Hypertension Research (2010) 33, 911–915

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ORIGINAL ARTICLE

Prevalence and risk factors for renal artery stenosis and

chronic kidney disease in Japanese patients with
peripheral arterial disease
Michiko Endo1, Hisao Kumakura1, Hiroyoshi Kanai1, Yoshihiro Araki1, Shu Kasama1, Hiroyuki Sumino1,
Shuichi Ichikawa1 and Masahiko Kurabayashi2

The prevalence and risk factors for renal artery stenosis (RAS) and chronic kidney disease (CKD) are unclear in Japanese
patients with peripheral arterial disease (PAD). To examine these issues, we performed renal angiography in 410 patients with
PAD. Renal function and damage were assessed using the estimated glomerular filtration rate (eGFR) and urinary level of
microalbumin (MA). Multiple logistic and multiple regression analyses were used to examine the relationships of potential risk
factors with RAS and CKD. In all, 94 subjects (22.9%) had RAS 450% and 45 subjects (11.0%) had RAS 475%. The
incidences of an abnormal level of MA and renal insufficiency (eGFR o60 ml min–1 per 1.73 m2) were 37.0 and 60.7%,
respectively. RAS X50% was associated with critical limb ischemia (CLI; hazard ratio (HR) 2.519; 95% confidence interval
(CI) 1.203–5.276, P¼0.014), coronary heart disease (CHD; HR 2.143; 95% CI 1.129–4.069; P¼0.020) and hypertension
(HR 1.907; 95% CI 1.009–3.628; P¼0.045). RAS X75% had a relationship with hypertension (HR 3.093; 95% CI
1.002–9.548; P¼0.048). eGFR was negatively correlated with age, uric acid and CHD (P¼0.013), and MA had a significant
positive correlation with low-density lipoprotein cholesterol, CLI, age, CHD and diabetes (Po0.001). These results show that
the prevalences of RAS and CKD are very high in Japanese patients with PAD; that CLI and CHD are major risk factors for RAS;
and that hyperuricemia, hypercholesterolemia and diabetes are risk factors for CKD in PAD. We also found that MA is a simple
and noninvasive marker of renal dysfunction and general vascular damage.
Hypertension Research (2010) 33, 911–915; doi:10.1038/hr.2010.93; published online 10 June 2010

Keywords: chronic kidney disease; microalbuminuria; peripheral arterial disease; renal artery stenosis

INTRODUCTION factors and cardiovascular morbidity.8,9 Therefore, in this study, we

Atherosclerotic renal artery stenosis (RAS) is a cause of severe investigated the prevalence of RAS and clinical factors related to RAS
hypertension, pulmonary edema and renal dysfunction.1,2 Recent in Japanese patients with PAD independent of hemodialysis. We also
studies have shown a high prevalence of RAS in patients with examined various risk factors for CKD based on evaluation of eGFR or
peripheral arterial disease (PAD) or coronary heart disease urinary microalbumin (MA) in patients with PAD.
(CHD).1,3 However, many cases of RAS do not present with specific
symptoms or signs of ischemia, unlike PAD or CHD, and there is little METHODS
information on the prevalence of RAS in Japanese patients with PAD. Patients
PAD is an atherosclerotic disease that has multiple atherosclerosis risk The subjects of the study were patients with PAD who were admitted to our
factors and a high incidence of coexisting atherosclerotic vascular hospital and received endovascular treatment between July 2004 and August
disease.4 PAD is also frequently associated with chronic kidney disease 2008 because of iliac or femoral artery stenosis of X70% on angiography.
(CKD),5,6 which also seems to be a risk factor for CHD and cerebral Before the start of the study, the patients received a full explanation of the
treatment and examination methods, and gave written informed consent. RAS
vascular disease.5,7 However, the prevalence and degree of CKD and
was evaluated by digital subtraction angiography performed just before the start
the associated risk factors in patients with PAD are also unclear.
of endovascular treatment. The rate of stenosis was calculated bilaterally using
Recent studies of the estimated glomerular filtration rate (eGFR) automatic software from the manufacturer (Phillips Med, Best, The Nether-
have shown that this parameter is a better predictor of mortality than lands) same as quantitative coronary angiography. Patients with a creatinine
serum creatinine alone in patients with PAD.5,6 Moreover, microalbu- level of X2.5 mg per 100 ml and those with severe proteinuria such as that in
minuria is independently associated with increased cardiovascular risk nephrotic syndrome were excluded from the study, because these patients were

