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Saudi Journal of Kidney Diseases and Transplantation
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Year : 2002  |  Volume : 13  |  Issue : 3  |  Page : 311-319
Atherosclerotic Ischemic Nephropathy as a Cause of Chronic Kidney Disease: What can be done to Prevent End-stage Renal Disease?

1 Long Island Hypertension and Nephrology, Seaview Boulevard, Port Washington, NY, USA
2 Division of Nephrology and Hypertension, Department of Medicine, North Shore University Hospital, Manhasset, NY, USA

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How to cite this article:
Mailloux LU, Husain A. Atherosclerotic Ischemic Nephropathy as a Cause of Chronic Kidney Disease: What can be done to Prevent End-stage Renal Disease?. Saudi J Kidney Dis Transpl 2002;13:311-9

How to cite this URL:
Mailloux LU, Husain A. Atherosclerotic Ischemic Nephropathy as a Cause of Chronic Kidney Disease: What can be done to Prevent End-stage Renal Disease?. Saudi J Kidney Dis Transpl [serial online] 2002 [cited 2020 Feb 24];13:311-9. Available from: http://www.sjkdt.org/text.asp?2002/13/3/311/33798

   Background Top

Over the past decade, data have accumulated implicating atherosclerotic renal artery stenosis (ARAS) as an increasingly significant cause of end-stage renal disease (ESRD), ranging anywhere from 5 to 22% of incident ESRD patients. [1],[2],[3],[4],[5],[6],[7],[8] This apparently progressive vascular disease has also become the center of clinical controversy in view of the ease with which it can be diagnosed and radiologically corrected by interventional means i.e. balloon angioplasty with stenting either by interventional radiologists, inter­ventional nephrologists or interventional cardiologists. [7],[8],[9],[10],[11] Most of the patients with ARAS also have a significant number of associated co-morbidities [1],[2],[5] [Figure - 1]. Also, patients with known unilateral athero­sclerotic renal artery occlusion and renal insufficiency have been shown to have high mortality rates and some progression into renal failure, but not necessarily from occlusion of the remaining renal artery. [12] In addition, ARAS is being recognized with increasing frequency in patients with coronary artery disease and peripheral vascular disease, in as many as 20% of the patients undergoing coronary angiography. [13],[14],[15],[16] The presence of a significant stenosis identified by various imaging procedures, especially during another imaging procedure, has made it more difficult to ignore these lesions. Whether or not they are hemodynamically and physiologically significant is hard to evaluate.

Fibromuscular dysplasia, on the other hand, often leads to development of hyper­tension at a young age and responds particularly well to percutaneous intervention. However, this disorder does not usually cause significant renal insufficiency or progressive renal disease,

   Clinical Dilemma Top

Atherosclerotic renal vascular disease is usually associated with a heavy burden of other vasculopathies, high mortality rate and poorer survival on dialysis. It can also be associated with hypertension, renal insufficiency and progressive renal failure leading to ESRD [Figure - 2]. The most difficult question to answer for nephrologists, cardiologists and other clinicians is: what proportion of patients with atherosclerotic renal vascular disease will develop prog­ressive renal failure? How significant is the renal artery lesion? Should an intervention be considered?

   Representative Cases Top

The following four patients represent typical situations facing the clinicians.


Mr. RK came for a second opinion about the initiation of dialysis. He is a 62-year-old vasculopath, who has a long cigarette smoking history and known diffuse vascular disease. He underwent aorto-femoral bypass in the late 1980's, carotid endarterectomy in the late 1990's, has had resistant hyper­tension, proteinuria and intermittent claudication with renal insufficiency. A renal biopsy, performed in 1986 for the nephrotic syndrome, had revealed focal and segmental glomerulosclerosis. After the biopsy, he developed some deterioration of his chronic renal insufficiency and full evaluation revealed left renal artery stenosis, which was surgically bypassed in 1988 with apparently stable renal function. During the last 1.5 years, renal function continued to deteriorate slowly but the patient was clinically stable. In the fall of 2001, he underwent angiography, revealing significant aortoiliac disease, stenosis of both renal arteries right > left, with the kidneys measuring approximately 8.5 and 8.8 cm, left and right respectively. Balloon angioplasty and stent deployment into the right renal artery was undertaken. The patient developed acute renal failure despite acetylcysteine, had several atheroemboli to the feet and developed clinical uremia requiring initiation of dialysis. Soon there­after, he had at least one cerebrovascular accident with some residual paresis. He now is on dialysis with ischemic hands and feet.


