ABI Predicts Renal Dysfunction in PAD Patients

BY MITCHEL L. ZOLER

VIENNA -- The ankle-brachial index predicted the risk of progression to end-stage renal disease, and declines in the ankle-brachial index over time were linked to an increased risk for death, cardiovascular events, and end-stage renal disease, all in patients with peripheral artery disease treated at one center.

The results also showed that treatment with either a statin or an ACE inhibitor was effective for slowing progression to end-stage renal disease in patients with peripheral artery disease (PAD), Dr. Harm H.H. Feringa said at the annual congress of the European Society of Cardiology.

The ability of the ankle-brachial index (ABI) to predict progression of renal dysfunction was explored by analyzing data collected from 1,940 patients with PAD and an ABI of less than 0.90 who were examined at Erasmus Medical Center in Rotterdam, the Netherlands, during 1988-2006. The average age of the patients was 64, their average ABI was 0.71, and the series excluded patients on dialysis. An ABI of 0.70 or less was measured in 72% of patients at baseline, and the average estimated glomerular filtration rate (GFR) was 78 mL/min per 1.73 m2. At baseline, 22% of patients had a GFR of 30-59 mL/min per 1.73 m2 indicating moderately reduced kidney function, 3% had a GFR of 15-29 mL/min per 1.73 m2 (severely reduced kidney function), and 2% had a GFR of less than 15 (renal failure). Median follow-up was 8 years.

During follow-up, 30% of the patients had worse renal function, 23% had a drop in their GFR of more than 25 mL/min per 1.73 m2, and 10% of the patients progressed to renal failure, while 40% had improved renal function, reported Dr. Feringa of the University of Rotterdam.

Patients with lower ABI values at baseline had an increased risk of greater progression of renal disease at the end of follow-up. In a multivariate analysis that controlled for other baseline variables, every 0.1 reduction in ABI at baseline was linked with a 34% increased risk of progression to renal failure during follow-up. "Patients with low ABIs need more intensive monitoring of renal function," Dr. Feringa said.

In the same analysis, treatment with agents from either of two drug classes was linked with a reduced risk for progression to renal failure: Treatment with a statin was associated with a 59% reduced risk, and treatment with an ACE inhibitor was linked with a 25% reduced risk. The finding was consistent with previously reported results from several other studies that examined the effect of statins or ACE inhibitors, he said.

NEW STUDIES APPEAR TO ESTABLISH A LINK BETWEEN LOW ABI VALUES AND THE PROGRESSION OF RENAL DISEASE IN PAD PATIENTS.

The second study involved 606 patients with PAD who were treated at Erasmus during 1996-2005. Their ABIs both at rest and after exercise were measured at baseline and after 1 year of follow-up. The patients' average age was 62 years, and their mean resting ABI at baseline was 0.69. Patients were followed for an average of 5 years, during which time they were tracked for all-cause death, which occurred in 14%; cardiac events, 6%; stroke, 8%; and progression to renal failure, 6%. Cardiac deaths accounted for about half of all deaths.

During the first year of follow-up, resting and exercise ABI each fell in about 75% of patients. Significant predictors of a drop in ABI included age, smoking, diabetes, and a history of stroke or myocardial infarction.

Patients were divided into quartiles based on their ABI change during the first year of follow-up. For changes in resting ABI, the quartiles were none (no change), and declines of 1%-5%, 6%-20%, and more than 20%. The quartiles for exercise ABI were similar. Clinical factors that raised the risk of patients having drops in their resting ABI included a history of stroke, which boosted the risk 4.6-fold; smoking, which raised the risk by 80%; and a prior MI, which raised the risk 60%. The risk of a drop in exercise ABI was raised 3-fold by diabetes, 2.3-fold by a history of stroke, and 90% by smoking.

A multivariate analysis that controlled for baseline differences in age, gender, smoking, hypertension, diabetes, and other factors showed statistically significant correlations between the decline in ABI over a 1-year period, both at rest and after exercise, and an increased incidence of each of the bad outcomes tallied during follow-up, Dr. Feringa said. (See chart.)

Commenting on this article, Dr. R. Eugene Zierler, University of Washington, Seattle, stated: "While the relationship between PAD (as assessed by the ABI) and the risk of death and non-fatal cardiovascular events is well-documented, the association of PAD and end-stage renal disease has received less attention. These new studies appear to establish a link between low ABI values and progression of renal disease. They also suggest that treatment with either statins or ACE inhibitors can reduce the rate of progression to end-stage renal disease in patients with PAD. Unfortunately, this summary does not give us any information on the status of the renal arteries in the study patients, so there is no way of distinguishing between ischemic nephropathy, primary parenchymal disease, and a combination both. Clearly, some patients with a component of ischemic nephropathy would benefit from revascularization in addition to pharmacologic treatment. However, the epidemiologic and natural history data provided by these studies is valuable because it focuses our attention on the patients at highest risk for poor outcomes and serves as the basis for clinical trials to determine the most appropriate therapeutic approaches."