Chronobiology in nephrology: the influence of circadian rhythms on renal handling of drugs and renal disease treatment

Abstract

Chronobiology studies the phenomenon of rhythmicity in living organisms. The circadian rhythms are genetically determined and regulated by external synchronizers (the daylight cycle). Several biological processes involved in the pharmacokinetics and pharmacodynamics of drugs are subjected to circadian variations. Chronopharmacology studies how biological rhythms influence pharmacokinetics, pharmacodynamics, and toxicity, and determines whether time-of-day administration modifies the pharmacological characteristics of the drug. Chronotherapy applies chronopharmacological studies to clinical treatments, determining the best biological time for dosing: when the beneficial effects are maximal and the incidence and/or intensity of related side effects and toxicity are minimal. Most water-soluble drugs or drug metabolites are eliminated by urine through the kidney. The rate of drug clearance in the urine depends on several intrinsic variables related to renal function including renal blood flow, glomerular filtration rate, the ability of the kidney to reabsorb or to secrete drugs, urine flow, and urine pH, which influences the degree of urine acidification. Curiously, all these variables present a circadian behavior in different mammalian models. The circadian rhythms have influence in the renal physiology, pathophysiology, and pharmacology, and these data should be taken into account in clinical nephrology practice.