Accurate measurement of albumin excretion rates is important in choosing treatment regimens that may reverse early diabetic renal damage. We report here determinations of slight albuminuria ("microalbuminuria") by radioimmunoassay of fresh specimens, frozen aliquots (stored at -20 degrees C for two, eight, and 24 weeks), and refrigerated specimens (stored at 4 degrees C for one, two, and eight weeks). Seven separate analyses were performed on 101 specimens of urine obtained from 37 subjects with insulin-dependent diabetes mellitus and from 10 nondiabetic healthy controls of a similar age. Storage of urine samples at -20 degrees C resulted in significantly lower measurements of microalbuminuria than in fresh urine (ANOVA, corrected for repeated measures: P = 0.01 to 0.0001). In contrast, storage of urine samples at 4 degrees C for as long as eight weeks did not significantly affect urinary albumin results. The pH values of the specimens were minimally altered and were not a likely cause of the decreased albumin values in the frozen specimens. We conclude that urine specimens for microalbuminuria measurements should either be analyzed as fresh specimens or stored at 4 degrees C and assayed as soon as possible.
We evaluated "borderline" increases in overnight albumin excretion rates (AERs)—i.e., those between the upper 95th percentile of normal (7.6 μg/min) and the lowest value currently considered predictive of nephropathy (30 μg/min)—to determine their importance and to see whether glucose control influenced subsequent changes in the "borderline" AER values. Between 1985 and 1990, we studied 190 subjects with insulin-dependent diabetes mellitus (Type I), analyzing a mean of 6.5 timed overnight urine samples collected per subject. Above-normal AERs were associated with a significantly (by ANOVA) higher mean age (P = 0.03), longer duration of diabetes (P = 0.0002), and greater mean glycohemoglobin values (P = 0.002). The transition rate between borderline and abnormal AERs was significantly higher (P<0.0001, chi-square test) than the direct transition rate between normal and abnormal AERs, thus showing the borderline AER to be a definite intermediate stage. Good and poor glucose control were clearly associated with improvement and worsening, respectively, of the borderline AER values (P = 0.032, chi-square test of trend). More attention to borderline AER values is clearly indicated.
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