Evolution of the Urinary Proteome During Human Renal Development and Maturation

Abstract

Renal development process in human is divided into 3 successive stages: pronephros, mesonephros, and metanephros. The tubules continue to mature for 1-2 year after birth. Research of urinary proteome during human renal development is still lacking. Most urine proteome studies focus on postnatal renal maturation period. A comparison between full-term infant and adult urinary protein pattern identified 648 infant-enriched protein spots, of which most were involved in cellular turnover and metabolism. The study of preterm infant urinary proteome compared with term infants suggests elevated IGFBP-1, IGFBP-2, and IGFBP-6, monocyte chemotactic protein-1, CD14, and sialic acid-binding Ig-like lectin 5 during nephrogenesis. Research in several congenital kidney and urinary tract anomalies, ureteropelvic junction obstruction and autosomal dominant polycystic kidney disease, has discovered novel biomarkers, which may help to imply the mechanisms underlying inherited disorders. Future exploration of urinary proteome evolution during renal maturation is needed and will help to find novel biomarkers specially suiting pediatric renal diseases.

Insulin-Like Growth Factor Binding Proteins in Kidney Disease

“…The abundance of IGFBP-6 in plasma of adults and children with CKD or ERSD were all significantly up-regulated ( Jarkovská et al, 2005 ; Christensson et al, 2018 ), Consistent with these, the monitoring of plasma IGFBP-6 before and after kidney transplantation and at the time of rejection showed that IGFBP-6 indicate the status of renal function in patients with chronic renal insufficiency ( Fukuda et al, 1998 ), level of IGFBP-6 increases significantly by 8–25 times with the decrease of renal function ( Jehle et al, 2000 ). Meanwhile, the urine abundance of IGFBP-6 gradually increased with kidney developments ( CharltonNorwood et al, 2012 ; Wang and Li, 2015 ), and is associated with developmental retardation in children with CKD ( Powell et al, 1997 ), suggesting that it was related to the kidney development process. However, these studies did not refer to the mechanism of IGFBP-6 involvement.…”