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

Abstract

Chronic kidney disease (CKD) patients are given calcium carbonate to bind dietary phosphorus and reduce phosphorus retention, and to prevent negative calcium balance. Data are limited on calcium and phosphorus balance in CKD to support this. The aim of this study was to determine calcium and phosphorus balance and calcium kinetics with and without calcium carbonate in CKD patients. Eight stage 3/4 CKD patients, eGFR 36 mL/min, participated in two 3-week balances in a randomized placebo-controlled cross-over study of calcium carbonate (1500 mg/d calcium). Calcium and phosphorus balance were determined on a controlled diet. Oral and intravenous 45calcium with blood sampling and urine and fecal collections were used for calcium kinetics. Fasting blood and urine were collected at baseline and end of each week of each balance period for biochemical analyses. Results showed that patients were in neutral calcium and phosphorus balance while on placebo. Calcium carbonate 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 tissue deposition. Fasting biochemistries of calcium and phosphate homeostasis were unaffected by calcium carbonate. If they can be extrapolated to effects of chronic therapy, these data caution against the use of calcium carbonate as a phosphate binder.

The Use of Fibroblast Growth Factor 23 Testing in Patients with Kidney Disease

“…For instance, in CKD patients, there remains no definitive evidence that serum phosphate lowering with oral binder therapy is associated with improvement in survival or for that matter, that restricting intestinal phosphate absorption even has the intended effect on overall phosphate balance. Indeed, in a recent study of stages 3 and 4 CKD patients treated with oral calcium carbonate, binder use was found to have no net effect on phosphate balance, at least in the short term (137). Thus, it could be argued that needing evidence of attenuated risk with FGF23 lowering demands substantially more from FGF23 than we ask of the mineral markers currently in use.…”

“…Thus, a detailed mechanistic appraisal of how cinacalcet lowers FGF23 levels and the role of PTH [either directly or indirectly through changes in 1,25(OH) 2 D and/or local processes in bone] (133,135,136) is certainly needed. The response in FGF23 levels to cinacalcet therapy is, like for PTH, quite variable: approximately one half of patients show little (if any) change in concentrations in FGF23 (124,126), and responsiveness seems unrelated to pretreatment levels (137).…”

Phosphate binders in patients with chronic kidney disease

“…20 However, there is little evidence of patient outcomes to support this recommendation. Another common adverse effect of these drugs is gastrointestinal upset, particularly constipation.…”

Rationale and Approaches to Phosphate and Fibroblast Growth Factor 23 Reduction in CKD

“…65,66 Similar findings have been observed in normophosphatemic patients with CKD stages 32 4 in whom phosphate binders, but not placebo, reduce 24-hour urine phosphate by 20%-50%. 30,42,45,67 The effects of phosphate binders on levels of FGF23 in patients with CKD are not consistent. Several studies suggest that non-calciumbased phosphate binders lower FGF23 levels in this population by 30%-40%, 30,31,45,[54][55][56][57] whereas calcium-based binders do not, 22,38 likely because calcium is a secondary stimulus for FGF23 production.…”