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Published in: BMC Nephrology 1/2019

Open Access 01-12-2019 | Glomerulonephritis | Research article

Urinary miRNA profile for the diagnosis of IgA nephropathy

Authors: Cheuk-Chun Szeto, Gang Wang, Jack Kit-Chung Ng, Bonnie Ching-Ha Kwan, Fernand Mac-Moune Lai, Kai-Ming Chow, Cathy Choi-Wan Luk, Ka-Bik Lai, Philip Kam-Tao Li

Published in: BMC Nephrology | Issue 1/2019

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Abstract

Background

IgA nephropathy (IgAN) is the most common primary glomerulonephritis worldwide. Urinary micro-RNA (miRNA) level is increasingly reported to as non-invasive markers of various kidney diseases. We aim to identify urinary miRNA targets for the diagnosis of IgAN.

Methods

In the development cohort, we performed complete miRNA profiling of urinary sediment in 22 patients with IgAN and 11 healthy controls (CTL). Potential miRNA targets were quantified by a separate validation cohort of 33 IgAN patients and 9 healthy controls.

Results

In the development cohort, we identified 39 miRNA targets that have significantly different expression between IgAN and CTL (14 up-regulated, and 25 down-regulated). Among the 8 miRNA targets chosen for validation study, urinary miR-204, miR-431 and miR-555 remained significantly reduced, and urinary miR-150 level was significantly increased in the IgAN as compared to CTL. The area-under-curve of the receiver operating characteristic (ROC) curve for urinary mi-204 level for the diagnosis of IgAN was 0.976, and the diagnostic performance of combining additional miRNA targets was not further improved. At the cut-off 1.70 unit, the sensitivity and specificity of urinary miR-204 was 100 and 55.5%, respectively, for diagnosing IgAN.

