Atherosclerosis and kidneys

Atherosclerosis and kidneysIntroduction:

Atherosclerosis has a considerable prevalence in Western countries, with variations related to age and genetic and environmental factors. It reaches all the arteries of the organism. Knowing that the kidneys are vascularized by two main arteries of 6 to 8 mm in diameter, which receive 20 to 25% of the cardiac output, it is surprising to note that for at least two decades the atherosclerosis of these vessels, generating renal ischemia, has place among the leading causes of chronic kidney failure. Rare are nevertheless the treatises on nephrology where, if the index is examined under the heading “atheroma” or “atherosclerosis”, we do not see ourselves referred to the chapter of renovascular hypertension rather than to those who kidney failure. Although hypertension is usually a sign of renal ischemia, it may not be in the forefront. We are in fact here in the field of chronic nephropathies leading to renal atrophy, the problem posed to the nephrologist being to avoid the progression of ischemia towards fibrosis and atrophy of the kidneys, stage prelude to the methods of extrarenal treatment on a particularly unfavorable terrain. This development would be all the more regrettable because, as a result of mechanical stenosis, atherosclerosis of the renal arteries is accessible to a mechanical treatment, restoring blood flow in the pre-glomerular circulation.

However, atherosclerotic plaques rarely form in a subject with renal parenchyma. Age, primary primary hypertension, and anterior nephropathy, such as type 2 diabetes, already exist in most of these patients whose kidneys are the site of a sclerosis (or nephroangiosclerosis) that can cause revascularization , however effective in terms of imaging, does not modify the rhythm of the evolution towards renal insufficiency.

Among these parenchymal lesions are two complications specific to atherosclerosis itself: cholesterol embolisms and alterations more or less related to atherogenic dyslipidemia.

It was therefore logical to divide this chapter of the Medico-Surgical Encyclopedia into three sections underlying the atherosclerotic disease: renal artery stenosis, cholesterol crystal embolism and other parenchymal lesions observed in patients of this kind .

Atherosclerotic stenosis of renal arteries:


The experiments of Goldblatt, which in 1934, genially created the notion of renovascular hypertension while giving the signal for the discovery of the renin-angiotensin system, deserve to be re-read. When he placed a sufficiently tight clip on the two renal arteries, the experimental animal died of uremia. At the beginning of renal artery surgery to treat renovascular hypertension, the Poutasse team in Chicago also had in the 1950s observed that the correction of bilateral stenosis could improve renal insufficiency in some of these patients. However, it was not until the early 1980s that, in a few cases, Hricik, then Ying, reported that in atherosclerotic patients with stenosis of both renal arteries or stenosis of a functionally unique kidney, of treatment with an angiotensin converting enzyme (ACE) inhibitor resulted in a sudden rise in serum creatinine. We will see later the physiopathological mechanism of this phenomenon but also its diagnostic limits. Renal ischemia of atherosclerotic origin finally reached the level of consciousness of the nephrologists and in 20 years, the publications on this subject numbered by hundreds. For about ten years, the enthusiasm of vascular surgeons and interventional radiologists led them to advocate revascularization in all cases where the height of the kidney was greater than 8 cm. More recently, a series of publications have been published that temper this activism and lead to greater circumspection in indications of revascularization.


The atherosclerotic plaques of the renal arteries are not different from those that reach other large arteries.

They are formed of intra- and extracellular lipids, smooth muscle cells, connective tissue and glycosaminoglycans. The “atheromatous” component and the “fibrous” component vary over time. The plaques tend to calcify, ulcerate and then cover a clot that covers the atheromatous component, rich in cholesterol crystals. These general data are known for a long time. However, in the area specific to renal arteries, two significant relationships must be emphasized. The first is that which connects to the coronary arteriosclerosis the plaques of interest to the renal arteries. The second is the frequency with which the occlusive disease of the renal arteries is accompanied by cholesterol embolism.

The localization of plaques is important to know, because it can explain some diagnostic difficulties by radiological imaging, their hemodynamic reverberation downstream and the vagaries of their treatment. They sit, singly or together, on the trunk of the artery, on their ostium (these are aortorenal plaques), or on the polar arteries. There are two difficulties for the radiologist: the ostium of these large trunks must be clearly distinguished from the ostium, and the extent of the stenosis must be appreciated, which to some extent determines the hemodynamic repercussion. A stenosis decreasing the renal artery size of < 50% is considered not to be haemodynamically functional. Beyond 70%, it is likely to be, but it is not a certainty.

Between the two, all varieties are possible, and we shall see later on what methods make it possible to judge the repercussion of the stenosis, which determines the therapeutic attitude.

Renal atherosclerotic stenoses are common, usually bilateral and usually progressive.


The notion that atherosclerosis of the renal arteries is a common and underestimated cause of chronic renal failure is ancient for vascular surgeons, much more recent for nephrologists. The frequency of the atherosclerotic plaques on the trunk or ostium of these vessels is large, but difficult to judge accurately. Greco and Breyer analyzed 11 publications published between 1975 and 1994, in order to establish the percentage of patients with more than 50% stenosis of the renal artery. Results ranged from 11% to 42%. Plouin et al took over the cases of 824 patients studied by angiography, of which 201 were over 60 years of age. Renal arterial stenosis was observed in 5.5% of those under 60 years of age and in 16.4% of those who were over the age of 60 years. In three studies conducted by cardiologists involving injecting the contrast agent into the renal arteries at the end of coronary or cavitary iodine opacification, plaques were present in 5%, 29% and 15% of the cases, respectively. The prevalence was 29% for coronary stenosis, 10% for normal coronary arteries. Aortic angiography performed in 385 atherosclerotic patients showed an aneurysm in 109 cases, an aorto-occlusive disease in 21 cases, and an iliofemoral arteritis in 189 cases. The frequency of renal artery stenosis was 38, 33 and 39%, respectively.

