Effects of Calcitriol on Type 5b Tartrate-Resistant Acid Phosphatase and Interleukin-6 in Secondary Hyperparathyroidism

Abstract

Background/Aims: Secondary hyperparathyroidism (SHP) is characterized by high bone turnover and elevated serum bone remodeling markers. Elevation of serum interleukin-6 (IL-6) levels is also characteristic of end-stage renal disease. This study investigates the effects of intravenous calcitriol on serum bone resorptive markers, namely, type 5b tartrate-resistant acid phosphatase (TRACP5b) and IL-6 in patients with SHP. Methods: Intravenous calcitriol therapy was given for 16 weeks to 24 patients on maintenance hemodialysis with plasma intact parathyroid hormone (iPTH) levels >300 pg/ml. Blood was drawn at baseline and every 4 weeks for 16 weeks for determination of the levels of biochemical parameters, iPTH, IL-6 and bone remodeling markers, including bone-specific alkaline phosphatase (bAP) and TRACP5b. Results: Only 21 patients responded to the calcitriol therapy, with significant decrements in serum iPTH after 4 weeks of therapy and thereafter. After 16 weeks of calcitriol therapy, 21 patients had significant decrements in serum iPTH (707.9 ± 317.8 vs. 205.0 ± 63.1 pg/ml, p < 0.01). Prior to treatment, a significant correlation was found between increased levels of serum iPTH and IL-6 levels (r = 0.45, p < 0.05). After treatment, there was also a significant and parallel lowering of levels of serum iPTH, IL-6 (8.52 ± 3.59 vs. 7.24 ± 2.81 pg/ml, p < 0.01), bAP (54.68 ± 36.17 vs. 24.55 ± 13.84 U/l, p < 0.01) and TRACP5b (3.41 ± 1.89 vs. 1.80 ± 0.55 U/l, p < 0.01). Our results additionally showed significant positive correlationsbetween baseline levels of serum IL-6 and those of iPTH, bAP and TRACP5b. After 16 weeks of calcitriol treatment, the correlation between IL-6 and iPTH levels lost significance but levels of serum IL-6, bAP and TRACP5b remained significantly correlated. Conclusions: Elevated levels of serum IL-6 and bone remodeling markers, namely, bAP and TRACP5b which are common features of SHP, are effectively suppressed by calcitriol therapy. This indicates that hyperparathyroidism not only accelerates bone remodeling but may also aggravate inflammation in patients on maintenance hemodialysis.

Calcitriol Treatment Increases Serum Levels of the Soluble Receptor of Advanced Glycation End Products in Hemodialysis Patients with Secondary Hyperparathyroidism

“…Moreover, because vitamin D has beneficial effects besides intact PTH suppression, we sought to investigate the influence of calcitriol on inflammatory marker levels, such as hsCRP, IL-6, sRAGE, and EN-RAGE, in HD patients with SHP. These patients manifested higher levels of serum inflammatory cytokines and oxidative stress, which are associated with higher all-cause and cardiovascular-specific mortality compared to non-SHP patients (Lu et al 2006;Tentori et al 2008). Vitamin D deficiency and SHP are thought to promote CVD in ESRD patients (Bucala and Cerami 1992;Block et al 2004), in addition to the traditional risk factors for CVD.…”

“…Observational clinical studies support hyperphosphatemia, abnormalities of parathyroid hormone (PTH), and increased vascular calcification as risk factors for CVD among patients with ESRD (Block and Port 2000;Ganesh et al 2001). ESRD patients with secondary hyperparathyroidism (SHP) have higher levels of serum inflammatory cytokines, which are associated with higher cardiovascular mortality than ESRD patients without SHP (Lu et al 2006;Tentori et al 2008). Thus the regulation of systemic vascular inflammation and calcification is an important problem among the hemodialysis (HD) patients.…”

Calcitriol Treatment Attenuates Inflammation and Oxidative Stress in Hemodialysis Patients with Secondary Hyperparathyroidism

“…Increased inflammation and oxidative stress have been proposed to play an important role in the pathogenesis of associated cardiovascular or infectious diseases contributing to low survival rates and quality of life in HD patients (Patel and Singh 2009a). Compared with non-SHP HD patients, patients with SHP may have a higher prevalence of serum inflammatory cytokines and oxidative stress, which are associated with high all-cause and cardiovascular-specific mortality (Lu et al 2006;Tentori et al 2008). High PTH levels, inflammation, and oxidative stress may act synergistically in the development and progression of renal osteodystrophy and cardiovascular disease in SHP patients.…”

Vitamin D and Immune System

“…Combination of Vitamin D with RAAS blockades can ameliorate renal fibrosis [141]. Active Vitamin D anti-inflammatory properties may be due to suppression of NF-B pathway which via regulation of many inflammatory cytokine enhances both inflammation and fibro genesis [140,142]. Active Vitamin D has immune modulatory effects in CKD patients which will ameliorate renal fibrosis and slow-down proteinuria development.…”