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Polyomavirus BK, BKV microRNA, and urinary neutrophil gelatinase-associated lipocalin can be used as potential biomarkers of lupus nephritis

OBJECTIVE: Lupus nephritis (LN) frequently progresses to end-stage renal disease. Finding a biomarker for LN and a predictor for the development of chronic kidney disease (CKD) is important for patients with systemic lupus erythematosus (SLE). METHODS: Ninety patients with SLE were divided into biop...

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Autores principales: Li, Yi-Jung, Wu, Hsin-Hsu, Liu, Shou-Hsuan, Tu, Kun-Hua, Lee, Cheng-Chia, Hsu, Hsiang-Hao, Chang, Ming-Yang, Yu, Kuang-Hui, Chen, Wei, Tian, Ya-Chung
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6331123/
https://www.ncbi.nlm.nih.gov/pubmed/30640964
http://dx.doi.org/10.1371/journal.pone.0210633
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author Li, Yi-Jung
Wu, Hsin-Hsu
Liu, Shou-Hsuan
Tu, Kun-Hua
Lee, Cheng-Chia
Hsu, Hsiang-Hao
Chang, Ming-Yang
Yu, Kuang-Hui
Chen, Wei
Tian, Ya-Chung
author_facet Li, Yi-Jung
Wu, Hsin-Hsu
Liu, Shou-Hsuan
Tu, Kun-Hua
Lee, Cheng-Chia
Hsu, Hsiang-Hao
Chang, Ming-Yang
Yu, Kuang-Hui
Chen, Wei
Tian, Ya-Chung
author_sort Li, Yi-Jung
collection PubMed
description OBJECTIVE: Lupus nephritis (LN) frequently progresses to end-stage renal disease. Finding a biomarker for LN and a predictor for the development of chronic kidney disease (CKD) is important for patients with systemic lupus erythematosus (SLE). METHODS: Ninety patients with SLE were divided into biopsy-proven LN (n = 54) and no kidney involvement (non-LN) (n = 36) groups and followed up for 54 months. RESULTS: Of 36 patients with LN, 3 (5.6%) had class II disease, 3 (5.6%) had class III, 35 (64.8%) had class IV, 10 (18.5%) had class V, and 3 (5.6%) had class VI (advanced sclerosis). Compared to the non-LN group, patients in the LN group had higher autoimmunity evidenced by a higher proportion of low C3 and C4 levels, positive anti-double-stranded DNA antibody levels, and lower estimated glomerular filtration rates (eGFR). Urinary neutrophil gelatinase-associated lipocalin (uNGAL) levels were significantly higher in the LN group (LN vs non-LN, 670 vs 33 ng/mL, respectively). The patients with LN had a higher urinary polyomavirus BK (BKV) load (3.6 vs 3.0 log copies/mL) and a lower urinary BKV miRNA (miR-B1) 5p level (0.29 vs 0.55 log copies/mL, p = 0.025), while there was no significant difference in the level of miR-B1-3p. Urinary miR-B1-5p level but not urinary BKV load was negatively correlated with uNGAL level (r = -0.22, p = 0.004). At the cutoff value of 80 ng/mL, the receiver operating characteristic curve analysis showed that uNGAL level as a predictor of the presence of LN had a high sensitivity (98%) and specificity (100%) (area under the curve [AUC], 0.997; p < 0.001). During the 54-month follow-up period, 14 (7%) patients with LN and none of the non-LN patients developed CKD. Multivariate Cox regression analysis revealed that baseline uNGAL level was the only predictive factor for CKD development, while baseline serum creatinine level and eGFR were not. CONCLUSION: An elevated urinary BKV viral load with a decreased level of miR-B1 implies the presence of LN. In addition, an increased uNGAL level is a good biomarker not only in predicting the presence of LN but also for prediction of CKD development in patients with SLE.