Note the frequency of association with an abdominal aortic aneurysm. Doppler-ultrasound studies in patients with multiple locations of atherosclerosis found a 15% prevalence of renal artery disease.

Appel et al extrapolating the results of a fairly limited study in hemodialysis patients concluded that in Caucasian Americans, renal ischemia of atherosclerotic origin could be responsible for 7% of cases of terminal renal insufficiency, the fourth leading cause of chronic renal failure in the United States. It should be noted that, on the other hand, this complication is not frequent in black subjects of African descent who, although frequently suffering from early hypertension and progressive nephroangiosclerosis, are little affected by atherosclerotic disease renal function, no more, as will be said later, than cholesterol embolisms.

Atherosclerotic renal stenosis is a special risk group in atherosclerotic patients. It is established that the plaques on the renal arteries occur almost always in subjects suffering from severe vascular disease.

The involvement of the renal arteries, nevertheless, implies in a significant number of cases that arteries with visceral destiny whose obstruction compromises the survival. This is particularly true of coronary arteries, and severity is magnified when the field is that of type 2 diabetes. Of the three cardiological studies cited above, there is a significant relationship between renal artery stenosis and coronary stenosis. Conlon et al analyzed the influence of atherosclerotic involvement of renal arteries on the overall survival of dialysed atheromatous patients compared to patients treated for nephropathy of another kind. There is a disturbing difference between the two groups. In addition, Conlon et al studied 3,987 patients undergoing coronary angiography. A significant stenosis, defined by a reduction of 75% or more of the artery size, was present in 4.8%, bilateral in 0.8% of cases. The survival at 4 years was 89% in the absence of significant stenosis and 57% in the absence of significant stenosis.

Depending on the degree of stenosis, 50%, 75% or greater than or equal to 95%, survival was 70%, 68% and 48%, respectively. Bilateral stenoses had a 4-year survival of 47% versus 59% for unilateral stenosis. These mortality values ​​were unrelated to the mode of treatment for coronary artery disease. This may be seen as an additional argument for early revascularization of the ischemic kidneys or, on the contrary, an incentive to remain very restrictive in the treatment of renal artery stenoses in large atherosclerotic patients. This is in any case the view now supported by the team of Textor, as by other investigators who argue that medical treatment alone is sufficient in a significant number of cases, and that even after angioplasty, mortality remains high , not by renal insufficiency but by vascular accidents, essentially coronary. We shall return to this aspect of the therapeutic decision.


Atherosclerosis of the renal arteries is very often bilateral, though rarely symmetrical. The appearance of stenosing plaques begins on one side, which may be due to renovascular hypertension, which often aggravates long-standing anterior primary hypertension or renders the drug treatment more difficult. Renal function is then normal or near normal. The appearance of stenotic lesions on the other side increases the arterial hypertension and coincides with the onset of ascension of serum creatinine. Out of 549 stenosed arteries, 252, or 46%, were on both sides. From a physiopathological point of view, it is therefore conceivable that we are here in a model of Goldblatt hypertension of the type “two kidneys, two clips” and that beyond a certain degree of bilateral ischemia, renovascular hypertension, without disappearing, is gradually giving way to renal insufficiency. This is all the more true as strictures in most cases tend to worsen over time.


The evolutionary potential of renal atherosclerotic stenosis is difficult to establish with certainty because of the absence of large series of patients followed over the years, between the time when a non-hemodynamically functional stenosis is diagnosed and the ischaemia resonates with function and survival of the kidney. The analysis of the literature shows however that in a majority of cases, renal ischemia progresses at the rate of the evolution of the plaque of atheroma, causes atrophy of the kidney and ends up being complicated by a thrombosis of the ” renal artery.

This was the case in the early observations of Ying et al and Hricik et al, who had drawn the attention of nephrologists to renal ischemia, a cause of chronic renal failure uncovered by IEC therapy. Half of their patients had bilateral involvement of their renal circulation, with stenosis on one side and old thrombosis on the other, an eloquent demonstration of the evolutionary character of renal atherosclerotic disease and the severity of the delay diagnostic.

Soon after, the Novick team in Cleveland, Ohio, insisted on the scalability of the atherosclerotic stenoses of the renal arteries. These vascular surgeons showed that when a stenosis is followed by successive angiographies, the risk of thrombosis depends on the severity of the initial stenosis. When the stenosis is 50%, the risk is 5% within 56 months.When it is 50 to 75%, it is 10% to 24 months. When it is greater than 75%, it is 39% at 13 months. These figures spoke for themselves, and the conclusion was clear that a diagnosed atherosclerotic stenosis must be monitored regularly, and that any scalability requires angioplastic or surgical intervention to prevent kidney loss.

In 1993, Rimmer and Gennari undertook a review of the literature to determine the rate of progression of renal atherosclerosis. Wollenweber et al, as early as 1968, reported a large series of Mayo Clinic patients followed by angiography and also showed the scalability of the atherosclerotic stenoses of the renal arteries. In addition, they documented the high prevalence of diffuse atherosclerotic lesions in such patients. At diagnosis, 33% had heart disease, 11% had cerebrovascular disease and 32% had peripheral arteritis. In patients who did not initially have coronary artery disease, 47% had signs of coronary artery disease within 5 years.

Of the 237 patients, half had a worsening of stenosis with time and 14% had thrombosis.

Each of these reports shows the progressive nature of the disease.

