Association Between Serum Phosphate Levels and Stroke Risk in Patients Undergoing Hemodialysis

Stroke is a major cause of mortality in patients with chronic kidney disease (CKD). The risk of stroke is increased in patients with CKD, and CKD patients, especially those undergoing hemodialysis, are at increased risks of hospitalization, disability, and death after stroke, which are associated with a negative impact on society. Although previous studies have identified traditional and nontraditional risk factors for stroke in hemodialysis patients, the incidence of stroke still remains unacceptably high. Increasing evidence suggests that CKD-related bone-mineral disorders are an important nontraditional risk factor for cardiovascular morbidity and mortality in CKD patients. Hyperphosphatemia is the hallmark of such CKD-related bone-mineral disorders. Multiple lines of evidence have indicated strong associations between higher serum phosphate levels and cardiovascular disorders in both the general and dialysis populations. Although several clinical studies examined the association between serum phosphate levels and the incidence of stroke in the general population, they assessed the risk of composite stroke, including both brain hemorrhage and brain infarction. They did not assess the relationships between phosphate levels and brain hemorrhage and infarction separately, potentially resulting in inconsistent results and a lack of association. We aimed to elucidate the associations between serum phosphate levels and the incidences of stroke in patients Background and Purpose—The contribution of serum phosphate levels to stroke risk in dialysis patients remains unclear. The present study aimed to elucidate the respective association between serum phosphate levels and the risk of brain hemorrhage or infarction in patients undergoing hemodialysis. Methods—A total of 3437 patients undergoing hemodialysis were followed up for a median of 3.9 years. The primary outcome was the occurrence of brain hemorrhage or infarction. Patients were divided into 4 groups based on their baseline serum phosphate levels (Q1–Q4). Stroke risk was estimated using a Cox proportional hazards model. Results—During the follow-up period, 75 patients experienced brain hemorrhage and 139 experienced brain infarction. The risk of brain hemorrhage was significantly higher in the highest (Q4) compared with the lowest quartile (Q1) as the reference value (multivariate-adjusted hazard ratio [95% confidence intervals]: Q1, 1.00; Q2, 1.76 [0.79–4.18]; Q3, 1.99 [0.92–4.67]; and Q4, 2.74 [1.27–6.47]; P=0.077 for trend; hazard ratio for every 1 mmol/L increase in serum phosphate level, 2.07 [1.10–3.81]; P=0.025). In contrast, the risk of brain infarction was significantly higher in Q1 (P=0.045) compared with Q3 as the reference value (Q1, 1.65 [1.01–2.73]; Q2, 1.35 [0.82–2.25]; Q3, 1.00; and Q4, 1.30 [0.77– 2.20]). Conclusions—Higher serum phosphate levels were associated with an increased risk of brain hemorrhage, whereas low levels were associated with an increased risk of brain infarction in hemodialysis patients. These results suggest the importance of managing serum phosphate levels within an appropriate range in hemodialysis patients. Clinical Trial Registration—URL: http://www.umin.ac.jp/. Unique identifier: UMIN000000556. (Stroke. 2016;47:2189-2196. DOI: 10.1161/STROKEAHA.116.013195.)