Abstract
The use of targeted proteomics to identify urinary biomarkers of kidney disease in urine can avoid the interference of serum proteins. It may provide better sample throughput, higher sensitivity, and specificity. Knowing which urinary proteins to target is essential. By analyzing the urine from perfused isolated rat kidneys, 990 kidney origin proteins with human analogs were identified in urine. Of these proteins, 128 were not found in normal human urine and may become biomarkers with zero background. A total of 297 proteins were not found in normal human plasma. These proteins will not be influenced by other normal organs and will be kidney specific. The levels of 33 proteins increased during perfusion with an oxygen-deficient solution compared to those perfused with oxygen. The 75 proteins in the perfusion-driven urine have a significantly increased abundance ranking compared to their ranking in normal human urine. When compared with existing candidate biomarkers, over ninety percent of the kidney origin proteins in urine identified in this study have not been examined as candidate biomarkers of kidney diseases.
Highlights
The identification of urinary biomarkers of kidney disease may be easier to accomplish than the identification of biomarkers for other diseases such as cancer
Despite substantial interest and investment, only a few novel urinary biomarkers are currently used in clinical practice [2]
Profiling is influenced by the preferential detection of highly abundant proteins
Summary
The identification of urinary biomarkers of kidney disease may be easier to accomplish than the identification of biomarkers for other diseases such as cancer. Clinical use is limited because comprehensive, profiling-based differential proteomics methods, which have limited sample throughput because of their prolonged sample analysis, are generally used in the discovery phase [3]. Highly abundant plasma proteins, which exhibit similar changes under many different renal conditions and lack specificity, are repeatedly identified [4]. These circumstances are often aggravated by proteinuria as a comorbidity [5]. Identifying quantitative changes in kidney origin protein levels in urine may yield information that is pertinent to the functions of renal cells and has a greater chance of detecting changes in renal function at an early stage. We used a modified isolated rat kidney perfusion model to analyze the kidney origin proteins present in the urinary tract
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