However, the incidence of progression varies widely. On average, in 49% of patients, the disease progresses, but with a difference of 29% to 71%. On the one hand, these variations stem from the reasons why a control angiogram was performed. By combining the four studies in which strictures were progressive, the mean prevalence of occlusion was 14%. Control of arterial hypertension had little effect on the progression of stenosing lesions and serum creatinine appeared to be a poor reflection of the progression of anatomical disease.

In two of these five reports, investigators attempted to quantify the rate of progression of renovascular disease. Schreiber et al showed that progression of stenosis was 1.5% per month. It was 0.38% per month in the report of Tollefson et al. In fact, the variability in patient-to-patient progression was high, and the authors note that it is not possible to quantify the rate of progression because of such variability.

Some patients remain stable for long periods while others progress rapidly. Factors influencing the speed of this progression are not identified. It should be noted that these studies were done before medical treatments were available to control lipid risk factors, ie, statins. It has been shown that these pharmacological agents, alone or in combination with other hypolipidemic agents, obtain not only stabilization but also regression of atherosclerotic plaques and vascular remodeling of the renal arteries like other large arteries.


Renal ischemia leads to a hemodynamic response to maintain the glomerular filtration rate in the face of decreased flow and pressure downstream of the stenosis. In a second stage, ischaemia leads to an atrophy of all the elements of the renal parenchyma invaded by fibrosis. Finally, in this area usually associated with old hypertension, smoking, dyslipidemia, glucose intolerance and disseminated plaques from the ascending aorta, the association with cholesterol embolisms is common. We are far from pure renal hypertension, like that of a fibromuscular disease of the young woman whose renal parenchyma is initially perfectly healthy.

Functional Consequences:

This section requires a reminder of the conditions that maintain glomerular filtration rate under normal conditions, and the defense of

glomerular filtration rate in the event of a drop in flow and pressure upstream. These mechanisms are the same as in the case of extracellular dehydration with hypovolemia, but their effect, in this case a shift from glomerulotubular equilibrium to increased sodium reabsorption, is inappropriate because it causes hypervolemia. It will be seen later that this phenomenon explains one of the clinical signs of renal ischemia of vascular origin: pulmonary edema called “flash”.

Ischemia leads to renin secretion with proportional release of angiotensin II (Ang II). The glomerular efferent arteriole is rich in Ang II receptors and its vasoconstriction preserves the hydrostatic pressure in the flocculus. It is conceivable that any pharmacological agent opposing this vasoconstriction results in collapse of the flocculus which decreases the glomerular filtration rate and leads to an appearance or an increase in renal insufficiency. This is the case for ACE inhibitors and is the basis of the captopril test to determine the haemodynamically functional stenosis. However, the rise of serum creatinine under IEC is not specific to renal artery stenosis. It can be observed in chronic nephropathies but also as a consequence of the lowering of blood pressure induced by any antihypertensive agent. This notion of “decreasing critical infusion pressure” has been elegantly demonstrated by Textor et al. Their protocol consisted in perfusing a vasodilator, nitroprusside, and simultaneously measuring the arterial pressure on the one hand, the renal plasma flow and the glomerular filtration rate on the other hand. It is found that for a given degree of blood pressure drop, renal perfusion declines rapidly. It is clear that the phenomenon is explained by the fact that a tight stenosis can only be crossed under the effect of sufficient blood pressure.

Organic consequences:

The normal kidney receives 20 to 25% of cardiac output every minute.

However, it requires only about 7% of the oxygen and the red blood cells thus delivered for the purposes of its metabolism. We know of cases of complete thrombosis of the renal artery where the maintenance of a vascularization by the meager collateral perirenal circulation preserves for some time the survival of the organ. However, an arterial stenosis leads to a progressive atrophy of the kidney, which can be followed by fine CT or Doppler ultrasound. The anatomopathological aspect of the ischemic kidneys has been studied experimentally and found in man. The ischemic kidney atrophies. Under the microscope are complex lesions of nephroangiosclerosis, cholesterol embolism, interstitial fibrosis, tubular atrophy lesions and glomerular obsolescence. The appearance is close to that of a chronic interstitial nephritis, associating an atrophy of the tubular cells with formation of protein cylinders in the lumen of the tubes, giving them a so-called “microcystic” aspect, inflammatory infiltrates of the interstitium, fibrosis interstitial, glomeruli of ischemic aspect and their obsolescence, with lesions of segmental and focal and then global hyalinosis.

It can be seen that this is far from the old notion of “endocrine kidney” protected, unlike the adelphous kidney, from the hypertension it creates by the stenosis that ischemia.

The pathophysiology of this degeneration and the accompanying fibrosis has been the subject of experimental work. In animals, a model of chronic reduction in renal perfusion pressure results in severe parenchymatous lesions despite poststenotic perfusion pressures of 60 mmHg. The mechanism of tubular lesions has been studied in rats. Truong et al observed phenomena in the ischemic kidney suggesting that a local immune reaction affects the tubes. It has also been shown that the tubular epithelium undergoes apoptosis phenomena followed by a multiplication of cells that remain viable, possibly under the effect of “renotropin”, a growth factor responsible for compensatory hypertrophy after unilateral nephrectomy .

This suggests that the ischemic kidney still has powerful tubular regeneration capabilities if its vascularization is restored by surgery or endoluminal angioplasty. This explains why in humans, after revascularization, renal function improves in 55% of cases, stabilizes in 31% of cases and only worsens in 14% of cases. Interestingly, these results are practically comparable for surgical treatment and angioplasty.

The association with tubulo-interstitial lesions of glomerular lesions of segmental and focal hyalinosis has also been reported. It is not known whether these non-specific lesions are due to ischemia itself or, conversely, are formed in areas of the kidney that are protected and subjected to a glomerular hyperfiltration regimen. Nevertheless, they probably explain the possibility of abundant proteinuria, which is well known in renal ischemic disease and whose relationships with the degree of stenosis and the severity of renal insufficiency have been analyzed by Conlon et al .