1Department of Internal Medicine, Cardiovascular Hospital of Central Japan (Kitakanto Cardiovascular Hospital), Shibukawa, Gunma, Japan and 2Department of Medicine and

Clinical Science, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan
Correspondence: Dr H Kumakura, Department of Internal Medicine, Cardiovascular Hospital of Central Japan (Kitakanto Cardiovascular Hospital), Shimohakoda 740 Hokkitu-
machi Shibukawa, Gunma 377-0061, Japan.
E-mail: Kumakura@sannet.ne.jp
Received 11 March 2010; revised 8 April 2010; accepted 14 April 2010; published online 10 June 2010
 Renal artery stenosis and CKD in PAD
M Endo et al
912

Table 1 Baseline clinical characteristics and risk factors in patients with PAD

Risk factor All patients, n¼410 RAS X50%, n¼94 (22.9%) RAS (), n¼316 (77.1%) P-value

Age (year) 71.0±9.1 72.9±8.3 70.5±9.2 0.043

Gender (male) 338 (82.6%) 81 (86.2%) 257 (81.3%) 0.394
CLI (vs. IC) 64 (15.6%) 22 (23.4%) 42 (13.3%) 0.062
ABI 0.60±0.25 0.53±0.24 0.62±0.25 0.007
BMI (kg m–2) 22.1±3.7 20.9±3.4 22.4±3.3 0.001
Hypertension 247 (60.2%) 71 (75.5%) 176 (55.6%) 0.007
DM 124 (30.2%) 27 (28.7%) 97 (30.7%) 0.778
eGFR (ml min–1 per 1.73 m2) 58.3±18.2 54.7±20.7 59.1±17.6 0.065
CHD 122 (29.8%) 39 (41.5%) 83 (26.3%) 0.020
Cerebral infarction 71 (17.3%) 26 (27.7%) 45 (14.2%) 0.009
Smoking 317 (77.3%) 71 (75.5%) 246 (77.8%) 0.757

Laboratory data
Total-C (mg per 100 ml) 192±40 191±36 192±40 0.824
LDL-C (mg per 100 ml) 119±35 121±34 119±35 0.646
HDL-C (mg per 100 ml) 49±23 47±13 50±25 0.412
Triglyceride (mg per 100 ml) 137±90 121±56 140±97 0.098
HbA1c (%) 6.2±3.6 5.9±0.1 5.9±0.1 0.286
Lipoprotein (a) (mg per 100 ml) 25.4±23.3 27.4±25.5 25.0±22.9 0.447
RLP-C (mg per 100 ml) 6.2±3.6 5.8±3.3 6.3±3.7 0.286
Uric acid (mg per 100 ml) 5.9±1.7 5.6±1.7 6.0±1.7 0.126
Homocysteine (nmol ml–1) 13.8±8.7 14.7±6.7 13.6±9.1 0.456
D-dimer (mg per 100 ml) 1.6±2.3 1.7±1.8 1.6±2.4 0.785
Fibrinogen (mg per 100 ml) 326±102 357±102 319±101 0.009
U-MA (mg per g Cr) 117±360 141±353 112±361 0.621

Abbreviations: ABI, ankle brachial pressure index; BMI, body mass index; CHD, coronary heart disease; CLI, critical limb ischemia; DM, diabetes mellitus; eGFR, estimated glomerular filtration rate;
HbA1c, glycosylated hemoglobin A1c; HDL-C, high-density lipoprotein cholesterol; IC, intermittent claudication; LDL-C, low-density lipoprotein cholesterol; PAD, peripheral arterial disease; RAS,
renal artery stenosis; RLP-C, remnant-like particle-cholesterol; Total-C, total cholesterol; U-MA, urinary microalbumin.

