Effect of Dietary Calcium and Phosphorus on Parathyroid Hormone Levels in Early Renal Failure

ABSTRACT & COMMENTARY

Synopsis: Calcium supplementation led to a reduction in PTH levels as long as phosphate was restricted in the diet.

Source: Am J Kidney Dis 1997;29:496-502.

Parathyroid hormone (pth) levels increase early in chronic renal failure (CRF) when glomerular filtration rates (GFR) are as high as 75% of normal. The major reason for the secondary hyperparathyroidism (HPT) is hypocalcemia, which results from phosphate retention and reduced calcitriol synthesis. Dietary calcium may be reduced in CRF, and this may contribute to hypocalcemia as well. However, some of the data supporting this hypothesis comes from experimental studies done in advanced CRF. Martinez et al conducted this study with two objectives: 1) the timing in renal failure, of the occurrence of abnormalities in calcium, phosphorus, and calcitriol; and 2) the effect of dietary calcium and phosphorus intake on these abnormalities. The first objective was studied in 157 patients with varying levels of renal function (creatinine clearance [CCR], 10 to > 100 mL/min), and the second objective was evaluated in 58 patients with CCR greater than 65 mL/min who had reduced calcitriol levels.

A significant decline in plasma calcitriol levels was noted at GFR levels below 80 mL/min. PTH levels increased progressively as renal function worsened and the increase became significant at CCR less than 40 mL/min. No significant changes in calcium or phosphorus were noted.

To assess the effect of dietary calcium and phosphorus, 58 patients with creatinine clearance greater than 65 mL/min were divided into two groups. Both groups A and B received a protein- and phosphate-restricted diet for 10 days followed by a phosphate load for 10 days. Additionally, Group B received calcium supplementation during the entire period. Phosphate loading resulted in worsening of PTH levels in both groups. Calcium supplementation led to a reduction in PTH levels as long as phosphate was restricted in the diet.

COMMENT BY KAMALJIT SETHI, MD

There are several important clinical implications for patients with mild-to-moderate renal insufficiency in terms of divalent ion metabolism.

1. In early renal failure (CCR > 50 mL/min), and even moderately severe renal failure (CCR, 25-50 mL/min), serum calcium and phosphorus levels may be normal.

2. PTH levels increase progressively, and calcitriol levels decline as renal function declines and CCR drops below 30 mL/min.

3. Elevated PTH levels can be reduced by restricting dietary phosphorus while increasing calcium intake.

4. PTH levels should be measured annually once CCR declines to below 50 mL/min.

5. The best way to increase calcium intake is by using calcium supplements. Increasing intake of dairy products will raise both calcium and phosphorus. CaCO3 given as 650-1300 mg between meals is a reasonable supplement. The same dose given with meals can serve as a phosphate binder. The aim should be to keep serum calcium at least at 9.5-10 mg/dL. Normalization of serum calcium suppresses hyperparathyroidism with reduction in PTH levels.

6. The use of aluminum-containing antacids should be avoided, as aluminum excess can cause bone disease.

7. It should be noted that serum creatinine levels of greater than 1.5 mg/dL, particularly in the elderly, may represent renal impairment. Creatinine clearance is the better measure of glomerular filtration rate at all ages and particularly in the elderly.

8. Renal consultation should be sought when serum creatinine levels are greater than 1.5 mg/dL in females and 2 mg/dL in males to ensure a comprehensive approach to management of renal failure (NIH Consensus Conference on Hemodialysis), including management of divalent ions.