Renal artery stenosis (RAS) is the cause of ischemic nephropathy and is an important cause of secondary hypertension. Since the early 1980s, the association of chronic kidney di-sease (CKD) and RAS has been clearly shown, and the pathogenetic role of RAS in the development of hypertension and ischemic nephropathy have been defined.1
Patients with end-stage renal disease (ESRD) who are on dialysis due to RAS have signi-ficantly poorer survival than patients dialyzed due to other causes. About 2% of such patients die annually, and the mean survival and percentage of patients alive at five years are 27 months and 12%, respectively. The prevalence of RAS in hypertensive patients is reported to be 1-10% and the prevalence of end-stage renal disease (ESRD) due to RAS has increased from 6-7% in 1978-1981 to 16.5% in 1982- 1985.23 Overall, RAS is the cause of ESRD in 10-20% of patients aged above 50 years.4
The "gold standard" method for diagnosing RAS is renal angiography, which is an inva-sive technique with known complications and, therefore, it should be performed if a high probability of stenosis is suspected. Many investigators investigated the criteria to detect patients at high risk for RAS.567
A strong correlation has been shown between coronary artery disease (CAD) and RAS.8 Yorgun and his colleagues reported that the only independent predictor factor of RAS is CAD.9 Some authors studied the risk factors for atherosclerotic renovascular diseases and their association with RAS.101112 The results of these studies is controversial and different risk factors have different roles in the evolution of atherosclerotic disorders.
The aim of our study was to determine the risk factors that strongly predict the presence of significant RAS in our CAD patients.
Materials and Methods
The study protocol was approved by the Ethics Committee of the Research Department of the Tehran University of Medical Sciences. All the patients signed a written consent form that was approved by the ethics committee.
We studied in a cross-sectional model 173 adult patients who underwent coronary angio-graphy; 146 patients had significant coronary artery stenosis (>50%). Renal angiography was simultaneously performed in these patients. All angiographic data were reviewed by two expert cardiologists to define the RAS seve-rity. Patients with any degree of stenosis were considered to have RAS. However, "signi-ficant RAS" was defined as ≥50% stenosis. The correlation between RAS and sex, age, diabetes mellitus (DM), hypertension, smoking, body mass index (BMI), serum creatinine le-vel and lipid profile were evaluated.
Before angiography, all data of the patients were collected and necessary laboratory tests were completed.
We used the software STATA version 9.1 (STATA, College Station, TX, USA) for sta-tistical analysis in this study. Qualitative and quantitative data were presented as percen-tages and mean ± standard deviation (SD), respectively. The chi-square test or Fisher’s test was selected to compare quantitative determinants and the Student’s two-tailed t-test was used for qualitative data. Multivariate logistic regression analysis was used to show the effect of factors. P <0.05 was considered as significant.
Table 1 shows the demographic data and the clinical characteristics of the patients. The total prevalence of RAS was 25.3%, whereas significant RAS (>50% stenosis) was observed in 17% of patients; 6.2% of patients had bilateral RAS. We did not find differences between males and females (P = 0.229 and P = 0.716, respectively) regarding the correlation between the severity of stenosis and the location of RAS. The age and BMI of both groups were similar, but hypertension and DM were signi-ficantly more prevalent in females. The dura-tion of hypertension was also longer in females with RAS.
Table 2 shows the characteristics of patients with significant RAS. The prevalence of significant RAS was higher in females than in males (47.1% vs. 13.7%; P = 0.001). Patients with significant RAS were also older than patients with normal renal arteries (P <0.001). A history of hypertension and DM was more prevalent in patients with significant RAS (P = 0.006 and P = 0.004, respectively). The dura-tion of hypertension and DM was also longer in these patients (P = 0.006 and P = 0.001, res-pectively). There were no significant diffe-rences between males and females with respect to hyperlipidemia and smoking. Regarding CAD, 30 patients (13%) had minimal CAD, 26 patients (18%) had single CAD, 44 patients (30%) had two-vessel disease and 57 patients (39%) had three-vessel disease. No relationship was found between the number of stenotic coronary arteries or their severity and those of the renal arteries (P = 0.763 and P = 0.473, respectively).
