Longer Dialysis, Lack of Transplant Among Risk Factors for Vascular Disease in Children With ESRD

About 5.4% of patients with end-stage renal disease (ESRD) who begin renal replacement therapy as children go on to have vascular events, and 4.1% of those patients die as a result of vascular events, though the real incidence rates are likely higher, according to new research.

New long-term data has identified key risk factors for vascular disease among children with end-stage renal disease (ESRD) who receive renal replacement therapy (RRT), but the study also highlights the difficulty in predicting which patients are at highest risk of death from vascular events.

It has already been established that children who develop ESRD have shorter life expectancies than their peers without ESRD. One of the leading risk factors for early death among this population is cardiovascular events. A 2004 study found 20-year survival among people who began RRT in childhood was 66%. The most common cause of death was cardiovascular disease.

Writing in Nephrology, corresponding author Amelia K. Le Page, MD, of Monash Children’s Hospital, in Australia, and colleagues, noted that little is known about clinically relevant vascular disease among pediatric patients with ESRD. The investigators decided to use a database of patients from Australia and New Zealand to quantify vascular events among children with ESRD, and to see if those data revealed any pertinent risk factors.

A search of the Australian and New Zealand Dialysis and Transplant Registry (ANZDATA) revealed 1268 patients who had commenced RRT as children (under age 18) between the years 1991 and 2017. Of those, 804 cases included follow-up after age 18.

With a median follow-up of 10.31 years, the investigators found 5.4% of the cohort reported vascular disease and 4.1% of patients died of vascular causes. On a cumulative basis, that translated to a vascular event rate (disease or death) of 5.5% at 10 years and 12.8% at 20-years. The median time between the start of RRT and the report of vascular disease was 11.65 years, Le Page and colleagues said, and the median age at report of vascular disease was 25.62 years.

When examining risk, the investigators found a number of key factors correlated with likelihood of vascular disease. Childhood vascular events were linked with non-Caucasian and non-indigenous ethnicity. Among those patients followed as adults, vascular events were associated with lack of childhood transplant, longer duration of childhood dialysis, and indigenous ethnicity.

While noting that there was only a small cohort of indigenous patients in the study, Le Page and colleagues said the higher incidence of cardiovascular events after age 18 was “consistent with the excess cardiovascular mortality seen for the overall Australian Indigenous population,” which they linked with high rates of cardiovascular risk factors and also long-term social inequalities.

While their data showed significant risk factors for vascular disease, it also showed that many patients with cardiovascular disease go undiagnosed. Fifty-one patients in the cohort died with a cardiovascular cause of death, representing one-third 32.48% of all deaths. However, among those who died as a result of vascular issues, only 25.49% had a diagnosed vascular disease prior to their death.

“This infrequent reporting of vascular disease but strong association with death highlights the need for recognition of risk and early prevention,” they said.

Le Page and colleagues said cumulative incidence calculations suggest that, 25 years after starting RRT, actual rates of vascular disease in this population is probably around 15% and vascular death is probably closer to 7.5%.

The investigators concluded that patients in the high-risk categories should be monitored closely as they become adults, with their physicians prioritizing screening and prevention in order to diagnose and treat vascular disease.

Reference

Le Page AK, Kennedy SE, Durkan A, Chaturvedi S, Walker A, Sypek MP. Incidence and predictors of vascular events following end-stage kidney disease in childhood. Nephrology (Carlton). Published online May 2, 2021. doi:10.1111/nep.13886. doi:10.1111/nep.13886