PTH, FGF23, and Intensive Blood Pressure Lowering in Chronic Kidney Disease Participants in SPRINT

The Systolic Blood Pressure Intervention Trial (SPRINT) demonstrated that intensive BP lowering reduced the risk of cardiovascular disease, but increased eGFR decline. Serum parathyroid hormone (PTH) and fibroblast growth factor-23 (FGF23) concentrations are elevated in CKD and are associated with cardiovascular disease. We evaluated whether intact PTH or intact FGF23 concentrations modify the effects of intensive BP control on cardiovascular events, heart failure, and all-cause mortality in SPRINT participants with CKD.

We measured PTH and FGF23 in 2486 SPRINT participants with eGFR<60 ml/min per 1.73 m² at baseline. Cox models were used to evaluate whether serum PTH and FGF23 concentrations were associated with cardiovascular events, heart failure, and all-cause mortality, and whether PTH and FGF23 modified the effects of intensive BP control.

The mean age of this subcohort was 73 years, 60% were men, and mean eGFR was 46±11 ml/min per 1.73 m². Median PTH was 48 (interquartile range [IQR], 35-67) pg/ml and FGF23 was 66 (IQR, 52-88) pg/ml. There were 261 composite cardiovascular events, 102 heart failure events, and 179 deaths within the subcohort. The adjusted hazard ratio (HR) per doubling of PTH concentration for cardiovascular events, heart failure, and all-cause mortality were 1.29 (95% confidence interval [95% CI], 1.06 to 1.57), 1.32 (95% CI, 0.96 to 1.83), and 1.04 (95% CI, 0.82 to 1.31), respectively. There were significant interactions between PTH and BP arm for both the cardiovascular (P-interaction=0.01) and heart failure (P-interaction=0.004) end points. Participants with a PTH above the median experienced attenuated benefits of intensive BP control on cardiovascular events (adjusted HR, 1.02; 95% CI, 0.72 to 1.42) compared with participants with a PTH below the median (adjusted HR, 0.67; 95% CI, 0.45 to 1.00). FGF23 was not independently associated with any outcome and did not modify the effects of the intervention.

SPRINT participants with CKD and a high serum PTH received less cardiovascular protection from intensive BP therapy than participants with a lower serum PTH.