Twenty-four-hour urine phosphorus in patients with moderate chronic kidney disease is highly variable and unreliable as a biomarker of dietary phosphorus intake and absorption, according to investigators.
Their results “suggest that caution must be used in interpreting 24-hour urine phosphorus in observational studies or in individual patients in the absence of intervention,” a research team led by Kathleen M. Hill Gallant, PhD, of Purdue University in West Lafayette, Indiana, and colleagues reported in the Clinical Journal of the American Society of Nephrology.
They noted that 24-hour urine phosphorus is commonly used as a surrogate measure for phosphorus intake and absorption in research studies.
Dr Hill Gallant and her colleagues conducted a secondary analysis of 8 patients with stage 3–4 CKD who previously had participated in in 2-week balance studies with tightly controlled phosphorus and calcium intakes. Researchers analyzed 13 24-hour urine collections per patient for variability and reliability of 24-hour urine phosphorus and phosphorus-to-creatinine ratio. The researchers calculated net phosphorus absorption as daily intake minus fecal excretion averaged over the entire balance period. They calculated whole-body phosphorus balance as daily intake minus fecal and urine excretion average over the entire balance period.
Dr Hill Gallant’s team observed wide day-to-day variation in 24-hour urine phosphorus within and among participants. Two 24-hour urine measures were required to achieve at least 75% reliability, they reported. Estimating dietary phosphorus intake from a single 24-hour urine sample resulted in underestimation up to 98% in some patients and overestimation up to 79% in others. The authors concluded that 24-hour phosphorus correlated negatively with whole-body retention, but was not related to phosphorus intake or net absorption.
“The results of this study show that 24-hour urine phosphorus is a highly variable measurement, even under optimal research center conditions for complete and timed collections, and that repeated measurements are necessary when a reliable value is needed,” they wrote.
Dr Hill Gallant and her collaborators said their results suggest that differences in whole-body phosphorus retention, not differences in intestinal phosphorus absorption, were responsible for the wide variation observed in their patients, who consumed the same fixed level of dietary phosphorus. “This may be due to differences in bone remodeling, extraskeletal tissue uptake, or kidney efficiency for phosphate excretion,” they noted.
Although study strengths included a well-controlled diet and 2-week balance study in a controlled setting with 13 days of 24-hour urine collections, the data come from only 8 patients with CKD, so generalizability is limited, the authors pointed out. “Our results also cannot be applied to the general population with preserved kidney function.”
The investigators stated that their findings do not preclude using changes in 24-hour urine phosphorus as an outcome associated with phosphorus absorption in interventional studies with therapies that have a known mechanism influencing phosphorus absorption, such as phosphate binders and low-phosphorus diets.
Stremke ER, McCabe LD, McCabe GP, et al. Twenty-four-hour urine phosphorus as a biomarker of dietary phosphorus intake and absorption in CKD. A secondary analysis from a controlled diet balance study. Clin J Am Soc Nephrol. 2018;13:1002-1012.