Repeated albuminuria measurements offer a far more accurate picture of the progression of diabetic chronic kidney disease than current practice which does not account for within-individual variability, Australian researchers say.

The Baker Heart and Diabetes Institute-led team compared four urine tests repeated within 28 days from 826 participants with type 2 diabetes (mean age 67, 65% male) in the PREDICT study cohort, finding that albuminuria levels in a repeated test could be as high or as low as four times the original result.

Results published in the American Journal of Kidney Diseases [link here] showed that based on a single collection increase from 2 to 5 mg/mmol, there was a 50% probability that urinary albumin-creatinine ratio had increased by at least 30%.

The probability rose to 97% when two collections were used at each time point.

The ranges of diagnostic uncertainty were 2.0-4.0 mg/mmol after an initial urinary albumin-creatinine ratio test, narrowing to 2.4-3.2 and 2.7-2.9 mg/mmol for the mean of two and three collections, respectively, the researchers noted.

“We know that for someone living with type 2 diabetes, that their urine albumin-creatinine ratio can vary on a day-to-day basis, reflecting fluctuations in blood pressure and behavioural factors including exercise and posture. However, many healthcare professionals may be surprised to see that it can vary by such a large extent,” said Dr Julian Sacre (PhD), a Clinical Diabetes and Epidemiology researcher.

“Although the method and timing of urine collections can be standardised, it is very difficult to control for all of the factors that underlie within-individual variability. Therefore, we would advocate for multiple urine collections on different days to get a complete picture of albuminuria.”

“If the first result is very high or very low, a repeat test is unlikely to call that into question and is probably unnecessary. However, if the first result lies close to the diagnostic threshold, the degree of within-individual variation can certainly be enough to mean that an individual’s albuminuria status would be classified differently from one day to the next. This presents a real challenge to our ability to accurately detect and interpret changes in albuminuria.”

Some factors correlated with higher within-individual urinary albumin-creatinine ratio variability including female sex and moderately increased albuminuria,  while other factors correlated with lower variability, including reduced estimated glomerular filtration rate and treatment with SGLT2 inhibitors, ACE inhibitors or ARBs.

However, the researchers did not recommend a specific number of tests.

“There is no single answer regarding the number of repeat collections required for the measurement of urinary albumin-creatinine ratio, rather, clinicians and researchers must determine the appropriate number based on the intended use,” Dr Sacre said.

“A key outcome of this study is in the development of some online tools for clinicians to access contemporary practical guidance on the number of urine collections required for a variety of clinical and research applications.”