Revascularization to preserve renal function in patients with atherosclerotic renovascular disease

There are a significant number of patients with advanced atherosclerotic renovascular disease whose blood pressure is well controlled with medical therapy but in whom such vascular disease poses a grave risk to overall renal function. This article reviews current concepts regarding screening, evaluation, and selection of patients with this disease for revascularization to preserve renal function. The underlying rationale for this approach is an increasing awareness that, in selected patients, atherosclerotic renovascular disease represents a surgically correctable cause of progressive renal failure.     

Atherosclerotic renovascular disease: diagnosis and treatment

The technical expertise and tools required to treat renovascular obstruction have become commonplace, and many series of patients revascularized with surgery, balloon angioplasty or endovascular stenting have been reported. Nevertheless, although hypertension and renal failure are easy to diagnose, their cause often remains elusive. Evidence is developing that patients with hypertension and atherosclerotic renal artery stenosis may often have hypertension and renovascular disease but not hypertension because of renovascular disease. As a result, diagnosis and therapy are increasingly directed towards the preservation of renal function, and the future of renal revascularization will depend on how well potential therapies address this goal.     

Renal artery stenosis and chronic ischemic nephropathy: epidemiology and diagnosis

Atherosclerotic renal artery stenosis (RAS) is the most common primary disease of the renal arteries and results in renovascular hypertension and ischemic nephropathy. Ischemic nephropathy from atherosclerotic RAS is increasingly recognized as a cause of chronic kidney disease (CKD) and in severe cases can lead to end-stage renal disease. The exact prevalence of atherosclerotic RAS is unknown because the disease is often asymptomatic and few are screened unless they have significant traditional cardiac risk factors or symptoms. A high prevalence of atherosclerotic RAS is seen in patients with advanced age, congestive heart failure, and extrarenal atherosclerosis. The primary reason for diagnosing ischemic nephropathy from renovascular disease is that the loss of kidney function is potentially reversible through treatment of the occlusion with surgical revascularization or percutaneous transluminal renal angioplasty. However, the benefits of revascularization have to be considered in the context of other comorbid disease and remain controversial. There are several tests available for the screening and diagnosis of atherosclerotic RAS; however, the diagnostic test of choice should be based on patient factors and institutional expertise because the best test is the one performed most often at the individual medical facility.     

Atherosclerotic renovascular disease in United States patients aged 67 years or older: risk factors, revascularization, and prognosis

BACKGROUND: Although atherosclerotic renovascular disease is increasingly recognized in chronic kidney disease, few national level studies have examined its clinical epidemiology. METHODS: Claims data from a 5% random sample of the United States Medicare population were used to select patients without atherosclerotic renovascular disease in the 2 years preceding December 31, 1999 (N= 1,085,250), followed until December 31, 2001. RESULTS: The incidence of atherosclerotic renovascular disease was 3.7 per 1000 patient-years. Major antecedent associations [P < 0.05, with adjusted hazards ratios (HR) > 1.5] included chronic kidney disease (adjusted HR 2.54), hypertension (2.42), peripheral vascular disease (2.00), and atherosclerotic heart disease (1.70). Adverse event rates after incident atherosclerotic renovascular disease greatly exceeded those in the general population (P < 0.0001): atherosclerotic heart disease, 303.9 per 1000 patient-years (vs. 73.5 in the general population); peripheral vascular disease, 258.6 (vs. 52.2); congestive heart failure, 194.5 (vs. 56.3); cerebrovascular accident or transient ischemic attack, 175.5 (vs. 52.9); death, 166.3 (vs. 63.3); and renal replacement therapy, 28.8 (vs. 1.3). Among atherosclerotic renovascular disease patients, 16.2% underwent a renal revascularization procedure, percutaneously in 96%. Revascularization was not associated with renal replacement therapy, congestive heart failure, or death but was associated with atherosclerotic heart disease (adjusted HR 1.42) (P= 0.004) and peripheral vascular disease (adjusted HR 1.38) (P= 0.002). CONCLUSION: Atherosclerotic renovascular disease is strongly associated with cardiovascular disease, both past and future. Absolute cardiovascular risk exceeds that of renal replacement therapy. Renal revascularization is used selectively and shows inconsistent associations with cardiovascular outcomes, renal replacement therapy, and death.     

Prevalence of atherosclerotic renal artery stenosis in patients starting dialysis.

