purification*; D003430:Cross-Sectional Studies; D004279:DNA, Viral / Q000097:blood / Q000302:isolation & purification* / Q000652:urine; D042241:Early Diagnosis; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D007674:Kidney Diseases / Q000097:blood / Q000175:diagnosis* / Q000188:drug therapy / Q000652:urine / Q000821:virology; D016030:Kidney Transplantation / Q000009:adverse effects*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D027601:Polyomavirus Infections / Q000097:blood / Q000175:diagnosis* / Q000188:drug therapy / Q000652:urine / Q000821:virology; D011237:Predictive Value of Tests; D015995:Prevalence; D011446:Prospective Studies; D015203:Reproducibility of Results; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D013997:Time Factors; D019562:Viral Load; D014766:Viremia / Q000175:diagnosis; D014775:Virus Activation
D004279:DNA, Viral