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2014 ; 9
(9
): 1545-52
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Evaluation of microRNAs miR-196a, miR-30a-5P, and miR-490 as biomarkers of
disease activity among patients with FSGS
#MMPMID25107948
Zhang W
; Zhang C
; Chen H
; Li L
; Tu Y
; Liu C
; Shi S
; Zen K
; Liu Z
Clin J Am Soc Nephrol
2014[Sep]; 9
(9
): 1545-52
PMID25107948
show ga
BACKGROUND AND OBJECTIVES: This study aimed to identify urinary microRNAs
(miRNAs) as biomarkers for FSGS disease activity. DESIGN, SETTING, PARTICIPANTS,
& MEASUREMENTS: Candidate urinary miRNAs were identified in pooled urine samples
from patients with active FSGS (FSGS-A) and FSGS in remission (FSGS-CR), and were
then validated using individual samples. Their levels were compared both under
different treatment responses in a prospective study of FSGS and in patients with
different membranous nephropathy (MN) and diabetic nephropathy (DN) disease
activity. The prediction of these miRNAs for treatment responses was further
analyzed in both retrospective and prospective cohorts of patients with FSGS.
RESULTS: All 54 miRNAs were included as candidate biomarkers, including those
with high levels in patients with FSGS-A (n=9) under the TaqMan Low Density Array
as well as those with conserved expression in kidneys and involved in immune
response. TaqMan probe-based quantitative RT-PCR confirmed the higher levels of
four miRNAs in patients with FSGS-A in two independent cohorts (n=18 and n=80).
Urinary miR-196a, miR-30a-5p, and miR-490 discriminated FSGS-A from FSGS-CR, with
an area under the curve of ? 0.80. After steroid treatment, their levels were
lower in steroid-responsive patients with FSGS (all P<0.001), but were unchanged
in steroid-resistant patients. The levels of miRNAs were similar between active
MN and MN in remission as well as active DN and incipient DN (all P>0.05).
Urinary miR-30a-5p marginally predicted the response to steroid treatment in
patients with FSGS-A, with an area under the curve of 0.63 (P=0.03). CONCLUSIONS:
The levels of urinary miR-196a, miR-30a-5p, and miR-490 are associated with FSGS
disease activity.