Ischemia leads to fibrosis. This fibrosis affects the renal medulla, and in particular the peritubular capillaries which, enclosed in the collagen, help to perpetuate the sclerosing process.

The pathophysiology of ischemic renal fibrosis involves primarily Ang II and endothelin, but also transforming growth factor (TGF) -b and platelet derived growth factor (PDGF) -b. In the rat, prolonged perfusion of Ang II at low-pressure doses results in lesions very similar to those of human ischemic kidney diseases, whereas in this protocol, the interstitium is strewn with osteopontin, chemoattractant of the macrophages which are scattered the interstitium, invaded by interstitial cells which undergo phenotypic transformation into myofibroblasts expressing α- SMA epitopes, and finally Ang II enhances the expression of TGF-β on fibroblasts.


The diagnosis of ischemia of vascular origin is not always evident. These patients of a certain age are often long-standing hypertensive patients, probably suffering from nephroangiosclerosis, sometimes obese and diabetic, who may also suffer from an unknown, glomerular or urological nephropathy. However, the fact of dealing with an atherosclerotic and polyvascular patient, a coronary, arterial, cerebrovascular history is enough to attract attention.Foot lesions consistent with cholesterol embolism have excellent orientation value. The fact that an unexpected ascent of serum creatinine has resulted from a new or enhanced antihypertensive treatment, more particularly by an angiotensin antagonist, is very evocative.

A particular clinical manifestation of the stenosis affecting the two kidneys or the artery of a functionally unique kidney is represented by the pulmonary oedema edema described by Pickering et al in 1988 and by many others in its train.These are sudden onset of pulmonary edema in patients whose myocardial function is not particularly compromised.In fact, if one recalls that the ischemia of the models of Goldblatt two kidneys, two clips and one kidney, one clip leads to a progressive retention of water and salt, one conceives that this hypervolemia ends up leading to an edema pulmonary, which has flash only its mode of clinical appearance, but which in fact is only the expression of “the last drop of water that makes the vase overflow”. These episodes of pulmonary edema represent the formal indication of endoluminal angioplasty.

This is followed immediately by sodium-rich polyuria, which can act as an obstacle lift and, once the pulmonary edema has been controlled, require a perfusion of saline to avoid dangerous hypovolemia.

Once mentioned, the diagnosis is simple and should range from the least invasive to the most risky investigations in this area. The discovery of an asymmetry of the kidneys on ultrasound is of major importance. There are rare stenoses in which renal atrophy is absolutely symmetrical. The next non-invasive stage is doppler ultrasound, which has been shown to be of major interest and technical limitations. The spiral scanner without injection of iodine passing through the aortorenal intersection can show exploitable images. Magnetic Resonance Imaging (MRI)   after injection of gadolinium is also well supported, but the images somewhat increase the apparent importance of stenoses. Finally, the spiral scanner after injection of iodine carries the risks related to the toxicity of the contrast product but the images that it obtains are often remarkable. In fact, the gold standard of imaging remains angiography by a Seldinger catheter, usually by the femoral, sometimes humeral route. It shows the stenosis and allows at the same time to treat it by angioplasty with the most often laying of a spring (stent). However, this method exposes both to the toxicity of iodine and to the risk of cholesterol embolisms. Some major ulcerative aortitis should carefully weigh the risk of cholesterol embolism compared to the expected therapeutic benefit.


There are three circumstances in which bilateral stenosis, or the stenosis of a functionally unique kidney vascularizing artery, may be complicated by acute renal failure.

One is functional, the other two organic.

Functional renal insufficiency:

The essential circumstance is the implementation of antihypertensive therapy. IEC and Ang II receptor antagonists are the main, but not exclusive, cause. For the first section, the physiopathological section concerning the hemodynamic consequences of a drop in flow and pressure in the pre-glomerular circulation will be referred to. The filtration pressure in the urinary chamber, limited by Bowman’s capsule, is the main determinant of the glomerular filtration rate. The progressive vasoconstriction of efferent arteriole, rich in Ang II receptors, is the normal response to any threat of flocculus collapse. It is easy to conceive that to abolish this last defense by a pharmacological process leads to a drop in the rate of glomerular filtration with a proportional rise of serum creatinine. With this in mind, we have seen above that any drop in blood pressure below a critical perfusion pressure can also decrease the glomerular filtration rate, as well as the implementation of IEC treatment can reduce the filtration rate glomerulonephritis in many nephropathies without renal insufficiency. Finally, acute renal insufficiency may also be due to excessive diuretic treatment with hypovolemia or the toxic effects of an iodine examination.

Occlusion of a remaining renal artery:

Atheromatous stenoses are bilateral and progressive. We have seen that in 14% of cases they lead to complete occlusion. The loss of a kidney is usually silent, at least clinically. Consequently, the progression of a stenosis on a functionally unique kidney can lead to anuria. In our experience, the stage before thrombosis is marked by an increasingly difficult control of arterial hypertension, the appearance of subintrant pulmonary edema and rapid rise of serum creatinine. Anuria is suddenly constituted and has the peculiarity of being complete, which is not usual in acute tubulopathies, where a diuresis even minimal, rich in sodium, persists. Ultrasound makes it possible to rule out the hypothesis of a urological obstacle on single kidney since the excretory cavities are not dilated. Such a complete aneurysm on the basis of atherosclerosis, arterial hypertension and pulmonary edema is not difficult to diagnose as long as one thinks of it.

