Type II Diabetes is the most common endocrine disease affecting 250 million people worldwide. Obesity has been identified as the principal risk factor associated with the rising prevalence of type II diabetes, which is predicted to reach 9% of the US population by 2025. Diabetic nephropathy is characterized by progressive albuminuria, which is the major cause of end-stage kidney disease , declining kidney function, and increased risk for cardiovascular disease.

The basic physiological processes of kidney function (filtration/reabsorption of sodium, water, and other electrolytes leading to control of sodium balance and blood pressure) are consistent across different species. In this talk first of all  I would show that using an existing systems model of renal hemodynamics, we can simulate the phenotypic behavior  (e.g., glomerular filtration rate [GFR], cardiac output, blood pressure, daily sodium excretion, etc.). After modeling the normal mice, I would show that our model can also predict kidney function of a diabetic mice. I would also show that how different drugs affects the disease progression and simulate their responses. Finally, I would show some results where our model can predict the kidney disease progression in humans.

These results confirm that this mechanistic model provides a sufficiently valid description of kidney function across different species. The results also enables us to further characterize differences in the timecourse of kidney disease progression, and use responses to benchmarking therapies and also to validate the model’s translational ability of drug therapies.

References

    1. H.S. Mahato et. al., Mathematical model of hemodynamic mechanisms and consequences of glomerular hypertension in diabetic mice. Nature Systems Biology and Applications, Vol 5, Issue 2, 2019.

Gast der Arbeitsgruppe Prof. Böhm