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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 PLoS+One
2017 ; 12
(11
): e0188316
Nephropedia Template TP
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The urine biomarker panel IGFBP7 x TIMP-2 (NephroCheck® parameter) does not
correlate with IGFBP7 and TIMP-2 gene expression in urinary sediment
#MMPMID29145491
Knafl D
; Müller M
; Pajenda S
; Genc Z
; Hecking M
; Wagner L
PLoS One
2017[]; 12
(11
): e0188316
PMID29145491
show ga
BACKGROUND: Acute kidney injury (AKI) is frequently observed in serious
infections, following nephrotoxic medication, surgery and trauma. Here we tested
whether the detection of two recently identified biomarkers for AKI, Tissue
Inhibitor of Metalloproteinase-2 (TIMP-2) and Insulin-Like Growth Factor Binding
Protein 7 (IGFBP7), depends on the expression of these proteins in cells of the
urinary sediment. METHOD: We collected urine samples of 33 kidney transplant
recipients and 14 non-transplanted patients who all had AKI (stages 1-3 according
to KDIGO), and measured [IGFBP7]x[TIMP-2] using the NephroCheck® Astute1 40 ?
meter. Concomitantly, we analyzed IGFBP7 and TIMP-2 mRNA expression by
quantitative polymerase chain reaction (qPCR) from urinary sediment of the same
patients, and correlated the results with [IGFBP7]x[TIMP-2] (protein), by linear
regression analysis. We also determined the association between [IGFBP7]x[TIMP-2]
and estimated glomerular filtration rate (eGFR), and between IGFBP7 and TIMP-2
mRNA expression and markers of inflammation. Light microscopy and confocal
immunofluorescence served to illustrate changes in the urinary sediment over the
time course of renal function improvement. RESULTS: Of the 47 analyzed AKI
patients, 14 presented with ascending urinary tract infection. Serum creatinine
(sCr), blood urea nitrogen (BUN) and eGFR in all patients were 3.9±2.28 mg/dL,
47.59±23.1 mg/dL and 22.88±16.0 mL/min/1.73m2, respectively, on average ±standard
deviation. [IGFBP7]x[TIMP-2] was 2.33±9.95 (ng/ml)2/1000, and did not associate
with IGFBP7 and TIMP-2 gene expression (r = -0.0220, p = 0.4216; respectively r =
0.0972, p = 0.1909). [IGFBP7]x[TIMP-2] did not associate with eGFR; IGFBP7 and
TIMP-2 mRNA expression. Improvement of renal function went along with
disappearance of casts, decrease in aquaporin1 positive renal epithelial cells
and leukocytes from the urinary sediment. CONCLUSION: The gene expression pattern
of IGFBP7 and TIMP-2 from urinary sediment, which contains desquamated renal
tubular epithelial cells, did not correlate with [IGFBP7]x[TIMP-2] protein,
indicating that IGFBP7 and TIMP-2 measured in the NephroCheck® test originated
predominantly from intact but stressed cells of the kidney itself.