He was on anti-hypertensives, statins for hyperlipidemia, calcium carbonate and erythropoietin.


This patient is a 75-years-old lady, who has known ischemic heart disease, hyper­tension, hyperlipidemia, and in late 2000 underwent coronary angiography for angina. During that procedure, aortography revealed stenosis of the right renal artery. Renal size by sonography revealed both kidneys to be approximately 11.0 cm in length. There have been no symptoms of renal failure or recent congestive heart failure.


Her medications included antihypertensives/ and statins. She has not used any over-the­counter nonsteroidal anti-inflammatory drugs (NSAIDs) but does take Tylenol for her severe arthritis. She has an allergy to sulfur and aspirin.

Physical examination in early 2002 revealed blood pressure to be 150/70 mm Hg. There was no fluid overload. The patient is well and very active.

Comment: This patient presents the dilemma of the incidental discovery of what appears to be renal artery stenosis in the presence of atherosclerotic vascular disease and hypertension. Renal function is normal. Over the course of 1.5 years, the kidney has not decreased in size and the patient is tolerating her multiple drug therapy with no ill effect. It does not appear that she has suffered any ill effect from lack of intervention.


Mrs. EP is an 88-year-old lady, who was referred for hypertension and renal insuf­ficiency. She was known to have hyper­tension for well over 40 years, coronary artery disease with angina pectoris, intermittent claudication and at least two transient ischemic attacks.

Medications: She was taking anti-hyper­tensives, statins and lorazepam. She had ingested some NSAIDs and Cox-2 inhibitors in the past. She also takes vitamins and calcium.

Initial physical examination revealed her to have blood pressures of 210/80-86 mm Hg on several occasions despite multiple anti-hypertensive drugs. There was no jugular venous distention, no gallop, negative hepato-jugular reflux, and no edema. There were bruits in the abdomen and over both femoral arteries with diminished tibial pulses and cool feet.

Data: Creatinine was 194 µmol/L with normal electrolytes (in the past she developed hyperkalemia on angiotensin converting enzyme (ACE) inhibitors). Renal duplex sonogram revealed a small left kidney. With treatment of her blood pressure, serum creatinine increased to 248 µmol/L. It was thought that she could have renal artery disease; duplex doppler assessment of her renal arteries revealed an atrophic left kidney and a high grade stenosis of the right renal artery. Renal angiography, balloon angioplasty and stent deployment were performed in October 2001. Her subsequent course revealed her serum creatinine to decrease to 194 µmol/L and blood pressure decreased to 160-170/74-76 mm Hg. Follow­up imaging revealed no duplex evidence of renal artery stenosis immediately post­procedure with good angiographic appearance of the stent. In January, the blood pressure increased again to the 190-210/90 mm Hg range with consequent increase in medi­cations. Losartan was added. She then developed severe angina, requiring coronary angiography and stenting of two coronary arteries. Blood pressure was extremely difficult to control during that hospita­lization and serum creatinine leveled off at 293 to 301 µmol/L. She also developed fluid retention and mild heart failure. Blood pressure remained markedly elevated and uncontrollable. Repeat duplex scanning revealed re-stenosis of the right renal artery proximal to the stent at the ostium of the renal artery. The patient was admitted and underwent C0 2 angiography with re-stenting of the right renal artery. In the spring of 2002, her serum creatinine has decreased to 212 µmol/L and blood pressure had minimally improved.

