Young Adults with ESRD at Increased Risk for Cardiovascular Disease and Mortality

In patients with end-stage renal disease (ESRD), including children and adults, cardiovascular disease (CVD) is a leading cause of morbidity and mortality. In individuals ≥45 years of age, 87% have developed CVD at the time of ESRD onset and approximately 50% of deaths are attributed to CVD. In children with ESRD in the United States, CVD-related mortality occurs in 23%; in other countries the percentage is as high as 50%. There have been numerous studies into the CVD-associated health status of children and adults with ESRD; however, there are few data available on the burden of CVD in young adults (ages 22-29 years) with ESRD.

In recent years, the US Renal Data System (USRDS) Annual Data Report has included surveillance data specific to young adults with ESRD. The report indicates that there may be differences in this patient population regarding the causes of ESRD, comorbidities, duration of pre-ESRD kidney disease, and health outcomes compared with children and older adults. Zubin J. Modi, MD, and colleagues, conducted a population-based cohort study to test the hypothesis that there is an association between young adult-onset ESRD and higher rates of CVD-related hospitalizations and mortality. Results of the study were reported online in JAMA Cardiology [doi:10.1001/jamacardio.2019.0375].

The study was conducted as part of the USRDS Coordinating Center contract with the National Institutes of Health and was approved by the University of Michigan institutional review board. Data were gathered from the USRDS for all patients 1 to 29 years of age who initiated renal replacement therapy for ESRD between January 1, 2003, and December 31, 2013. Hospitalization data were obtained from Centers for Medicare & Medicaid Services (CMS) claims data. Data on mortality were obtained from CMS ESRD Death Notification Forms (Form 2746).

The study cohort was categorized into three groups based on age at ESRD incidence: (1) young adults, 22 to 29 years of age; (2) adolescents, 12 to 21 years of age; and (3) children, one to 11 years of age. International Classification of Diseases, Ninth Revision discharge codes were used to identify hospitalizations for CVD.

The primary outcomes of interest were cardiovascular hospitalizations and cardiovascular mortality. The researchers computed 1-year, 3-year, and 5-year mortality rates adjusted by sex, race, ethnicity, and primary cause of ESRD. Patients were followed up until they died, were lost to follow-up, recovered, or survived until the end of the study period (December 31, 2014). Data analysis was conducted between May 2016 and December 2017.

The total study cohort included 33,156 patients with incident ESRD ages one to 29 years (20,245 young adults, 10,024 adolescents, and 2887 children). Of the total study population, 16.2% (n=5357) died, 3.6% (n=1195) were lost to follow-up, 6.8% (n=2247) recovered, and 73.4% (n=24,357) survived to the end of the study period. The group of young adults had the highest percentage of blacks, the lowest proportion of those with private insurance, the highest proportion of uninsured, high rates of being overweight or obese, and were least likely to have received nephrology care prior to the diagnosis of ESRD.

Most of the participants in the young adult group had ESRD cause other than glomerulonephritis or congenital, hereditary, or cystic disease. Of the other causes, the most common were unspecified hypertension or large vessel disease (34.1%, n=4142/12,136) or diabetes mellitus (30.4%, n=4057/12,136). Of those with ESRD secondary to diabetes, approximately two-thirds had type 1 diabetes mellitus (n=2656 of 4057 with diabetes). At onset of ESRD, hypertension and diabetes were the most common comorbidities (n=15,791/20,245 and n=4537/20,245, respectively).

During the 5-years following onset of ESRD, the adjusted CVD hospitalization rate for young adults remained high and stable, and converged with rising rates in adolescents. Rates in children remained low and stable over the follow-up period. For young adults, the adjusted CVD hospitalization rates were 138 per 1000 patient-years (95% confidence interval [CI], 121-159) at year 1; 147 per 1000 patient-years (95% CI, 134-162) at 3 years; and 146 (95% CI, 134-160) per 1000 patient-years at 5 years.

The rates for young adults were significantly higher than those for adolescents (74 per 1000 person-years at 1 year, 102 per 1000 person-years at 3 years, and 116 per 1000 person-years at 5 years). The rates for children at 1 ,3, and 5 years were 48, 37, and 33 per 1000 person-years, respectively. In young adults, heart failure, coronary artery disease, arrhythmias, and valvular heart disease were the most common causes of cardiovascular hospitalization over 5 years.

Compared with preemptive transplant, hemodialysis and peritoneal dialysis were associated with a higher risk of CVD (hazard ratio [HR], 14.14; 95% CI, 5,.92-34.28 and HR, 8.47; 95% CI, 3.50-20.53, respectively). Other factors associated with cardiovascular hospitalization included age >21 years at onset of ESRD, black race, female sex, enrollment in public insurance or no insurance (vs private insurance) at ESRD onset, and ESRD cause other than congenital, hereditary, or cystic diseases. Comorbidities present at ESRD onset that were associated with higher risk of hospitalization were heart failure, coronary artery or cardiac disease, hypertension, and diabetes. Patients with a more recent year of ESRD onset had a higher risk of cardiovascular hospitalization.

There were 5357 all-cause deaths in the study population. Of those, 2019 (37.7%) were attributed to CVD. CVD accounted for 39.1% (n=1577/4038) deaths among the young adults. The 5-year mortality cumulative incidence attributable to CVD causes was 7.3% in young adults, 4.0% in adolescents, and 1.7% in children. The rates of cardiovascular mortality in young adults were higher at all three study points than in adolescents and children.

Limitations to the study cited by the authors included excluding patients with ESRD onset prior to age 1 year or adults >29 years; the lack of data on all potential risk factors; lack of access to data on the use of anti-hypertensive or lipid-lowering medications; and lack of detailed information on pre-ESRD management.

In conclusion, the researchers said, “Young adults form a unique population that share features of both adult and pediatric ESRD, requiring specialized clinical and research attention to improve outcomes. CVD mortality accounts for almost 40% of all deaths in patients with ESRD, beginning in young adulthood, and is up to 500 times the rates documented in the general population. Potentially modifiable risk factors for this young adult population may include optimizing healthcare for the underlying kidney disease and other coexisting conditions before the onset of ESRD and increasing access to preemptive transplant. Both modifiable and nonmodifiable risk factors, including race and sex, provide additional opportunities to explore the genetic, biologic, environmental, and social determinants of the observed differential CVD mortality. These findings provide the basis for continued rigorous evaluation of CVD in young adults with incident ESRD. Identified modifiable risk factors may also be future targets for interventions. Together, these steps may lead to improved implementation of age-appropriate treatment and patient management strategies and overall cardiovascular health of this unique population.”

Takeaway Points

  1. Young adults, ages 22 to 29 years, are at higher risk for cardiovascular disease (CVD) associated with end-stage renal disease (ESRD) than other age groups.
  2. Results of a population-based cohort study found that young adults with ESRD had a higher risk for hospitalization related to CVD compared with adolescents (12 to 21 years) and children (one to 11 years).
  3. Adjusted hazard ratios for CV mortality were higher for young adults with all causes of ESRD than children; adolescents had a lower risk for CV mortality than young adults for all causes of ESRD except glomerulonephritis.