Mathematical modeling of renal crystal formation in hyperoxaluria – a rare childhood disease.

Project Title: Mathematical modeling of renal crystal formation in hyperoxaluria – a rare childhood disease.

Project Duration: May 22 – July 28, 2017 (10 weeks), 40 hours per week.

Project Mentors

Primary Faculty Mentor: Dr. K. Melissa Hallow

Chemical, Materials, and Biomedical Engineering

College of Engineering

Epidemiology and Biostatistics

College of Public Health

https://hallowlab.wordpress.com/

hallowkm@uga.edu

404-668-7168

 

Post-doc mentor: Dr. Hari Mahato

Chemical, Materials, and Biomedical Engineering

College of Engineering

hsmahato@uga.edu

 

Project Description:

Hyperoxaluria is a rare but severe disease, affecting mainly children and adolescents. It is caused by overproduction of oxalate by the liver, leading to excessive formation of calcium oxalate crystals in the kidney and eventually in other organs as well. Currently the only treatment for hyperoxaluria is a double kidney-liver transplant, and without this, most patients progress to kidney failure and death. But new treatments are being developed which may directly address the overproduction of oxylate by the liver. However, testing of these drugs is challenging, because the disease is rare and develops mostly in pediatric patients. In this project, the student will implement and extend previously published models of oxylate kinetics and stone formation to investigate the factors that affect stone formation and serum oxylate levels. In particular, we will evaluate the degree to which oxylate production must be reduced to prevent stone formation at different levels of GFR (a key measure of renal function). The knowledge generated will be useful for the development and evaluation of new drugs to treat this disease.

This project is highly interdisciplinary, and will involve applying engineering approaches to model a physiologic system, and to consider the pharmacologic effects of drugs on the body.

 

REU Student Role and Responsibility:

Hypothesis: In hyperoxaluria, the degree of renal function (or impairment in function), as measured by glomerular filtration rate (GFR), is critical in determining renal and blood supersaturation of oxylate, and will impact the response to pharmacologic interventions on oxylate productin.

In this project, the student will:

  • Implement a previously published mathematical model of renal oxylate production and clearance
  • Extend the model to incorporate effects of renal function on renal oxylate clearance and saturation
  • Extend the model to incorporate theoretical drug effects on liver oxylate production
  • Evaluate the effect of degree of oxylate suppression, and degree of renal function impairment, on blood and renal oxylate supersaturation.

 

Expected Outcome for REU student:

  • Student is expected to contribute to a conference abstract and/or publication on this work.