Table 3 shows the multivariate logistic regression analysis of the risk factors of athe-rosclerosis and RAS. Female sex was a strong predictor of RAS (P = 0.001). Older age (P = 0.046) and serum creatinine (P = 0.018) had a good correlation with RAS. The probability of RAS occurrence increased in patients with a longer duration of hypertension (P = 0.032), but DM failed to show this correlation (P = 0.157). None of the patients had contrast nephropathy.
RAS is a common finding in atherosclerotic patients. It is a progressive disorder and total occlusion of arteries occurs in many of these patients.1314151617 This is associated with a signi-ficant increase in morbidity and mortality in 1-2 years.1819 It has been shown that the pre-valence of lesion progression, renal atrophy and renal artery occlusion were approximately 20%, 10% and 5% per year, respectively.20
The prevalence of RAS and its association with other atherosclerotic disorders have been shown in several studies. Apple et al21 summarized seven studies published between 1964 and 1994 about the prevalence of renal artery diseases. This review showed that the prevalence of RAS in non-dialysis patients was 7-50%. This wide range of prevalence was due to the different health status of the patients (including comorbidity). The prevalence of RAS in patients with CAD and renal insuf-ficiency was 25%, whereas it was around 19% in patients with CAD who were not suffering from renal insufficiency.
Recently, researchers have focused on scree-ning for RAS by renal angiography during coronary angiography.22 There is no evidence-based guideline to indicate which patients should undergo renal angiography during coronary angiography.2324 In one study, it has been shown that 60% of patients with peri-pheral atherosclerosis and <30% of patients with coronary artery stenosis have RAS.25 Yuqiang et al showed that there was a 10.9% coexistent rate between coronary artery ste-nosis and RAS.26 Alhaddad et al27 showed that in patients with CAD, age and serum creatinine were important risk factors for predic-ting RAS. However, they found that sex and blood pressure were not important predictors of RAS. The total prevalence of RAS in that study was 13.5%, but significant RAS was found only in 7.7% of patients. Aqel et al28 showed that other than age and renal function, peripheral vascular disease (but not CAD) was a predictive factor for RAS. A total of 28% and 16% of their patients had RAS with ste-nosis >50% and >75%, respectively. Buller et al29 showed that 14.3% of patients had >50% RAS and 7.3% of patients had >75% stenosis. They also reported that age, blood pressure, peripheral vascular disease, serum creatinine and female sex were important risk factors of RAS. Cohen et al30 also reported that females were more vulnerable to RAS. The prevalence of RAS more than 70% stenosis was 17% in this study. Crowley et al31 believed that cerebrovascular diseases were important for predicting RAS. In their study, RAS was found in 6.3% of patients. Harding et al32 reported that besides age, female sex and peripheral vascular diseases, CAD severity rather than the number of coronary arteries involved were risk factors for RAS. The prevalence of overall and significant RAS was reported to be 30% and 11%, respectively. Jean et al8 showed that 92% of CAD patients had RAS, but only 7% of RAS patients had CAD. They concluded that only CAD and renal function were predictive factors for RAS. Landri et al33 stated that patients with increased serum creatinine and coronary artery involvement were more likely to have RAS, but without these two factors only 5.2% of patients had RAS. Oliver et al34 showed that, in contrast to many other studies, male sex was a risk factor of RAS. They reported that 14.2% of patients had RAS.
In the present study, 25.3% of patients had RAS and 17.1% had significant RAS. These values were higher than many other studies. In our study, 6.2% of patients had bilateral RAS; this was more prevalent than other studies.
Our present study demonstrated that females were more likely to be affected by RAS. Even after omitting the confounding factors, this effect was significant. In contrast with many other communities in Iran, female sex is known to be an important risk factor for cardio-vascular disease.35 It is therefore unsurprising to see a higher prevalence of RAS in females than in males. The present study also showed that the risk factors of atherosclerosis (e.g., hypertension, DM, hyperlipidemia) were more prevalent in females.
Another important result of the present study was the good correlation between the duration of hypertension and evolution of RAS. Studies have shown that 13-50% of patients with hypertension and cardiovascular diseases have RAS832 and that if renal failure is added, the prevalence of RAS increases to 60%.363738 One explanation for the relationship between RAS and the duration of hypertension is that, like many other countries, hypertensive patients in Iran do not have good control of blood pres-sure (although they might be more vulnerable to the side-effects of uncontrolled hypertension, including progressive atherosclerosis). Aqel et al28 did not show a relationship between RAS and control of blood pressure, but the number of related studies is limited. More studies are needed to reveal this relationship.
