Oral calcium carbonate affects calcium but not phosphorus balance in stage 3-4 chronic kidney disease

Kathleen M Hill, Berdine R Martin, Meryl E Wastney, George P McCabe, Sharon M Moe, Connie M Weaver, Munro Peacock, Kathleen M Hill, Berdine R Martin, Meryl E Wastney, George P McCabe, Sharon M Moe, Connie M Weaver, Munro Peacock

Abstract

Patients with chronic kidney disease (CKD) are given calcium carbonate to bind dietary phosphorus, reduce phosphorus retention, and prevent negative calcium balance; however, data are limited on calcium and phosphorus balance during CKD to support this. Here, we studied eight patients with stage 3 or 4 CKD (mean estimated glomerular filtration rate 36 ml/min) who received a controlled diet with or without a calcium carbonate supplement (1500 mg/day calcium) during two 3-week balance periods in a randomized placebo-controlled cross-over design. All feces and urine were collected during weeks 2 and 3 of each balance period and fasting blood, and urine was collected at baseline and at the end of each week. Calcium kinetics were determined using oral and intravenous (45)calcium. Patients were found to be in neutral calcium and phosphorus balance while on the placebo. Calcium carbonate supplementation produced positive calcium balance, did not affect phosphorus balance, and produced only a modest reduction in urine phosphorus excretion compared with placebo. Calcium kinetics demonstrated positive net bone balance but less than overall calcium balance, suggesting soft-tissue deposition. Fasting blood and urine biochemistries of calcium and phosphate homeostasis were unaffected by calcium carbonate. Thus, the positive calcium balance produced by calcium carbonate treatment within 3 weeks cautions against its use as a phosphate binder in patients with stage 3 or 4 CKD, if these findings can be extrapolated to long-term therapy.

Trial registration: ClinicalTrials.gov NCT01161407.

Figures

Figure 1
Figure 1
Randomized cross-over study design.
Figure 2
Figure 2
Calcium balance in stage 3/4 CKD patients with and without calcium carbonate. Calcium balance was greater with calcium carbonate compared with placebo. Ca intake was experimentally controlled and statistical analysis does not apply. White bars = placebo; Black bars = calcium carbonate. Ca = calcium; NS = not significant (p > 0.05). Data are presented as least squares mean ± pooled SEM.
Figure 3
Figure 3
Phosphorus balance in stage 3/4 CKD patients with and without calcium carbonate. Phosphorus balance was not different between calcium carbonate and placebo but urine phosphate was lower on calcium carbonate. P intake was experimentally controlled and statistical analysis does not apply. White bars = placebo; Black bars = calcium carbonate. P = phosphorus; NS = not significant (p > 0.05). Data are presented as least squares mean ± pooled SEM.
Figure 4
Figure 4
Illustration of calcium kinetics (33). ECF = extracellular compartment. 45Ca = 45Calcium radiotracer; Va = rate of calcium absorption; Vf = rate of endogenous calcium excretion; VF = rate of fecal calcium excretion; Vu = rate of urine calcium excretion; Vo+ = rate of bone formation; Vo− = rate of bone resorption. Bone balance is Vo+ minus Vo−, and overall calcium retention is dietary calcium minus urine and fecal calcium.
Figure 5
Figure 5
Calcium kinetics in stage 3/4 CKD patients with and without calcium carbonate. Calcium absorption (Va, mg/d) and bone balance (VBal=Vo+ minus Vo− ) were higher, and endogenous secretion (Vf) was unchanged with calcium carbonate compared with placebo. White bars = placebo; Black bars = calcium carbonate. Ca = calcium; NS = not significant (p > 0.05). Data are presented as least squares mean ± pooled SEM.
Figure 6
Figure 6
Comparison of calcium kinetics on placebo of stage 3/4 CKD patients with healthy postmenopausal women. Stage 3/4 CKD patients (white bars, n = 8, current study, on controlled diet + placebo) had similar rate of calcium absorption (Va), endogenous calcium excretion (Vf), bone formation (Vo+), bone resorption (Vo−), and “bone” balance (VBal) compared with healthy postmenopausal women [grey bars, n = 13, historical data (21)]. Data are presented as mean ± pooled SEM.

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