Consecutive First-Morning Urine Samples to Measure Change in the Albumin-to-Creatinine Ratio: A Pilot Study of a Home Urine Collection Protocol

Abstract

Background: Multiple first-morning urine samples are recommended for measuring the urine albumin-to-creatinine ratio (ACR); however, this can be challenging in community-based research. Methods: The objectives of the study are to pilot-test a home urine collection protocol and examine how the average and variance of ACR varied with the number of urine collections and time to laboratory analysis. This is a prospective observational pilot study. This study was conducted in London, Ontario, Canada at the London Health Sciences Centre (2012–2013). The patients were adults with chronic kidney disease (mean estimated glomerular filtration rate, 36 mL/min/1.73 m 2 ). Participants collected a first-morning 20-mL urine sample on three consecutive days. This process was repeated after 3 months. Samples were picked up by hospital courier and analyzed for ACR on the same day; additional aliquots were analyzed after a delay of 24–48 h (stored at 4 °C) and 3–9 months (stored at −80 °C). The geometric mean of the percentage change in ACR between baseline and 3 months was calculated and compared between single samples and the average of two vs. three consecutive samples. Results: Of 31 patients enrolled, 26 (83.9 %) submitted all six urine samples. The geometric mean of ACR for three consecutive samples at baseline was 87, 83, and 80 mg/mmol, and the corresponding percentage increase from baseline to 3 months was 15 % (95 % confidence interval (CI), −9 to 46 %), 33 % (95 % CI, 10 to 59 %), and 22 % (95 % CI, −6 to 57 %). Compared with single urine collections at baseline and follow-up, averaging ACR values from two consecutive first-morning urine samples improved the sample variance and reduced the required sample size to detect a given treatment effect by approximately 30 %. No further gain in statistical efficiency was achieved with three urine samples. Results were similar when the laboratory analysis was delayed by 24–48 h, but a delay of 3–9 months resulted in systematic overestimation of the ACR. Our study's generalizability is limited by its small sample size and reliance on a clinic-based population from a single urban center. Conclusions: We successfully used a home urine collection protocol to obtain multiple first-morning urine samples in patients with chronic kidney disease. Statistical efficiency was improved by averaging ACR values from two consecutive first-morning urine samples at baseline and follow-up.