Global Sensitivity Analysis in a Mathematical Model of the Renal Interstitium

TL;DR

This paper develops a computational model of the rat kidney to analyze how arterial blood pressure and tissue flexibility affect renal interstitial fluid pressure, using sensitivity analysis to understand parameter influences.

Contribution

It introduces a novel computational model of the renal interstitium and applies global sensitivity analysis to explore parameter effects on interstitial pressure.

Findings

Elevated arterial pressure can lead to increased or decreased interstitial pressure.

Vessel compliance before afferent arterioles mainly controls pressure transitions.

Monte Carlo sampling effectively captures model behavior across parameter ranges.

Abstract

The pressure in the renal interstitium is an important factor for normal kidney function. Here we develop a computational model of the rat kidney and use it to investigate the relationship between arterial blood pressure and interstitial fluid pressure. In addition, we investigate how tissue flexibility influences this relationship. Due to the complexity of the model, the large number of parameters, and the inherent uncertainty of the experimental data, we utilize Monte Carlo sampling to study the model's behavior under a wide range of parameter values and to compute first- and total-order sensitivity indices. Characteristically, at elevated arterial blood pressure, the model predicts cases with increased or reduced interstitial pressure. The transition between the two cases is controlled mostly by the compliance of the blood vessels located before the afferent arterioles.