Use of a proximity extension assay proteomics chip to discover new biomarkers associated with albuminuria

Albuminuria is the abnormal appearance of albumin in urine: it is a sign of kidney malfunction and is considered as a significant risk marker for CVD (also associated with diabetes). Urine albumin-to-creatinine ratio (ACR) is the main clinical measurement of albuminuria, and has been suggested to be the single strongest risk indicator for CVD mortality. Despite widespread clinical use, the mechanistic relationship between albuminuria and CVD is still not well understood. This study used the ULSAM & PIVUS cohorts to look for possible relationships between plasma levels of CVD markers and albuminuria (as measured by urine ACR). The two cohorts were used in a discovery/validation approach, with 26 proteins identfied in the ULSAM (n=662) cohort, and five of these validated using PIVUS (n=757). Higher levels of T-cell immunoglobulin mucin-1, placenta growth factor, growth/differentiation factor-15, urokinase plasminogen activator surface receptor and kallikrein-11 were all significantly associated with a higher ACR in both cohorts. Significance was demonstrated after adjusting for other factors, such as sex, established cardiovascular risk factors, antihypertensive treatment, prevalent cardiovascular disease and glomerular filtration rate. All associations were also significant in separate analyses of patients without diabetes. Looking from the pathophysiological perspective, the 5 identifed proteins were all strongly associated with interesting biological processes relating to CVD and/or renal disease: tubular injury, atherosclerosis, endothelial function, heart failure, inflammation, glomerulosclerosis and podocyte injury. The authors concluded that multiplex proteomics is a very promising approach to explore novel aspects of the interplay between kidney function and the cardiovascular system, with significant clinical implication for improved risk prediction, diagnosis and patient monitoring, as well as the potential for developing novel drugs.