Doppler ultrasound and arteriography should be requested without delay, because if the renal parenchyma remains viable for some time due to collateral circulation, the progression of this hot ischemia, which initially leads to reversible tubular necrosis, does not take long to lead to irreversible lesions. Treatment can be considered by angioplasty or surgical revascularization without any delay. Recurrence of diuresis may be rapid, or occur after several weeks of hemodialysis.

Cholesterol Crystal Embolies:

We have shown that atherosclerotic stenoses of the renal arteries are frequently associated with cholesterol embolisms.

They can be responsible for acute renal failure, whether spontaneous or consecutive to the triggering factors discussed below.


The epidemiological elements we have analyzed illustrate a major public health problem: that of a remarkably frequent cause of chronic uraemia, but, unlike parenchymal nephropathies, accessible to a simple treatment in principle, since it consists in restoring the caliber of a large diameter vessel to suppress downstream ischemia.

This simplicity of principle had given rise to a series of striking publications, mostly from the Novick group at the Cleveland Clinic, relating to the interest of revascularization for nephronic protection. In some patients treated with hemodialysis, revascularization obtained a restoration of renal function allowing the return to a conservative treatment.

In 1995, Bonelli et al observed that angioplasty improved renal function in 70% of these patients.

Curiously, ten years later, Textor, who was a member of this medical and surgical team, adopted a more nuanced attitude regarding the need to intervene (surgically or by angioplasty) on renal atherosclerotic stenosis. After enumerating the literature on stenosis evolution and the risk of terminal renal insufficiency, he defends a relatively wait-and-see attitude, based on two arguments: stability of renal function in half of the cases and l from preliminary papers in abstract form, that since 1991 it appears that the scalability of these lesions is less than in the past. In his argumentation there is an indisputable element, that of the risk of cholesterol embolisms caused by surgical intervention or interventional radiology.

Chabova et al, of the Textor team, studied 68 patients aged 71.8 ± 0.9 years with a stenosis > 70%, treated without revascularization, followed for at least 6 months after angiography, with a decline of 38.9 ± 2.8 months. The other vascular beds were affected in 66/68 of them. Serum creatinine averaged between 125 and 180 μmol / L. Five patients had to be revascularized. Five others have evolved towards terminal renal insufficiency. During the observation period, 19 patients died of causes unrelated to their kidney disease, the majority of which were myocardial infarction. The authors draw the pessimistic conclusion that atherosclerotic patients with stenosis of the renal arteries do not die from the kidney but mostly from comorbidities, essentially coronary.

Similarly, Dejani et al, based on a series of 20 elderly patients with ischemic disease due to proximal involvement of their renal arteries and serum creatinine greater than 180 μmol / L, emphasize that only 25% are improved by angioplasty and that the complications of this procedure are numerous and severe.

A documented discussion for and against the decision to deal with a critical review of Plouin et al with a simple decision algorithm and a discussion by members of the same team on this still controversial subject.

Confronted with contradictory points of view, emanating from those who advocated activism in the treatment of atherosclerotic stenoses of the renal arteries, the question now arises as to what is the evolution of a stenosis of this a newly diagnosed type, and the risk of a wait-and-see approach in the context of nephronic preservation, which remains the main goal of surgery and angioplasty.

In fact, three elements must obviously be considered in any decision to revascularize. The first is the downstream haemodynamic repercussion on the pre-glomerular circulation. It is not always proportional to the importance of the stenosis. Some stenoses of the order of 60% already cause a decrease in glomerular filtration. Others, severe, of the order of 80%, are surprisingly well supported. The second is the scalability of renal atrophy over time. The third is the importance of the already established kidney sclerotic lesions, which in renal function are unlikely to improve after revascularization. We shall consider these three headings successively.

How to evaluate the haemodynamic repercussion of a stenosis discovered by the imaging methods?

There are cases in which the only aspect of the stenosis is not only that it is hemodynamically functional, but also that there is a definite risk of thrombosis. A filiform parade followed by a poststenotic dilation is very evocative of such an eventuality. In this regard, it is worth recalling that MRI after injection of gadolinium often tends to increase the apparent degree of stenosis.

Renal scintigraphy before and after oral administration of 25 mg of captopril is a non-invasive method that has been applied for a long time in the field of renal hypertension and which produces characteristic curves indicating that glomerular hemodynamics is maintained only by the action of Ang II on efferent arteriole. This method, considered reliable and reproducible, implies that a nuclear medicine laboratory is available, which is not the case everywhere.Finally, it appears that for significant reductions in renal function, with a creatinine clearance of less than 40 mL / min, the sensitivity of the method for predicting reversibility of renal insufficiency after revascularization is mediocre. It has also been proposed to monitor the evolution of serum creatinine after the initiation of treatment with ACE inhibitors.Thus, Krijnen et al have combined a number of clinical and biological criteria, including the degree of ascent of serum creatinine under IEC, to develop an index of suspicion of ischemic disease, with a reliable discrimination between hypertension essential and renovascular hypertension.

This approach has been the subject of much criticism. Moreover, it applies much more to renovascular hypertension than to ischemic disease by involvement of the two renal arteries. In fact, ultrasound-doppler seems to be the most reliable method, but with two reservations: it implies good technical conditions, that is to say the absence of marked obesity or digestive interpositions, and it depends on the experience of the investigator.

How can I assess scalability?

