Effects of low and high dietary phosphorus intake on fractional magnesium absorption and balance: results of a pilot cross-over controlled-feeding balance study in adults with moderate chronic kidney disease

Chronic kidney disease-mineral bone disorder (CKD-MBD) is common in CKD and is characterized by laboratory abnormalities in mineral metabolism, increased vascular calcification, cardiovascular events, bone disease, fractures, and mortality. Phosphorus (P) and calcium (Ca) metabolism are closely linked, and abnormalities in these are central to the development and progression of CKD-MBD. Magnesium (Mg) is also intertwined with Ca and P metabolism. Inadequate Mg intake and hypomagnesemia are common in CKD and are associated with CKD-MBD outcomes such as increased vascular calcification and elevated parathyroid hormone (PTH). In the diet, both Mg and Ca bind with P to form relatively insoluble salts, reducing absorption of P but also of either bound cation. Mg balance has been minimally studied in CKD but may offer insights on whole-body Mg physiology beyond what serum Mg may show, and within shorter timeframes than outcomes like vascular calcification, bone changes, clinical events, or death. Here, we report Mg balance and fractional Mg absorption by dual stable isotope from a cross-over pilot study of adults with moderate CKD (NCT04019379) that had a primary aim of determining effects of high versus low dietary P on Ca and P absorption and balance. For this study, our hypothesis was that a high P diet would decrease fractional Mg absorption and Mg balance compared with a low P diet. N=3 adults with moderate CKD were studied in a two-phase crossover, controlled feeding, metabolic balance study on two diet P levels (LP, 800 mg/d; HP 1500 mg/d). Diets were low Ca (500 mg/d) and Mg was 240-370 mg/d. Each cross-over phase included a 1-week diet equilibration followed by a 1-week inpatient metabolic balance with a 3-week washout between phases. Complete timed urine and feces were collected. Oral 26Mg and IV 25Mg isotopes were administered at the beginning of the inpatient period and serial blood samples were collected and analyzed for isotope enrichment to determine fractional Mg absorption. Diet, urine, and fecal samples were analyzed for total minerals and Mg balance was calculated as intake minus urine and fecal excretion. Serum intact parathyroid hormone (PTH), intact fibroblast growth factor-23 (FGF23), and 1,25-dihydroxyvitamin D (1,25D) were measured at baseline and end of each phase. Participants (N=3) included two women and one man, ages 34-71 y, with eGFR 29-41 mL/min/1.73m2. Fractional Mg absorption tended to be lower with the HP diet (0.25 ± 0.06, LSmean ± SE) compared with the LP diet (0.43 ± 0.06), p = 0.15. From these data, the estimated sample size needed for 80% power to detect a statistically significant difference at the level of α=0.05 (two-tailed) is n=7. Dietary P level did not appear to affect overall Mg balance. We previously reported (Hill Gallant, JASN 2023, 34(suppl):128) that intestinal fractional P absorption (by 33P isotope) varied widely among these participants (51-95%) and was not affected by dietary P level; however, absolute P absorption (mg/d) was ~2x greater with the HP diet compared to LP diet, reflecting the ~2x greater P intake. Fractional intestinal Ca absorption (by 44Ca isotope) and Ca balance also varied among these participants, with one showing markedly lower Ca absorption with the HP diet versus the LP diet. The effects observed for HP versus LP diets on fractional absorption of P, Ca, and Mg from these pilot data suggest that fractional Mg absorption may be most consistently affected by a high P intake. Given that Mg intake and status are commonly inadequate in patients with CKD and the potential protective role of Mg, the effects of dietary P intake and other factors on Mg balance and absorption warrants further investigation. This study was funded by NIH grant R03 DK122225. This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.