Abstract:
Identification of the most significant parameter set in a mathematical model is very
important to understand the model behavior. Sensitivity analysis is carried out to
accomplish this purpose. Chronic Kidney Disease of unknown etiology has been
identified as a disease with very high death rates in many tropical countries around the
world including Sri Lanka, India, Egypt, and some Mesoamerican countries. Heavy metal
exposure is one of the identified evidential factors of this disease progression. Oxidative
stress is the main pathological mechanism that leads the kidney tubular cells to cell death
pathways with heavy metal exposure. Oxidative stress is raised due to the unbalanced
production of reactive oxygen species inside the cells. In this study, a sensitivity analysis
was carried out on an existing mathematical model of the Redox system of the body to
identify the parameters which are significant in controlling the process of reactive oxygen
generation. After simulating the existing mathematical model, a sensitivity analysis was
carried out including a local sensitivity analysis which gives the individual effect
followed by a global sensitivity analysis which gives the group effect of parameter
perturbations. According to the study, five parameters out of sixteen parameters in the
mathematical model were identified from the local sensitivity analysis as the most
sensitive parameters. Global sensitivity analysis was used to rank them according to the P
values of the KS test. A constant was identified which is related to superoxide variation in
the system has the highest sensitivity. Also, most of the identified sensitive parameters are
correlated with enzyme driven reactions. According to the researchers' perspective, heavy
metal exposure also affects the enzymes in the redox system of the body. Therefore, when
modeling heavy metal toxicity we can conclude that much consideration should be given
to those reactions correlated with enzymes.
Keywords: CKDu, Oxidative stress, Mathematical modeling, Sensitivity analysis,
Parameters
