Table 1.

Advantages and disadvantages of urine specimens for protein biomarker discovery [1,2,28,30,31,44,89,155].

Parameter	Advantages	Disadvantages
Specimen volume	Large quantities available
Ease of collection	Non-invasive collection
Urine production	Urine is produced continuously throughout the day and can be collected to match normal diurnal variation. First morning urine samples are generally more concentrated than randomly collected specimens.	Some urinary proteins and chemical constituents are affected by diet, hydration, exercise, metabolism, circadian rhythms and hormones.
Protein quantity	Abundant source of soluble proteins/peptides that is less complex than blood.
Protein stability	Urine proteins remain relatively stable at room temperature and 4°C for up to 6 hours.
Pathophysiology	Urine reflects the plasma proteome as well as kidney proteome due to glomerular filtration, tubular reabsorption, and secretion.	A wide spectrum of renal pathologies produces similar urinary proteomic markers, e.g. albuminuria.
Constituents	Multiple chemical, cellular, and proteomic constituents are present in urine, many of which are well-defined in normal and pathologic states. Multiple analytes can be selected for data comparison between and within individuals/data sets.	Inter and intra-individual variability requires the use of multiple parameters for comparing urinary proteome data. Thoroughly annotated clinical information and/or urine biochemical and microscopic analyses may be needed to accurately compare urine proteomic data.
Analysis	Low molecular weight soluble proteins can be readily quantified by mass spectrometry. Urine proteins can be quantified by multiple methods. Urine biochemical analysis can be easily performed with urine test strips (dipstick). Cellular elements can be identified with bright field microscopy. Strategies for detecting low abundance urinary proteins are well documented and commercially available.	High abundance proteins mask the presence of low abundance proteins, thus requiring depletion and/or enrichment strategies for detecting low abundance proteins.