In contrast to the study by Dzielinska and coworkers,1011 we did not find a significant correlation between the number and severity of the involved coronary arteries and RAS. How-ever, the risk factors for CAD (e.g., sex, hyper-tension) play an important part in RAS; there-fore, CAD should be considered to be a risk factor for RAS per se. Like Dzielinska and coworkers, Brent et al also recommended that patients with hypertension and multi-vessel CAD are good candidates for renal artery angiography.12 They showed that increased carotid intima-media thickness is associated with an increased prevalence of RAS. In accor-dance with many studies (including the present study), they found a good correlation between even moderate renal impairment and RAS in patients undergoing coronary angiography.
The most important limitation of our study was the short-term follow-up of patients. It seems necessary to ascertain whether the risk factors for the evolution of RAS have a role in the progression of stenosis. The other limi-tation was the selection of patients with con-firmed CAD. We could not discuss the preva-lence of overall RAS in patients with risk factors for atherosclerosis.
We conclude that the present study showed that RAS is a common finding in patients with CAD. The prevalence of RAS was increased in females suffering from long-term hyper-tension and CKD. Accordingly, we believe that all females with a history of long-standing hypertension should be considered, if they have a plan for coronary angiography, for both coronary and renal artery angiography simul-taneously.
Conflict of Interest
The authors report no conflicts of interest. The authors alone are responsible for the con-tent and writing of the paper.
1. Wierema TK, Yaqoob MM. Renal Artery Stenosis in Chronic Renal Failure. Caution Is Advised for Percutaneous Revascularization. Eur J Int Med
2. Rimmer JM, Gennari FJ. Atherosclerotic Renovascular Disease and Progressive Renal Failure. Ann Intern Med
3. Mailloux LU, Bellucci AG, Mossey RT, et al. Predictors of survival in Patients Undergoing Dialysis. Am J Med
4. Preston RA, Epstein M. Ischemic Renal Causes. An Emerging Cause of Chronic Renal Failure and End-stage Renal Disease. J Hypertens
5. Textor SC. Ischemic Nephropathy: Where Are We Now? J Am Soc Nephrol
6. Zuccala A, Zucchelli P. Ischemic Nephro-pathy: Diagnosis and Treatment. J Nephrol
7. Ziegelbaum M, Novick AC, Hayes J, Vidt DG, Risius B, Gifford RW Jr. Management of Renal Arterial Disease in the Elderly Patient. Surg Gynecol Obstet
8. Jean WJ, al-Bitar I, Zwicke DL, Port SC, Schmidt DH, Bajwa TK. High Incidence of Renal Artery Stenosis in Patients with Coro-nary Artery Disease. Cathet Cardiovasc Diag
9. Yorgun H, Kabakci G, Canpolat U, et al. Frequency and Prediction of Renal Artery Stenosis in Hypertensive Patients Undergoing Coronary Angiography. Eur Heart J
10. Dzielinska Z, Januszewicz A, Demkow M, et al. Cardiovascular Risk Factors in Hypertensive Patients with Coronary Artery Disease and Coexisting Renal Artery Stenosis. J Hypertens
11. Dzielinska Z, Januszewicz A, Kadziela J, et al. Predictive Risk Factors of Renal Artery Stenosis in Hypertensive Patients with Coro-nary Artery Diseases Undergoing Coronary Angiography. J Hypertens
12. Berent H, Kuczynska K, Wocial B, Dutkiewicz-Raczkowska M, Symonides B. Non-Tradi-tional Risk Factors in Patients with Renal Artery Stenosis. J Hypertens
13. Schreiber MJ, Pohl MA, Novick AC. The Natural History of Atherosclerotic and Fibrous Renal Artery Disease. Urol Clin North Am
