P1264LOW PHOSPHATE AND LOW CALCIUM LEVELS PREDICT A HIGHER RISK FOR CARDIOVASCULAR EVENTS OF MAINTENANCE HEMODIALYSIS PATIENTS
Authors: Takahiro Kuragano , Nakanishi Takeshi 
Published: June 2020

Abstract

Background and Aims
It has been reported that higher serum levels of phosphate (P) and calcium (Ca) are associated with a higher risk of cardiovascular disease (CVD) and premature death of maintenance hemodialysis (MHD) patients. Thus, several clinical guidelines recommend that serum P and Ca levels in MHD patients be maintained within the optimal range. However, in the current situation in which the guidelines have penetrated widely, there are few reports that have investigated the association between chronic kidney disease (CKD)-mineral and bone disorder (MBD)-related factors and adverse events in MHD patients.

Method
The study design was a 3-year multicenter, observational study. A total of 989 MHD patients were enrolled in this study. The blood levels of Hb, ferritin, iron, total iron-binding capacity, β2-microglobulin, creatinine, total protein, albumin, total cholesterol, Ca and P were measured every 3 months. The blood levels of high-sensitivity C-reactive protein (hCRP) and intact parathyroid hormone (int-PTH) were also measured every six months. The correlation between CKD-MBD factors and adverse events was evaluated by the time-dependent Cox hazard model.

Results
In 82% of patients, 83% of patients, and 78% of patients, serum P levels, serum Ca levels, and int-PTH levels, respectively, were maintained in the target ranges (3.5≤P≤6.0 mg/dL, 8.4≤Ca≤10.0 mg/dL, 60≤int-PTH≤240 pg/mL) that were recommended by the 2012 guidelines of the Japanese Society for Dialysis Therapy. After correcting for age, sex, past history of CVD, Hb, albumin, and hCRP, compared with the patients with target levels of P, patients with low P levels (&lt;3.5 mg/dL) had a significantly higher risk for CVD (P=0.042, HR: 2.27), hospitalization (P=0.034, HR: 2.44), and all-cause mortality (P=0.03, HR: 2.29). On the other hand, there was no association between higher serum P levels and adverse events. Compared with the patients who maintained target int-PTH levels, patients with lower (&lt;60) (P=0.025, HR: 1.46) and higher (&gt;240 pg/mL) (P=0.04, HR: 1.44) int-PTH levels had a significantly higher risk for hospitalization. There was no significant correlation between serum Ca and adverse events. Furthermore, compared with the patients who maintained the target levels of both Ca and P, the patients with target Ca and low P levels (P=0.042, HR: 2.75) had a significantly higher risk for CVD. Compared with the patients who maintained the target levels of both Ca and P, the patients with low Ca and low P levels (P&lt;0.001, HR: 4.4) and target Ca and low P levels (P=0.22, HR: 2.0) had a significantly higher risk for hospitalization.

Conclusion
After correcting for several clinical factors, we found that patients who maintained low serum P levels had a significantly higher risk for CVD and all-cause mortality than patients who maintained higher Ca and P levels. Undoubtedly, extremely high serum P, Ca, and int-PTH levels should be treated according to the guidelines. However, in the current situation in which the guidelines have penetrated widely, CKD-MBD management, in which the clinical conditions of low P, Ca, and int-PTH are considered, is needed.