Intestinal Phosphorus Absorption in Moderate CKD and Healthy Adults Determined Using a Radioisotopic Tracer

Abstract

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.

Keywords: CKD-MBD; chronic kidney disease; intestinal absorption; nutrition; phosphorus.

Copyright © 2021 by the American Society of Nephrology.

Figures

Graphical abstract

Figure 1.

Intestinal phosphorus absorption study design and protocol. Subjects followed a controlled study diet for 6 days at home, with all food provided as meal packouts. On Day 7, subjects were admitted to the CRC and began the intestinal phosphorus absorption test protocol which included an oral dose of 33P on Day 7 and an IV dose of 33P on Day 8. Urine and sequential blood draws were collected for determination of intestinal phosphrous absorption by kinetic modeling. Subjects completed the study and were discharged from the CRC on the morning of Day 9. IV, intravenous.

Figure 2.

Intestinal phosphorus absorption in patients with CKD and healthy adults. (A) fractional intestinal absorption in patients with CKD and healthy adults. (B) Absolute intestinal phosphorus absorption in milligrams per day. Black lines indicate the means, and error bars are SEMs; triangles indicate values for subjects with CKD, and circles indicate values for healthy subjects.

Figure 3.

Measures of urinary phosphorus excretion and relationships with intestinal phosphorus absorption. (A) The 24-hour uP for each study group. (B) FEPi for each study group. (C) The relationship between 24-hour uP and fractional intestinal phosphorus absorption. (D) The relationship between 24-hour uP and absolute intestinal phosphorus absorption (milligrams per day). Black lines indicate the means, and error bars are SEMs; triangles indicate values for subjects with CKD, and circles indicate values for healthy subjects. Solid lines are the regression fit, shaded areas are the 95% confidence limits, and the dotted lines indicate the 95% prediction limits.

Figure 4.

Serum values of phosphorus regulatory hormones. (A) Serum 1,25D, (B) iPTH, and (C) iFGF23 in patients with CKD and healthy adults. Black lines indicate the means, and error bars are SEMs; triangles indicate values for subjects with CKD, and circles indicate values for healthy subjects.

Figure 5.

The relationship between phosphorus regulatory hormones and fractional intestinal phosphorus absorption. (A) The relationship between 1,25D and fractional phosphorus absorption. (B) The relationship between serum iPTH and fractional phosphorus absorption. (C) The relationship between serum iFGF23 and fractional phosphorus absorption. Solid lines are the regression fits, shaded areas are the 95% confidence limits, and the dotted lines indicate the 95% prediction limits. Triangles indicate values for subjects with CKD, and circles indicate values for healthy subjects.

Figure 6.

The relationship between phosphaturic hormones and urinary phosphorus excretion. (A) The relationship between 24-hour uP and serum iFGF23. (B) The relationship between FEPi and serum iFGF23. (C) The relationship between 24-hour uP and serum iPTH. (D) The relationship between FEPi and serum iPTH. (E) The relationship between TmP/GFR and serum iPTH. (F) The relationship between TmP/GFR and serum iFGF23. Solid lines are the regression fits, shaded areas are the 95% confidence limits, and the dotted lines indicate the 95% prediction limits. Triangles indicate values for subjects with CKD, and circles indicate values for healthy subjects.