Association of bone-derived biomarkers with vascular calcification in chronic hemodialysis patients.

BACKGROUND: Abdominal aortic calcification (AAC) is commonly observed in chronic dialysis patients and is associated with cardiovascular and all-cause mortality. We investigated the factors associated with AAC and analyze the relationship between bone-derived biomarkers and AAC. METHODS: We enrolled 227 stable hemodialysis patients. Vascular calcifications were assessed using lateral lumbar radiography of the abdominal aorta. Demographic data were collected and serum levels of biochemical and bone-derived biomarkers, including sclerostin, Dickkopf-1 (DKK-1), and fibroblast growth factor 23 (FGF23), were measured. RESULTS: One hundred sixty-one patients (71.0%) had AAC. Patients with AAC score≧13 were older, with higher body mass index (BMI), serum calcium, calcium phosphate product, high-sensitivity C-reactive protein (hsCRP), and FGF23 levels. Sclerostin and DKK-1 levels were inversely associated with AAC severity, and FGF23 was directly related to vascular calcification. Hypertension, vascular disease, hsCRP, FGF23, and sclerostin were independent AAC determinants. CONCLUSIONS: Chronic hemodialysis patients have a high prevalence of vascular calcifications. Levels of circulating sclerostin, DKK-1, and FGF23 were related to AAC severity. Sclerostin and FGF23 were independently associated with AAC.

Gelsolin and adipokines are associated with protein-energy wasting in hemodialysis patients.

Protein-energy wasting (PEW) contributes to mortality in hemodialysis (HD) patients. Adipokines regulate energy homeostasis and body weight. Circulating gelsolin can modulate inflammation and is correlated with HD mortality. Whether adipokines and gelsolin play important roles in PEW remains unclear. Based on the criteria proposed by the International Society of Renal Nutrition and Metabolism, we examined the associations between PEW and biomarkers (gelsolin, leptin, adiponectin, interleukin-6, tumor necrosis factor alpha [TNF-α]) in 188 stable HD patients. Patients with PEW had significantly lower serum leptin levels, and tended to have higher adiponectin, TNF-α, and lower gelsolin levels. Logistic regression analysis revealed that gelsolin, leptin, adiponectin, and blood urea nitrogen were independently associated with PEW score. Serum creatinine, TNF-α, gender, renin-angiotensin system (RAS) blockade, and lipid-lowering agents were not associated with PEW score. Patients on lipid-lowering agents had lower PEW scores and those with RAS blockade had higher PEW scores. Our study confirms that gelsolin, adiponectin, and leptin are significant associates with PEW in HD patients. Further understanding of how these factors contribute to PEW may help design novel therapeutic strategies for PEW in chronic kidney disease.

Comparison between calcitriol and calcitriol plus low-dose cinacalcet for the treatment of moderate to severe secondary hyperparathyroidism in chronic dialysis patients.

AIM: Uremic hyperparathyroidism (UHPT) has been shown to contribute to the development and progression of chronic kidney disease-mineral bone disorder. UHPT is frequently observed in chronic dialysis patients, and patients with UHPT are associated with increased risk of all-cause and cardiovascular mortality. Cinacalcet is a novel agent that increases sensitivity to the calcium-sensing receptor and is approved for control of UHPT. Nevertheless, cinacalcet is costly and information regarding efficacy of low-dose cinacalcet on UHPT is limited. METHODS: We conducted a retrospective study to evaluate treatment with either low-dose calcitriol combined with low-dose cinacalcet (25 mg) (d-cinacalcet) or calcitriol alone (VitD) in dialysis patients with moderate to severe UHPT. A total of 81 dialysis patients were enrolled (40 subjects in d-cinacalcet group and 41 subjects in VitD group). Demographic data including age, gender, duration on dialysis and biochemical data were reviewed and recorded. RESULTS: At the end of the study, the intact parathyroid hormone (iPTH) levels of the d-cinacalcet group declined significantly (from 1166.0 ± 469.3 pg/mL to 679.8 ± 421.6 pg/mL, p < 0.0001), while there was no significant change in the VitD group. Significant decrease of serum calcium (Ca: 9.9 ± 0.6 mg/dL vs. 9.6 ± 0.8 mg/dL, p = 0.002), phosphorus (P: 5.9 ± 1.3 mg/dL vs. 4.9 ± 0.9 mg/dL, p < 0.0001) and calcium phosphate product (Ca × P: 58.7 ± 15.0 mg2/dL2 vs. 46.9 ± 8.9 mg2/dL2, p < 0.0001) were observed in the d-cinacalcet group. In addition, the subjects in the d-cinacalcet group had a greater proportion to achieve Kidney Disease Outcomes Quality Initiative (KDOQI)-recommended biochemical targets than the subjects in the VitD group (Ca: 48% vs. 24%; P: 78% vs. 32%; Ca × P: 85% vs. 37%; iPTH: 15% vs. 0%). CONCLUSIONS: We conclude that combination therapy of low-dose cinacalcet and calcitriol is more effective than calcitriol alone as a treatment for moderate and severe UHPT in chronic dialysis patients. Furthermore, this therapy is associated with improvement in hyperphosphatemia and hypercalcemia.

Biomarkers associated with vascular and valvular calcification in chronic hemodialysis patients.

BACKGROUND: Cardiovascular calcification, including arterial intimal and medial calcification (AIC and AMC) and valvular calcification (VC) are important predictors of outcome in chronic dialysis patients. We aimed to compare their prevalence and analyze respective risk factors in hemodialysis (HD) patients. METHODS: A total of 81 HD patients were enrolled. Vascular calcification was assessed by plain film radiography of the pelvis and VC was diagnosed by echocardiography. Demographic data was reviewed and serum levels of calcification-relevant biomarkers were determined. Patients with and without calcification were then compared. RESULTS: The prevalence study indicated that 36 patients had AIC (44.4%), 17 had AMC (21%) and 60 (74.1%) had VC. Patients with vascular calcification were older, and had a higher prevalence of diabetes. Their IL-6, osteoprotegerin, and uric acid levels were higher. Serum fetuin-A was lower in patients with VC. Logistic regression analysis revealed age, uric acid and diabetes to be independently associated with AIC; uric acid, diabetes and osteoprotegerin with AMC. Fetuin-A was the sole associate of VC. CONCLUSIONS: It is concluded that the prevalence of cardiovascular calcification in chronic HD patients was high with cardiac valve involvement more frequent. Factors associated with different type of calcification were not identical. Changes in biomarkers may represent clinical clues for assessment of cardiovascular calcification in HD patients.