1 Department of Nephrology and Hypertension, and 2 Department of Radiology, University Medical Center Utrecht, Utrecht, The Netherlands
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Abstract |
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Methods. Forty-nine of 80 consecutive patients (37 males, 12 females) starting renal replacement therapy in our centre gave informed consent and underwent spiral computed tomographic angiography of their renal arteries. A renal artery diameter reduction of 50% or more assessed by two radiologists was considered as a significant stenosis.
Results. Twenty of 49 patients (41%) had an ARAS, and in eight cases (16%) this was bilateral or unilateral with a single kidney. Women were more likely to have an ARAS than men; 75 (9/12) vs 30% (11/37, P<0.01). However, relatively more women declined participation. Non-participants and participants did not differ in respect to other relevant clinical data. Nonetheless, findings in these patients would be negative, the prevalence of ARAS would still be 31% in women and 22% in men (NS). In 13 patients with ARAS the registered diagnosis of ESRF either was hypertension, renovascular disease or unknown. Assuming that in these patients atherosclerotic renovascular disease was the cause of renal failure, a total of 13 patients (13/49, 27%) entered the dialysis programme because of this problem.
Conclusions. These results suggest that ARAS is an important cause of ESRF.
Keywords: atherosclerosis; renal artery stenosis; renal failure; renal replacement therapy
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Introduction |
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Studies in Europe and in the USA suggest that renal artery stenosis is a frequent cause of ESRF [59]. In the elderly it is probably the most common cause and the incidence is increasing faster than other causes of ESRF [911]. However, the true prevalence is still unknown: most data are based on uncontrolled local registries [5,6,9]. Only two studies were specifically designed to investigate the prevalence of ARAS in patients starting dialysis. Both were relatively small, and suffered from possible selection bias [7], or used indirect methods to diagnose renal artery stenosis [8].
We studied the prevalence of ARAS in patients 45 years of age or older who were soon starting renal replacement therapy. We used spiral CT angiography (SCTA), which has emerged as a highly accurate non-invasive method to visualize the renal arteries and to identify renal artery stenoses [12,13].
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Subjects and methods |
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Methods
For each included patient we examined all clinical data. Hypercholesterolaemia was defined as serum cholesterol levels of >6.5 mmol/l or the use of lipid-lowering drugs.
SCTA was performed with a commercially available scanner (Tomoscan SR 7000; Philips Medical Systems, Best, The Netherlands), according to our protocol as described before [13]. SCTA-, MRA- and intra-arterial angiography images were evaluated independently by two radiologists. A renal artery diameter reduction of 50% or more in the two-dimensional plane assessed by two radiologists was considered as a significant renal artery stenosis. A 50% reduction in the two dimensional plane corresponds with a 75% reduction of the arterial lumen, which has shown to be haemodynamically significant [14]. In case of disagreement about the presence of a significant stenosis a third radiologist evaluated these scans.
Statistical analysis
All values are expressed as mean±standard deviation. For the comparison of statistical significance between two groups, the Student's t-test was used. Differences between frequency distributions were tested by 2 test or Fisher's exact test for small samples. A difference was considered significant if P<0.05.
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Results |
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Nearly all patients were hypertensive or treated for hypertension, irrespective of the presence of renal artery stenosis. The number of antihypertensive drugs and the duration of hypertension were not different between patients with and without ARAS. Prevalence of a history of diabetes, hypercholesterolaemia, smoking and presence of clinically manifest extrarenal atherosclerotic disease was also not different (Table 1). Mean pole-to-pole kidney size was significantly less in kidneys with a stenosis as compared with kidneys of patients without a stenosis (9.1±1.4 vs 10.0±2.6 cm, P<0.05). The survival rate 30 months after starting renal replacement therapy was not significantly different for patients with and without ARAS (65%, 13/20 vs 79%, 23/29).
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Discussion |
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This is the first study in which all patients entering dialysis were investigated for the anatomical presence of a renal artery stenosis irrespective their renal diagnosis. We used SCTA as a minimal invasive method to visualize the renal arteries. It is a robust and highly sensitive and specific method to diagnose ARAS and it may be even superior to standard angiography [13].
