Contribution of Intestine, Bone, Kidney, and Dialysis to Extracellular Fluid Calcium Content

Abstract

Calcium (Ca) balance is the net of Ca intake and output from the body over a period of time. The concept of Ca balance does not consider the redistribution of Ca that often occurs in patients with chronic kidney disease (CKD), especially those who are on dialysis, which is often in the form of soft tissue and/or vascular calcification. In this article, we consider movement of Ca with respect to the extracellular fluid (ECF) and develop a mathematical formulation for Ca homeostasis with respect to the ECF that includes input and output from the diet, the bone, the kidney, and dialysis. We consider calcium homeostasis in healthy individuals and in patients with excess parathyroid hormone, excess 1,25-dihydroxyvitamin D 3 , and metabolic acidosis; patients who have CKD and are not on dialysis; and, finally, patients who have CKD and are on dialysis. On the basis of a number of assumptions, dialysis patients with a daily intake of >37.5 mmol of elemental Ca (1.5 g) have movement of Ca into the ECF even without supplemental activated vitamin D. Addition of activated vitamin D, which increases intestinal Ca absorption and can increase resorption of Ca from bone, leads to the movement of Ca into the ECF at virtually all levels of intake; however, there are numerous unanswered questions regarding Ca homeostasis in patients with CKD, including how much of the Ca, administered as a phosphate binder, is absorbed and what is the fate of this absorbed Ca. Until these pressing questions are answered with well-designed experiments, we do not know whether we are doing more harm than good for our dialysis patients by administering additional Ca as a phosphate binder, especially when they also receive activated vitamin D.

Increased biological response to 1,25(OH)2D3in genetic hypercalciuric stone-forming rats

“…The source of the increased UCa in the GHS rats cannot simply be due to the decreased renal tubule Ca reabsorption found in these animals (90) or SCa would be lower and PTH higher in GHS compared with SD rats, which has not been observed (24). The augmented UCa must be due either to a greater increase in intestinal Ca absorption and/or bone Ca resorption, the only two potential sources for UCa (15). Previously, we have shown that when cultured with a similar amount of 1,25D (54) GHS rat bone releases more Ca than bone from SD rats, supporting the current findings.…”

Mechanistic Insights into Vascular Calcification in CKD

“…7 Although free (ionized) serum calcium levels are tightly regulated, transient hypercalcemic episodes, particularly in dialysis patients, as seen during hemodialysis or with the use of vitamin D analogs or calcium-based phosphate binders, may potentially influence vascular calcification. [99][100][101] Moreover, it is important to remember that serum calcium does not reflect the total body levels, and the majority of dialysis patients are thought to have high total body calcium stores 102 ; careful calcium balance studies are required to better understand calcium homeostasis in CKD patients, including how much of the ingested calcium, administered through diet or as a phosphate binder, is absorbed and the fate of this absorbed calcium. Furthermore, in low bone turnover states, fluxes in serum calcium and phosphate cannot be buffered by adynamic bone, 103 resulting in ectopic soft tissue and vascular calcification.…”

Calcium Builds Strong Bones, and More Is Better—Correct? Well, Maybe Not

“…However, the cause of abnormal bone in CKD is not calcium deficiency but rather is far more complex (52,53). Furthermore, a recent formal balance study demonstrated that patients with CKD stage 4 who were not receiving calcitriol or vitamin D analogues had a neutral calcium balance at 800 mg calcium intake but a significant positive calcium balance at 2000 mg (diet plus supplement) (54).…”