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spelling pubmed-63311232019-02-01 Polyomavirus BK, BKV microRNA, and urinary neutrophil gelatinase-associated lipocalin can be used as potential biomarkers of lupus nephritis Li, Yi-Jung Wu, Hsin-Hsu Liu, Shou-Hsuan Tu, Kun-Hua Lee, Cheng-Chia Hsu, Hsiang-Hao Chang, Ming-Yang Yu, Kuang-Hui Chen, Wei Tian, Ya-Chung PLoS One Research Article OBJECTIVE: Lupus nephritis (LN) frequently progresses to end-stage renal disease. Finding a biomarker for LN and a predictor for the development of chronic kidney disease (CKD) is important for patients with systemic lupus erythematosus (SLE). METHODS: Ninety patients with SLE were divided into biopsy-proven LN (n = 54) and no kidney involvement (non-LN) (n = 36) groups and followed up for 54 months. RESULTS: Of 36 patients with LN, 3 (5.6%) had class II disease, 3 (5.6%) had class III, 35 (64.8%) had class IV, 10 (18.5%) had class V, and 3 (5.6%) had class VI (advanced sclerosis). Compared to the non-LN group, patients in the LN group had higher autoimmunity evidenced by a higher proportion of low C3 and C4 levels, positive anti-double-stranded DNA antibody levels, and lower estimated glomerular filtration rates (eGFR). Urinary neutrophil gelatinase-associated lipocalin (uNGAL) levels were significantly higher in the LN group (LN vs non-LN, 670 vs 33 ng/mL, respectively). The patients with LN had a higher urinary polyomavirus BK (BKV) load (3.6 vs 3.0 log copies/mL) and a lower urinary BKV miRNA (miR-B1) 5p level (0.29 vs 0.55 log copies/mL, p = 0.025), while there was no significant difference in the level of miR-B1-3p. Urinary miR-B1-5p level but not urinary BKV load was negatively correlated with uNGAL level (r = -0.22, p = 0.004). At the cutoff value of 80 ng/mL, the receiver operating characteristic curve analysis showed that uNGAL level as a predictor of the presence of LN had a high sensitivity (98%) and specificity (100%) (area under the curve [AUC], 0.997; p < 0.001). During the 54-month follow-up period, 14 (7%) patients with LN and none of the non-LN patients developed CKD. Multivariate Cox regression analysis revealed that baseline uNGAL level was the only predictive factor for CKD development, while baseline serum creatinine level and eGFR were not. CONCLUSION: An elevated urinary BKV viral load with a decreased level of miR-B1 implies the presence of LN. In addition, an increased uNGAL level is a good biomarker not only in predicting the presence of LN but also for prediction of CKD development in patients with SLE. Public Library of Science 2019-01-14 /pmc/articles/PMC6331123/ /pubmed/30640964 http://dx.doi.org/10.1371/journal.pone.0210633 Text en © 2019 Li et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Li, Yi-Jung
Wu, Hsin-Hsu
Liu, Shou-Hsuan
Tu, Kun-Hua
Lee, Cheng-Chia
Hsu, Hsiang-Hao
Chang, Ming-Yang
Yu, Kuang-Hui
Chen, Wei
Tian, Ya-Chung
Polyomavirus BK, BKV microRNA, and urinary neutrophil gelatinase-associated lipocalin can be used as potential biomarkers of lupus nephritis
title Polyomavirus BK, BKV microRNA, and urinary neutrophil gelatinase-associated lipocalin can be used as potential biomarkers of lupus nephritis
title_full Polyomavirus BK, BKV microRNA, and urinary neutrophil gelatinase-associated lipocalin can be used as potential biomarkers of lupus nephritis
title_fullStr Polyomavirus BK, BKV microRNA, and urinary neutrophil gelatinase-associated lipocalin can be used as potential biomarkers of lupus nephritis
title_full_unstemmed Polyomavirus BK, BKV microRNA, and urinary neutrophil gelatinase-associated lipocalin can be used as potential biomarkers of lupus nephritis
title_short Polyomavirus BK, BKV microRNA, and urinary neutrophil gelatinase-associated lipocalin can be used as potential biomarkers of lupus nephritis
title_sort polyomavirus bk, bkv microrna, and urinary neutrophil gelatinase-associated lipocalin can be used as potential biomarkers of lupus nephritis
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6331123/
https://www.ncbi.nlm.nih.gov/pubmed/30640964
http://dx.doi.org/10.1371/journal.pone.0210633
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