Reversible (Patho)Physiologically Relevant Test Interventions: Rationale and Examples.

Kathleen Cantow,Adam Hosszu,Mechthild Ladwig-Wiegard,Erdmann Seeliger,Bert Flemming,Andrea Fekete

doi:10.1007/978-1-0716-0978-1_4

Abstract

Renal tissue hypoperfusion and hypoxia are early key elements in the pathophysiology of acute kidney injury of various origins, and may also promote progression from acute injury to chronic kidney disease. Here we describe test interventions that are used to study the control of renal hemodynamics and oxygenation in experimental animals in the context of kidney-specific control of hemodynamics and oxygenation. The rationale behind the use of the individual tests, the physiological responses of renal hemodynamics and oxygenation, the use in preclinical studies, and the possible application in humans are discussed.This chapter is based upon work from the COST Action PARENCHIMA, a community-driven network funded by the European Cooperation in Science and Technology (COST) program of the European Union, which aims to improve the reproducibility and standardization of renal MRI biomarkers.

Highlights

Renal tissue hypoperfusion and hypoxia have been suggested to play a pivotal role in the pathophysiology of other kidney diseases including diabetic kidney disease [15– 19]
These pathophysiological concepts have largely been generated by preclinical studies that used either invasive quantitative probes or noninvasive functional magnetic resonance imaging (MRI) techniques to gain insight into renal hemodynamics and oxygenation
Invasiveness is the major disadvantage of the gold standard physiological probes such as perivascular flow probes for measurement of total renal blood flow, laser-Doppler-optodes for assessment of local tissue perfusion, and Clark-type electrodes or fluorescence-quenching optodes for measurements of local tissue partial pressure of oxygen, which precludes their use in humans

Summary

Introduction

Kidney diseases are a global health burden with steadily increasing incidence and prevalence [1–5]. Renal tissue hypoperfusion and hypoxia have been suggested to play a pivotal role in the pathophysiology of other kidney diseases including diabetic kidney disease [15– 19] These pathophysiological concepts have largely been generated by preclinical studies that used either invasive quantitative probes or noninvasive functional magnetic resonance imaging (MRI) techniques to gain insight into renal hemodynamics and oxygenation. While functional MRI including blood oxygenationsensitized T2* (aka blood oxygenation level-dependent MRI; BOLD-MRI) offers noninvasive techniques to obtain insight into renal perfusion and oxygenation, its major weakness is its qualitative nature Before it can be used for quantitative characterization of renal tissue perfusion and oxygenation, it needs to be calibrated with the gold standard invasive techniques in various (patho)physiological scenarios [20–24].

Specifics of Renal Hemodynamics and Oxygenation

Short Periods of Occlusion of the Renal Artery or Renal Vein

Short Periods of Changes in the Inspiratory Gas Mixture

Findings

Administration of Drugs and Endogenous Vasoactive Substances