Abstract

Diabetic kidney disease (DKD), which results in flawed glomerular filtration, affects 33% of patients with diabetes. No treatments currently exist specific to DKD due to the lack of assays that can reproduce the complex pathophysiology of DKD. Injury and dysfunction to podocytes, glomerular epithelial cells, have been shown to be a fundamental component of DKD pathology. This research investigates the design of an organ-on-chip platform that recapitulates the microenvironment of the glomerulus to support the culture of functional podocytes and allow for mechanistic examination of filtration function. The most important part of this platform is to imitate the filtration function of the glomerulus. First, a filtration assay of the fluidic platform with just the control membrane was performed, using albumin and inulin (two important protein markers of kidney filtration). Next, human podocyte cells were seeded onto the membrane of the fluidic platform and another filtration assay was performed. The percent protein clearance and urinary clearance was calculated. With the addition of podocytes, the percent protein clearance for albumin decreased by 37.4% and the percent protein clearance of inulin increased by 6.4%; the urinary clearance of albumin decreased and the urinary clearance of inulin increased. These results displayed that podocytes were functional on the glomerulus-on-chip platform because they replicated their role in the human body, preventing the secretion of albumin and promoting the secretion of inulin. Quantifying clearances of albumin and inulin allows for future comparison of the change in the amount of protein filtered after further biological components are added.