not eligible for endovascular treatment using an iodinated contrast material. Society of Nephrology: eGFR (ml min–1 per 1.73 m2)¼194(Scr)1.094
Patients receiving hemodialysis were also excluded from the study. (age)0287(0.739 if female).14 CKD was divided into five stages according
to NKF-K/DOQl (The National Kidney Foundation–Kidney Disease Outcomes
Quality Initiative) guidelines.15 Glomerular function was also assessed by
Risk factors
measuring the urinary level of MA. Microalbuminuria was diagnosed based
Smoking history, hypertension, diabetes mellitus (DM), cerebral infarction and
on MA X30 mg per g Cr.
CHD were studied as risk factors for arteriosclerosis. Hypertension was defined
as blood pressure of X140/90 mm Hg recorded at least twice, or intake of
antihypertensive agents. Diabetes was defined as a fasting plasma glucose level Statistical analysis
of 4126 mg per 100 ml for at least two measurements, or antidiabetic Data are expressed as mean values±s.d. The groups of patients with and
therapy.10 An electrocardiogram was recorded and echocardiography and a without RAS were compared using a t-test and proportions were compared
brain computed tomography scan were performed for each patient. Cerebral using w2 test with Yates’ correction. Factors with Po0.07 in this paired analysis
infarction was considered positive when the patient had a history of this were used in multivariate logistic analysis to determine predictors of RAS
condition or when lesions due to cerebral infarction were found in brain (hypertension, CHD, cerebral infarction, CLI, ankle brachial pressure index,
computed tomography. CHD was considered to be present when the patient body mass index, fibrinogen, age and eGFR). Relationships between eGFR or
had a history of this disease or showed a positive sign in stress/rest myocardial MA and the following risk factors were studied using stepwise forward multiple
perfusion scintigraphy. Intermittent claudication and critical limb ischemia regression analysis: smoking, CLI, hypertension, DM, cerebral infarction and
(CLI) were defined using the criteria of the Inter-Society Consensus for the CHD as categorical factors; and age, ankle brachial pressure index, LDL
Management of Peripheral Arterial Disease.4 cholesterol, high-density lipoprotein cholesterol, triglyceride, lipoprotein (a),
Blood was collected during fasting in the morning for determination of total remnant-like particle-cholesterol, glycosylated hemoglobin A1c, homocysteine,
cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein uric acid, D-dimer and fibrinogen as continuous variables. SPSS v.16.0 (SPSS,
cholesterol, triglyceride, lipoprotein (a), remnant-like particle-cholesterol, Chicago, IL, USA) was used for all calculations. A P-value of o0.05 was
glycosylated hemoglobin A1c, homocysteine, glucose, uric acid, creatinine, considered to indicate a significant difference.
D-dimer and fibrinogen. Freshly voided samples were collected for determina-
tion of urinary MA and creatinine. The degree of albuminuria was expressed as RESULTS
the MA/creatinine ratio (mg per g Cr). Lipid abnormalities were diagnosed Patient characteristics
based on total cholesterol X220 mg per 100 ml or intake of lipid-lowering The subjects were 410 patients with PAD (338 males and 72 females)
agents,11,12 high-density lipoprotein cholesterol o40 mg per 100 ml,4,12 trigly- aged 38–97 years old (mean 71.0±9.1 years old). The characteristics
ceride X150 mg per 100ml,12,13 and LDL cholesterol X140 mg per 100 ml.12 of the patients, including complications and risk factors, are shown in
Table 1. Patients with RAS X50% were significantly older, and had
Assessment of renal function higher fibrinogen and a lower ankle brachial pressure index and body
The glomerular filtration rate was estimated using the MDRD (Modification of mass index compared with those without RAS. Hypertension, CHD
Diet in Renal Disease) equation for creatinine, as modified by the Japanese and cerebral infarction were significantly more common in patients

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 Renal artery stenosis and CKD in PAD
M Endo et al
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70 Table 2 Correlations between eGFR and other risk factors in stepwise

forward multiple regression analysis
60
Risk factor Units b 95% CI P-value
50
Age Year 0.329 0.927 to 0.457 0.001
40 Uric acid mg per 100 ml 0.203 3.244 to 0.945 0.001
CHD 0.142 9.823 to 1.177 0.013
%

