Advances in Urinary Proteome Analysis and Biomarker Discovery

Abstract

Noninvasive diagnosis of kidney diseases and assessment of the prognosis are still challenges in clinical nephrology. Definition of biomarkers on the basis of proteome analysis, especially of the urine, has advanced recently and may provide new tools to solve those challenges. This article highlights the most promising technological approaches toward deciphering the human proteome and applications of the knowledge in clinical nephrology, with emphasis on the urinary proteome. The data in the current literature indicate that although a thorough investigation of the entire urinary proteome is still a distant goal, clinical applications are already available. Progress in the analysis of human proteome in health and disease will depend more on the standardization of data and availability of suitable bioinformatics and software solutions than on new technological advances. It is predicted that proteomics will play an important role in clinical nephrology in the very near future and that this progress will require interactive dialogue and collaboration between clinicians and analytical specialists.

Urinary Proteomics in Diabetes and CKD

“…Recent advances in proteomics enable screening of a vast array of proteins simultaneously, aiding assessment of their potential role in the development and progression of disease. 1 Urine is well suited for proteomic analysis to identify predictive biomarkers and to unravel the pathogenetic mechanisms of chronic renal disease. The online combination of capillary electrophoresis (CE) and electrospray mass spectrometry (MS) was developed for the rapid (approximately 45 min per sample), sensitive, and automated approach for such an analysis.…”

“…We sequenced only some biomarkers, because the procedure is challenging. 1,9 The most striking observation was the decreased excretion of specific collagen fragments in patients with diabetes compared with healthy control subjects; several additional collagen fragments were less common in patients with diabetic nephropathy compared with normoalbuminuric diabetic patients. This observation sup- Distribution of potential differential-diagnostic biomarkers for diabetes in the patients with normoalbuminuria and healthy control subjects.…”

Urinary Protein Biomarkers in Chronic Kidney Disease

“…Those are the main reasons why the urine is widely used for proteomic biomarkers discovery [17,23,24]. Single-protein biomarkers are not effective and suitable to reflect complex diseases, such as CKD and therefore combination and simultaneous use of multiple biomarkers should improve the diagnostic performance [4,17,25]. Combination of multiple biomarkers in high-dimensional classifiers, substantially outperform linear combination of biomarkers [26].…”

Urinary Proteome Analysis using Capillary Electrophoresis Coupled to Mass Spectrometry: A Powerful Tool in Clinical Diagnosis, Prognosis and Therapy Evaluation

“…quadrupole, time-of-flight (TOF) or Fourier transform ion cyclotron resonance. We will briefly outline the advantages and shortcomings of the different technological platforms, and subsequently focus on CE-MS. For a more detailed review of the technologies, we refer to (32).…”

“…An alternative strategy is the identification of several markers, which may not be »optimal« for use alone, but work in concert, and combining them to a disease-specific pattern (32). Recently, a number of different proteomic techno logies have been introduced to establish disease-specific marker patterns for clinical diagnosis and therapeutic moni toring as an alternative to single bio marker based approaches.…”