Intestinal phosphorus absorption in moderate ckd and healthy adults determined using a radioisotopic tracer

Elizabeth R. Stremke; Gretchen N. Wiese; Sharon M. Moe; Meryl E. Wastney; Ranjani N. Moorthi; Kathleen M.Hill Gallant

doi:10.1681/asn.2020091340

Intestinal phosphorus absorption in moderate ckd and healthy adults determined using a radioisotopic tracer

Elizabeth R. Stremke
, Gretchen N. Wiese
, Sharon M. Moe
, Meryl E. Wastney
, Ranjani N. Moorthi
, Kathleen M.Hill Gallant

Research output: Contribution to journal › Article › peer-review

26 Scopus citations

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 m 2) 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.

Original language	English (US)
Pages (from-to)	2057-2069
Number of pages	13
Journal	Journal of the American Society of Nephrology
Volume	32
Issue number	8
DOIs	https://doi.org/10.1681/asn.2020091340
State	Published - Aug 2021

Bibliographical note

Funding Information:
This project was supported in part by National Institute of Diabetes and Digestive and Kidney Diseases grants K01 DK102864 (to K.M. Hill Gallant), R01 DK110871 (to S.M. Moe), and K23 DK102824 (to R.N. Moorthi); National Institute of Arthritis and Musculoskeletal and Skin Diseases grant P30 AR072581 (to S.M. Moe); and Veterans Administration grant VA Merit BX001471 (to S.M. Moe). The Indiana Clinical and Translational Science Institute is funded in part by National Center for Advancing Translational Sciences award UL1 TR002529. E.R. Stremke received support in part through National Center for Advancing Translational Sciences award TL1 TR002531.

Funding Information:
K.M. Hill Gallant has received speaker honorarium from Ardelyx and grant support from Chugai. K.M. Hill Gallant reports ownership interest in the Laboratory for Advanced Medicine (stock). S.M. Moe receives consulting fees from Amgen, Ardelyx, and Sanifit and grant support from Chugai and Keryx/Akebia. S.M. Moe also reports ownership interest in Eli Lilly (stock); and membership on the editorial board of the American Journal of Nephrology. M.E. Wastney is employed by Metabolic Modeling Services. G.N. Wiese reports honoraria from Nutrition Today (Wolters Kluwer). G.N. Wiese is employed by U.S. Renal Care at the time of article publication. E.R. Stremke is employed by Fresenius Medical Care North America at the time of article publication. All remaining authors have nothing to disclose.

Publisher Copyright:
© 2021 by the American Society of Nephrology.

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@article{46f804314a23418b8fc3a6508447db0e,

title = "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 m 2) 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.",

author = "Stremke, \{Elizabeth R.\} and Wiese, \{Gretchen N.\} and Moe, \{Sharon M.\} and Wastney, \{Meryl E.\} and Moorthi, \{Ranjani N.\} and Gallant, \{Kathleen M.Hill\}",

note = "Funding Information: This project was supported in part by National Institute of Diabetes and Digestive and Kidney Diseases grants K01 DK102864 (to K.M. Hill Gallant), R01 DK110871 (to S.M. Moe), and K23 DK102824 (to R.N. Moorthi); National Institute of Arthritis and Musculoskeletal and Skin Diseases grant P30 AR072581 (to S.M. Moe); and Veterans Administration grant VA Merit BX001471 (to S.M. Moe). The Indiana Clinical and Translational Science Institute is funded in part by National Center for Advancing Translational Sciences award UL1 TR002529. E.R. Stremke received support in part through National Center for Advancing Translational Sciences award TL1 TR002531. Funding Information: K.M. Hill Gallant has received speaker honorarium from Ardelyx and grant support from Chugai. K.M. Hill Gallant reports ownership interest in the Laboratory for Advanced Medicine (stock). S.M. Moe receives consulting fees from Amgen, Ardelyx, and Sanifit and grant support from Chugai and Keryx/Akebia. S.M. Moe also reports ownership interest in Eli Lilly (stock); and membership on the editorial board of the American Journal of Nephrology. M.E. Wastney is employed by Metabolic Modeling Services. G.N. Wiese reports honoraria from Nutrition Today (Wolters Kluwer). G.N. Wiese is employed by U.S. Renal Care at the time of article publication. E.R. Stremke is employed by Fresenius Medical Care North America at the time of article publication. All remaining authors have nothing to disclose. Publisher Copyright: {\textcopyright} 2021 by the American Society of Nephrology.",

year = "2021",

month = aug,

doi = "10.1681/asn.2020091340",

language = "English (US)",

volume = "32",

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TY - JOUR

T1 - Intestinal phosphorus absorption in moderate ckd and healthy adults determined using a radioisotopic tracer

AU - Stremke, Elizabeth R.

AU - Wiese, Gretchen N.

AU - Moe, Sharon M.

AU - Wastney, Meryl E.

AU - Moorthi, Ranjani N.

AU - Gallant, Kathleen M.Hill

N1 - Funding Information: This project was supported in part by National Institute of Diabetes and Digestive and Kidney Diseases grants K01 DK102864 (to K.M. Hill Gallant), R01 DK110871 (to S.M. Moe), and K23 DK102824 (to R.N. Moorthi); National Institute of Arthritis and Musculoskeletal and Skin Diseases grant P30 AR072581 (to S.M. Moe); and Veterans Administration grant VA Merit BX001471 (to S.M. Moe). The Indiana Clinical and Translational Science Institute is funded in part by National Center for Advancing Translational Sciences award UL1 TR002529. E.R. Stremke received support in part through National Center for Advancing Translational Sciences award TL1 TR002531. Funding Information: K.M. Hill Gallant has received speaker honorarium from Ardelyx and grant support from Chugai. K.M. Hill Gallant reports ownership interest in the Laboratory for Advanced Medicine (stock). S.M. Moe receives consulting fees from Amgen, Ardelyx, and Sanifit and grant support from Chugai and Keryx/Akebia. S.M. Moe also reports ownership interest in Eli Lilly (stock); and membership on the editorial board of the American Journal of Nephrology. M.E. Wastney is employed by Metabolic Modeling Services. G.N. Wiese reports honoraria from Nutrition Today (Wolters Kluwer). G.N. Wiese is employed by U.S. Renal Care at the time of article publication. E.R. Stremke is employed by Fresenius Medical Care North America at the time of article publication. All remaining authors have nothing to disclose. Publisher Copyright: © 2021 by the American Society of Nephrology.

PY - 2021/8

Y1 - 2021/8

N2 - 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 m 2) 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.

AB - 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 m 2) 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.

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JO - Journal of the American Society of Nephrology

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Intestinal phosphorus absorption in moderate ckd and healthy adults determined using a radioisotopic tracer

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