30 Abbreviations: CHD, coronary heart disease; CI, confidence interval; eGFR, estimated glomerular
filtration rate.
R2¼0.156, F for change in R2¼6.277, P¼0.013.
20

10
Table 3 Correlations between urinary level of microalbumin and other
0 risk factors in stepwise forward multiple regression analysis
RAS(≥75%) RAS(≥50%) MA eGFR
(≥30mg/g·Cr) (<60 mL/min) Risk factor Units b 95% CI P-value

Figure 1 Prevalence of abnormal levels of renal artery stenosis (RAS),

LDL cholesterol mg per 100 ml 0.255 1.224–3.579 o0.001
microalbumin (MA) and renal dysfunction (estimated glomerular filtration
CLI 0.186 70.18–344.98 0.003
rate (eGFR) o60 ml min–1).
Age Year 0.143 0.878–10.9434 0.022
CHD 0.137 11.263–206.44 0.029
DM 0.128 5.289–201.71 0.039
0.5 1 2 4 10
Risk factor Hazard ratio (95%CI) p-value Abbreviations: CHD, coronary heart disease; CI, confidence interval; CLI, critical limb ischemia;
CLI 2.519 (1.203-5.276) 0.014 DM, diabetes mellitus; LDL, low-density lipoprotein.
CHD 2.143 (1.129-4.069) 0.020 R2¼0.127, F for change in R2¼6.827, Po0.001.
Hypertension 1.907 (1.009-3.628) 0.045
Cerebral Infarction 1.446 (0.690-3.034) 0.329
ABI 0.722 (0.596-1.075) 0.077
BMI 0.678 (0.448-1.687) 0.869
relationship between eGFR and potential risk factors indicated that
Fibrinogen 1.003 (0.999-1.005) 0.075 eGFR was negatively correlated with age, uric acid and CHD (Table 2,
eGFR 0.993 (0.976-1.011) 0.455 P¼0.013). MA was positively correlated with LDL cholesterol, CLI,
Age 1.008 (0.970-1.047) 0.699 age, CHD and DM (Table 3, Po0.001).
Figure 2 Relationship between renal artery stenosis and risk factors in
multiple logistic analysis. ABI, ankle brachial pressure index; BMI, body
Peripheral endovascular treatment and RAS or renal dysfunction
mass index; CHD, coronary heart disease; CLI, critical limb ischemia; eGFR, The initial success rate of endovascular treatment of PAD in all
estimated glomerular filtration rate. subjects was 95.4% (391/410). There was no significant correlation
of this rate with RAS, eGFR or MA.

with RAS. The prevalences of CLI and eGFR showed a tendency to DISCUSSION
differ between the two groups. There were no significant differences in Our study of patients with PAD showed that 22.9% had RAS 450%
other background data. and 11.0% had RAS 475%. In a meta-analysis of patients with
atherosclerotic risk factors such as hypertension, DM, CHD, CKD or
Prevalence of RAS and renal dysfunction PAD, the prevalence of RAS has been reported to be 15.4%.16 In
In all, 94 subjects (22.9%) had RAS X50% and 45 (11.0%) had RAS multiple series of PAD cases, the rates of RAS varied from 12.0
X75% (Figure 1). An abnormal level of MA was present in 25.1% to 45.5%, with a pooled prevalence of 25.3%.16 Wilms et al.17 found
(Figure 1). Only 4.2% of patients (n¼17) had normal kidney function a 22% prevalence of RAS X50% in patients with PAD (mean age 62.4
(eGFR X90 ml min–1 per 1.73 m2), 35.1% (n¼144) had mildly years old), and Amighi et al.1 recently reported a prevalence of RAS
impaired kidney function (eGFR 60–89 ml min–1 per 1.73 m2), X60% on angiography of 15.6% in patients with PAD (mean age 70.6
58.5% (n¼240) had moderate renal insufficiency (eGFR 30– years old). Thus, our results for the rate of RAS in Japanese patients
59 ml min–1 per 1.73 m2), 2.0% (n¼8) had severe renal insufficiency with PAD are similar to those found in previous studies.
(eGFR 15–29 ml min–1 per 1.73 m2) and 0.2% (n¼1) had renal failure Yamashita et al.18 reported that RAS also occurs frequently in
(eGFR o15 ml min–1per .73 m2). Thus, the prevalence of renal dys- Japanese patients with CHD and that the prevalence of RAS is higher
function (eGFR o60 ml min–1 per 1.73 m2) was 60.7% (Figure 1). in patients with established CHD: 10, 9 and 19% in patients with 1-,
2- and 3-vessel disease, respectively. Our results suggest that the
Risk factors for RAS and renal dysfunction prevalence of RAS in patients with PAD is higher than that in patients
Examination of the relationship between RAS X50% and potential with established CHD. Moreover, we found that hypertension, CLI
risk factors using multiple logistic analysis revealed correlations with and CHD were closely associated with RAS in patients with PAD. As
CLI, CHD and hypertension (Figure 2). The hazard ratio (HR) was 2.5 the severity or number of atherosclerotic risk factors increased, the
times higher in cases with CLI (Po0.05) and 2.1 times higher in cases prevalence of RAS also increased. However, many cases of RAS do not
with CHD (Po0.05). Multiple logistic analysis of RAS X75% and present with specific symptoms of ischemia, unlike CHD or PAD, and
potential risk factors revealed a significant correlation with hyperten- incidental RAS has been reported to be an independent predictor of
sion alone (HR 3.093; 95% confidence interval (CI) 1.002–9.548; mortality in patients with PAD.19 Therefore, screening for RAS is very
P¼0.048). Stepwise forward multiple regression analysis of the important for management of patients with PAD.