BACKGROUND: Atherosclerotic renal artery stenosis (ARAS) can lead to end-stage renal failure (ESRF). We determined the prevalence of ARAS in patients 45 years of age or older starting renal replacement therapy. METHODS: Forty-nine of 80 consecutive patients (37 males, 12 females) starting renal replacement therapy in our centre gave informed consent and underwent spiral computed tomographic angiography of their renal arteries. A renal artery diameter reduction of 50% or more assessed by two radiologists was considered as a significant stenosis. RESULTS: Twenty of 49 patients (41%) had an ARAS, and in eight cases (16%) this was bilateral or unilateral with a single kidney. Women were more likely to have an ARAS than men; 75 (9/12) vs 30% (11/37, P<0.01). However, relatively more women declined participation. Non-participants and participants did not differ in respect to other relevant clinical data. Nonetheless, findings in these patients would be negative, the prevalence of ARAS would still be 31% in women and 22% in men (NS). In 13 patients with ARAS the registered diagnosis of ESRF either was hypertension, renovascular disease or unknown. Assuming that in these patients atherosclerotic renovascular disease was the cause of renal failure, a total of 13 patients (13/49, 27%) entered the dialysis programme because of this problem. CONCLUSIONS: These results suggest that ARAS is an important cause of ESRF.     

Treatment of renovascular hypertension by unilateral nephrectomy. A follow-up study in patients above 60 years of age

The long term results of surgical intervention in 26 elderly patients with renovascular hypertension are presented. All patients were above 60 years of age at the day of operation. The majority of the patients had atherosclerotic renovascular disease with only one case of fibromuscular dysplasia. Several patients had severe extrarenal atherosclerotic disease. The diagnosis of renovascular hypertension was based upon the results of isotope renography, renal arteriography and renal vein catheterization. All patients underwent unilateral nephrectomy. Notably, no deaths or complications occurred in relation to surgery. At the follow-up study, blood pressure was lowered and the requirement for antihypertensive drugs reduced in 86% of the patients. We conclude that unilateral nephrectomy in elderly high risk patients with renovascular hypertension is a safe and efficient procedure.     

Fibromuscular dysplasia of the renal artery: Management and outcome

Renovascular hypertension may be caused by atherosclerotic disease or less commonly by fibromuscular dysplasia (FMD) of the renal arteries. Fibromuscular dysplasia is the commonest cause of renal artery stenosis in the younger age group and affects women predominantly. A review of our clinical database identified all patients with renovascular hypertension. All relevant clinical, biochemical and radiological findings on those with FMD were noted. The outcome of percutaneous transluminal renal angioplasty (PTRA) or reconstructive surgery was evaluated. Eight out of 62 (13%) patients with hypertension secondary to renovascular disease had FMD (all female; bilateral in four; mean age at diagnosis 37.6 years; age range 12–70 years). The mean duration of hypertension before the diagnosis of FMD was 3.3 years (range 3 months–10 years). A renal artery bruit was detected in five, hypertensive retinopathy in three and one had mild renal insufficiency. Twelve PTRAs were attempted on 10 stenotic lesions in six women. This cured the hypertension in three, while the other three have required less antihypertensive therapy. Percutaneous transluminal renal angioplasty was complicated by a trivial renal artery dissection in one, and a small upper pole infarction in another. One patient required a repeat PTRA. The other two women presented before the availability of PTRA and had successful reconstructive surgery. Fibromuscular dysplasia was the cause of hypertension in eight out of 62 (13%) patients with renovascular hypertension. Percutaneous transluminal renal angioplasty has shown encouraging results with a low complication rate. If technically feasible, PTRA should be attempted on all patients with FMD of the renal artery.     

Renovascular disease and renal insufficiency--diagnosis and treatment

Renovascular disease as cause of end-stage renal disease has become more frequent during the last decade. In order to minimize the need for dialysis treatment non-invasive screening for the disease is needed. However, both ultrasonic duplex scanning and renal scintigraphy are not sufficient for detection of all stenosis. Furthermore, there is little data on non-invasive tests in patients with renal insufficiency. Renal arteriography is the gold standard for detection of renovascular disease. One disadvantage is the risk of contrast-agent induced acute renal insufficiency. This problem can be avoided using carbon dioxide angiography. In the near future spiral computed tomography and magnetic resonance angiography may be alternatives for identifying patients with renovascular disease. Ischaemic nephropathy is potentially curable. Percutaneous transluminal renal angioplasty is first line treatment in most cases. Intervention often results in improvement or preservation of renal function which is very important in order to avoid chronic dialysis.     