A work by Caps et al evaluated the risk of atrophy of kidneys with atherosclerotic stenosis of the renal arteries. The aim was to determine the incidence and risk factors for nephron reduction in patients with at least one renal artery. The participants were followed prospectively by echodoppler performed every 6 months. Renal atrophy was defined as a decrease in kidney length greater than 1 cm. A total of 204 kidneys in 122 subjects were followed for an average of 33 months. The cumulative incidence of renal atrophy over a 2-year period was 5.5%, 11.7% and 20.8% in kidneys where the degree of renal artery stenosis was respectively classified as null, lower to 60%, and greater than or equal to 60%.Other factors contributing to a high risk of renal atrophy included systolic blood pressure greater than 180 mmHg, renal artery systolic velocity greater than 400 cm / s and renal diastolic velocity less than or equal to 5 cm / s. The number of kidneys progressing to atrophy per patient was correlated with elevated serum creatinine. In patients with atherosclerotic stenoses of the renal artery, this work allowed to identify a significant risk of renal atrophy according to three factors. The risk was greatest when systolic blood pressure was high in patients with the largest stenosis and in those with the lowest cortical blood flow. Hemodynamic criteria (echodoppler), a clinical criterion (hypertension), and a biological criterion (serum creatinine) can be used to identify prospectively patients with stenosis atherosclerotic kidney in whom progression may lead to kidney loss.

How to judge the degree of renal sclerosis?

Muray et al reported that a rapid decline in renal function has a good predictive value on the improvement that can be expected from angioplasty. All recent publications highlight the fact that altered but non-progressive renal function predicts most often a failure of revascularization.

It is recognized that when the height of a kidney is less than 8 cm, atrophy and sclerosis do not indicate any improvement in the function of the ischemic organ. The criteria obtained by ultrasound-doppler seem the most reliable to predict the success or uselessness of a revascularization. Radermacher et al found that when the index of resistance is greater than 80, dilation does not affect the progression of renal insufficiency.

Below 80, it produces a definite decrease in serum creatinine over time. Again, echodoppler is a remarkable method for diagnosing and guiding therapeutic indications of renal ischemic disease.

Wright et al reach the same conclusions: the success of revascularization depends very logically on the degree of sclerosis of the ischemic kidney.


Atherosclerotic stenoses of the renal arteries have for 20 years acquired right of cited among the major causes of chronic renal insufficiency in subjects aged over 50 years, with diffuse atheromatous disease. The frequency of these arterial diseases and the aging of the population make it, or could do so, as in the United States, the fourth cause in order of frequency of chronic uraemia leading to dialysis. Unlike other nephropathies, this cause of terminal renal insufficiency is available for treatment by vascular surgery or interventional radiology, a treatment capable of improving renal function or stabilizing it in the majority of cases. Everything here depends on three factors: the precocity of the diagnosis, the degree of sclerosis of the kidney and the decision of when to act. This time depends essentially on the evolution of the stenoses and on the renal circulation downstream. Whereas 10 years ago the indication of relieving renal ischemia for nephronic protection seemed to be gained, doubt appeared to be established in the minds, according to non-evolutive cases and where medical treatment (control blood pressure and lipid-lowering medications) is credited with success.

There are also considerations based on the formidable risk of cholesterol embolism, which is the greatest in patients who would benefit most from these therapies.

The current means of evaluating the progression of renal atherosclerotic plaques, as well as the improvement of surgical and angioplastic techniques, as well as the treatment of cholesterol embolism, are in favor of an activist approach to l renal ischemia when iterative investigations have demonstrated its evolution and renal sclerosis is not too great. In this area as in others, dogmatism is not appropriate and each patient must be evaluated on his / her own account.

The conclusions of a 1993 review cited in this text seem to us, with all the reservations expressed above, still valid: “Depending on the information available, the diagnosis and intervention should be considered with conviction in patients at high risk of renovascular disease, whose renal insufficiency is clearly progressive “.

Cholesterol embolism disease:

The migration of atheromatous material, including cholesterol crystals and some limestone debris, is a serious accident of atherosclerotic disease. The first reference worthy of interest dates from an autopsy series published in 1945. A more general clinical review was published in 1969. In fact, the frequency of the disease clearly increased after the onset of vascular surgery, interventional radiology and finally the liberal use of anticoagulants and fibrinolytics.The affection is protean. Its manifestations range from the autopsy or biopsy of some chronically distilled crystals in an atherosclerotic patient without much clinical translation to the very serious picture of multiviscal embolisms threatening life and of which acute renal failure is only one manifestation. Moreover, the crystals housed in the small arteries induce an inflammatory reaction which has signs close to those of an angiitis.

The ulcerated plate, which can sit from the origin of the butt to the rest of the aorta, is covered with a “dressing” clot that covers a nest of crystals of cholesterol. It can be understood that the crushing by a surgical clamp, the passage of a Seldinger catheter, an angioplasty balloon, or the dissolution of the clot during anticoagulant or fibrinolytic treatment, by suppressing the latter protection, release the crystals in the traffic. They migrate into the large-sized visceral arteries and lodge in the visceral arteries from 150 to 200 μm in diameter.

In the kidney, this is the case for arterial arteries. However, crystals are also found in smaller arteries: interlobular arteries, afferent glomerular arteriole and even in the capillaries of the glomerular flocculus.


The exact frequency of cholesterol embolism disease is difficult to appreciate. Indeed, the one found in the autopsy series is far superior to that diagnosed clinically, but the clinical severity of the disease has not always been significant.In 1957, Thurlbeck and Castleman found 4% in moderately atherosclerotic patients over 65 years of age, but the incidence was 77% in older patients with diffuse atherosclerosis. Most had been operated on by an abdominal aortic aneurysm. If one considers the frequency of the discovery of cholesterol crystals on a renal biopsy (obvious selection bias), in a recent review Modi and Rao collecting the results of 755 biopsies find only 1.1% of cholesterol embolisms.Greenberg et al., Analyzing the results of 500 renal biopsies, reported crystals in only 1.6% of the cases. Another possible bias is whether the diagnosis is made during chronic renal insufficiency without great particularities or, on the contrary, in a patient with a severe clinical form, with multiplacental involvement and skin signs. Here renal biopsy is not always performed, but when it is done, finds crystals in the majority of cases.