Conclusions

Urinary miR-150, miR-204, miR-431 and miR-555 levels are significantly different between IgAN and healthy controls; urinary miR-204 level alone has the best diagnostic accuracy.
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Literature
1.
go back to reference Donadio JV, Grande JP. IgA nephropathy. N Engl J Med. 2002;347:738–48.PubMed Donadio JV, Grande JP. IgA nephropathy. N Engl J Med. 2002;347:738–48.PubMed
2.
go back to reference Li PK, Ho KK, Szeto CC, Yu L, Lai FM. Prognostic indicators of IgA nephropathy in the Chinese--clinical and pathological perspectives. Nephrol Dial Transplant. 2002;17:64–9.PubMed Li PK, Ho KK, Szeto CC, Yu L, Lai FM. Prognostic indicators of IgA nephropathy in the Chinese--clinical and pathological perspectives. Nephrol Dial Transplant. 2002;17:64–9.PubMed
3.
go back to reference Szeto CC, Lai FM, To KF, Wong TY, Chow KM, Choi PC, Lui SF, Li PK. The natural history of immunoglobulin a nephropathy among patients with hematuria and minimal proteinuria. Am J Med. 2001;110:434–7.PubMed Szeto CC, Lai FM, To KF, Wong TY, Chow KM, Choi PC, Lui SF, Li PK. The natural history of immunoglobulin a nephropathy among patients with hematuria and minimal proteinuria. Am J Med. 2001;110:434–7.PubMed
4.
go back to reference Working Group of the International IgA Nephropathy Network and the Renal Pathology Society. The Oxford classification of IgA nephropathy: pathology definitions, correlations, and reproducibility. Kidney Int. 2009;76:546–56. Working Group of the International IgA Nephropathy Network and the Renal Pathology Society. The Oxford classification of IgA nephropathy: pathology definitions, correlations, and reproducibility. Kidney Int. 2009;76:546–56.
5.
go back to reference Bartel DP. MicroRNAs: genomics, biogenesis, mechanism and function. Cell. 2004;116:281–97.PubMed Bartel DP. MicroRNAs: genomics, biogenesis, mechanism and function. Cell. 2004;116:281–97.PubMed
6.
go back to reference Serino G, Sallustio F, Cox SN, Pesce F, Schena FP. Abnormal miR-148b expression promotes aberrant glycosylation of IgA1 in IgA nephropathy. J Am Soc Nephrol. 2012;23:814–24.PubMed Serino G, Sallustio F, Cox SN, Pesce F, Schena FP. Abnormal miR-148b expression promotes aberrant glycosylation of IgA1 in IgA nephropathy. J Am Soc Nephrol. 2012;23:814–24.PubMed
7.
go back to reference Fang Y, Yu X, Liu Y, Kriegel AJ, Heng Y, Xu X, Liang M, Ding X. miR-29c is downregulated in renal interstitial fibrosis in humans and rats and restored by HIF-α activation. Am J Physiol Renal Physiol. 2013;304:F1274–82.PubMed Fang Y, Yu X, Liu Y, Kriegel AJ, Heng Y, Xu X, Liang M, Ding X. miR-29c is downregulated in renal interstitial fibrosis in humans and rats and restored by HIF-α activation. Am J Physiol Renal Physiol. 2013;304:F1274–82.PubMed
8.
go back to reference Szeto CC, Chan RW, Lai KB, Szeto CY, Chow KM, Li PK, Lai FM. Messenger RNA expression of target genes in the urinary sediment of patients with chronic kidney diseases. Nephrol Dial Transplant. 2005;20:105–13.PubMed Szeto CC, Chan RW, Lai KB, Szeto CY, Chow KM, Li PK, Lai FM. Messenger RNA expression of target genes in the urinary sediment of patients with chronic kidney diseases. Nephrol Dial Transplant. 2005;20:105–13.PubMed
9.
go back to reference Szeto CC, Kwan BC, Tam LS. Urinary mRNA in systemic lupus erythematosus. Adv Clin Chem. 2013;62:197–219.PubMed Szeto CC, Kwan BC, Tam LS. Urinary mRNA in systemic lupus erythematosus. Adv Clin Chem. 2013;62:197–219.PubMed
10.
go back to reference Szeto CC. Urine miRNA in nephrotic syndrome. Clin Chim Acta. 2014;436:308–13.PubMed Szeto CC. Urine miRNA in nephrotic syndrome. Clin Chim Acta. 2014;436:308–13.PubMed
11.
go back to reference Szeto CC, Li PK. MicroRNAs in IgA nephropathy. Nat Rev Nephrol. 2014;10:249–56.PubMed Szeto CC, Li PK. MicroRNAs in IgA nephropathy. Nat Rev Nephrol. 2014;10:249–56.PubMed
