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Chronobiology Methods Quantify Phosphate Dynamics ( Ohronome ) in Blood and Urine

Biological variability, as well as technical (analytical) sources of variation, determines the width of the reference interval and can be a terrible foe of clinical chemistry. It is all too often ignored by implication if not by explicit lip-service to homeostasis. Like the deus & machina, the organism is presumed to be able to “right” itself, irrespective of time (1, 2). So far, so good. The trouble arises when the investigator of a putative homeostasis also assumes that the mechanism of righting assures relative constancy in a time-invariant fashion and hence undertakes a study at some convenient but unspecified and not necessarily pertinent time. Alternatively, as in the paper by Kemp et al. in this issue (3), variability can be resolved into dynamic characteristics of ever-present, partly periodic change: the amplitude and acrophase assess the extent and timing of reproducible, rhythmic change. By comparison with the arithmetic mean, a usually more accurate and more precise location index is provided by the rhythm-adjusted mean (MESOR; midline-estimating statistic of rhythm), which takes into consideration the time structore of a physiological variable. Relations among physiological mechanisms in health and disease can then be quantified within the very range in which everyday functions occur. A new dimension is added to clinical chemistry (4-9) by the methods of chronobiology, the science (logos) of life’s (bios) structure in time (chronos) (4). Most if not all variables in clinical chemistry undergo rhythmic changes with different frequencies. The rhythms can be algorithmically formulated and validated by inferential methods. Circadian rhythms (with one cycle in 20-28 h), ultradian rhythms (with one cycle in <20 h), and infradian rhythms (with one cycle in >28 h) all characterize, with age trends, the body’s time structure: the chronome. The word chronome (6) was coined from “chronos” (time) and “nomos” (rule), in analogy to genome, from “gene” and “chromosome.” In this editorial we will amplify on the approach and methods of Kemp et al. (3), who quantified changes in phosphate metabolism (Pi) along the 24-h scale-circadiana-and the attendant uncertainties. The prefix circa was introduced for several reasons (10). First, it indicates the genetic basis of rhythms indirectly supported by their free run under constant environmental conditions with an average period close to, yet statistically significantly different from, an environmental match (10-12). Free-running, which is being shown for a growing number of variables, remains to be investigated for the case of changes in N. Second, the definition of circa-rhythms further emphasizes the statistical uncertainty with which a period length can be estimated (10). Given the definition of circadian, the meaning of diurnal was restricted to the daylight span of the 24-h day, so as to avoid constructions such as “a diurnal [24-h] rhythm in diurnal [daytime] epilepsy.”