Intestinal Phosphorus Absorption in Moderate CKD and Healthy Adults Determined Using a Radioisotopic Tracer
Authors: Stremke Elizabeth R. , Wiese Gretchen N. , Moe Sharon M. , Wastney Meryl E. , Moorthi Ranjani N. , Hill Gallant Kathleen M. 
Published: July 2021

Significance Statement
Reducing intestinal phosphorus absorption through dietary restrictions and phosphate binders is common in managing and preventing CKD-MBD. Yet, how CKD pathophysiology affects intestinal phosphorus absorption is poorly understood. This study determined intestinal phosphorus absorption in patients with moderate CKD compared with healthy adults using a direct 33P radiotracer method in a controlled feeding study setting. Intestinal phosphorus absorption with dietary intake typical for the general population is not detectably different in patients with moderate CKD compared with control subjects, despite lower 1,25-dihydroxyvitamin D levels. These human data corroborate recent findings in CKD rat models. Understanding which factors influence intestinal phosphorus absorption in patients with CKD—particularly the apparent lack of intestinal compensation in the context of declining kidney function and reduced 1,25-dihydroxyvitamin D—will better inform approaches to reduce phosphorus absorption and prevent CKD-MBD in patients with CKD.

Background
Reducing intestinal phosphorus absorption is a cornerstone in CKD-MBD management. Yet, knowledge gaps include how CKD pathophysiology affects intestinal phosphorus absorption. In vivo rodent studies suggest that intestinal phosphorus absorption remains inappropriately normal in early-moderate CKD, despite declining 1,25-dihydroxyvitamin D (1,25D). We measured intestinal phosphorus absorption in patients with moderate CKD versus healthy adults using a direct radiotracer method.

Methods
Patients with CKD and healthy adults matched for age, sex, and race were enrolled in this 8-day controlled diet study: the first 6 days outpatient and the final 2 days inpatient. Oral and intravenous doses of 33P and serial blood and urine sampling determined intestinal phosphorus absorption during the final 2 days. Secondary outcomes included fasting biochemistries and 24-hour urine phosphorus (uP).

Results
In total, n=8 patients with CKD (eGFR=29–55 ml/min per 1.73 m2) and n=8 matched healthy controls completed the study. On a controlled diet, no difference in fractional intestinal phosphorus absorption was detected between patients with CKD and healthy adults (0.69 versus 0.62, respectively; P=0.52), and this was similar for 24-hour uP (884 versus 935 mg/d, respectively; P=0.70). Fractional intestinal phosphorus absorption was not significantly related to 24-hour uP. Patients with CKD had higher serum intact PTH and intact FGF23 and lower 1,25D. The relationship between 1,25D and fractional intestinal phosphorus absorption was not statistically significant.

Conclusions
Intestinal phosphorus absorption with typical dietary intake did not differ in patients with moderate CKD compared with controls, despite lower serum 1,25D levels. In this setting, a relationship between 24-hour uP and fractional or absolute intestinal absorption was not evident. Further investigation is needed to determine what factors influence intestinal phosphorus absorption in CKD and the apparent lack of compensation by the intestine to limit phosphorus absorption in the face of declining kidney function and reduced 1,25D. Whether this is evident across a range of dietary phosphorus intakes, as well as CKD severity, also needs to be determined.

Clinical Trial registry name and registration number:
Phosphorus Absorption in Healthy Adults and in Patients with Moderate Chronic Kidney Disease, NCT03108222