Role of circadian rhythms in potassium homeostasis

Abstract

It has been known for decades that urinary potassium excretion varies with a circadian pattern. In this review, we consider the historical evidence for this phenomenon and present an overview of recent developments in the field. Extensive evidence from the latter part of the past century clearly shows that circadian potassium excretion does not depend on endogenous aldosterone. Of note is the recent discovery that the expression of several renal potassium transporters varies with a circadian pattern that appears to be consistent with substantial clinical data regarding daily fluctuations in urinary potassium levels. We propose the circadian clock mechanism as a key regulator of renal potassium transporters, and consequently renal potassium excretion. Further investigation into the regulation mechanism of renal potassium transport by the circadian clock is warranted to increase our understanding of the clinical relevance of circadian rhythms to potassium homeostasis.

Keywords: Kidney; blood pressure; clock; gene regulation; nephron.

Figure 1. Transcriptional Regulation and Feedback Control in the Circadian Clock

In the positive loop, Bmal1 and Clock heterodimerize to drive transcription of Period (Per) and Cryptochrome (Cry). In the negative loop, Per/Cry inhibit the action of Bmal1/Clock, thereby inhibiting their own expression. This transcriptional mechanism is responsible for the regulation of many circadian target genes, which vary in a tissue specific manner. In the kidney, these targets almost certainly include a variety of potassium transporters.

Figure 2. The Circadian Pattern of Urinary Potassium Excretion is Disrupted in Chronic Kidney Disease Patients

Data from Agarwal and Koopman et al. were used to generate a comparison between day and night urinary potassium excretion in normal subjects compared to CKD subjects. *P<0.05.