Kidney Week

Abstract: FR-PO539

PTH, FGF23, and Effects of Intensive Blood Pressure Lowering in SPRINT Participants with CKD

Session Information

• Hypertension: Clinical and Translational
  November 03, 2017 | Location: Hall H, Morial Convention Center
  Abstract Time: 10:00 AM - 10:00 AM

Category: Hypertension

• 1104 Hypertension: Clinical and Translational - Salt and Hypertension

Authors

• Ginsberg, Charles, UCSD, San Diego, California, United States

Charles Ginsberg,

• Craven, Timothy, Wake Forest University School of Medicine, Winston-Salem, North Carolina, United States

Timothy Craven,

• Chonchol, Michel, University of Anschutz Medical Center, Aurora, Colorado, United States

Michel Chonchol,

• Cheung, Alfred K., University of Utah, Salt Lake City, Utah, United States

Alfred K. Cheung,

• Sarnak, Mark J., Tufts Medical Center, Boston, Massachusetts, United States

Mark J. Sarnak,

• Killeen, Anthony Alexander, University of Minnesota, Minneapolis, Minnesota, United States

Anthony Alexander Killeen,

• Raphael, Kalani L., VA Salt Lake City Health Care System, Salt Lake City, Utah, United States

Kalani L. Raphael,

• Bhatt, Udayan Y., The Ohio State University, Dublin, Ohio, United States

Udayan Y. Bhatt,

• Chen, Jing, Tulane School of Medicine, New Orleans, Louisiana, United States

Jing Chen,

• Chertow, Glenn Matthew, Stanford University School of Medicine, Palo Alto, California, United States

Glenn Matthew Chertow,

• Freedman, Barry I., Wake Forest University School of Medicine, Winston-Salem, North Carolina, United States

Barry I. Freedman,

• Oparil, Suzanne, University of Alabama at Birmingham , Birmingham, Alabama, United States

Suzanne Oparil,

• Wall, Barry M., VA Medical Center, Memphis, Tennessee, United States

Barry M. Wall,

• Wright, Clinton B., NINDS, Rockville, Maryland, United States

Clinton B. Wright,

• Shlipak, Michael, San Francisco VA Medical Center, San Francisco, California, United States

Michael Shlipak,

• Ix, Joachim H., UCSD, San Diego, California, United States

Joachim H. Ix,

Background

Serum FGF23 and PTH levels are elevated in CKD patients, and are associated with CVD events. Prior work has demonstrated that the association with CVD events may be modified by tubular resistance to FGF-23, thereby giving insight into kidney tubule function above and beyond eGFR. We hypothesized that the therapeutic benefits of intensive blood pressure (BP) control may also be modified by tubular resistance to PTH and FGF-23.

Methods

Among 2486 SPRINT participants with baseline eGFR < 60 ml/min/1.73m², we measured intact FGF23 and intact PTH. We evaluated whether the effect of randomization to intensive vs. standard BP arms on CVD, HF events, and all-cause mortality was modified by serum PTH or FGF-23 levels.

Results

Mean age was 73 yrs, 60% were female, mean eGFR was 46±9 ml/min/1.73m². Median [IQR] iFGF23 was 66 [52, 88] pg/ml, and median iPTH was 48 [35, 67] pg/ml. PTH modified the effect of intensive BP lowering for CVD events (p_int=0.01) and HF (p_int=0.003). In stratified analyses, intensive BP lowering was associated with lower risk of CVD (HR 0.68, 95% CI 0.45-1.00) and HF (HR 0.41, 95% CI 0.20-0.85) among participants with PTH <48 pg/ml; but not those with PTH >48 pg/ml. FGF23 did not modify the association of intensive BP control with any of the 3 outcomes.

Conclusion

Lower serum PTH levels may identify a subset of CKD patients who receive the greatest benefit from intense BP lowering. Further work is necessary to elucidate if tubular resistance to PTH is the mechanism responsible for these findings.

Effect of Randomization to Intensive Blood Pressure Lowering for CVD and HF Events, Stratified by PTH Above vs. Below the Median

Models adjusted for age, gender, race, randomized treatment arm, eGFR-Cr-Cys, urine ACR, prevalent CVD, prevalent HF, SBP, # anti-hypertensive meds at baseline, smoking, BMI, Total chol., HDL chol.

Funding

• NIDDK Support