PHOSPHATE HOMEOSTASIS AND APPARENT TREATMENT RESISTANT HYPERTENSION IN PATIENTS WITH CHRONIC KIDNEY DISEASE: THE CRIC STUDY

Objective: Abnormal phosphate (Pi) homeostasis is associated with inflammation, vascular calcification, and endothelial dysfunction in patients with chronic kidney disease (CKD). Apparent treatment resistant hypertension (ATRH) is common and associated with high risk of cardiovascular disease and mortality in CKD. We studied the associations of Pi indices with risk of ATRH in CKD patients.Design and method: The CRIC Study recruited 3939 CKD participants without liver cirrhosis in the US. After excluding participants with missing ATRH information at baseline, 3556 participants were included in this analysis. ATRH was assessed at the baseline visit and defined as systolic blood pressure (BP) greater than or equal to 140 mm Hg or diastolic BP greater than or equal to 90 mm Hg while taking greater than or equal to 3 antihypertensive medications or systolic BP less than 140 mm Hg and diastolic BP less than 90 mm Hg while taking greater than or equal to 4 antihypertensive medications. Pi overload index was calculated as [serum Pi x (urinary Pi-to-creatinine ratio) x alkaline phosphatase (ALP- a marker reflecting bone turnover)] to synergistically reflect the effect of high Pi intake on serum Pi, kidneys, and bones. Logistic regression models were used to examine the multivariable associations of baseline Pi overload index, serum Pi, FGF23, parathyroid hormone (PTH), and urinary Pi-to-creatinine ratio with ATRH, adjusting for age, sex, race/ethnicity, body mass index, physical activity, weekly drinking, 24-hour urinary sodium, eGFR, use of diuretics, use of non-steroidal anti-inflammatory drugs, HbA1c, interleukin-6, tumor necrosis factor alpha, and transforming growth factor beta. Results: There were 1241 participants with ATRH. The average age was 61 years for those with ATRH and 59 for those without. Among those with ATRH, 62% were men and 47% were Black. There were independent, dose-response associations of Pi indices with ATRH (Table). Conclusions: These findings suggest that Pi overload is independently associated with ATRH. Maintaining normal Pi homeostasis may improve blood pressure control and related clinical outcomes. Future studies are warranted to confirm these findings.