Multiscale Modeling of a Virtual Kidney during the Onset and Progression of Diabetic Kidney Disease

Fig. 1 Kidney glomerulus that includes several tissue regions susceptible to damage in diabetic kidney disease

Overview

Diabetic kidney disease (DKD) is a serious complication of both type 1 and type 2 diabetes and is the leading cause of kidney failure. Yet, it is still not clear how the many underlying chemical, physical, and biological processes interact to damage the kidneys during diabetes. It is challenging to monitor the damage to the kidneys inside a patient. The regions of the kidney that are damaged are very small and are deep within the body. It takes a long time for irreversible damage to accumulate to the point where non-invasive urine samples contain detectable quantities of proteins that leaked through the kidneys.

This project involves connecting several processes that have been shown individually to contribute to injury in kidneys due to diabetes into a sophisticated computer simulation. This computational tool will aid in understanding how the processes interact and how diabetic kidney damage begins and changes over time. In the long-term, results from this project will help to predict the impacts of many competing factors on kidney health during diabetes management. The computer simulation produced in the project can also be used to test and optimize treatments to slow the progression of DKD. The project also will involve a set of educational activities related to the scientific work. Several undergraduate and graduate students including women and underrepresented minorities are working with Dr. Ford Versypt to conduct the research and educational activities.

Educational modules related to the research have been delivered to a variety of groups including K-12 students, college students, and grandparents. Physical models of kidney tissues have been 3D-printed and shared with students and educators. The activities will expose many students and members of the public to biomedical engineering and computational science through engaging scientific demonstrations and interactive experiences.

Resulting Publications

S. M. Ruggiero and A. N. Ford Versypt, SBMLtoODEpy: A Software Program for Converting SBML Models into ODE Models in Python, Journal of Open Source Software, 4(41), 1643, 2019. DOI: 10.21105/joss.01643
M. R. Pilvankar, H. L. Yong, and A. N. Ford Versypt, A Glucose-Dependent Pharmacokinetic/Pharmacodynamic Model of ACE Inhibition in Kidney Cells, Processes, 7(3), 131, 2019. DOI: 10.3390/pr7030131 Cover article: https://www.mdpi.com/2227-9717/7/3
C. V. Eastep, G. K. Harrell, A. N. McPeak, and A. N. Ford Versypt, A MATLAB App to Introduce Chemical Engineering Design Concepts to Engineering Freshmen through a Pharmaceutical Dosing Case Study, Chemical Engineering Education, 53(2), 85–90, 2019.
M. R. Pilvankar, M. A. Higgins, and A. N. Ford Versypt, Mathematical Model for Glucose Dependence of the Local Renin-Angiotensin System in Podocytes, Bulletin of Mathematical Biology, 80(4), 880–905, 2018. DOI: 10.1007/s11538-018-0408-4
A. N. Ford Versypt, G. K. Harrell, and A. N. McPeak, A Pharmacokinetic/Pharmacodynamic Model of ACE Inhibition of the Renin-Angiotensin System for Normal and Impaired Renal Function, Computers & Chemical Engineering, 104, 311–322, 2017. DOI: 10.1016/j.compchemeng.2017.03.027
A. N. Ford Versypt, G. K. Harrell, and A. N. McPeak, ACEInhibPKPD: An Open-Source MATLAB App for a Pharmacokinetic/Pharmacodynamic Model of ACE Inhibition, Journal of Open Source Software, 2(17), 340, 2017. DOI: 10.21105/joss.00340
A. N. Ford Versypt†, E. Makrides†, J. C. Arciero, L. Ellwein, and A. T. Layton, Bifurcation Study of Blood Flow Control in the Kidney, Mathematical Biosciences, 263, 169–179, 2015. DOI: 10.1016/j.mbs.2015.02.015
J. C. Arciero†, L. Ellwein†, A. N. Ford Versypt†, E. Makrides, and A. T. Layton, Modeling Blood Flow Control in the Kidney, T. Jackson, A. Radunskaya (eds.), Applications of Dynamical Systems in Biology and Medicine, The IMA Volumes in Mathematics and its Applications 158, Springer, New York, 55 –74, 2015. DOI: 10.1007/978-1-4939-2782-1_3
G. K. Harrell†, A. N. McPeak†, and A. N. Ford Versypt, A Pharmacokinetic Simulation-Based Module to Introduce Mass Balances and Chemical Engineering Design Concepts to Engineering Freshmen, Proceedings of the ASEE Annual Conference, Columbus, OH, 2017. https://peer.asee.org/27493