Comments: Clinically, it would appear that only a small portion of this patient's renal insufficiency and hypertension is due to ischemic nephropathy. This case, however, shows that re-stenosis can occur quite rapidly and that she can also tolerate angiotensin receptor blockers (ARBs) as one of the medications, without hyperkalemia.


Mrs. HL is an 82-year-old lady with an over 30 years history of hypertension, apparently easily controlled over that period of time. In December 2001, she experienced a large cerebrovascular accident with resulting hemiparesis and transient aphasia. Blood pressure at the time of admission to the emergency room and subsequently in the hospital, ranged from 180-210/90-104 mm Hg.

Medications: Her medications included anti-hyptensives, digoxin, vitamins and coumadin. Although, there was a previous cough and hyperkalemic reaction to ACE inhibitors, neither these agents nor ARBs were prescribed.

Physical examination revealed an alert elderly lady with obvious left sided weakness. There was no jugular venous distention, no gallop, negative hepato jugular reflux, and no edema. There were multiple bruits over the carotid artery, in the abdomen and in the femoral arteries. Blood pressure was 196/104 mm Hg.

Hospital Course: Labetalol, diuretics and calcium channel blockers were prescribed, with slight improvement in blood pressure control. The patient was eventually trans­ferred to a rehabilitation facility where she experienced a seizure and was readmitted with blood pressure again uncontrolled. Valsartan was prescribed. Duplex Doppler renal sonogram revealed high-grade stenosis of the right renal artery with normal renal size and a small atrophic left kidney. The Valsartan was continued and the patient developed acute renal failure, with the creatinine increasing from 106 µmol/L to 380 µmol/L within seven days. The Valsartan was discontinued with prompt improvement in kidney function. Blood pressure was in normal range while on the ARB.

Comments: This elderly lady had clear-cut significant renal artery stenosis with blood pressure control and renal failure while on the angiotensin receptor blocking agent. This suggests that the renal artery lesion was functionally significant. Now, on four other classes of anti-hypertensive agents, including Clonidine, Labetolol, diuretic and Felodipine, her blood pressure is marginally controlled, in the 150-160/80 mm Hg range. She is recuperating in rehabilitation from her recent stroke and seizure activity. Renal angiography, balloon angioplasty and stent deployment will be scheduled after she recovers from her recent vascular events.

   Diagnosis of ARAS Top

ARAS should be suspected in some particular settings: severe or refractory hypertension, an acute change in blood pressure course, asymmetry in renal size, recurrent episodes of flash pulmonary edema that can occur in patients with normal left ventricular systolic function, or an increase in the plasma creatinine concentration following the administration of an ACE inhibitor or an ARB agent [Table - 1]. However, some patients may have few, if any, of these processes except for diffuse and systemic atherosclerosis.

Based on retrospective arteriographic studies, rates of progression of renal artery stenosis [even to total occlusion] were estimated to range from 36 to 53% [17],[18] [Figure - 3]. In more recent studies using duplex doppler ultrasound in 170 patients followed for nearly three years, there was an overall progression in 31% of the patients. [19] The cumulative incidence of progression over three years was related to the original degree of stenosis, e.g. 18%, 28% and 49% progression for renal arteries initially classified as being normal, <60% stenosis and > 60% stenosis respectively, p<0.03 log rank test, with only nine renal artery occlusions. [19] Similarly, there was a 21% incidence of significant decrease in kidney size, which was associated with rising systolic blood pressure levels. [20] Renal atrophy correlated with changes in the serum creatinine. These data suggest that there is an inevitable, but slow, progression of ARAS in the susceptible patients. Although the absolute risk of developing ESRD is unknown, a recent editorial by Zierler stated a cumulative 5­year incidence of 11.8%. [21]

