Accurate protein estimates can be obtained more quickly in lupus patients.

BOSTON—It may be possible to get accurate urine protein excretion estimates in lupus nephritis patients in three or 12 hours instead of 24, according to researchers at Johns Hopkins University in Baltimore.

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The 24-hour protein/creatinine (P/C) ratio is the gold standard mea-sure of 24-hour total urine protein excretion, but it is well known that this type of collection is highly inconvenient and prone to errors, said Martina Ziegenbein, MD, a lupus fellow at Johns Hopkins Lupus Center in Baltimore (currently a rheumatologist at Marshfield Clinic Minocqua Center in northern Wisconsin).


“The 24-hour urine collection is unreliable and cumbersome, prone to errors of over-collection or undercollection,” she said. “We wanted to investigate more convenient yet reliable method for protein quantitation.”


Dr. Ziegenbein, who presented study findings here at the American College of Rheumatology annual meeting, and her colleagues studied 25 patients with biopsy-proven lupus nephritis and a spot urine P/C ratio of greater than 0.2 or 24-hour urine protein greater than 0.15 g.


The subjects started their 24-hour collection at 6 am and then six consecutive time intervals or urine collections were obtained: 6-9 am, 9 am-noon, noon-3 pm, 3-6 pm, 6 pm–midnight, and midnight to 6 am. The researchers also collected a random (spot) urine sample from the first morning urine sample before and after the completion of the 24-hour collection.


The researchers used mixed effects analysis to compare ln (natural log) P/C ratio across time intervals to assess for diurnal variation. They also used intra-class coefficients (ICC) and 95% lower confidence limits (LCL) to calculate each timed and “spot” urine collection with the 24-hour P/C ratios.


Fifteen patients had greater than 1 g and seven patients had greater than 3 g proteinuria. The researchers observed a diurnal rhythm, with the lowest P/C ratio between 6 am and midnight and peak P/C ratio between 3 pm and 6 pm. They also found that the 6 am–6 pm (0-12 hr) and 6 pm–6 am (12-24 hr) urine collections had the highest correlation with the 24-hr P/C ratios, spot 2 ratios the least.


The investigators performed a unique study of urine collections among patients with lupus nephritis. They confirmed that spot urine P/C ratios are less reliable than timed urine collections in estimating 24-hr P/C ratio. They further demonstrated that the 0-12 hr and 12-24 hr urine collections showed excellent correlation to 24-hr P/C ratio. Thus, these two time intervals could be considered as an alternative to 24-hr urine collection in proteinuria quantitation in clinical trials.