Circadian variation in renal blood flow and kidney function in healthy volunteers monitored with noninvasive magnetic resonance imaging.

Per Eckerbom,Fredrik Palm,Peter Hansell,Eleanor Cox,Per Liss,Jan Weis,Charlotte Buchanan,Susan Francis

doi:10.1152/ajprenal.00311.2020

Abstract

Circadian regulation of kidney function is involved in maintaining whole body homeostasis, and dysfunctional circadian rhythm can potentially be involved in disease development. Magnetic resonance imaging (MRI) provides reliable and reproducible repetitive estimates of kidney function noninvasively without the risk of adverse events associated with contrast agents and ionizing radiation. The purpose of this study was to estimate circadian variations in kidney function in healthy human subjects with MRI and to relate the findings to urinary excretions of electrolytes and markers of kidney function. Phase-contrast imaging, arterial spin labeling, and blood oxygen level-dependent transverse relaxation rate (R2*) mapping were used to assess total renal blood flow and regional perfusion as well as intrarenal oxygenation in eight female and eight male healthy volunteers every fourth hour during a 24-h period. Parallel with MRI scans, standard urinary and plasma parameters were quantified. Significant circadian variations of total renal blood flow were found over 24 h, with increasing flow from noon to midnight and decreasing flow during the night. In contrast, no circadian variation in intrarenal oxygenation was detected. Urinary excretions of electrolytes, osmotically active particles, creatinine, and urea all displayed circadian variations, peaking during the afternoon and evening hours. In conclusion, total renal blood flow and kidney function, as estimated from excretion of electrolytes and waste products, display profound circadian variations, whereas intrarenal oxygenation displays significantly less circadian variation.

Highlights

Many processes in humans and animals, including sleep-wake patterns, cardiac output, blood pressure and numerous renal functions are influenced by circadian rhythm [1]
Mean regional renal perfusion and R2* values in cortex, outer and inner medulla over the 24h period for all, female and male study subjects are shown in Discussion In this study we demonstrate circadian variations in total renal blood flow and global renal perfusion in healthy volunteers using completely non-invasive high-resolution magnetic resonance imaging
Total renal blood flow was collected in this study using PC-magnetic resonance imaging (MRI) and regional blood flow using Arterial Spin Labeling (ASL) with a FAIR labelling scheme

Summary

Introduction

Many processes in humans and animals, including sleep-wake patterns, cardiac output, blood pressure and numerous renal functions are influenced by circadian rhythm [1]. Recent years have seen a growing interest in this field with a steadily increasing number of published studies and in 2017 the Nobel prize in Physiology or Medicine was awarded for the discovery of specific circadian clock genes This growing interest has, at least in part been driven by the finding that disruption of circadian patterns is associated with disease [4, 5]. The rise in melatonin at night has been shown to affect a number of biological processes, to promote sleep and to decrease body temperature [8, 9]. It has been demonstrated in animal models that melatonin alters blood flow to assorted vascular beds by the activation of different melatonin receptors [10, 11]. Our research group and others have previously shown that non-invasive magnetic resonance imaging (MRI)

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