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 Renal artery stenosis and CKD in PAD
M Endo et al
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RAS reflects a high overall atherosclerotic burden that manifests as Study limitations
coronary, cerebrovascular and peripheral vascular disease.2 The goals The limitations of our study are as follows. First, the subjects were
of therapy for RAS center on effective reduction of blood pressure and limited to patients with PAD who received endovascular treatment
stabilization of renal function. Revascularization with angioplasty or a because of iliac or femoral artery stenosis of X70% on angiography.
stent is a direct hemodynamic treatment,20 but a recent comparison of Second, patients with a creatinine concentration of X2.5 mg per
randomized revascularization with medical therapy for RAS found no 100 ml or nephrotic syndrome and those receiving hemodialysis
significant difference in the clinical benefit.21 Further studies are were excluded from the study. Therefore, evaluation of RAS in this
needed to confirm the optimal treatment for improving mortality group was not achieved, because these patients with CKD are not
and stabilization of renal function in patients with RAS. suited to endovascular treatment and most patients under hemodia-
Several studies have suggested that CKD is a prognostic indicator of lysis have occluded trunks or distal branches of the renal artery. Third,
CVD,5,22,23 and an association between survival and eGFR or esti- the sample sizes were relatively small, the study was performed at a
mated creatinine clearance in patients with PAD has recently been single facility and we did not use population-based data. Therefore,
proposed.6,24,25 O’Hare et al.24 found that CKD was a strong inde- further studies are needed to reveal the precise prevalence and risk
pendent predictor of mortality in patients with CLI and that the factors for RAS in patients with PAD.
mortality risk was highest among patients with eGFR o30 ml min–1
per 1.73 m2. It has also been shown that eGFR is an independent CONCLUSION
predictor of death and limb loss after infrainguinal bypass.25 Patients with PAD had high rates of complication with RAS and CKD.
Hyperuricemia has been reported to be a risk factor for develop- CLI, CHD and hypertension were found to be major risk factors for
ment of CKD, and elevated levels of uric acid independently increase RAS; eGFR showed negative correlations with age, uric acid and CHD;
the risk for onset of new CKD in the general population and in and MA was positively correlated with LDL cholesterol, CLI, age, CHD
patients with DM.26,27 In this study, eGFR was negatively correlated and DM in our PAD population, which had the limitations noted
with age, uric acid and CHD. The mechanisms underlying hyperur- above. These results indicate that complication with CHD is an
icemia as a result of reduced renal clearance of uric acid may involve a important and comprehensive risk factor for RAS and CKD in
reduced GFR or dysfunctional handling of filtered uric acid by patients with PAD.
proximal tubules.28 In a community-based study of Japanese adults,
hyperuricemia and age emerged as significant risk factors for renal
failure, and hyperuricemia was more strongly predictive than protei-
nuria.29 Our study also highlights the correlation between CKD and 1 Amighi J, Schlager O, Haumer M, Dick P, Mlekusch W, Loewe C, Bohmig G,
the level of uric acid. As CKD seems to be a risk factor in PAD,4 Koppensteiner R, Minar E, Schillinger M. Renal artery stenosis predicts adverse
treatment for hyperuricemia is important in patients with PAD. cardiovascular and renal outcome in patients with peripheral artery disease. Eur J
Clin Invest 2009; 39: 784–792.
Glomerular function was also assessed by measuring the urinary 2 Garovic VD, Textor SC. Renovascular hypertension and ischemic nephropathy.
level of MA. Urinary MA excretion because of DM has been proposed Circulation 2005; 112: 1362–1374.
3 Ghaffari S, Sohrabi B, Siahdasht RB, Pourafkari L. Prevalence and predictors of renal
to be a sign of atherosclerotic involvement of systemic arterial disease, artery stenosis in hypertensive patients undergoing coronary angiography. Hypertens
in addition to CKD.7,8 Furthermore, any degree of albuminuria is a Res 2009; 32: 1009–1014.