Fine et al, after an analysis of the literature, showed how the clinical diagnosis underestimated the visceral involvement found at autopsy: in 75 cases, the frequency of clinical diagnosis of stomach, intestine and pancreas was 26.7%; that of the spleen, liver and adrenals of 1.33%; that of the kidneys by 22.7%. At autopsy, of 92 cases, the corresponding values ​​were respectively 95.6%, 100% and 83.7%. The celiac trunk and the renal arteries are thus particularly vulnerable territories, which is conceived by considering the part of the cardiac output that they receive. In fact, the entire body may be interested in cholesterol embolisms. Among the serious consequences, myocardial embolism and paraplegia have been described by migration in the anterior spinal artery of Adamkiewicz. Retinal embolism is common, on the order of 20% of cases, and often associated with strokes.

The other tissues of the organism are also practically all the target of the cholesterol embolisms. This is the case above all of the skin, the retina, the muscle, the bone marrow. We cite here the locations accessible to the clinical examination for the first two, as to biopsies with little invasiveness for the other two.

They are valuable to support the diagnosis without going as far as the renal biopsy, whose risks must be seriously weighed in this field.


The usual field of cholesterol embolism is represented by a man of more than 55 years, smoker and hypertensive, white, often lean. The affection is rare in black subjects.

Factors causing crystals to swarm in the general circulation are numerous, but united by two common elements, isolated or associated: the trauma of an atheroma plaque, whether ulcerated or not, and the disappearance of the clot overlying the atheromatous porcine d an ulcerated plate. Non-iatrogenic factors remain a possible cause of the disease but in a minority of cases. The rupture of a plate can indeed be spontaneous.

The existence of extensive ulcerated aortitis can also lead to chronic swarming of crystals, distilled in the circulation over time. In the excellent journal of Scolari et al, embolisms were spontaneous in 21% of cases and iatrogenic in 79% of the others.

The iatrogenic factors predominate, but especially in the acute forms threatening the renal function and often the life.The most commonly identified is vascular surgery, coronary artery surgery in particular, but also the aorta and its branches. The effect of a clamp on an atheromatous artery is to crush the plates. Moreover, this surgery usually involves prior angiography and is followed by the administration of heparin. Seldinger catheter angiographies and angioplasties have become a major cause of the condition. It seems that the femoral pathway is more dangerous in this area than the humeral way. Among the most common medicinal factors presently are anticoagulant treatments with antivitamin K, heparin and fibrinolytic.


The six most comprehensive reviews on this condition, which contain 521 cases, agree in their analysis of the diagnostic signs of kidney disease of cholesterol embolisms.

Extrarenal Signs:

The extrarenal signs are frequent and largely contributory to the diagnosis. These include cutaneous, muscular, ocular, neurological and digestive signs.

The cutaneous signs, observed according to the series in 35 to 96% of the cases, are made of purple toes, livedo reticularis which can go as far as the loins, of partial necroses of the toes.

In an atherosclerotic subject, these anomalies, which predominate in the lower extremities, are all too easily connected with an arteritis; nevertheless the posterior and pedal tibial pulses are not necessarily abolished, which must direct towards ischemic lesions of the microcirculation. The cutaneous biopsy oriented by a zone of livedo should not bear on the feet: the wound would not heal. Located higher, it finds crystals in the hypodermis. Falanga et al, in a short series of 24 patients, diagnosed cholesterol embolism in 22 of them (92%). In their review of 52 patients, Scolari et al found crystals in the skin in 100% of their patients.

Muscle pain can simulate polymyositis. The muscle is an easy biopsy localization, but with a lower yield: 21 times out of 129 in the Lye et al.

Crystals are found in the fundus in 6 to 25% of cases.

Abdominal pain is frequent and sometimes accompanied by digestive hemorrhages. They represent the attainment of mesenteric and pancreatic territory. They are accompanied by undernutrition. Fever may accompany the alteration of the general condition.

Biological signs:

Cholesterol embolisms do not cause mechanical occlusion of the vessels in which they are housed. They also provoke an inflammatory reaction with foreign bodies. It is indeed a microcrystalline angeitis. Three biological abnormalities, inconstant but suggestive when they exist, can be explained: hypocomplementemia, eosinophilia and eosinophiluria, objectified by Hansel staining.

Renal involvement:

The incidence of kidney damage is not clearly established.

Considering that in the case of cholesterol embolisms the renal circulation is interested in more than 80% of the cases, one can estimate that it is histologically of extreme frequency. However, it is necessary to distinguish the forms in which a few crystals are housed in the kidney, without clinical translation, massive kidney embolisms, accompanied by renal insufficiency, hypertension and cardiac failure. These are the ones that pose a real problem to the nephrologist and the resuscitator and which will be discussed here.

The appearance in time of this microcrystalline nephropathy after the triggering event, if it exists, is variable. It can also be said that his diagnosis is often delayed. Three forms must be distinguished. Massive embolisms are revealed early after surgery, angiography or angioplasty. Elsewhere, it takes several weeks before the diagnosis is evoked: on average 5.3 weeks after arteriography in the Frock et al. A third variety is characterized by subacute or chronic renal insufficiency, evolving by successive surges, which probably coincide with waves of embolism, each occurring after a triggering element: angiography, surgical recovery, new anticoagulant treatment. It is then difficult to start between cholesterol embolism, nephroangiosclerosis, diagnosis of ease on this ground, or the toxicity of iodine.

