Immature megalin expression in the preterm neonatal kidney is associated with urinary loss of vitamin carrier proteins.

Abstract

Vitamin A and D deficiencies are common in preterm infants. Megalin is an endocytic receptor in the proximal tubule, which reabsorbs retinol-binding protein (RBP) and vitamin D-binding protein (VDBP). Although the proximal tubule is immature in preterm infants, little is known about megalin expression during kidney development. In this study, we establish the abundance of megalin in the developing human kidney and its relationship to the urinary excretion of vitamin carriers in preterm infants. We analyzed a postmortem group (20-40 weeks gestation), where we used morphometric means of measuring megalin and its ligands in kidney tissue and a living group of patients (28-40 weeks), where urinary RBP and VDBP were measured. The presence of megalin, RBP, and VDBP increased in the proximal tubule through gestation. At birth the urinary concentration of RBP and VDBP were higher in the 28-32 week group compared to the 38-40 week group and a significant inverse correlation of tissue megalin and urinary loss of RBP and VDBP existed. Preterm infants experience vitamin carrier protein losses, which are associated with decreased megalin expression. This developmental expression of megalin in the kidney has clinical implications in the prevention of vitamin deficiencies in preterm babies.