risk factor for cardiovascular events in individuals with or without 4 Norgren L, Hiatt WR, Dormandy JA, Nehler MR, Harris KA, Fowkes FG. Inter-Society
Consensus for the Management of Peripheral Arterial Disease (TASC II). J Vasc Surg
DM.30,31 Increased urinary MA excretion reflects generalized endothe- 2007; 45 (Suppl S): S5–S67.
lial dysfunction and more widespread vascular damage.32,33 In this 5 Sarnak MJ, Levey AS, Schoolwerth AC, Coresh J, Culleton B, Hamm LL, McCullough
study, multiple regression analysis revealed a significant positive PA, Kasiske BL, Kelepouris E, Klag MJ, Parfrey P, Pfeffer M, Raij L, Spinosa DJ, Wilson
PW. Kidney disease as a risk factor for development of cardiovascular disease: a
correlation of MA with LDL cholesterol, CLI, age, CHD and DM. statement from the American Heart Association Councils on Kidney in Cardiovascular
This suggests that systemic atherosclerosis, as represented by CLI, Disease, High Blood Pressure Research, Clinical Cardiology, and Epidemiology and
Prevention. Circulation 2003; 108: 2154–2169.
CHD and higher LDL cholesterol, is also a cause of hypermicroalbu- 6 Maithel SK, Pomposelli FB, Williams M, Sheahan MG, Scovell SD, Campbell DR,
minuria in patients with PAD. MA is thought to reflect both renal LoGerfo FW, Hamdan AD. Creatinine clearance but not serum creatinine alone predicts
damage and general vascular damage. The association of MA with long-term postoperative survival after lower extremity revascularization. Am J Nephrol
2006; 26: 612–620.
systemic atherosclerosis is of interest, as noninvasive determination of 7 Nakamura M, Yamashita T, Yajima J, Oikawa Y, Ogasawara K, Kirigaya H, Sagara K,
the subgroup of patients with a high risk of coexistent diseases caused Koike A, Sawada H, Aizawa T. Impact of reduced renal function on prognosis in
by atherosclerosis is difficult. Many patients with CKD have few Japanese patients with coronary artery disease: a prospective cohort of Shinken
Database 2007. Hypertens Res 2009; 32: 920–926.
clinical symptoms, which explains why the disease awareness of 8 Hillege HL, Janssen WM, Bak AA, Diercks GF, Grobbee DE, Crijns HJ, Van Gilst WH,
CKD is low despite the high prevalence rates, and increased MA De Zeeuw D, De Jong PE. Microalbuminuria is common, also in a nondiabetic,
nonhypertensive population, and an independent indicator of cardiovascular risk factors
excretion may also be a marker of CHD in patients with PAD.34 Thus, and cardiovascular morbidity. J Intern Med 2001; 249: 519–526.
measurement of the excretion rate of MA using a simple and 9 Jager A, Kostense PJ, Ruhe HG, Heine RJ, Nijpels G, Dekker JM, Bouter LM, Stehouwer
noninvasive procedure may be useful in non-diabetic patients with CD. Microalbuminuria and peripheral arterial disease are independent predictors of
cardiovascular and all-cause mortality, especially among hypertensive subjects: five-
PAD, in addition to measurement of eGFR. year follow-up of the Hoorn Study. Arterioscler Thromb Vasc Biol 1999; 19: 617–624.
The initial success rate of endovascular treatment of PAD was not 10 Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Report of
significantly correlated with RAS, eGFR or MA. However, we have the expert committee on the diagnosis and classification of diabetes mellitus. Diabetes
Care 2003; 26(Suppl 1): S5–S20.
reported that the in-stent neointimal proliferation rate shows a 11 Okamura T, Tanaka H, Miyamatsu N, Hayakawa T, Kadowaki T, Kita Y, Nakamura Y,
significant positive correlation with the serum creatinine level at 6 Okayama A, Ueshima H. The relationship between serum total cholesterol and all-cause
or cause-specific mortality in a 17.3-year study of a Japanese cohort. Atherosclerosis
months after endovascular treatment.35 We have also reported a 10- 2007; 190: 216–223.
year patency after endovascular treatment of the iliac artery.36 The 12 Teramoto T, Sasaki J, Ueshima H, Egusa G, Kinoshita M, Shimamoto K, Daida H,
restenosis rate showed no significant correlation with the serum Biro S, Hirobe K, Funahashi T, Yokote K, Yokode M. Executive summary of
Japan Atherosclerosis Society (JAS) guideline for diagnosis and prevention of
creatinine level, and only stent use and the postprocedural stenosis atherosclerotic cardiovascular diseases for Japanese. J Atheroscler Thromb 2007;
rate were significant restenosis factors for long-term patency. 14: 45–50.

