Identification, confirmation, and replication of novel urinary microrna biomarkers in lupus nephritis and diabetic nephropathy

Mariana Cardenas-Gonzalez, Anand Srivastava, Mira Pavkovic, Vanesa Bijol, Helmut G. Rennke, Isaac E. Stillman, Xiaolan Zhang, Samir Parikh, Brad H. Rovin, Maryam Afkarian, Ian H. De Boer, Jonathan Himmelfarb, Sushrut S. Waikar, Vishal S. Vaidya

    Research output: Contribution to journalArticle

    28 Citations (Scopus)

    Abstract

    BACKGROUND: The prevalence of chronic kidney disease (CKD) is increasing, leading to significant morbidity and mortality. Kidney biopsy remains the gold standard for diagnosing the underlying etiology of CKD, but the procedure carries complication risks. The aim of this study was to identify novel noninvasive biomarkers correlating with kidney function and histopathology in biopsyproven CKD patients. METHODS: We profiled 2402 urinary microRNAs (miRNAs) to identify and confirm differentially expressed miRNAs associated with kidney function and histopathology in patients with diabetic nephropathy (n = 58) or lupus nephritis (n = 89), important etiologies of CKD, compared with healthy controls (n = 93 and 119, respectively). Top performing miRNAs were then measured in 2 independent multi-institutional cohorts of patients with diabetes mellitus with (n = 74) or without nephropathy (n = 71) and systemic lupus erythematosus with (n=86) or without (n=37) nephritis. RESULTS: In patients with diabetic nephropathy, miR- 2861, miR-1915-3p, and miR-4532 were downregulated (10-fold, P < 0.0001) and were associated with estimated glomerular filtration rate (P < 0.01) and interstitial fibrosis/tubular atrophy (P < 0.05). The c-statistics for miR-2861, miR-1915-3p, and miR-4532 were 0.91, 0.86, and 0.85, respectively. In lupus nephritis patients, miR-3201 and miR-1273e were downregulated (3-fold, P < 0.0001) and associated with endocapillary glomerular inflammation (P<0.01), with c-statistics of 0.97 and 0.91, respectively. CONCLUSIONS: Wehave identified novel miRNAs that correlate with histopathological lesions and functional markers of kidney damage to facilitate sensitive, specific, and noninvasive detection of diabetic nephropathy and lupus nephritis.

    Original languageEnglish (US)
    Pages (from-to)1515-1526
    Number of pages12
    JournalClinical Chemistry
    Volume63
    Issue number9
    DOIs
    StatePublished - Sep 1 2017

    Fingerprint

    Lupus Nephritis
    Diabetic Nephropathies
    Biomarkers
    MicroRNAs
    Chronic Renal Insufficiency
    Kidney
    Statistics
    Down-Regulation
    Biopsy
    Medical problems
    Nephritis
    Glomerular Filtration Rate
    Systemic Lupus Erythematosus
    Atrophy
    Diabetes Mellitus
    Fibrosis
    Inflammation
    Morbidity
    Mortality

    ASJC Scopus subject areas

    • Clinical Biochemistry
    • Biochemistry, medical

    Cite this

    Cardenas-Gonzalez, M., Srivastava, A., Pavkovic, M., Bijol, V., Rennke, H. G., Stillman, I. E., ... Vaidya, V. S. (2017). Identification, confirmation, and replication of novel urinary microrna biomarkers in lupus nephritis and diabetic nephropathy. Clinical Chemistry, 63(9), 1515-1526. https://doi.org/10.1373/clinchem.2017.274175

    Identification, confirmation, and replication of novel urinary microrna biomarkers in lupus nephritis and diabetic nephropathy. / Cardenas-Gonzalez, Mariana; Srivastava, Anand; Pavkovic, Mira; Bijol, Vanesa; Rennke, Helmut G.; Stillman, Isaac E.; Zhang, Xiaolan; Parikh, Samir; Rovin, Brad H.; Afkarian, Maryam; De Boer, Ian H.; Himmelfarb, Jonathan; Waikar, Sushrut S.; Vaidya, Vishal S.

    In: Clinical Chemistry, Vol. 63, No. 9, 01.09.2017, p. 1515-1526.