The high prevalence of ARAS in patients starting with dialysis confirms the observations that renovascular disease might be an important cause of renal failure in the elderly. Reported estimations vary between 11.2 and 38.7% [510]. This wide range probably reflects the lack of uniformity in definition and mode of diagnosis in these studies (Table 2). In two registry reports using EDTA diagnostic code system [5,9] patients were classified as suffering from renovascular disease (without further precision) based on the physicians opinion of the most likely diagnosis. In Mailloux et al. [6] study the classification was based on either angiography, or a suggestive renography in the absence of significant proteinuria or abnormalities in the urine sediment. The estimated prevalence is these three studies was 11.2 [5], 18 [10] and 16.6% [6]. Scoble et al. [7] concluded from their angiographic study that atherosclerotic renal disease accounted for 14% of elderly patients starting dialysis. However, renal angiography was performed only if no other diagnosis was made or renovascular disease was suspected on clinical grounds. As in neither of these studies [57,10] the diagnosis of renovascular disease was considered or explored in case of another available diagnosis, the diagnosis of renovascular disease was probably underestimated.
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Given the apparent abundance of atherosclerotic renal artery disease in elderly patients starting dialysis, two questions are important: was it the (main) cause of renal failure, and could angioplasty have prevented or postponed the need for dialysis. In 13 patients with ARAS the registered diagnosis of ESRF was either hypertension, renovascular disease or unknown. Assuming that in these patients ARAS was indeed the cause of renal failure, a total of 13/49 (27%) patients entered the dialysis programme because of this problem. In the 31 subjects who could not be studied, at least six (19%) fulfilled these criteria. Therefore, it is unlikely that the high frequency of ARAS in the patients who underwent SCTA was due to selection bias.
All 12 cases of unilateral stenosis were newly identified. In four of these no other cause of renal failure was known. Of course, this single abnormality cannot cause renal failure. On the other hand, it is well known that atherosclerotic renovascular disease is complex: it also involves renal parenchymal changes in ipsilateral as well as contralateral kidneys, due to, respectively, ischaemia or high perfusion pressure, in addition to metabolic factors and smoking [15]. The relevance of a unilateral stenosis for overall renal function thus depends upon the severity of parenchymal disease in the contralateral kidney. Indeed, we observed that many patients with unilateral ARAS and no apparent other renal disease display a decrease in renal function upon starting ACE-inhibition [16], or show a halt in progression of renal dysfunction upon stenting [3]. Conceivably, treatment of a single renal artery stenosis can also be beneficial to slow down progression of renal failure in patients who also have some other primary form of parenchymal disease, but that is difficult to prove and to our knowledge their are no examples reported in the literature.
Eight patients had bilateral ARAS and in seven it was the only recognized cause of renal failure. Five had been treated for ARAS in an earlier stage. Two of these had patent renal arteries at the time of starting dialysis and in another three re-stenosis was found but re-intervention was not successful or contra-indicated. In the remaining three patients with bilateral disease (38%) this was newly diagnosed. Our study was not designed to study the effect of rescue revascularization in these patients with terminal renal failure. In fact, our experience in that context is limited, and only few data are available in the literature. Altogether, the efficiency of rescue therapy, whether surgical or radiological, is limited and seems to be of benefit only in carefully selected patients with sufficient viable kidney mass [7,17]. One larger series in 20 patients presenting with ARAS and ESRF showed that surgical intervention could improve renal function, and 14 patients were still off dialysis one year later [18]. Based on this scarce information, it seems defendable to search for this diagnosis in cases of quickly progressing unexplained renal failure [18], in order to try rescue revascularization. That renal artery stenting at an earlier stage of renal dysfunction can stabilize or slow down progression has so far been shown only in uncontrolled studies [3,4,19]. Controlled studies are needed to answer the question whether early treatment is indeed helpful. An answer is much needed, as the efficiency of late rescue therapy is limited and mortality of patients with ARAS entering dialysis is relatively high [4,20].
A trend for a high mortality in patients with ARAS entering dialysis was also seen in present study: after 30 months 65% of the patients with renal artery stenosis were alive compared with 79% of the patients with other causes of renal failure. This survival rate was better than survival rate of 45% reported in the same category of dialysis patients 10 years ago in the US [20]. Most patients die from cardiovascular diseases. Possibly the more widespread use of statins, ACE-inhibitors and improvements in intervention cardiology is having a beneficial effect on survival.
In conclusion, ARAS may be an important cause of ESRF, and can also occur in patients with known causes of renal parenchymal disease.
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Acknowledgments |
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Conflict of interest statement. None declared.
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Notes |
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References |
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