12.
go back to reference Wang G, Kwan BC, Lai FM, Chow KM, Kam-Tao Li P, Szeto CC. Expression of microRNAs in the urinary sediment of patients with IgA nephropathy. Dis Markers. 2010;28:79–86.PubMed Wang G, Kwan BC, Lai FM, Chow KM, Kam-Tao Li P, Szeto CC. Expression of microRNAs in the urinary sediment of patients with IgA nephropathy. Dis Markers. 2010;28:79–86.PubMed
13.
go back to reference Wang G, Kwan BC, Lai FM, Chow KM, Li PK, Szeto CC. Urinary miR-21, miR-29, and miR-93: novel biomarkers of fibrosis. Am J Nephrol. 2012;36:412–8.PubMed Wang G, Kwan BC, Lai FM, Chow KM, Li PK, Szeto CC. Urinary miR-21, miR-29, and miR-93: novel biomarkers of fibrosis. Am J Nephrol. 2012;36:412–8.PubMed
14.
go back to reference Levey AS, Bosch JP, Lewis JB, Greene T, Rogers N. Roth D. A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Modification of diet in renal disease study group. Ann Intern Med. 1999;130:461–70.PubMed Levey AS, Bosch JP, Lewis JB, Greene T, Rogers N. Roth D. A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Modification of diet in renal disease study group. Ann Intern Med. 1999;130:461–70.PubMed
15.
go back to reference Wang G, Szeto CC. Methods of microRNA quantification in urinary sediment. Methods Mol Biol. 2013;1024:211–20.PubMed Wang G, Szeto CC. Methods of microRNA quantification in urinary sediment. Methods Mol Biol. 2013;1024:211–20.PubMed
16.
go back to reference NanoString Technologies, Inc. nCounter® miRNA expression assay user manual. Seattle, Washington, 2013. NanoString Technologies, Inc. nCounter® miRNA expression assay user manual. Seattle, Washington, 2013.
17.
go back to reference Helsel DR. Less than obvious – statistical treatment of data below the detection limit. Environ Sci Technol. 1990;24:1766–74. Helsel DR. Less than obvious – statistical treatment of data below the detection limit. Environ Sci Technol. 1990;24:1766–74.
18.
go back to reference Wang G, Lai FM, Tam LS, Li EK, Lai KB, Chow KM, Li PK, Szeto CC. Messenger RNA expression of podocyte associated molecules in the urinary sediment of patients with lupus nephritis. J Rheumatol. 2007;34:2358–64.PubMed Wang G, Lai FM, Tam LS, Li EK, Lai KB, Chow KM, Li PK, Szeto CC. Messenger RNA expression of podocyte associated molecules in the urinary sediment of patients with lupus nephritis. J Rheumatol. 2007;34:2358–64.PubMed
19.
go back to reference Trimarchi H, Barratt J, Cattran DC, Cook HT, Coppo R, Haas M, Liu ZH, Roberts IS, Yuzawa Y, Zhang H, Feehally J. Oxford classification of IgA nephropathy 2016: an update from the IgA nephropathy classification working group. Kidney Int. 2017;91:1014–21.PubMed Trimarchi H, Barratt J, Cattran DC, Cook HT, Coppo R, Haas M, Liu ZH, Roberts IS, Yuzawa Y, Zhang H, Feehally J. Oxford classification of IgA nephropathy 2016: an update from the IgA nephropathy classification working group. Kidney Int. 2017;91:1014–21.PubMed
20.
go back to reference Wang G, Kwan BCH, Lai FMM, Chow KM, Ng KCJ, Luk CWC, Li PKT, Szeto CC. Urinary sediment mRNA level of extracellular matrix molecules in adult nephrotic syndrome. Clin Chim Acta. 2016;456:157–62.PubMed Wang G, Kwan BCH, Lai FMM, Chow KM, Ng KCJ, Luk CWC, Li PKT, Szeto CC. Urinary sediment mRNA level of extracellular matrix molecules in adult nephrotic syndrome. Clin Chim Acta. 2016;456:157–62.PubMed
21.
go back to reference Wei PZ, Kwan BC, Chow KM, Cheng PM, Luk CC, Lai KB, Li PK, Szeto CC. Urinary mitochondrial DNA level in non-diabetic chronic kidney diseases. Clin Chim Acta. 2018;484:36–9.PubMed Wei PZ, Kwan BC, Chow KM, Cheng PM, Luk CC, Lai KB, Li PK, Szeto CC. Urinary mitochondrial DNA level in non-diabetic chronic kidney diseases. Clin Chim Acta. 2018;484:36–9.PubMed
22.
