Worsening calcification propensity precedes all-cause and cardiovascular mortality in haemodialyzed patients

Abstract

A novel in-vitro test (T50-test) assesses ex-vivo serum calcification propensity which predicts mortality in HD patients. The association of longitudinal changes of T50 with all-cause and cardiovascular mortality has not been investigated. We assessed T50 in paired sera collected at baseline and at 24 months in 188 prevalent European HD patients from the ISAR cohort, most of whom were Caucasians. Patients were followed for another 19 [interquartile range: 11–37] months. Serum T50 exhibited a significant decline between baseline and 24 months (246 ± 64 to 190 ± 68 minutes; p < 0.001). With serum Δ-phosphate showing the strongest independent association with declining T50 (r = −0.39; p < 0.001) in multivariable linear regression. The rate of decline of T50 over 24 months was a significant predictor of all-cause (HR = 1.51 per 1SD decline, 95% CI: 1.04 to 2.2; p = 0.03) and cardiovascular mortality (HR = 2.15; 95% CI: 1.15 to 3.97; p = 0.02) in Kaplan Meier and multivariable Cox-regression analysis, while cross-sectional T50 at inclusion and 24 months were not. Worsening serum calcification propensity was an independent predictor of mortality in this small cohort of prevalent HD patients. Prospective larger scaled studies are needed to assess the value of calcification propensity as a longitudinal parameter for risk stratification and monitoring of therapeutic interventions.

Signaling pathways involved in vascular smooth muscle cell calcification during hyperphosphatemia

“…A nanoparticle-based assay was developed, which detects the influence of serum on spontaneous transformation of primary CPPs into secondary CPPs and, thus, the balance between inhibitors and promoters of calcification in the serum [ 12 ]. Serum calcification propensity was suggested as a biomarker for cardiovascular disease [ 163 ] and shown to predict cardiovascular and all-cause mortality in CKD [ 164 , 165 ].…”

Lumenal calcification and microvasculopathy in fetuin-A-deficient mice lead to multiple organ morbidity

“…Furthermore, the accumulation of fetuin-A-containing mineral particles was noted in the peritoneal dialysate of a patient suffering from calcifying peritonitis [10] and in patients suffering from chronic kidney disease (CKD) [11]. Recent work has shown that both the abundance of CPP [12][13][14] and the kinetics of CPP formation [15][16][17][18] in serum of CKD patients can be used to monitor the propensity for calcification of these patients. The function of fetuin-A as an inhibitor of calcification is underscored by clinical studies showing that low fetuin-A serum levels are associated with calcification disease [19][20][21][22][23][24][25].…”

Cardiovascular Calcification in Chronic Kidney Disease—Therapeutic Opportunities

“…An association of shorter T 50 times with increased all-cause and CV mortality, as well as CV events, could be demonstrated in pre-dialysis CKD patients, HD patients, and KTR (Table 6) [76,107,[116][117][118]. Aortic pulse wave velocity (APWV), as a quantification tool of progressive arterial stiffness and vascular calcification, showed conflicting results in association with T 50 [116,118].…”

“…Mean: 212 min (10th-90th percentile: 109-328 min) 1.7 Association of low T50 with increased all-cause mortality and CVD [117] HD patients (n = 188) Mean: 246 ± 64 min 3.7…”