Biomarkers total urinary protein

Urinary Total Protein and Albumin Urinary total protein and albumin have been nsed for decades as glomerular injury biomarkers and, more recently, were qualified as measurements of glomerular filtration and tubular reabsorption function (Ferguson et al., 2008 Bonventre et al., 2010). Compared with blood concentrations of protein/albumin, a small amount of protein and albumin (microalbumin, which is below the albumin detection threshold by the conventional urinary dipstick 30-300 mg/L) enters the filtrate by the glomerulus and is reabsorbed and subsequently catabolized in the normal kidney proximal tubnle (Vaidya et al., 2008 Charlton et al., 2014). Therefore, increased urinary protein/albumin can reflect glomerular injury, tubular injury, or combined effects, though albuminuria can be observed in rats secondary to other effects such as dehydration or hypertensive conditions (Haschek et al., 2013). 

The polymyxin program did not proceed into the clinic but translatability was still addressed using samples from patients treated with a variety of standard of care antibiotics (piperacilhn/tazobactam, vancomycin, penicillin V, tobramycin, gentamicin, ampicillin, cefuroxime, clindomycin, clarithromycin, cefepime, daptomycin IV, bumetanide, vibramycin, and cyclophosphamide) compared to samples from healthy volunteers. This sample set was analyzed for sCr, BUN, urinary total protein, and urinary microalbumin as well as the emerging biomarkers urinary KIM-1, urinary NGAL, and urinary NAG. Much like the large animal studies with polymyxin B, the response for the antibiotic-treated cohort produced increases in all urinary- and serum-based... 

Between 2008 and 2010, the FDA (2008), the EMA (2008), and the PMDA (2010) qualified the use of seven urinary biomarkers for GLP rat studies to support the safe conduct of early-phase clinical trials KlM-1, CLU, TFF-3, p2-microglobulin, CysC, albumin, and total protein. These are detailed below. 

---