G. Brunori

A High Calcium-Phosphate Product Is Associated with High C-Reactive Protein Concentrations in Hemodialysis Patients

Background: An elevated Ca×PO₄ product and C-reactive protein (CRP) have been associated with coronary artery calcification and increased cardiovascular mortality in hemodialysis (HD) patients. However, it has not been defined, so far, whether and how both parameters are related to each other. For this reason we have evaluated in a cross-sectional and in an interventional study the possible correlation between Ca×PO₄ and CRP and the effect of the correction of a high Ca×PO₄ on CRP levels. Methods: 47 uremic patients (age 65 ± 16 years) on regular chronic HD were selected from a total population of 125 prevalent patients treated at our Institution. Patients had no clinical evidence of either acute infectious or inflammatory diseases for at least 4 weeks before the study. They were on regular bicarbonate HD for 6–329 months (median 42). CRP, hemoglobin (Hb), serum albumin (sAlb), protein catabolic rate (PCRn), serum calcium (Ca), serum phosphorus (PO₄), Ca×PO₄, intact PTH, Kt/V, presence of ischemic heart disease (IHD) and/or peripheral vascular disease (PVD) were recorded. CRP was Ln-transformed in all statistical analyses because of positive skewness. Results: The main findings were: LnCRP 2.17 ± 0.77 mg/l, Ca 10.1 ± 0.4 mg/dl, PO₄ 5.8 ± 0.6 mg/dl, Ca×PO₄ 59 ± 6 mg²/dl², andPTHint 218 ± 195 ng/ml. 18/47 had IHD, 18/47 PVD. A significant hyperbolic correlation between Ca×PO₄ and CRP was observed. A piecewise linear regression model analysis identified a break-point for Ca×PO₄ at 55 mg²/dl². Comparison of CRP levels after the division of the patients into two groups according to Ca×PO₄ break-point (group A, Ca×PO₄ ≤55 mg²/dl², n = 16 patients; group B, Ca×PO₄ >55 mg²/dl², n = 31 patients) showed that CRP levels were significantly lower in patients in group A (LnCRP 1.43 ± 0.22 mg/l) than in group B (LnCRP 2.55 ± 0.67 mg/l, p < 0.0001). Multiple regression analysis bearing LnCRP as dependent variable confirmed Ca×PO₄ as the most significant variable among the other variables examined. In 22 patients with Ca×PO₄ ≧60 mg²/dl², we performed intensive lowering of the Ca×PO₄ product in order to reach and maintain a Ca×PO₄ ≤55 mg²/dl² for 3 months. At the end of observation, a significant reduction in Ca×PO₄ and LnCRP was observed (Ca×PO₄ pre 62.8 ± 1.9 vs. post 46.3 ± 6.2 mg²/dl²: p < 0.0001; LnCRP pre 2.32 ± 0.36 vs. post 1.83 ± 0.14 mg/l: p < 0.0001). No significant variation in the other biochemical parameters was observed. Conclusions: Our data show that in chronic HD patients in steady clinical conditions with no clinical evidence of either infectious or inflammatory diseases, a high Ca×PO₄ is associated with high CRP concentrations. Intensive lowering of Ca×PO₄ reduces CRP.