    Research output: Contribution to journalArticle

    Cardenas-Gonzalez, M, Srivastava, A, Pavkovic, M, Bijol, V, Rennke, HG, Stillman, IE, Zhang, X, Parikh, S, Rovin, BH, Afkarian, M, De Boer, IH, Himmelfarb, J, Waikar, SS & Vaidya, VS 2017, 'Identification, confirmation, and replication of novel urinary microrna biomarkers in lupus nephritis and diabetic nephropathy', Clinical Chemistry, vol. 63, no. 9, pp. 1515-1526. https://doi.org/10.1373/clinchem.2017.274175
    Cardenas-Gonzalez, Mariana ; Srivastava, Anand ; Pavkovic, Mira ; Bijol, Vanesa ; Rennke, Helmut G. ; Stillman, Isaac E. ; Zhang, Xiaolan ; Parikh, Samir ; Rovin, Brad H. ; Afkarian, Maryam ; De Boer, Ian H. ; Himmelfarb, Jonathan ; Waikar, Sushrut S. ; Vaidya, Vishal S. / Identification, confirmation, and replication of novel urinary microrna biomarkers in lupus nephritis and diabetic nephropathy. In: Clinical Chemistry. 2017 ; Vol. 63, No. 9. pp. 1515-1526.
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    abstract = "BACKGROUND: The prevalence of chronic kidney disease (CKD) is increasing, leading to significant morbidity and mortality. Kidney biopsy remains the gold standard for diagnosing the underlying etiology of CKD, but the procedure carries complication risks. The aim of this study was to identify novel noninvasive biomarkers correlating with kidney function and histopathology in biopsyproven CKD patients. METHODS: We profiled 2402 urinary microRNAs (miRNAs) to identify and confirm differentially expressed miRNAs associated with kidney function and histopathology in patients with diabetic nephropathy (n = 58) or lupus nephritis (n = 89), important etiologies of CKD, compared with healthy controls (n = 93 and 119, respectively). Top performing miRNAs were then measured in 2 independent multi-institutional cohorts of patients with diabetes mellitus with (n = 74) or without nephropathy (n = 71) and systemic lupus erythematosus with (n=86) or without (n=37) nephritis. RESULTS: In patients with diabetic nephropathy, miR- 2861, miR-1915-3p, and miR-4532 were downregulated (10-fold, P < 0.0001) and were associated with estimated glomerular filtration rate (P < 0.01) and interstitial fibrosis/tubular atrophy (P < 0.05). The c-statistics for miR-2861, miR-1915-3p, and miR-4532 were 0.91, 0.86, and 0.85, respectively. In lupus nephritis patients, miR-3201 and miR-1273e were downregulated (3-fold, P < 0.0001) and associated with endocapillary glomerular inflammation (P<0.01), with c-statistics of 0.97 and 0.91, respectively. CONCLUSIONS: Wehave identified novel miRNAs that correlate with histopathological lesions and functional markers of kidney damage to facilitate sensitive, specific, and noninvasive detection of diabetic nephropathy and lupus nephritis.",
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    AU - Cardenas-Gonzalez, Mariana

    AU - Srivastava, Anand

    AU - Pavkovic, Mira

    AU - Bijol, Vanesa

    AU - Rennke, Helmut G.

    AU - Stillman, Isaac E.

    AU - Zhang, Xiaolan

    AU - Parikh, Samir

    AU - Rovin, Brad H.

    AU - Afkarian, Maryam

    AU - De Boer, Ian H.

    AU - Himmelfarb, Jonathan

    AU - Waikar, Sushrut S.

    AU - Vaidya, Vishal S.

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    N2 - BACKGROUND: The prevalence of chronic kidney disease (CKD) is increasing, leading to significant morbidity and mortality. Kidney biopsy remains the gold standard for diagnosing the underlying etiology of CKD, but the procedure carries complication risks. The aim of this study was to identify novel noninvasive biomarkers correlating with kidney function and histopathology in biopsyproven CKD patients. METHODS: We profiled 2402 urinary microRNAs (miRNAs) to identify and confirm differentially expressed miRNAs associated with kidney function and histopathology in patients with diabetic nephropathy (n = 58) or lupus nephritis (n = 89), important etiologies of CKD, compared with healthy controls (n = 93 and 119, respectively). Top performing miRNAs were then measured in 2 independent multi-institutional cohorts of patients with diabetes mellitus with (n = 74) or without nephropathy (n = 71) and systemic lupus erythematosus with (n=86) or without (n=37) nephritis. RESULTS: In patients with diabetic nephropathy, miR- 2861, miR-1915-3p, and miR-4532 were downregulated (10-fold, P < 0.0001) and were associated with estimated glomerular filtration rate (P < 0.01) and interstitial fibrosis/tubular atrophy (P < 0.05). The c-statistics for miR-2861, miR-1915-3p, and miR-4532 were 0.91, 0.86, and 0.85, respectively. In lupus nephritis patients, miR-3201 and miR-1273e were downregulated (3-fold, P < 0.0001) and associated with endocapillary glomerular inflammation (P<0.01), with c-statistics of 0.97 and 0.91, respectively. CONCLUSIONS: Wehave identified novel miRNAs that correlate with histopathological lesions and functional markers of kidney damage to facilitate sensitive, specific, and noninvasive detection of diabetic nephropathy and lupus nephritis.

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