Measurement of albumin excretion in a 24-h urine collection has long been the “gold standard” for quantitative evaluation of albuminuria in diabetic patients; however, collection errors due to improper timing and missed samples may lead to significant over- and underestimation of albuminuria. For convenience and consistency, the American Diabetes Association (1) and the National Kidney Foundation (2) have recently recommended measurement of albumin-to-creatinine ratio (ACR) in a random spot urine collection for diagnosis of microalbuminuria. Microalbuminuria is diagnosed if ACR ranges between 30 and 300 mg/g creatinine. The guidelines recommended using a first-morning sample because of the potentially higher correlation with 24-h albumin excretion, but a random sample is considered acceptable if a first-morning specimen is not available. Measurement of ACR using a first-morning or random urine sample may differ significantly, as exercise stress, diurnal variation, and other factors may affect urinary albumin excretion. We provide data from a cross-sectional study evaluating potential differences in ACR obtained from first-morning and random spot urines collected on the same day.
A total of 717 adult diabetic patients with and without nephropathy were recruited from the outpatient clinic of the Diabetes Center, Tokyo Women’s Medical University Hospital, Tokyo, Japan. Patients were instructed to bring a first-morning urine specimen to the clinic and then provide a random urine specimen immediately upon arriving at the clinic on the same day. ACR was calculated from urinary albumin and creatinine concentrations determined using radioimmunoassay and Jaffe’s method, respectively. Paired samples with a random urinary ACR of more than 1,000 mg/g were excluded to provide a more accurate range for estimating the relationship between measurements.
Paired samples were analyzed from 668 patients (289 women and 379 men, mean age 58 ± 12 years, 95% with type 2 diabetes). The majority (75%) of random spot urine was collected during a morning visit (8:30 a.m. to 12:00 p.m.). There was a strong relationship between ACRs measured from first-morning and spot urine samples, yielding a linear correlation on a logarithmic scale: log10 ACR (first-morning sample) = 0.8589 · log10 ACR (random spot sample) −0.0604 (r = 0.871). Applying this equation, ACR values of 30–300 mg/g in a first-morning urine specimen would correspond to values of 51–391 mg/g in random spot collection. Using the ACR cutoff value of 30–300 mg/g, 135 patients (20%) would receive a diagnosis of microalbuminuria based on first-morning urine, whereas 234 patients (35%) would receive this diagnosis based on a random spot collection.
This rather large discrepancy between ACR from first-morning and random spot urine may have important implications in the diagnosis of microalbuminuria in diabetes. We advocate strict adherence to the use of first-morning urine or possibly an upward adjustment of the range for diagnosis of microalbuminuria using ACR from random spot urine. Further analysis of the relationship of ACR in first-morning and random spot urines to 24-h urinary albumin excretion, as well as their value in predicting future development of clinical proteinuria, is required.