Recovery of renal function after 90 d on dialysis: implications for transplantation in patients with potentially reversible causes of renal failure

Abstract: Background: Late recovery of renal function in patients requiring dialysis is a well recognized but uncommon phenomenon. Moves to increase the number of live donor transplants and the recognition that early transplantation is associated with better graft survival means it is possible that patients who are going to recover renal function may be transplanted unnecessarily. Design: Prospective survey of patients receiving dialysis for more than 90 d in south west Scotland from 1 January 1994 to 31 December 2005. Methods: Routine measurement of residual renal function by combined urea and creatinine clearance allowed us to detect late recovery whenever this occurred. Results: Eight of 202 (4%) patients recovered sufficient renal function to stop dialysing after 90‐d treatment. The likely cause of the renal failure in five of these patients was atheroembolism. One with atherosclerotic renovascular disease had been stented and would have received a live related renal transplant had his sister not had second thoughts about the procedure. Conclusion: It may be sensible to postpone transplantation in patients with certain types of renal failure, perhaps particularly patients with renovascular disease who have recently undergone a failed revascularization procedure.     

Fibromuscular dysplasia of the renal artery: Management and outcome

SUMMARY: Renovascular hypertension may be caused by atherosclerotic disease or less commonly by fibromuscular dysplasia (FMD) of the renal arteries. Fibromuscular dysplasia is the commonest cause of renal artery stenosis in the younger age group and affects women predominantly. A review of our clinical database identified all patients with renovascular hypertension. All relevant clinical, biochemical and radiological findings on those with FMD were noted. the outcome of percutaneous transluminal renal angioplasty (PTRA) or reconstructive surgery was evaluated. Eight out of 62 (13%) patients with hypertension secondary to renovascular disease had FMD (all female; bilateral in four; mean age at diagnosis 37.6 years; age range 12–70 years). the mean duration of hypertension before the diagnosis of FMD was 3.3 years (range 3 months-10 years). A renal artery bruit was detected in five, hypertensive retinopathy in three and one had mild renal insufficiency. Twelve PTRAs were attempted on 10 stenotic lesions in six women. This cured the hypertension in three, while the other three have required less antihypertensive therapy. Percutaneous transluminal renal angioplasty was complicated by a trivial renal artery dissection in one, and a small upper pole infarction in another. One patient required a repeat PTRA. the other two women presented before the availability of PTRA and had successful reconstructive surgery. Fibromuscular dysplasia was the cause of hypertension in eight out of 62 (13%) patients with renovascular hypertension. Percutaneous transluminal renal angioplasty has shown encouraging results with a low complication rate. If technically feasible, PTRA should be attempted on all patients with FMD of the renal artery.     

Contemporary surgical management of renovascular disease.

To examine the treatment methods and early results of renovascular repair in our contemporary patient population, we reviewed our surgical experience during a recent 54-month period. From January 1987 to July 1991, 200 patients ranging in age from 5 to 80 years (mean, 56 years) were operated on for correction of nonatherosclerotic (43 patients) and atherosclerotic (157 patients) renovascular disease. The group included 92 men and 108 women, with blood pressures ranging from 300/198 mm Hg to 120/70 mm Hg (mean, 205/113 mm Hg). Defined by preoperative serum creatinine, 129 patients (65%) had evidence of renal insufficiency (Cr greater than or equal to 1.3 mg/dl), whereas 71 patients (36%) had severe renal insufficiency (Cr greater than 2.0 mg/dl; 11 patients were dependent on dialysis). One hundred forty-seven patients with atherosclerotic renovascular disease (94%) demonstrated organ-specific atherosclerotic damage. Operative management of 291 kidneys included unilateral renal artery repair in 117 patients (58%), bilateral repair in 78 patients (39%), and primary nephrectomy in five patients (2.5%). Simultaneous aortic reconstruction was required in 64 patients (32%). There were five operative deaths (2.5% mortality rate) and four occluded renovascular repairs (1.4% primary failure) within 30 days of surgery. Hypertension was considered cured in 21% and improved in 70% of 195 operative survivors. In 70 patients with severe renal insufficiency before operation, estimated glomerular filtration rate was improved in 49% (8 of 11 patients removed from dialysis), unchanged in 36%, and worsened in 15%. Renal function response was significantly influenced by the site of disease and the operation. Twenty-six additional postoperative deaths occurred during follow-up (range, 6 to 58 months; mean, 24.4 months). Extreme atherosclerotic-renovascular disease, preoperative renal insufficiency, failure to improve renal function, and progression to dependence on dialysis after operation were associated with follow-up deaths. Although most patients had a beneficial outcome, failure to improve extreme renal insufficiency was associated with a rapid rate of death during a relatively short follow-up period.     

