Urinary exosomal viral microRNA as a marker of BK virus nephropathy in kidney transplant recipients

被引:54
作者
Kim, Myeong Hee [1 ]
Lee, Yu Ho [2 ]
Seo, Jung-Woo [2 ]
Moon, Haena [2 ]
Kim, Jin Sug [2 ]
Kim, Yang Gyun [2 ]
Jeong, Kyung-Hwan [2 ]
Moon, Ju-Young [2 ]
Lee, Tae Won [2 ]
Ihm, Chun-Gyoo [2 ]
Kim, Chan-Duck [3 ]
Park, Jae Berm [4 ]
Chung, Byung Ha [5 ]
Kim, Young-Hoon [6 ]
Lee, Sang-Ho [2 ]
机构
[1] Kyung Hee Univ, Dept Lab Med, Seoul, South Korea
[2] Kyung Hee Univ, Div Nephrol, Dept Internal Med, Seoul, South Korea
[3] Kyungpook Natl Univ Hosp, Div Nephrol, Dept Internal Med, Daegu, South Korea
[4] Samsung Med Ctr, Dept Surg, Seoul, South Korea
[5] Catholic Univ Korea, Div Nephrol, Dept Internal Med, Coll Med,St Marys Hosp, Seoul, South Korea
[6] Inje Univ, Div Nephrol, Dept Internal Med, Coll Med, Pusan, South Korea
关键词
POLYOMAVIRUS-ASSOCIATED NEPHROPATHY; JC-VIRUS; ACCURATELY PREDICTS; REPLICATION; PLASMA; BIOMARKERS; INFECTION; DIAGNOSIS; DISEASE; BLOOD;
D O I
10.1371/journal.pone.0190068
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Objective Bkv-miR-B1-5p, one of the microRNAs encoded by BK virus, was recently reported to be elevated in the blood among the patients with BK virus nephropathy (BKVN). Urinary exosome was suggested to be a possible source of biomarker for kidney diseases, but it was unknown whether it could contain viral microRNA as well as human microRNAs. The aim of this study was to evaluate whether urinary exosomal BK viral microRNA were expressed during replication and could be used to diagnose BKVN in kidney transplant recipients. Materials and methods In a cross-sectional multicenter study, we collected and analyzed 458 graft biopsies from 385 kidney transplant recipients. Urine samples were collected at the time of graft biopsy, and microRNAs in urinary exosome were measured once. For 13 patients with BKVN and 67 age, sex-matched kidney transplant recipients, we measured BK viral microRNA B1-5p, 3p and human microRNA-16 in urinary exosomal fraction and compared the diagnostic value with BK viral load in plasma and urine. Results Pathology proven BKVN was diagnosed in 13 patients (2.8%). High levels of bkv-miR-B1-5p and bkv-miR-B1-3p were shown in all patients with BKVN. Meanwhile, plasma BK viral load assay (cut-off value of >= 4.0 log(10) copies/mL) showed false negative in 3 cases and urinary BK viral load assay (cut-off value of >= 7.0 log(10) copies/mL) showed false negative in 1 case among these 13 patients. The receiver operator characteristics curve analysis for bkv-miR- B1-5p and bkv-miR-B1-5p/miR-16 showed excellent discriminative power for the diagnosis of BKVN, with area under the curve values of 0.989 and 0.985, respectively. Conclusions This study suggests that urinary exosomal bkv-miR-B1-5p and bkv-miR-B1-5p/miR-16 could be surrogate markers for the diagnosis of BKVN.
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页数:14
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