   Treatment Modalities and Outcomes Top

The clinical approch to patients with suspected significant ARAS is difficult to follow because of the lack of clear-cut evidence supporting any given path. First the diagnosis must be suspected based on the patient's presentation [Table - 1]. In the older patient with multiple medical problems, one must rely heavily on imaging techniques and clinical acumen to make a decision about moving forward. Functional tests such as captopril renography and renal vein renins are of limited value in patients with renal dysfunction and in those with multiple medications that often include beta blockers, ARBs, ACE inhibitors, etc. Yet, lurking in the background (and subcons­ciously in the mind of most nephrologists and cardiologists) is the fear that missing the diagnosis of a significant renal artery lesion will eventually lead to uncontrolled refractory hypertension with its many vascular complications that are often disastrous clinically and eventually doom the patient to ESRD. A prudent approach is necessary so that an appropriate diagnosis is made and that the patient is dealt with in a clinically appropriate manner. Likewise, there are some clear-cut contra-indications to inter­vention, including advanced age with many co-morbid conditions, stable renal function, relatively easily controlled blood pressure, elevated resistive index of the non-stenotic kidney and apparent unilateral renal artery stenosis [Table - 2].

Appropriate data suggest that surgical techniques lead to longer lasting successful outcomes for control of blood pressure in the patient with ARAS. [22],[23],[24] Angioplasty with stent deployment is successful in dilating the stenotic blood vessel but does not appear to offer a long-lasting benefit to the patient. [19],[20],[25],[26] As a result, it is quite likely that when a physician moves forward it is often unclear whether the evaluation is logical and eventual outcome, of any benefit.

Intrarenal resistive indices along with hilar waveforms and the renal/aortic flow ratios are all helpful in detecting the presence of ARAS. In a recent study, a resistive index > 0.8 in the contralateral kidney predicts failure of intervention in patients with ARAS. [27] This would appear to be a valuable functional test, especially in patients with renal insuf­ficiency. There are several tests of research interest; ultrafast spiral computerized tomo­gram angiography (but requires contrast), CO 2 /gadolinium angiography (pictures almost as good as the gold standard contrast angiogram), captopril dynamic magnetic resonance angiography (MRA), and high speed MRA with gadolinium [Table - 3].

The following clinical plan is suggested as logical and rational. [Figure - 4] presents a possible algorithm:

Clinical scenario 1:

The seriously ill arteriopath: Compile a comprehensive vascular disease inventory; if too many vascular beds are involved, then perhaps no intervention should be performed.

Clinical scenario 2:

The patient with difficult to control hyper­tension: (i.e. at least four classes of agents at near to maximal dosing, unacceptable rise in serum creatinine with ACE inhibitors or ARBs) or with a combination of the two, stable cardiac condition. Perform appropriate imaging (duplex doppler, renal arterial study vs MRA with gadolinium depending on resource available in the community and body habitus). Other options include dis­continuation of ACE inhibitors or ARBs to see if renal function improves, but blood pressure may increase and become difficult to control. [28] The major decision in this clinical scenario is to decide whether interventional radiology or cardiology is chosen first before vascular surgical expertise is called in.

Comment: This is the more typical clinical scenario where patients with atherosclerotic vascular disease also have ARAS with both hypertension and renal insufficiency. Imaging would most likely show renal artery stenosis, often significant unilaterally with atherosclerosis of the aorta and some other abnormalities on the contralateral kidney. The procedure is performed in an attempt to assist with blood pressure control and hopefully prevent further renal functional deterioration.

Clinical scenario 3:

An elderly patient with many clinical features of atherosclerotic peripheral vascular disease and either ARAS diagnosed at the time of other imaging procedure or because of hypertension or other clinical indication. However, treatment with anti-hypertensives (ACE-inhibitors and/or ARBs) causes minimal increases in serum creatinine while con­trolling the blood pressure.

There is no change in kidney size by sonography during follow-up. No inter­vention is planned.

   Conclusions Top

Renal vascular disease is more common than anticipated in elderly ESRD patients, especially in white patients with other vascular co-morbidities. Significant incidental ARAS may be detected in as many as 20% of patients undergoing coronary angio­graphy or in the presence of peripheral vascular disease.

