Genetics Ups Risk of Cardiac Arrest in Dialysis Patients

Pam Harrison

April 17, 2015

Heritable factors appear to contribute to the risk for cardiac arrest in patients receiving dialysis, according to a study published online April 16 in the Journal of the American Society of Nephrology.

"The discovery of predictive markers for cardiac arrest in [end-stage renal disease] could alter the practice of nephrology, because the risk of cardiac arrest is 5% per year in the dialysis population," write Kevin Chan, MD, from Fresenius Medical Care North America, Massachusetts General Hospital, Boston, Massachusetts, and colleagues.

They found that genetically related family members receiving dialysis who were not living together had an 88% greater risk for cardiac arrest (odds ratio [OR], 1.88; 95% confidence interval [95% CI], 1.25 - 2.84) compared with phenotypically matched unrelated control patients who were also receiving dialysis.

Overall, the investigators found that 4.3% of both members of family pairs involved in the cohort study died of cardiac arrest compared with 2.6% of control pairs. They calculated that genetically related family members who lived together had a 66% greater risk for cardiac arrest compared with dialysis patients who were not related (OR, 1.66; 95% CI, 1.20 - 2.28).

In contrast, spouses receiving dialysis, who lived together in the same environment but who were unrelated genetically, had no increase in risk for cardiac arrest (OR, 0.95; 95% CI, 0.60 - 1.59).

"Taken altogether, our study suggests that family history significantly increased the risk of fatal cardiac arrest by approximately 70% among patients on dialysis," Dr Chen and colleagues write. "[A]nd we did not see a large change in risk among family members who cohabited or lived apart."

The team identified 5117 pairs of patients who came from the same family among a population of close to 650,000 patients with end-stage renal disease drawn from chronic dialysis facilities.

Some 4053 of these pairs were genetically related and were further classified into pairs who lived together (n = 2449) and pairs who lived in separate environments (n = 1604).

Another 1064 of these pairs were non–genetically related spouses.

Multivariable logistic modelling was used to determine the effect size of inherited and acquired factors associated with cardiac arrests.

Results showed that patients with a nonspouse relative who had previously died from a cardiac arrest had a 45% increased risk of dying from a cardiac arrest relative to patients without a family history of cardiac arrest (OR, 1.45; 95% CI, 1.19 - 1.75).

Other significant factors associated with an increased risk for cardiac arrest included age, black race, serum potassium levels, erythropoietin doses, and documented coronary artery disease.

Protective factors associated with a lower risk for cardiac arrest included higher albumin levels and a lower calcium dialysate bath.

"These findings...suggest that genetic factors — or differences in DNA sequence — contribute to the high risk of sudden death among patients on dialysis," Dr Chan said in a news release. "It paves the way for more detailed genetic studies in the dialysis population to find specific genes that could explain the high risk of cardiac arrest and potentially new treatments for these patients."

Patients receiving dialysis are 20 times more likely to have a cardiac arrest compared with the general population.

Dr Chen and one coauthor receive salary support from Fresenius Medicare North America. The other authors have disclosed no relevant financial relationships.

J Am Soc Nephrol. Published online April 16, 2015. Abstract

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