Mathematical Modeling of Nephrin Loss in Diabetic Kidney Disease

Abstract

Diabetic kidney disease is the leading cause of kidney failure. The job of the kidneys is to filter the blood. However, when the kidneys are damaged, the filtration system is less efficient. The kidney has many different cells and areas. In this project we focused on podocyte cells, which compose the outer filtration barrier. In between podocyte cells, a protein called nephrin connects the podocytes like Velcro. The blood is filtered through this area to excrete waste and excess water. Diabetes can cause the nephrin to lose its Velcro abilities causing it to disconnect from the podocyte cells and be excreted in the urine. The loss of nephrin causes the mountain and valley landscape of the podocytes and the gaps between them to become distorted. The damaged filtration system allows not only the waste materials to be removed but excess proteins are excreted into the urine. Diabetic complications can cause the nephrin to lose the Velcro ability and be excreted. We will present an empirical model for predicting category of proteinuria (protein in the urine) based on loss on nephrin expression using human biopsy data for Type 2 Diabetes patients. The model relates the % of nephrin lost to the mRNA of nephrin and the urinary protein concentration. This noninvasive modeling research provides quantitative guidance for the threshold where nephrin loss causes long-term damage to the kidney clinically detectable by the presence of protein in the urine.