14. Meaney TF, Dustan HP, McCormack LJ. Natural History of Renal Arterial Disease. Radiology
15. Dean RH, Tribble RW, Hansen KJ, O′niel E, Craven T, Redding JF 2nd. Evolution of Renal Insufficiency in Ischemic Nephropathy. Ann Surg
16. Dean RH, Kieffer RW, Smith BM, et al. Renovascular Hypertension. Arch Surg
17. Zierler Re, Bergelin RO, Davidson RC, et al. A prospective Study of Disease Progression in Patients with Atherosclerotic Renal Artery Stenosis. Am J Hypertens
18. Tollefson DF, Ernst CB. Natural History of Atherosclerotic Renal Artery Stenosis Asso-ciated with Aortic Disease. J Vasc Surg
19. Conlon PJ, Athirakul K, Kovalik E, et al. Survival in Renal Vascular Disease. J Am Soc Nephrol
20. Caps MT, Zierler RE, Polissar NL, et al. Risk of Atrophy in Kidneys with Atherosclerotic Renal Artery Stenosis. J Urol
21. Apple RG, Freedman BJ, Hansen KJ. Reno-vascular Diseases and Progressive Renal Insufficiency. Semin Dial
22. Holmes DR. Incidental Renal Artery Stenosis among a Prospective Cohort of Hypertensive Patients Undergoing Coronary Angiography. Mayo Clin Proc
23. White CJ. Open Renal Arteries are Better than Closed Renal Arteries. Cathet Cardiovasc Diagn
24. Vahist A, Heller EN, Brown EJ, Alhaddad IA. Renal Artery Stenosis: A Cardiovascular Perspective. Am Heart J
25. Olin JW. The Prevalence of Atherosclerotic Renal Artery Stenosis and Clinical Clues to the Diagnosis. J Invasive Cardiol
26. Fang Y, Shu X, Yang C, et al. Stenotic Coexistence among Coronary, Renal and Extracrainal Arteries in Chinese Patients. J Thromb Thrombolysis
27. Alhaddad IA, Blum S, Heller EN, et al. Renal Artery Stenosis in Minority Patients Under-going Diagnostic Cardiac Catheterization: Prevalence and Risk Factors. J Cardiovasc Pharmacol Ther
28. Aqel RA, Zoghbi GJ, Baldwin SA, et al. Prevalence of Renal Artery Stenosis in High-Risk Veterans Referred to Cardiac Catheterization. J Hypertens
29. Buller CE, Nogareda JG, Ramanathan K, et al. The Profile of Cardiac Patients with Renal Artery Stenosis. J Am Coll Cardiol
30. Cohen MG, Pascua JA, Garcia-Ben M, et al. A Simple Prediction Rule for Significant Renal Artery Stenosis in Patients Undergoing Cardiac Catheterization. Am. Heart J
31. Crowley JJ, Santos RM, Peter RH, et al. Progression of Renal Artery Stenosis in Patients Undergoing Cardiac Catheterization. Am. Heart J
32. Harding MB, Smith LR, Himmelstein SI, et al. Renal Artery Stenosis: Prevalence and Asso-ciated Risk Factors in Patients Undergoing Routine Cardiac Catheterization. J Am Soc Nephrol
33. Leandri M, Lipiecki J, Lipiecka E, et al. Prevalence of Renal Artery Stenosis in Patients Undergoing Cardiac Catheterization: When Should Abdominal Aortography Be Performed? Results in 467 Patients. J Radiol
34. Ollivier R, Boulmier D, Veillard D, et al. Frequency and Predictors of Renal Artery Stenosis in Patients with Coronary Artery Disease. Cardiovasc Revasc Med
35. Sadeghi N, Sadeghi S, Abbasi Mood Z, Karimi A. Determinants of Operative Mortality Follo-wing Primary Coronary Artery Bypass Surgery. Eur J Cardiothorac Surg
36. Holley KE, Hunt JC, Brown AL, Kincaid OW, Sheps SG. Renal Artery Stenosis, A Clinical-Pathological Study in Normotensive and Hypertensive Patients. Am J Med
37. Eyler WR, Clark MD, Garman JE, Rian RL, Meininger DE. Angiography of the Renal Areas Including a Comparative Study of Renal Artery Stenosis in Patients with and without Hypertension. Radiology
38. Olin JW, Melia M, Young JR, Graor RA, Risius B. Prevalence of Atherosclerotic Renal Artery Stenosis in Patients with Atheroscle-rosis Elsewhere. Am J Med