Between 1991 and 2000, the number of patients in the United States receiving renal replacement therapy for end-stage renal disease (ESRD) has doubled, and by 2015, the number is expected to increase by an additional 50%.^1,2 Because older age is a principal risk factor for chronic kidney disease and the population is aging, we hypothesized that the proportion of ESRD caused by atherosclerotic renovascular disease (ARVD) is increasing. Because this issue has largely been ignored over the last decade, our goal was to describe the clinical epidemiology of ARVD in dialysis patients in the United States, focusing primarily, but not exclusively, on annual trends in disease burden.

Patients and methods

We used the US Renal Data System (USRDS) to obtain all data. All patients beginning maintenance dialysis therapy in the years 1996 through 2001 who were 67 years of age or older and used Medicare as the primary payer for at least the 2 preceding years were included in the study. The USRDS database was linked to Medicare claims accrued in the 2 years before dialysis initiation to identify claims indicating ARVD and a renal revascularization procedure before dialysis initiation.

Physician-rated cause of kidney failure is one of the data fields completed for federal registration of new maintenance dialysis patients. A secondary study outcome was to determine the concordance between ARVD listed as cause of kidney failure at dialysis initiation and ARVD determined by previous claims diagnosis, based on the hypothesis that US dialysis physicians may underestimate the proportion of ESRD attributable to ARVD.

Results

In the 2 years preceding dialysis initiation, 9.2% of patients (146 973) had diagnostic claims indicating ARVD. As shown in Table 1 (click for table), the percentage of patients with prior ARVD increased to 11.2% in 2001 from 7.1% in 1996. This association persisted in multivariate analyses. The rising prevalence of prior ARVD was not matched by an increase in physician-reported cause of ARVD at dialysis initiation: renovascular disease was listed as the primary cause of ESRD in 5.2% of patients, a figure that remained unchanged over the study period. There was a pronounced geographic variation in the prevalence of prior ARVD. For example, compared with Network 1 (New England), the adjusted odds ratio (AOR) for ARVD was 0.44 for Network 17 (Northern California and Pacific Islands).

As shown in Table 2 (click for table), 16.2% of patients with ARVD underwent a renal revascularization procedure before starting dialysis. Performance of revascularization was more common in the later study years, especially in 2000 and 2001. Geographic variation was also notable. Multivariate analyses suggested that the areas most likely to perform revascularization were Network 13 (Arkansas, Louisiana, and Oklahoma; AOR = 2.07), Network 14 (Texas; AOR = 1.79), and Network 6 (Georgia, North Carolina, and South Carolina; AOR = 1.72). Revascularization was least likely to be performed in Network 3 (New Jersey, Puerto Rico, and US Virgin Islands; AOR = 0.96), Network 2 (New York; AOR = 1.00), and Network 1 (New England; AOR = 1.00).

Table 3 (click for table) shows the relationship between ARVD preceding dialysis initiation and subsequent outcomes. Atherosclerotic renovascular disease showed a temporally antecedent association with peripheral vascular disease (adjusted hazard ratio [AHR] = 1.56), atherosclerotic heart disease (AHR = 1.28), cerebrovascular accident/transient ischemic attack (AHR = 1.20), and congestive heart failure (AHR = 1.12). Patients with ARVD who did and did not undergo a revascularization procedure were compared with patients without ARVD. Among ARVD patients, patients who underwent revascularization were less likely to die and more likely to have peripheral vascular disease, cerebrovascular accident/transient ischemic attack, and atherosclerotic heart disease.

Discussion

The prevalence of prior ARVD increased progressively from 1996 to 2001. Peripheral vascular disease and atherosclerotic heart disease were associated with a greater probability of having ARVD. The geographic variations in ARVD prevalence were notable. Renal revascularization was performed in 16.2% of ARVD patients before beginning dialysis, and the revascularization rates increased over the course of the study. There was a discrepancy between the cause of ESRD reported at the initiation of dialysis and the diagnoses indicating ARVD shown on the Medicare claims. ARVD correlated with higher rates of cardiovascular disease on dialysis therapy, but the death rates were slightly lower, a perplexing result perhaps related to the selection criteria used in the study. ARVD patients who had undergone revascularization also had higher rates of cardiovascular events but lower death rates.

There were almost twice as many patients with diagnostic claims of prior ARVD compared with patients with ARVD listed as the cause of ESRD at the time of dialysis initiation. It is noteworthy that ARVD could well be an incidental finding without a causal relationship to the pathogenesis of renal failure.³ Hence, it is not certain whether the results of this study are attributable to coding issues with diagnostic claims, heterogeneity in the use of diagnostic tests of the renal arteries, or real changes in pathogenesis of ESRD. Despite these limitations, however, these results must lead to concern that the problem of ARVD in ESRD patients is increasing over time.^4-10

The use of renal revascularization among ARVD patients increased modestly over the duration of the study. Although noncontrolled studies have suggested that ESRD can be delayed by revascularization in patients with critical ARVD,^11-13 convincing evidence from large randomized trials remains conspicuously absent. In this regard, results from the Angioplasty and Stent for Renal Artery Lesions (ASTRAL) trial should be enlightening. ASTRAL, which is examining renal function in approximately 800 ARVD patients randomly assigned to receive either revascularization or medical management alone, is expected to be completed in 2008.¹⁴

Many observations in this study suggested that the diagnosis and treatment of ARVD were influenced by factors other than disease severity. For example, older patients and African Americans had a lower likelihood of receiving a claims diagnosis of ARVD, as well as a lower likelihood of undergoing revascularization when ARVD was diagnosed. Similarly, the variability across ESRD networks was considerable and unexplained by comorbidity profiling.

In this study, ARVD was associated with higher rates of cardiovascular events, an outcome pattern duplicated among ARVD patients with or without revascularization. For unknown reasons, however, ARVD and revascularization correlated with slightly decreased mortality rates. We speculate that survivor bias may be responsible for these paradoxical findings. In particular, patients with ARVD who live long enough for ESRD to occur may be self-selected by virtue of a decreased susceptibility to death from cardiovascular disease.

This study had several limitations, one of which was the retrospective design and use of diagnostic claims to define comorbidity profiles and cardiovascular events. The accuracy of ARVD claims could not be verified in the sense that no information about the severity of angiographic lesions could be confirmed. It is conceivable that ARVD was an incidental finding in many patients, discovered during work-up for disease in nonrenal vascular beds. Because Medicare coverage is available to older US patients, generalizations to younger patients should be made with caution.

Conclusion

ARVD appears to be a common finding among older dialysis patients in the United States. Although ARVD is rapidly increasing, existing databases have failed to identify this worrisome trend. If confirmed, the findings from this study suggest that ARVD should be seriously considered in older patients with advanced chronic kidney failure.

References