Hypertension Research
 Renal artery stenosis and CKD in PAD
M Endo et al
915

13 Castelli WP. Lipids, risk factors and ischaemic heart disease. Atherosclerosis 1996; 26 Weiner DE, Tighiouart H, Elsayed EF, Griffith JL, Salem DN, Levey AS. Uric acid
124(Suppl): S1–S9. and incident kidney disease in the community. J Am Soc Nephrol 2008; 19:
14 Matsuo S, Imai E, Horio M, Yasuda Y, Tomita K, Nitta K, Yamagata K, Tomino Y, 1204–1211.
Yokoyama H, Hishida A. Revised equations for estimated GFR from serum creatinine in 27 Chen N, Wang W, Huang Y, Shen P, Pei D, Yu H, Shi H, Zhang Q, Xu J, Lv Y, Fan Q.
Japan. Am J Kidney Dis 2009; 53: 982–992. Community-based study on CKD subjects and the associated risk factors. Nephrol Dial
15 National Kidney Foundation. K/DOQI clinical practice guidelines for chronic Transplant 2009; 24: 2117–2123.
kidney disease: evaluation, classification, and stratification. Am J Kidney Dis 2002; 28 Perez-Ruiz F, Calabozo M, Erauskin GG, Ruibal A, Herrero-Beites AM. Renal under-
39: S1–S266. excretion of uric acid is present in patients with apparent high urinary uric acid output.
16 de Mast Q, Beutler JJ. The prevalence of atherosclerotic renal artery stenosis in risk Arthritis Rheum 2002; 47: 610–613.
groups: a systematic literature review. J Hypertens 2009; 27: 1333–1340. 29 Iseki K, Oshiro S, Tozawa M, Iseki C, Ikemiya Y, Takishita S. Significance of
17 Wilms G, Marchal G, Peene P, Baert AL. The angiographic incidence of renal artery hyperuricemia on the early detection of renal failure in a cohort of screened subjects.
stenosis in the arteriosclerotic population. Eur J Radiol 1990; 10: 195–197. Hypertens Res 2001; 24: 691–697.
18 Yamashita T, Ito F, Iwakiri N, Mitsuyama H, Fujii S, Kitabatake A. Prevalence and 30 Gerstein HC, Mann JF, Yi Q, Zinman B, Dinneen SF, Hoogwerf B, Halle JP, Young J,
predictors of renal artery stenosis in patients undergoing cardiac catheterization. Rashkow A, Joyce C, Nawaz S, Yusuf S. Albuminuria and risk of cardiovascular events,
Hypertens Res 2002; 25: 553–557. death, and heart failure in diabetic and nondiabetic individuals. JAMA 2001; 286:
19 Mui KW, Sleeswijk M, van den Hout H, van Baal J, Navis G, Woittiez AJ. Incidental 421–426.
renal artery stenosis is an independent predictor of mortality in patients with peripheral 31 Hoshide S, Matsui Y, Shibasaki S, Eguchi K, Ishikawa J, Ishikawa S, Kabutoya T,
vascular disease. J Am Soc Nephrol 2006; 17: 2069–2074. Schwartz JE, Pickering TG, Shimada K, Kario K. Orthostatic hypertension detected by
