Researchers may have a new target with which to study cardiovascular risks in patients on hemodialysis (HD) who suffer from secondary hyperparathyroidism (SHPT): rs11063112, a single-nucleotide polymorphism (SNP) in fibroblast growth factor 23 (FGF23).

Using 1494 DNA samples from the Evaluation of Cinacalcet HCl Therapy to Lower Cardiovascular Events Trial (EVOLVE), Sharon Moe, MD, of Indiana University School of Medicine, and collaborators investigated polymorphisms in FGF23, its co-receptor alpha-klotho, or FGF23 receptors and their possible correlations with cardiovascular (CV) events and mortality. Investigators obtained DNA samples from 1083 participants of European ancestry and 411 participants of African ancestry.

Overall, patients with the SNP rs11063112 variant had a significant 32% and 40% increased risk of CV mortality and heart failure, respectively, compared with those who did not have the variant, according to results in the American Journal of Nephrology. The presence of the variant was associated with a significant 32% and 37% increased risk of CV mortality and heart failure, respectively, in patients of European ancestry, and a significant 31% and 51% increased risk among those of African ancestry. They found no such associations with the other SNPs.

“If validated, these results may help to recognize those patients receiving dialysis who are at increased risk for these events, or to identify persons who might be better suited for participation in clinical trials with FGF23-lowering therapies,” Dr Moe and the team stated.

EVOLVE trial participants had moderate to severe SHPT treated with the calcimimetic cinacalcet or placebo along with standard of care (i.e., phosphate binders and vitamin D therapy). The current study was the largest genetic study in HD patients to date with a long follow-up (up to 64 months). The findings, however, are not generalizable to other dialysis patients or to kidney transplant recipients.

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Reference

Schwantes-An TH, Liu S, Stedman M, et al. Fibroblast growth factor 23 genotype and cardiovascular disease in patients undergoing hemodialysis. Am J Nephrol. 2019;49:125–132. DOI:10.1159/000496060