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.

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Journal
Hypertension Research
Published
2026-06-17
DOI
https://doi.org/10.1038/s41440-026-02706-5
Primary Topic
Parathyroid Disorders and Treatments
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article
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article

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

Siyi Geng, Mahboob Rahman, Joshua D. Bundy, Debbie L. Cohen et al.
Hypertension Research
Parathyroid Disorders and Treatments
article

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

Siyi Geng, Mahboob Rahman, Joshua D. Bundy, Debbie L. Cohen, Şuayp Oygen, Panduranga S. Rao, Jiang He, Alan S. Go, for the CRIC Study Investigators, Amanda H. Anderson, L. Lee Hamm, Eleanor Lederer, Laura M. Dember, Robert Toto, James P. Lash, Arnold Alper, Haowen Qin, Hua He, Halil K. Erol, Paola Lanza, Lawrence J. Appel, Alvin G. Kwon, Jing Chen
article en

Abstract

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.

Hypertension Research
Tulane University (US), Kaiser Permanente (US), University of Arizona (US), Johns Hopkins University (US), University of Utah (US), University of Michigan (US), Johns Hopkins Medicine (US), University of Alabama at Birmingham (US), University of Illinois Chicago (US), Southwestern Medical Center (US), VA North Texas Health Care System (US), University School (US), Case Western Reserve University (US), University of Pennsylvania (US), The University of Texas Southwestern Medical Center (US)
Kaiser Permanente, University of Pennsylvania, Tulane University, Johns Hopkins University, Case Western Reserve University, School of Medicine, Case Western Reserve University, Deutsches Krebsforschungszentrum, Georgia Clinical and Translational Science Alliance, National Institutes of Health, University of Illinois at Urbana-Champaign, Perelman School of Medicine, University of Pennsylvania, University of California, San Francisco, Michigan Institute for Clinical and Health Research, Medical School, University of Michigan, University of Illinois at Chicago, Clinical and Translational Science Collaborative of Cleveland, School of Medicine, Case Western Reserve University, National Institute of Diabetes and Digestive and Kidney Diseases, National Center for Research Resources, National Center for Advancing Translational Sciences
Good health and well-being
Openalex Percentile: Top 8%
Parathyroid Disorders and Treatments
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