Pretransplant Status Predicts Renal Failure in Heart Transplant Patients

May 02, 2007

May 2, 2007 (San Francisco) –– Renal failure is a recognized complication of heart transplantation, but prospective identification of patients likely to suffer such problems has not been straightforward. Now, 2 studies presented at the 27th annual meeting and scientific sessions of the International Society for Heart and Lung Transplantation have identified key characteristics that could aid in the process and improve heart transplant patient selection.

“If we can identify early risk factors for the development of chronic kidney disease it may inform ways to prevent it. It may also inform strategies for patient selection for heart transplantation, and for patient selection of combined heart and kidney transplant,” said Gregory D. Lewis, MD, postdoctoral fellow in the cardiology division at the Massachusetts General Hospital in Boston, during his presentation of the 1 of the studies.

Dr. Lewis and colleagues looked for predictors of early renal disease in 4457 patients who underwent cardiac transplant between 1995 and 2006 and were recorded in the Cardiac Transplant Research Database (CTRD). To be included in the study, each patient had to have at least 1 follow-up form in the database, with follow-up visits scheduled at 3, 6, and 12 months, and annually thereafter.

The researchers found that the risk of developing stage IV or V kidney disease, defined by the National Kidney Foundation classification system, occurred in 2 phases in the population. There was a sharp spike in the incidence during the first year after transplant surgery and a relatively small but continuous risk thereafter. The cumulative risk of chronic kidney disease was 6% at 1 year after transplantation, 10% at 3 years, and 14% at 5 years.

The risk factors associated with developing kidney disease within the first year include being female (relative risk [RR], 2.7; P < .0001), being older (RR, 2.5 for 60 vs 30 years; P = .005), lower pretransplant glomerular filtration rate (GFR) (RR, 3.0 for 30.0 vs 70 mL/min per 1.73 m2; P < .0001), larger body surface area (RR, 1.5 for 2.0 vs 1.5 m2; P = .02), and a mismatch between the recipient and donor body surface area (RR, 2.1 for 0.5 vs 0.0 m2, P = .0003). Surprisingly, pretransplant diabetes did not appear to be a significant predictor in this data set (RR, 1.3; P = .07), despite having been found to be a significant predictor in several smaller studies.

In addition to recipient characteristics, the researchers found several other predictors of chronic kidney disease, including longer myocardial ischemic time (RR, 1.8 for <2 vs >2 h; P < .0001), earlier transplant date (RR, 1.4 with groups compared in 5-year intervals; P = .02), and initial use of cyclosporine vs tacrolimus (RR, 3.2; P = .02). Remarkably, donor hypertension was also found to be a risk factor (RR, 1.6; P = .01).

The group also identified several factors that predicted the development of late-onset chronic kidney disease. Those included being female (RR, 1.9; P < .0001), lower preoperative GFR (RR, 3.0 for 30 vs 70 mL/min per 1.73 m2; P < .0001), older age (RR, 3.5 for 60 vs 30 yr; P < .0001), pretransplant insulin-dependent diabetes (RR, 2.4; P = .002), hypertension before transplant (RR, 1.5; P = .008), and peripheral vascular disease (RR, 1.8; P = .02).

The severity of pretransplant renal disease had a significant impact on posttransplant survival. Patients with a GFR below 30 mL/min per 1.73 m2 before transplantation had a 9% reduction in 5-year survival compared with those with flow greater than 30 mL/min per 1.73 m2. Moreover, patients who developed stage IV or V chronic kidney disease within 2 years of transplantation had a 16% reduction in 5-year survival compared with those who had better renal function.

“I think the question is very important and provocative, and it certainly requires an answer,” said Mark J. Zucker, MD, director of cardiothoracic transplantation of Beth Israel Medical Center in Newark, New Jersey, and associate clinical professor of medicine at Mount Sinai School of Medicine in New York. Knowing what to do with patients who have class IV and V kidney disease “is easy,” he said. “What happens in the middle group is harder.

“They looked at enough patients in CTRD, which is a good database, to provide us with an overview for a certain period of time,” Dr. Zucker told Medscape. There were limitations to the study, he noted, including a lack of information about acute renal problems in the immediate time period after transplantation. “If you’re going to look at the cohort at 12 months, 18 months, you really need to know if there was acute renal injury,” he said.

In an independent study, Mark J. Russo, of the division of cardiothoracic surgery and the International Center for Health Outcomes and Innovation Research at Columbia University in New York, and colleagues, also found that pretransplant kidney function was a strong predictor of posttransplant survival. Specifically, a multivariate analysis of 20,325 patients in the United Network for Organ Sharing database who underwent heart transplantation between 1995 and 2005 showed that pretransplant estimated GFR (eGFR) was significantly associated with posttransplant survival (P < .001).

In addition, a threshold analysis delineated 3 separate survival strata within the population, distinguishing among patients whose eGFR was below 33 mL/min per 1.73 m2, between 33 and 53 mL/min per 1.73 m2, and above 53 mL/min per 1.73 m2. A Kaplan-Meier plot for survival shows nonoverlapping curves for each group, with lower eGFR groups having poorer survival at all time points.

“eGFR is a strong predictor of post-transplant survival and should be considered when assessing patients for cardiac transplant,” Russo concluded. “The grey area [in eGFR] between 33 and 53 [mL/min per 1.73 m2] does exist, but for patients with an estimated glomerular function below 33 [mL/min per 1.73 m2], we can confidently tell that those are the patients we should not offer a heart transplant alone. If possible, perhaps we should offer them a combined heart and kidney transplant.”

The authors of both studies report no relevant financial relationships.

ISHLT 27th Annual Meeting and Scientific Sessions: Abstract 217. Presented April 26, 2007; Abstract 406. Presented April 27, 2007.

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