Heart Disease Screening Showed No Kidney Transplant Benefit

Mitchel L. Zoler, PhD

April 28, 2023

Testing asymptomatic, low-risk patients for coronary heart disease (CHD) prior to undergoing a kidney transplant showed no benefit, and a signal for possible harm, in a recently published study of more than 79,000 US Medicare patients during 2000-2014, suggesting that routine use of such pretransplant screening should stop.

"We are testing more than we need to on medical grounds, and this sentiment is starting to spread among the transplant community," said Xingxing S. Cheng, MD, lead author of the study, in an interview.

"The evidence is very clear that guideline-directed medical therapy works, but it is very underutilized in patients with kidney disease, especially those with end-stage kidney disease. This is where the focus needs to shift," said Cheng, a transplant nephrologist at Stanford University, Stanford, California.

This call to halt routine use of CHD screening prior to kidney transplantation because of its unproven benefit received endorsement from a trio of physicians who wrote an editorial that accompanied the report from Cheng and her co-authors.

CHD Testing 'Comes With Substantial Harms'

"While well-intentioned, CHD testing comes with substantial harms," wrote Rohini V. Kopparam, MD, Deborah Grady, MD, and Rita F. Redberg, MD, in their editorial. With this potential for harm and the absence of evidence supporting a benefit "pre-operative evaluation before kidney transplant should only be done in the context of a randomized trial," said the editorialists, who all work at the University of California, San Francisco.

The new findings by Cheng came out fewer than 3 months after publication in October 2022 of a Scientific Statement from a panel of the American Heart Association chaired by Cheng that called for screening before a kidney transplant with a 12-lead ECG and a resting heart assessment with transesophageal echocardiography in "all kidney transplantation candidates without known CHD, except a very low-risk subgroup: age < 40 years, no diabetes, no smoking, no peripheral artery disease or cerebrovascular disease, and not on dialysis." In short, Cheng's new report appeared to show that this suggested approach was misguided.

"Research always precedes practice," explained Cheng. "It takes time to change culture," and the 2022 Scientific Statement reflected the best judgement of the diverse group of experts on the writing panel at the time they wrote it.

Data From Low-Risk Medicare Patients

The study run by Cheng and her co-authors included all 79,334 low-risk adults listed for a first-time kidney transplant during the 15-year study window who had Medicare coverage for at least 1 year before and at least 1 year after the time of their listing. They defined low risk as people without any major risk factors, including > 60 years old, having diabetes, and having known CHD.

A total of 34,688 of these patients (44%) underwent CHD testing at some time the year before their transplant, including 8125 (23% of the total tested) who had their testing at the time of or before joining the kidney-recipient waitlist, and 26,563 (77%) who underwent testing after joining the waitlist. The proportion of listed low-risk patients who underwent testing varied widely across the centers where they were treated.

The study's primary outcome was a composite of death or acute myocardial infarction (MI) within 30 days after kidney transplantation occurred and was adjusted for several potential confounders including age, sex, race, education, and type of dialysis received.

This endpoint occurred in 4604 patients (5.3%) in the study cohort, with slightly fewer than half dying and slightly more having an acute MI.

CHD Screening Produced No Significant Outcome Difference

The analysis showed no significant difference in the incidence of the primary outcome associated with pretransplant CHD testing, but did show a numerically increased rate of the adverse outcome of 1.95 percentage points among patients who underwent testing, a difference that fell just short of significance, a "directionality pointing toward possible harm," wrote the authors.

"Even what appears to be innocuous screening may be associated with harm when used broadly in asymptomatic patients," wrote Cheng and her co-authors. For example, they noted that during the earliest years included in this study, 2000-2003, patients identified with CHD through screening may have received the standard of care for percutaneous coronary intervention at that time, which was placement of a bare-metal stent that may have led to an excess of acute MIs or deaths.

Another possible explanation, they added, is that the numerical difference seen was caused by residual confounding between those who had screening and those who did not despite the study's effort to adjust for potential confounding factors.

Unnecessary pretransplant CHD testing can lead to an array of potentially adverse consequences, wrote the editorialists, including "false-positive results, increased anxiety, invasive diagnostic and therapeutic procedures without clear benefit, and, specifically in this population, delays or denial of transplant listing."

In addition, testing and any treatment it might lead to can produce unnecessary cost and effort for the patient and the healthcare system as a whole, the editorial said. And some patients with advanced chronic kidney disease can rapidly progress to end-stage disease if they receive nephrotoxic contrast agents for invasive angiography.

Cheng, Kopparam, Grady, and Redberg report no relevant financial relationships.

JAMA Intern Med. Published January 23, 2023. Abstract.

Mitchel L. Zoler is a reporter with Medscape and MDedge based in the Philadelphia region. He can be reached on Twitter: @mitchelzoler.

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