title: Methodological issues on the use of urinary alpha-1-microglobuline in epidemiological studies.
abstract: BACKGROUND
  Alpha-1-microglobulin (A1M) is a low molecular weight protein that can be measured in urine and used as a marker for tubular function, assuming that the normal variability within and between individuals is known. The aims of this study were to investigate this variability, to find the optimal way of sampling and quantifying A1M in spot urine samples to reflect the 24 h excretion and to examine storage stability. Method. Timed urine specimens were collected from 29 healthy volunteers at fixed time points over 24 h on two separate days. Volumes, creatinine and specific gravity were determined. All samples were analysed with a commercial ELISA for A1M.
  
  
  RESULTS
  We found a clear diurnal variation in A1M excretion rate and a gender effect (higher in males). The excretion rate was higher in the daytime, with high urinary flow, compared to overnight values. A1M excretion in spot urine samples was highly correlated with the 24 h excretion at all times except 22:00 in male subjects. Urinary A1M adjusted for creatinine concentration correlated well with the 24 h excretion. Variability within individuals was only 20% of the total variability in 24 h A1M excretion, but 43% in first morning urine. Expressed as CV, the intra-individual variability (between days) was 29% in 24 h excretion.
  
  
  CONCLUSIONS
  We conclude that diurnal variation and gender should be taken into account when comparing groups. Moreover, in spot samples (e.g. first morning samples) adjustment of A1M for creatinine or specific gravity is a reliable alternative to 24 h urine.
authors.affiliation: Department of Occupational and Environmental Medicine, Sahlgrenska University Hospital and Academy, PO Box 414, S-405 30 Göteborg, Sweden. lena.andersson@amm.gu.se
authors.forename: Lena
authors.initials: L
authors.lastname: Andersson
authors.forename: Börje
authors.initials: B
authors.lastname: Haraldsson
authors.forename: Caroline
authors.initials: C
authors.lastname: Johansson
authors.forename: Lars
authors.initials: L
authors.lastname: Barregard
mesh_terms: D000328:Adult; D000510:Alpha-Globulins / Q000652:urine*; D015415:Biomarkers / Q000652:urine*; D002940:Circadian Rhythm / Q000502:physiology*; D003404:Creatinine / Q000652:urine; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007684:Kidney Tubules / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009017:Morbidity / Q000639:trends; D015588:Observer Variation; D011379:Prognosis; D012016:Reference Values; D051437:Renal Insufficiency / Q000453:epidemiology* / Q000652:urine*; D015203:Reproducibility of Results; D013548:Sweden / Q000453:epidemiology
chemical_list: D000510:Alpha-Globulins; D015415:Biomarkers; C016001:alpha-1-microglobulin; D003404:Creatinine