go back to reference Wang G, Kwan BC, Lai FM, Chow KM, Li PK, Szeto CC. Elevated levels of miR-146a and miR-155 in kidney biopsy and urine from patients with IgA nephropathy. Dis Markers. 2011;30:171–9.PubMed Wang G, Kwan BC, Lai FM, Chow KM, Li PK, Szeto CC. Elevated levels of miR-146a and miR-155 in kidney biopsy and urine from patients with IgA nephropathy. Dis Markers. 2011;30:171–9.PubMed
23.
go back to reference Min QH, Chen XM, Zou YQ, Zhang J, Li J, Wang Y, Li SQ, Gao QF, Sun F, Liu J, Xu YM, Lin J, Huang LF, Huang B, Wang XZ. Differential expression of urinary exosomal microRNAs in IgA nephropathy. J Clin Lab Anal. 2018; in press. Min QH, Chen XM, Zou YQ, Zhang J, Li J, Wang Y, Li SQ, Gao QF, Sun F, Liu J, Xu YM, Lin J, Huang LF, Huang B, Wang XZ. Differential expression of urinary exosomal microRNAs in IgA nephropathy. J Clin Lab Anal. 2018; in press.
24.
go back to reference Liang S, Cai GY, Duan ZY, Liu SW, Wu J, Lv Y, Hou K, Li ZX, Zhang XG, Chen XM. Urinary sediment miRNAs reflect tubulointerstitial damage and therapeutic response in IgA nephropathy. BMC Nephrol. 2017;18:63.PubMed Liang S, Cai GY, Duan ZY, Liu SW, Wu J, Lv Y, Hou K, Li ZX, Zhang XG, Chen XM. Urinary sediment miRNAs reflect tubulointerstitial damage and therapeutic response in IgA nephropathy. BMC Nephrol. 2017;18:63.PubMed
25.
go back to reference Chen SJ, Wu P, Sun LJ, Zhou B, Niu W, Liu S, Lin FJ, Jiang GR. miR-204 regulates epithelial-mesenchymal transition by targeting SP1 in the tubular epithelial cells after acute kidney injury induced by ischemia-reperfusion. Oncol Rep. 2017;37:1148–58.PubMed Chen SJ, Wu P, Sun LJ, Zhou B, Niu W, Liu S, Lin FJ, Jiang GR. miR-204 regulates epithelial-mesenchymal transition by targeting SP1 in the tubular epithelial cells after acute kidney injury induced by ischemia-reperfusion. Oncol Rep. 2017;37:1148–58.PubMed
26.
go back to reference Chen Y, Qiu J, Chen B, Lin Y, Chen Y, Xie G, Qiu J, Tong H, Jiang D. Long non-coding RNA NEAT1 plays an important role in sepsis-induced acute kidney injury by targeting miR-204 and modulating the NF-κB pathway. Int Immunopharmacol. 2018;59:252–60.PubMed Chen Y, Qiu J, Chen B, Lin Y, Chen Y, Xie G, Qiu J, Tong H, Jiang D. Long non-coding RNA NEAT1 plays an important role in sepsis-induced acute kidney injury by targeting miR-204 and modulating the NF-κB pathway. Int Immunopharmacol. 2018;59:252–60.PubMed
27.
go back to reference Rodrigues JC, Haas M, Reich HN. IgA nephropathy. Clin J Am Soc Nephrol. 2017;12:677–86.PubMed Rodrigues JC, Haas M, Reich HN. IgA nephropathy. Clin J Am Soc Nephrol. 2017;12:677–86.PubMed
28.
go back to reference Chan RW, Szeto CC. Advances in the clinical laboratory assessment of urinary sediment. Clin Chim Acta. 2004;340:67–78.PubMed Chan RW, Szeto CC. Advances in the clinical laboratory assessment of urinary sediment. Clin Chim Acta. 2004;340:67–78.PubMed
29.
go back to reference Wei PZ, Kwan BC, Chow KM, Cheng PM, Luk CC, Li PK, Szeto CC. Urinary mitochondrial DNA level is an indicator of intra-renal mitochondrial depletion and renal scarring in diabetic nephropathy. Nephrol Dial Transplant. 2018;33:784–8.PubMed Wei PZ, Kwan BC, Chow KM, Cheng PM, Luk CC, Li PK, Szeto CC. Urinary mitochondrial DNA level is an indicator of intra-renal mitochondrial depletion and renal scarring in diabetic nephropathy. Nephrol Dial Transplant. 2018;33:784–8.PubMed
Metadata
Title
Urinary miRNA profile for the diagnosis of IgA nephropathy
Authors
Cheuk-Chun Szeto
Gang Wang
Jack Kit-Chung Ng
Bonnie Ching-Ha Kwan
Fernand Mac-Moune Lai
Kai-Ming Chow
Cathy Choi-Wan Luk
Ka-Bik Lai
Philip Kam-Tao Li
Publication date
01-12-2019
Publisher
BioMed Central
Published in
BMC Nephrology / Issue 1/2019
Electronic ISSN: 1471-2369
DOI
https://doi.org/10.1186/s12882-019-1267-4

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