The usual screening tests work well in younger patients with normal renal function. Duplex doppler ultrasound has the highest specificity, but some technical failure rate. Normal ACE-inhibitor scintigraphy may obviate the need for renal angiography in patients with adequate renal function. However, digital intra-arterial angiography remains the 'gold standard' of diagnostic tests. Magnetic resonance angiography is a promising new technique due to stronger magnets, gadolinium and new software. Although the natural history of ARAS is not well established, progression and occlusion of the renal arteries ultimately is the outcome, with progression of stenosis occurring in up to 49% of patients. The diagnosis of ARAS should be suspected earlier when it is safe to perform invasive procedures and surgical therapeutic options. Medical or surgical therapy is dictated by the patient's co-existing vascular condition. Angioplasty has no significant role in therapy, but stents are helpful. Attention should be paid to all cardiovascular disease risk factors before the chronic kidney disease progresses to uremia. Small kidneys are contraindications to interventional therapy. It is quite clear that renal vascular disease is a significant cause of ESRD in the USA [Figure - 5]. Whether its incidence is really increasing or more nephrologists are looking for it, is unclear. It has also been reported that about 15 to 20% of patients undergoing cardiac catheterization have renal vascular disease. Based on these data, not all patients with anatomic renal artery stenosis progress to ESRD. In 2002, the clinician is still faced with the dilemma of deciding which patient will progress to ESRD and how to approach a patient with atherosclerotic renal vascular disease.

There is a need for a prospective randomized clinical trial comparing surgical therapies to interventional and aggressive medical therapy in these patients with diffuse atherosclerosis. In the absence of such trials, the clinician should treat the overall patient as aggressively as is possible, i.e. smoking cessation, cholesterol manage­ment, low goal blood pressure, ACE inhibition/ARB if tolerated, aspirin, folate administration, exercise and prudent diet, to deliver optimal medical care. If the patient is stable on this therapy then there is no need for intervention. It may be necessary to evaluate blood pressure control by 24­hour monitoring. If renal function deterio­rates and blood pressure cannot be controlled on such an aggressive routine, then the patient should be offered more invasive diagnoses and therapy.

