Summary:The temporal courses of dipeptidyl peptidase IV γ-glutamyltransferase and alanine aminopeptidase were followed over 70 days in the morning urine of 15 healthy persons. Subsequent to basic statistical analysis a two-step procedure was performed, including spectral analysis and the fit of a cosine function by non-linear regression. The excretion of the 3 enzymes followed an infradian biorhythm with a mean period length of 10.04 for dipeptidyl peptidase IV, 13.34 for γ-glutamyltransferase and 10.17 for alanine aminopeptidase. In addition to the basic rhythmic process described by the fitted cosine functions, in most of the enzyme patterns steap peaks of very high excretory activity appeared which was verified in repeated measurements.These infradian biorhythms with changes in the range of 100% and more, as well as their interindividual variations, have to be considered in assessing the excretion of enzymes.70 days in 15 volunteers of both sexes, 26 to 55 years Urine enzymes are now widely accepted as sensitive old. The detection of relevant periodicities in the indicators for the early detection of renal alterations individual patterns of all volunteers was ensured by (see I.e. (1, 2) for references). Since Gr tsch et al. (3) applying spectral analysis and non-linear regression. reported, for the rat, the existence of biological rhythms in the excretion of y^glutajuyltransferase, Nacetyl^jD-glucosaminidase and alanine aminopepti-Materials and Methods dase with dominant periods in the infradian range of The urinary enzyme excretion was determined once daily on 70 7 and 9 days, respectively, it has been obvious, that consecutive days in 15 healthy adults (8 women, 7 men, mean ι.j ^ 11 j 't_ j · ·,· i t />· /rx age 39.4, range 26-55 years). Urines were collected between 5 beyond the well described circadian rhythms (4, 5) and 9 a m and imme di at eiy centrifuged (15 min, 1800*).enzymuria can also be subjected to infradian rhythmic Subsequent to centrifugation the samples were filtered on Sechanges. phadex G 50 (medium) with 154 mmol/1 NaCl solution (6). The fraction with a relative molecular mass M r > 10 000 was stored Therefore, our study was designed to clarify whether at ~2 0 °c after addin ? sodium ^^ solution ( 15 mmol/1).or not such infradian changes are also present in man. γ-Glutamyltransferase activity was pursued at 37 °C for 5 min, The urinary excretion of γ-glutamyltransferase (EC usin a continuous method. The reaction mixture contained 4.0 ο ο >· > o\ ι · · s* /c^ ο A \4 o\ j mmol/1 glutamyl-4-nitroanilide and 101 mmol/1 glycylglycine 2.3.2.2), alanine aminopeptidase (EC 3.4.11.2) and bufTer ' p § 820 fa OQ. Spectrophotometric reading were taken dipeptidylpeptidase IV (EC 3.4.14.5) was followed for at 405 nm.

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Urinary excretion of alanine aminopeptidase (EC 3.4.11.2) was examined in 30 patients (22 women, 8 men, ränge 38 -81 years; mean age 55.4) receiving gentamicin in a therapeutic dosage, which was based on the monitored blood creatinine concentration. In general, therapy lasted 10 days. The excretion of 24 individuals displayed significant infradian rhythms with periods between 2.2 and 8.1 days. In 10 of these 24 patients (42%) a circaseptan period was detected. The high portion of circaseptan rhythms might have been induced by the detrimental effects of gentamicin on the proximal tubule and the resulting processes of reconstitution.

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Summary:The enzyme excretion of dipeptidylpeptidase IV (EC 3.4.14.5), γ-glutamyltransferase (EC 2.3.2.2), and alanine aminopeptidase (EC 3.4.11) was pursued in three different age groups of female volunteers over a period of 70 days. The first group (1-3 years: n = 6) consisted of girls living in a children's home, the second (26-50 years, n = 7) of medical staff and the third (65-87 years, n = 7) of the inhabitants of an old-age home. Subsequent to basic statistics the excretion patterns were analyzed by spectral analysis with the maximum entropy method.The mean values of all enzymes displayed a distinct age-dependency. The highest levels of enzyme excretion were found in the early childhood. In all groups infradian changes of enzyme excretion were detected. In excretion of γ-glutamyltransferase, longer periods between 12 and 24 days predominated during the early childhood, whereas in the middle, and in particular in the higher age, shorter dominant periods occurred more frequently. The excretion of alanine aminopeptidase displayed a similar tendency. Circaseptan periods (7 ± 1 days) were rarely observed among the dominant periods of the maximum entropy method spectra. A correlation analysis of the individual excretion patterns revealed that the excretion of all three brush-border enzymes is most tightly correlated in the early childhood (coefficients of correlation up to 0.9). In contrast, the correlation between enzyme and creatinine excretion was low in all age groups.