UF Researchers Link Poor Kidney Function With Risk Of Dying From Cardiovascular Disease In Transplant Patients
GAINESVILLE, Fla. — For patients in the end stages of renal failure, receiving a kidney transplant doesn’t just improve kidney function – it also has another striking benefit that until now has been less widely appreciated: Their risk of dying from cardiovascular disease plummets, University of Florida researchers report.
That startling improvement occurs despite the fact that the anti-rejection medicines they must take for the rest of their lives can cause high blood pressure, trigger diabetes and raise cholesterol, all factors traditionally associated with an increased chance of developing cardiovascular disease or dying from it.
However, sustaining optimal kidney function in the first year after transplantation and beyond is critical, experts say. Even though kidney transplantation in and of itself lowers patients’ chances of dying from cardiovascular disease, UF physicians have found that if kidney function begins to decline, that risk climbs nonetheless. Those with the worst kidney function a year after transplantation were more than twice as likely to die from cardiovascular disease within 10 years of the operation as those awaiting transplant.
The researchers described their findings, gleaned from a review of the medical records of nearly 60,000 kidney transplant patients, June 1 at the annual meeting of the American Transplant Congress in Washington, D.C. They also published the data in a recent issue of the journal Transplantation.
“Simply transplanting someone decreases their risk of heart disease dramatically,” said Dr. Bruce Kaplan, a professor of medicine and of pharmacology and therapeutics at UF’s College of Medicine. “Obviously what we do with a transplant is give you renal function. Just by changing that we decrease the risk of heart problems so much, despite making all the classic factors associated with heart disease worse. If people go back on dialysis, the risk goes back up, from a 0.5 percent a year risk of cardiovascular death to an 8 percent a year risk. That’s a huge increase.”
Still under consideration is what effect the news will have on the population at large, particularly as the number of patients who develop cardiovascular disease escalates. Some studies of patients who did not undergo transplantation also have linked chronic kidney failure with a substantially increased chance of dying from cardiovascular disease, Kaplan said, independent of whether patients had known risk factors such as high blood pressure or high cholesterol.
Meanwhile, cardiovascular disease is rampant in patients with chronic kidney disease and is the No. 1 reason why patients with end-stage renal disease die. Cardiovascular disease also is up to 100 times more common in patients with kidney disease than in people of the same age and sex who don’t have kidney problems. Increasing evidence also suggests even mild degrees of impaired kidney function may increase the risk of cardiovascular disease-related death.
About 50,000 patients currently await kidney transplantation – a number expected to double by 2010, according to the United Network for Organ Sharing. Yet the availability of donor kidneys is strikingly low. Each year, only 10,000 kidney transplants are performed in the United States. Most transplant recipients have waited up to three years for their organs.
UF researchers analyzed the medical records of nearly 60,000 adults registered in the United States Renal Data System who received a kidney transplant between 1988 and 1998 and had survived at least a year after the operation.
Kidney function is assessed by measuring blood levels of creatinine, a protein that reflects the ability of the kidneys to filter substances. Generally, the lower the creatinine level the better.
“Our bodies make creatinine – it comes from muscles – and we make the same amount every day,” said Kaplan, also medical director of the kidney and pancreas transplant program at the Shands Transplant Center at UF. “If you accumulate creatinine, that means your kidney function got worse.”
Kaplan collaborated on the study with Dr. Herwig-Ulf Meier-Kriesche, an associate professor of medicine at UF and the clinical director of renal transplant at Shands at UF medical center, and Dr. Rajendra Baliga, a fellow in the division of nephrology, hypertension and transplantation at UF. Together they determined nearly 2,000 people died from a cardiovascular cause during the study period, a number that accounted for 30 percent of all the deaths that occurred. They also looked at how many patients died from infections or cancer.
The researchers took into account other factors that potentially could have influenced the results, such as donor and recipient age, gender, race, cause of end-stage renal disease, length of dialysis before transplantation, year of transplantation, donor source and age, delayed graft function and immunosuppressive regimen.
“We looked at different grades of renal function and found a continuum: As renal function worsened, the risk of dying from cardiovascular disease went up markedly,” Kaplan said.
“Our study could not say the risk was independent of blood pressure or lipids; we were limited in that extent,” he added. “However, since our study, other studies of smaller size involving non-transplant patients have found it is truly independent of those factors.”
Dr. Robert S. Gaston, a professor of medicine and surgery at the University of Alabama at Birmingham, where he also serves as medical director of kidney and pancreas transplantation, said the UF study is notable.
“These important data are in keeping with recent findings that link early chronic kidney disease in the population-at-large to increased cardiovascular risk,” Gaston said. “They also tell us that maintaining excellent kidney function during the first year after transplantation has important long-term benefits.”
The findings add to the relatively new notion that not all episodes of organ rejection are bad in the long run.
“It used to be said that any episode of organ rejection was bad and was going to hurt a patient’s outcome,” Kaplan said. “That’s not true. It’s the rejections that cause permanent functional damage that bode the worst prognosis.”
The jury’s still out on why kidney function appears to be so strongly associated with cardiovascular disease. Theories abound, Kaplan said, and some researchers have speculated about the influence of inflammation and certain proteins produced when the kidneys are failing.
“But right now we’re really at a point where much of it is still unexplained,” he said.