Phosphate homeostasis and apparent treatment-resistant hypertension in chronic kidney disease: the Chronic Renal Insufficiency Cohort (CRIC) study.

Abnormal phosphate homeostasis is associated with inflammation, vascular calcification, and endothelial dysfunction in chronic kidney disease (CKD). Apparent treatment-resistant hypertension (ATRH) is common in CKD and is associated with increased cardiovascular mortality. We examined the associations between phosphate homeostasis-related biomarkers and ATRH in patients with CKD. The Chronic Renal Insufficiency Cohort (CRIC) Study enrolled 3939 participants with CKD in the United States between 2003 and 2008. After excluding those with missing ATRH data, 3752 were analyzed. ATRH was defined as blood pressure (BP) ≥ 140/90 mm Hg while taking ≥3 antihypertensive medications, or BP < 140/90 mm Hg while taking ≥4 medications. In addition to phosphate homeostasis-related biomarkers, we calculated the phosphate burden index as the combined effect of phosphate retention on circulation and bone metabolism: index = serum phosphate × parathyroid hormone. Elastic Net and multivariable regression models assessed associations between phosphate biomarkers and ATRH. Participants with ATRH were older and more often male and Black. The adjusted odds ratios (95% confidence intervals) for the highest quartiles compared with the lowest quartile were 1.42 (1.09-1.86) for serum phosphate, 1.48 (1.15-1.91) for the urine phosphate-to-creatinine ratio, and 2.30 (1.72-3.08) for phosphate burden index. These associations were also significant in linear regression models for the urine phosphate-to-creatinine ratio and the phosphate burden index. We conclude that higher levels of phosphate-related biomarkers are independently associated with ATRH. Future studies should investigate whether targeting abnormal phosphate homeostasis can reduce ATRH risk in patients with CKD.