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Biomarkers of kidney disease identified using a novel rat model and evaluated in human CKD patients
Author(s) -
Harmon Ashlyn C.,
Johnson Ashley C.,
Driesbach Albert,
Garrett Michael R.
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.1115.19
Subject(s) - microvesicles , kidney disease , exosome , western blot , kidney , renal function , urine , proteomics , biomarker , population , medicine , biology , endocrinology , microrna , biochemistry , gene , environmental health
Urine exosomes are cell‐like vesicles that originate from kidney tubules under normal and pathological conditions. Proteins and mRNA contained within these exosomes can potentially provide a rich source of non‐invasive biomarkers to predict chronic kidney disease (CKD) progression. We have developed a novel rat model [S.SHR(11)] that demonstrates accelerated kidney injury and decreased kidney function compared to the already susceptible Dahl salt‐sensitive (S) rat. Global shotgun proteomics was performed using multidimensional protein identification technology (MuDPIT) on exosome samples collected from each strain. A total of 403 unique proteins were identified and ~5% demonstrated a two‐fold difference between strains. In particular, ERK2 and ATP9A were increased in S.SHR(11) and confirmed by western blot analysis in isolated exosomes. Both proteins were evaluated in urine exosomes from a unique CKD population collected at the University. CKD patients exhibited prominent expression in exosomes, which was either greatly reduced (ERK2) or not observed in healthy subjects (ATP9A). In summary, we have successfully used a novel rat model to identify biomarkers that correlate with decline in kidney function. The continuation of these studies could provide specific noninvasive biomarkers to better predict decline in kidney function in humans. Supported by RO1‐HL094446 (MRG) and T32‐HL105324 (ACH).