20 White CJ. Catheter-based therapy for atherosclerotic renal artery stenosis. Circulation self-measured home blood pressure monitoring: a new cardiovascular risk factor for
2006; 113: 1464–1473. elderly hypertensives. Hypertens Res 2008; 31: 1509–1516.
21 The ASTRAL Investigators. Wheatley K, Ives N, Gray R, Kalra PA, Moss JG, Baigent C, 32 Stehouwer CD, Nauta JJ, Zeldenrust GC, Hackeng WH, Donker AJ, den Ottolander GJ.
Carr S, Chalmers N, Eadington D, Hamilton G, Lipkin G, Nicholson A, Scoble J. Urinary albumin excretion, cardiovascular disease, and endothelial dysfunction in non-
Revascularization versus medical therapy for renal-artery stenosis. N Engl J Med 2009; insulin-dependent diabetes mellitus. Lancet 1992; 340: 319–323.
361: 1953–1962. 33 Clausen P, Jensen JS, Jensen G, Borch-Johnsen K, Feldt-Rasmussen B. Elevated
22 Walsh CR, O’Donnell CJ, Camargo Jr CA, Giugliano RP, Lloyd-Jones DM. Elevated urinary albumin excretion is associated with impaired arterial dilatory capacity in
serum creatinine is associated with 1-year mortality after acute myocardial infarction. clinically healthy subjects. Circulation 2001; 103: 1869–1874.
Am Heart J 2002; 144: 1003–1011. 34 Sonmez K, Eskisar AO, Demir D, Yazicioglu MV, Mutlu B, Dogan Y, Izgi A, Mansuroglu
23 Kagiyama S, Matsumura K, Ansai T, Soh I, Takata Y, Awano S, Sonoki K, Yoshida A, D, Bakal RB, Elonu OH, Turan F. Increased urinary albumin excretion rates can be a
Takehara T, Iida M. Chronic kidney disease increases cardiovascular mortality in marker of coexisting coronary artery disease in patients with peripheral arterial disease.
80-year-old subjects in Japan. Hypertens Res 2008; 31: 2053–2058. Angiology 2006; 57: 15–20.
24 O’Hare AM, Bertenthal D, Shlipak MG, Sen S, Chren MM. Impact of renal insufficiency 35 Kumakura H, Kanai H, Araki Y, Koizumi A, Kasama S, Sumino H, Ichikawa S. Effects of
on mortality in advanced lower extremity peripheral arterial disease. J Am Soc Nephrol antiplatelet agents and other factors on neointimal proliferation in iliac artery stenting:
2005; 16: 514–519. Intravascular ultrasound analysis. Ann Vasc Dis 2009; 2: 100–108.
25 Arvela E, Soderstrom M, Alback A, Aho PS, Tikkanen I, Lepantalo M. Estimated 36 Koizumi A, Kumakura H, Kanai H, Araki Y, Kasama S, Sumino H, Ichikawa S,
glomerular filtration rate (eGFR) as a predictor of outcome after infrainguinal bypass in Kurabayashi M. Ten-year patency and factors causing restenosis after endovascular
patients with critical limb ischemia. Eur J Vasc Endovasc Surg 2008; 36: 77–83. treatment of iliac artery lesions. Circ J 2009; 73: 860–866.

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