Comparison of effects of calcitriol and calcium carbonate on secretion of interleukin-1  and tumour necrosis factor-  by uraemic peripheral blood mononuclear cells

Abstract

We studied 26 non-dialysed patients with chronic renal failure [creatinine clearance (CCr) 32.6 +/- 12.7 ml/min]. They were divided into three groups according to their CCr and serum intact parathyroid hormone (PTH) and were given 0.5 micrograms/day oral calcitriol (calcitriol group, n = 8), 3 g/day calcium carbonate (CaCO3 group, n = 10), or neither (control uraemic group, n = 8). Serum intact PTH decreased from 154 +/- 75 to 90 +/- 43 pg/ml in the calcitriol group (P < 0.01) and from 162 +/- 97 to 77 +/- 62 pg/ml in the CaCO3 group (P < 0.001). Calcium carbonate was also effective in suppressing serum tartrate-resistant acid phosphatase, alkaline phosphatase and intact osteocalcin levels, while calcitriol did not suppress serum osteocalcin. Secretion of interleukin-1 beta (IL-1 beta) and tumour necrosis factor-alpha (TNF-alpha) by phytohaemagglutinin A (PHA)-activated peripheral blood mononuclear cells (PBMC) was greater in uraemic patients than in age-matched healthy controls (n = 8). Calcitriol was effective in suppressing secretion of both cytokines, while calcium carbonate was capable of suppressing only TNF-alpha secretion. CCr decreased from 37.4 +/- 15.4 to 33.0 +/- 11.8 ml/min (P < 0.05) in the CaCO3 group, while it did not decrease in either the calcitriol group or the control uraemic group during a 6 month period. These results suggest that supplementation with calcitriol is necessary to maintain bone formation and normalize IL-1 beta and TNF-alpha secretion by activated PBMC in uraemic patients.

Supplementation with Alfacalcidol Increases Protein Intake and Serum Albumin Concentration in Patients Undergoing Hemodialysis with Hypoalbuminemia: Possible Role of Tumor Necrosis Factor-α

“…The present finding that baseline serum sTNFR-II concentration is high in hemodialyzed patients and that it decreases significantly after supplementation with alfacalcidol, is consistent with findings published previously [23,38]. Tsukamoto et al [23] have demonstrated that TNF-· secretion by photohemagglu- tinin A-activated peripheral mononuclear blood cells (PBMC) is greater in uremic patients not undergoing dialysis than in age-matched healthy controls, and that the stimulated secretion of TNF-· is balanced by oral supplementation with 1,25-(OH) 2 D 3 . Riancho et al [38] have demonstrated that 1,25-(OH) 2 D 3 therapy induces a reduction in the secretion of TNF-· by PBMC to 53% of control value in hemodialyzed patients.…”

“…Furthermore, 1,25-(OH) 2 D 3 has been observed to reduce the synthesis of IL-1, IL-6, and TNF-· [21][22][23]. Recently, we have reported that a deficiency in vitamin D may play a critical role in the development of hypoalbuminemia in patients with end-stage renal disease [24].…”

Clinical immunology The effects of calcitriol with calcium carbonate supplementation on inflammatory biomarkers in chronic kidney disease patients’ with low vitamin D

“…A study by Tsukomoto et al . demonstrated that pro-inflammatory cytokines (IL-1β and TNF-α) were suppressed by calcitriol whereas CaCO 3 suppressed TNF-α only [ 20 ]. Since TNF-α stimulates IL-6 production, it is logical that reduction of TNF-α by either calcitriol or CaCO 3 or both will in turn lower IL-6 levels as seen in our study.…”

Shining D' light on chronic kidney disease: Mechanisms that may underpin the cardiovascular benefit of vitamin D

“…Intervention trials in CKD addressing inflammation have again been limited, performed predominantly in the haemodialysis (HD) population and yielded mixed results 68–77 . There is much heterogeneity between the available published work, and it is difficult to compare studies.…”

“…There is much heterogeneity between the available published work, and it is difficult to compare studies. However, it would appear that prolonged use (>3 months) of substantial doses of 1,25‐OHD (6.14 ± 1.25 µg/week) may reduce circulating inflammatory burden (as determined by IL‐1β, IL‐6, TNFα or hsCRP), by up to 60% 69,73,74 . Whether this observation translates into clinically meaningful outcomes and is applicable to earlier stages of CKD or administration of other forms of vitamin D has yet to be elucidated.…”