   References Top

1.Mailloux LU, Napolitano B, Bellucci AG, et al. Renal vascular disease causing end­stage renal disease, incidence, clinical correlates, and outcomes: a 20-year clinical experience. Am J Kidney Dis 1994;24:622-9.  Back to cited text no. 1    
2.Fatica RA, Port FK, Young EW. Incidence trends and mortality in end-stage renal disease attributed to renovascular disease in the United States. Am J Kidney Dis 2001;37(6):1184-90.  Back to cited text no. 2    
3.Appel RG, Bleyer AJ, Reavis S, Hansen KJ. Renovascular disease in older patients beginning renal replacement therapy. Kidney Int 1995;48:171-6.  Back to cited text no. 3    
4.Greco BA, Breyer JA. Atherosclerotic ischemic renal disease. Am J Kidney Dis 1997;29:167-87.  Back to cited text no. 4    
5.United States Renal Data Systems. USRDS 2001 ADR. US Dep't of Health and Human Services. Bethesda, MD August 2001.  Back to cited text no. 5    
6.Safian RD, Textor SC. Renal-artery stenosis. N Engl J Med 2001;344:431-42.  Back to cited text no. 6    
7.Baboolal K, Evans C, Moore RH. Incidence of end-stage renal disease in medically treated patients with severe bilateral atherosclerotic renovascular disease. Am J Kidney Dis 1998;31:971-7.  Back to cited text no. 7    
8.Plouin PF, Rossignol P, Bobrie G. Athero­sclerotic renal artery stenosis: to treat conservatively, to dilate, to stent, or to operate? J Am Soc Nephrol 2001;12:2190-6.  Back to cited text no. 8    
9.Isles CG, Robertson S, Hill D. Management of renovascular disease: a review of renal artery stenting in ten studies. QJM 1999; 92(3):159-67.  Back to cited text no. 9    
10.Burket MW, Cooper CJ, Kennedy DJ, et al. Renal artery angioplasty and stent placement: predictors of a favorable outcome. Am Heart J 2000;139:64-71.  Back to cited text no. 10    
11.Jaff MR, Olin JW. Atherosclerotic stenosis of the renal arteries. Indications for intervention. Tex Heart Inst J 1998;25:34-9.  Back to cited text no. 11    
12.Cheung CM, Wright JR, Shurrab AE, et al. Epidemiology of renal dysfunction and patient outcome in atherosclerotic renal artery occlusion. J Am Soc Nephrol 2002; 13:149-57.  Back to cited text no. 12    
13.Harding MB, Smith LR, Himmelstein SI, et al. Renal artery stenosis: prevalence and associated risk factors in patients undergoing routine cardiac catheterization. J Am Soc Nephrol 1992;2:1608-16.  Back to cited text no. 13    
14.Rihal CS, Textor SC, Breen JF, et al. Incidental renal artery stenosis among a prospective cohort of hypertensive patients undergoing coronary angiography. Mayo Clin Proc 2002;77:309-16.  Back to cited text no. 14    
15.Choudhri AH, Cleland JG, Rowlands PC, et al. Unsuspected renal artery stenosis in peripheral vascular disease. BMJ 1990; 301:1197-8.  Back to cited text no. 15    
16.Leertouwer TC, Pattynama PM, van den Berg-Husmans A. Incidental renal artery stenosis in peripheral vascular disease: a case for treatment? Kidney Int 2001;59: 1480-3.  Back to cited text no. 16    
17.Meaney TF, Dustan HP, McCormack LJ. Natural history of renal arterial disease. Radiology 1968;91:881-7.  Back to cited text no. 17    
18.Tollefson DF, Ernst CB. Natural history of atherosclerotic renal artery stenosis associated with aortic disease. J Vasc Surg 1991;14:327-31.  Back to cited text no. 18    
19.Caps MT, Perissinotto C, Zierler RE, et al. Prospective study of atherosclerotic disease progression in the renal artery. Circulation 1998;98(25):2866-72.  Back to cited text no. 19    
20.Caps MT, Zierler RE, Polissar NL, et al. Risk of atrophy in kidneys with athero­sclerotic renal artery stenosis. Kidney Int 1998;53:735-42.  Back to cited text no. 20    
21.Zierler RE. Screening for renal artery stenosis: is it justified? Mayo Clin Proc 2002;77:307-8.  Back to cited text no. 21    
22.Novick AC. Long-term results of surgical revascularization for renal artery disease. Urol Clin North Am 2001;28:827-31.  Back to cited text no. 22    
23.Cherr GS, Hansen KJ, Craven TE, et al. Surgical management of atherosclerotic renovascular disease. J Vasc Surg 2002;35: 236-45.  Back to cited text no. 23    
24.Hansen KJ, Thomason RB, Craven TE, et al. Surgical management of dialysis­dependent ischemic nephropathy. J Vasc Surg 1995;21:197-209.  Back to cited text no. 24    
25.Yutan E, Glickerman DJ, Caps MT, et al. Percutaneous transluminal revascula­rization for renal artery stenosis: Veterans Affairs Puget Sound Health Care System Experience. J Vasc Surg 2001;34:685-93.  Back to cited text no. 25    
26.Tullis MJ, Caps MT, Zierler RE, Dadal RE. Blood pressure, antihypertensive medication and atherosclerotic renal artery stenosis. Am J Kidney Dis 1999;33:675-81.  Back to cited text no. 26    
27.Radermacher J, Shavan A, Bleck J, et al. Use of doppler ultrasonography to predict outcome of therapy for renal artery stenosis. N Engl J Med 2001;344:410-7.  Back to cited text no. 27    
28.van de Ven PJ, Beutler JJ, Kaatee R, et al. Angiotensin converting enzyme inhibitor­induced renal dysfunction in athero­sclerotic renovascular disease. Kidney Int 1998;53:986-93.  Back to cited text no. 28    

Correspondence Address:
Lionel U Mailloux
Long Island Hypertension and Nephrology, 50 Seaview Boulevard, Port Washington, NY 11050
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PMID: 18209426

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  [Table - 1], [Table - 2], [Table - 3]


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