LAUSR

Although blood is the most common source for biomarkers, urine has not been completely ignored. There have been some urinary biomarker studies with clinical samples. However, most—if not all—biomarker researchers lack confidence in urine as a good biomarker source. Many researchers think that good results from urine are a statistical accident. To demonstrate the validity of urinary biomarkers, large-scale studies are needed. Until such convincing evidence exists, what funding agent could support research in this field? The reason why I propose that it is now time to begin largescale urinary biomarker studies is because of the growing evidence from animal studies. Why are studies with 100 clinical samples not convincing, but less than 10 samples from animals are good enough? This is because in animal studies there is very few confounding factor. The only major change is disease development and, of course, the animals’ growth during the study. As long as all animals in the same group show consistent urinary protein changes, the changes are very likely associated with the disease—especially if some of the differential proteins were previously reported to relate to the disease. If this phenomenon had only been shown in one animal model, it may not yet be the time to start large-scale clinical studies. However, early urinary protein changes have been reported in all animal models tested so far in the laboratory. There is no better way to convince people than to list each one of these models here. In 2008, when YanWang et al. first tried to identify urinary proteins that can differentiate two different glomerular diseases in a rat model, they found that urinary proteins changed even when there were no apparent pathological changes in the kidney (Wang et al., 2008). We thought that urinary changes happened that early only for kidney disease. This may not be true for other systemic diseases involving other organs. At that time, we did not have the biomarker theory yet. We only worked on kidney diseases, which we believed was reflected in the urine at early stages, just like most other people who worked on urine. For quite a few years, rarely anyone worked on animal models until we had a new biomarker theory and roadmap. The theory stated that: (i) biomarkers are measurable changes associated with a biological process (continuously from healthy normal stage to disease stage); (ii) controlled by homeostatic mechanisms, all cell bathing fluids—including blood and cerebral spinal fluid—remove these early changes; (iii) and body waste like urine and breath, which accumulate these early changes, are good biomarker sources (Gao, 2013). The roadmap was to use animal models to minimize confounding factors and reproduce the very early disease situation, identify the changes in urine (or other bodily waste), and later verify the changes in clinical samples (Gao, 2014). We tested this theory and roadmap using an anticoagulant experiment and then for kidney diseases. Li et al. showed that the number of proteins that changed in urine was much higher than that in blood when all other conditions were the