Serum activin A and bone metabolism in patients undergoing hemodialysis

Activin A, which promotes osteoclast differentiation, increases with declining kidney function, but its role in bone metabolism in kidney failure remains unclear. We found that higher activin A levels were associated with increased bone turnover markers, independent of parathyroid hormone levels.

Activin A, produced by various cells including bone marrow stromal cells, immune cells, and osteoblasts, is thought to promote osteoclast differentiation. Serum activin A levels rise with declining kidney function, but its role in bone metabolism in kidney failure remains incompletely understood.

Serum activin A levels were measured in 35 healthy individuals and 654 patients undergoing maintenance hemodialysis. Associations of serum activin A with tartrate-resistant acid phosphatase isoform 5b (TRACP5b), bone-specific alkaline phosphatase (BALP), and metacarpal bone mineral density were assessed using both unadjusted and multivariable-adjusted linear regression analyses. Serum activin A levels were also compared between patients with and without a history of fracture, and between those who developed incident fractures during follow-up and those who did not.

The median serum activin A level in hemodialysis patients was 733 pg/mL (interquartile range (IQR), 591-912), approximately 2.6-fold higher than that of healthy controls (277 pg/mL; IQR, 216-289; P < 0.001). Patients with higher activin A levels had longer dialysis durations, a higher prevalence of polycystic kidney disease, and higher serum phosphorus and alkaline phosphatase levels. Higher activin A levels were significantly associated with increased TRACP5b levels independently of intact parathyroid hormone levels, with a similar trend observed for BALP. Serum activin A levels were not associated with metacarpal bone mineral density, history of fracture, or incident fractures.

These findings suggest that in patients with kidney failure, elevated activin A may contribute to high bone turnover, although its ability to predict fracture risk appears limited. Further studies are warranted to investigate its potential as a therapeutic target.