Purely clinical signs, apart from hypertension, are quite limited. There may be renal infarction pain accompanied by macroscopic haematuria, which is rare. The usual picture is that of renal insufficiency of variable gravity. It can be acute, oligoanuric, requiring an exarenal purification immediately and occurring immediately after an invasive procedure, which is the case of about one third of the patients. However, it should be remembered that after the triggering event, the signs and symptoms of cholesterol embolism may not appear until several weeks later.

The evolution can then be progressive and be done by pushes interspersed of successive stages over several weeks or months.

It is often understood that each of these evolutive surges coincided with a new attack of emboligenic plaques: new angiography, vascular re-intervention, resumption of anticoagulant treatment. Finally, evolution can be marked only by chronic and slowly evolving renal insufficiency. Clinical manifestations of the condition in an elderly person are marked by fever, inflammatory state, eosinophilia, impaired general status, weight loss, skin signs and deterioration of renal function accompanied by a proteinuria. It is therefore conceivable that various undifferentiated diagnoses of toxicity of an iodinated contrast agent, renal insufficiency by ischemia of large trunks, angiitis, bacterial endocarditis, thrombotic microangiopathy, retroperitoneal fibrosis complicating an aneurysm, abdominal aorta.

Hypertension is almost constant, severe and sometimes malignant.

It causes or promotes heart failure and pulmonary edema which add to the difficulties of treatment.

Until recently, cholesterol embolism disease was considered to be beyond any therapeutic resource. A personal series of 67 patients allowed Belenfant et al to analyze the main causes of death in these patients with an average serum creatinine of 540 ± 225 μmol / L; 61% of patients were in pulmonary edema, 33% had gastrointestinal ischemia, 90% had cutaneous signs, and 22% had retinal embolism. The triggering causes were angiography (85%), anticoagulant therapy (76%) and / or vascular surgery (33%). The protocol adopted was based on:

– discontinuation of any anticoagulant treatment and interventional radiology or surgery;

– intensive treatment of hypertension, heart failure and pulmonary edema by a vasodilator, loop diuretics and artificial kidney ultrafiltration;

– iterative hemodialysis and parenteral nutrition;

– prednisone.

Mortality during hospitalization was 16%. Of the survivors, 32% had to continue hemodialysis due to irreversible renal failure. Survival at 1 year was 87%, which compares favorably with the most recent series, where it was 64 to 81%.The survival at 4 years was 52%.

Although other series of the literature do not mention a particular therapeutic protocol and do not show a significantly worse mortality, it is possible that the patients of Belenfant et al, all admitted to a nephrological intensive care unit, included selection bias among the most severe cases.

The recent notion that statins have a stabilizing effect on atheromatous plaques and are endowed with anti-inflammatory effects strongly encourages their inclusion in any therapeutic protocol of this condition as primary and secondary prevention.

Renal parenchymatous lesions and atherosclerotic disease:

It is difficult to disentangle age-related kidney damage, complicated old hypertension from nephroangiosclerosis, arterial stenosis with downstream ischemia and cholesterol embolism, and those with a causal relationship to atherosclerotic disease. Nevertheless, two elements must be brought to the debate.

The first is a Kasiske study that, in order to dissociate age-related kidney lesions from atherosclerosis, conducted an autopsy in 57 patients with moderate atherosclerosis (Group I) and 57 with severe atherosclerosis (group II). The two groups were matched for age, sex, hypertension, body conformation, organ weight, and extent of coronary lesions.The surface area of ​​the glomerular sections, the thickness of the arched and interlobular arteries and the interstitial fibrosis were measured by histomorphometry.

In group I, the incidence of sclerosed glomeruli was 8.3 ± 7.0% vs 15.4 ± 16.3% in group II (p < 0.01). The relative surface area of ​​the vascular walls was 60 ± 12% in group II compared with 55 ± 11% (p < 0.05) in group I. The mean surface area of ​​non-sclerous glomeruli was greater in group II ± 6 000 μm 2 ) compared to group I (19 600 ± 3 700 μm 2 , p < 0.01), suggesting compensatory hypertrophy. Interstitial fibrosis was similar in both groups. The relative impact of age, sex of body conformation of systemic atherosclerosis, hypertension, nephroangiosclerosis and interstitial fibrosis on glomerulosclerosis and glomerular hypertrophy was studied by multivariate analysis. Age and nephroangiosclerosis were significantly related to glomerulosclerosis. The surface area of ​​glomerular sections was correlated with heart weight and coronary lesions. On the other hand, there was no correlation between glomerular surface area and glomerulosclerosis.

This work suggests that diffuse atherosclerotic disease is accompanied by glomerular lesions which, more than with the extent of the vascular plaques, could be linked to the very causes of atherosclerotic disease, that is to say disorders lipid.

There are many experimental protocols for genetically hyperlipidemic strains of rats that are glomerular lesions.Reference can be found in the article by Poirier et al.

In man, studies on the links between atherogenic lipids and kidney have been mostly devoted to the dyslipidemia of constituted nephropathies, but it is more than likely that the lipid disorders that accelerate the course of kidney disease are not insignificant on an elderly kidney with nephroangiosclerosis.

The normal kidney produces oxidative lipids whose source is the glomerular mesangial cell. Renal insufficiency decreases the production of antioxidants, is accompanied by hypertriglyceridemia which increases the production of free radicals and modifies the structure of low density lipoproteins. Glucose intolerance and / or the existence of a nephrotic syndrome increase these risk factors for glomerular lesions. Recent work on the protective role of statins on these various phenomena is under way, which shows very interesting results. It is very likely that this therapeutic class will play a very favorable role, not only on the evolution of the atheroma plaque and its consequences, ischemia and cholesterol embolisms, but also on the resulting nephropathy.