Kidney Week

Abstract: FR-PO317

Association of Serum Alkaline Phosphatase with CKD and Cognitive Function in Patients with Diabetes and Acute Coronary Syndrome

Session Information

• CKD: Clinical, Outcomes, Trials - II
  November 08, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: CKD (Non-Dialysis)

• 2102 CKD (Non-Dialysis): Clinical, Outcomes, and Trials

Authors

• Haarhaus, Mathias, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden

Mathias Haarhaus,

• Ray, Kausik K., School of Public Health, Imperial College London, London, United Kingdom

Kausik K. Ray,

• Schwartz, Gregory G., School of Medicine, University of Colorado, Aurora, Colorado, United States

Gregory G. Schwartz,

• Kulikowski, Ewelina, Resverlogix Corp., Calgary, Alberta, Canada

Ewelina Kulikowski,

• Johansson, Jan O., Resverlogix Inc., San Francisco, California, United States

Jan O. Johansson,

• Sweeney, Michael, Resverlogix Inc., San Francisco, California, United States

Michael Sweeney,

• Khan, Aziz, Resverlogix Corp., Calgary, Alberta, Canada

Aziz Khan,

• Halliday, Christopher, Resverlogix Corp., Calgary, Alberta, Canada

Christopher Halliday,

• Lebioda, Kenneth E., Resverlogix Corp., Calgary, Alberta, Canada

Kenneth E. Lebioda,

• Wong, Norman Cw, Resverlogix Corp., Calgary, Alberta, Canada

Norman Cw Wong,

• Winblad, Bengt, Karolinska Institutet, Huddinge, Sweden

Bengt Winblad,

• Zetterberg, Henrik, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden

Henrik Zetterberg,

• Brandenburg, Vincent, Rhein-Maas-Klinikum, Würselen, Germany

Vincent Brandenburg,

• Beddhu, Srinivasan, Veterans Affairs Salt Lake City Healthcare System, Salt Lake City, Utah, United States

Srinivasan Beddhu,

• Tonelli, Marcello, University of Calgary, Calgary, Alberta, Canada

Marcello Tonelli,

• Zoccali, Carmine, CNR IFC, Clinical Epidemiology of Renal Diseases and Hypertension, Reggio Calabria, Italy

Carmine Zoccali,

• Kalantar-Zadeh, Kamyar, Harold Simmons Center for Kidney Disease Research and Epidemiology, University of California Irvine, School of Medicine, Orange, California, United States

Kamyar Kalantar-Zadeh,

Background

Patients with diabetes and chronic kidney disease (CKD) have increased risk for cardiovascular disease events and vascular dementia. Alkaline phosphatase (ALP) is a risk marker and possible risk mediator for cardiovascular (CV) disease, Alzheimer’s disease and vascular dementia. ALP has been reported to cross the blood brain barrier and to predict cognitive risk in CKD patients, potentially via vascular mechanisms or dephosphorylation of tau. Apabetalone is a bromodomain and extraterminal (BET) inhibitor selective for bromodomain 2, lowers ALP in a dose-response fashion and is being evaluated for prevention of CV disease events in the phase 3 BETonMACE trial. We examined baseline data from that trial to define the associations of ALP with CKD and cognitive function.

Methods

BETonMACE compares cardiovascular outcomes with apabetalone or placebo in 2425 patients with diabetes and acute coronary syndrome. CKD was defined by eGFR < 60 mL/min/1.73m². Cognition was assessed by the Montreal Cognitive Assessment tool (MoCA) in patients aged 70 and older at baseline (n=467) including in CKD patients (n=86).

Results

CKD was present in 11% (n=263) and was associated with age, female sex, longer history of diabetes, and higher ALP. Approximately half of the population showed MoCA score <26 suggesting early cognitive impairment. Lower MoCA score was associated with: a) higher ALP, and, b) with presence of CKD.

Conclusion

Elevated ALP is associated with poorer cognitive function and greater prevalence of CKD. Apabetalone, which lowers ALP, is being evaluated for effects on CV events, CKD, and cognitive function in the phase 3 BETonMACE trial reporting 2019.