TY - JOUR
T1 - Identification, confirmation, and replication of novel urinary microrna biomarkers in lupus nephritis and diabetic nephropathy
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.
N1 - Funding Information:
Employment or Leadership: V. Bijol, Harvard Medical School, Brigham and Women’s Hospital; V.S. Vaidya, Pfizer Inc. Consultant or Advisory Role: None declared. Stock Ownership: V.S. Vaidya, Pfizer Inc. Honoraria: None declared. Research Funding: M. Cardenas-Gonzalez, fellowships from National Council of Science and Technology (CONACyT, Grant 234833) and Fundación México en Harvard, A. C.; A. Srivastava, NIH grant F32DK11106; B.H. Rovin, NIDDK; S.S. Waikar, NIH U01DK085660, R01DK093574, U01DK104308; V.S. Vaidya, NIH/ NIEHS. Work in the Vaidya laboratory was supported by Outstanding New Environmental Sciences (ONES) award from NIH/NIEHS (ES017543) and Innovation in Regulatory Science Award from Burroughs Wellcome Fund (BWF-1012518). Expert Testimony: None declared. Patents: None declared.
Publisher Copyright:
© 2017 American Association for Clinical Chemistry.
PY - 2017/9/1
Y1 - 2017/9/1
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.
AB - 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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U2 - 10.1373/clinchem.2017.274175
DO - 10.1373/clinchem.2017.274175
M3 - Article
C2 - 28667184
AN - SCOPUS:85028504666
VL - 63
SP - 1515
EP - 1526
JO - Clinical Chemistry
JF - Clinical Chemistry
SN - 0009-9147
IS - 9
ER -