The natural history of atherosclerotic and fibrous renal artery disease

Summary Individuals with atherosclerotic or fibrous renal artery disease may develop renovascular hypertension and/or renal dysfunction. Traditionally, the motivation for identifying patients with renal artery stenosis was the treatment of renovascular hypertension. However, recent interest has centered on the investigation of patients suspected of having renal artery stenosis that might account for progressive azotemia. While specific forms of fibrous and/or atherosclerotic renal artery disease can lead to a compromise in renal function, differences may exist in the age of presentation, predominat sex, angiographic appearance and overal natural history. Recognition of these differences is helpful in deciding on the most likely lesion type, appropriate workup and treatment. Since renal artery stenosis can lead to radiologic and functional alterations, clinical markers of progression, such as renal size and serum creatinine measurements, are helpful in identifying patients with advancing disease. The regulators of fibrous disease progression are less clear than those responsible for atherosclerotic progression in the renal artery. Uncontrolled systemic hypertension, intrarenal hypertension, hyperlipidemia, cigarette smoking, and obesity all may potentially contribute to progressive atherosclerosis. Individuals identified with progressive azotemia due to renal artery stenosis may benefit from improved perfusion flow by renal revascularization or balloon angioplasty provided no significant parenchymal disease is present.     

Renovascular hypertension

Renovascular hypertension is the most common cause of secondary hypertension. Interest in identifying patients with renal artery stenosis has been stimulated recently by advances in three areas. First, is the realization that not only can renal artery stenosis cause renovascular hypertension, but it can also lead to progressive renal failure (ischemic nephropathy) caused by progression of disease, usually atherosclerotic in nature. Second, advances in percutaneous transluminal renal angioplasty and, especially, the recent use of renal stents has led to a less invasive management of these patients as compared with traditional renal revascularization. Finally, the development of newer less invasive diagnostic techniques, both for the identification of patients with renal artery stenosis and to follow patients with known renal artery stenosis, has simplified the diagnostic aspect of the disease.     

Incidence of end-stage renal disease in medically treated patients with severe bilateral atherosclerotic renovascular disease

Incidence of end-stage renal disease in medically treated patients with severe bilateral atherosclerotic renovascular disease. Atherosclerotic renovascular disease is an important cause of end-stage renal disease (ESRD). The exact incidence of ESRD and the rate of decline in glomerular filtration rate (GFR) in patients with this condition is unknown. We report the mortality, the rate of decline in renal function, and incidence of ESRD in 51 patients with bilateral atherosclerotic renovascular disease followed-up for a median period of 52 months. None of these patients had undergone any surgical or radiological intervention. Renal function was determined by serial measurements of serum creatinine. Bilateral atherosclerotic renovascular disease was associated with a high mortality rate; the crude mortality rate at 60 months was 45%. Assessment of renal function showed impaired renal function at time of angiography and a nonuniform and variable decline in renal function during the period of observation. The median GFR decreased from 39 mL/min (range, 15 to 80 mL/min) at time of angiography to 31 mL/min (range, 10 to 70 mL/min) and 24 mL/min (range, 10 to 40 mL/min) at 24 and 60 months, respectively (P < 0.05). The calculated mean rate of decline in GFR for all patients was 4 mL/min/yr (range, 1 to 16 mL/min/yr). Over the 5 years, there was a progressive increase in the incidence of ESRD. Of the original 51 patients who underwent angiography, six patients reached ESRD. The crude incidence of ESRD was, therefore, 12%. Patients who reached ESRD were characterized by advanced azotemia at the time of angiography (median GFR, 25 mL/min) and a rapid decline in GFR (8 mL/min) compared with patients who did not reach ESRD during the observation period (median GFR, 43 mL/min and an average rate of decline GFR of 3 mL/min).     

Prospective multicentre study of the natural history of atherosclerotic renal artery stenosis in patients with peripheral vascular disease

BACKGROUND: Many patients with peripheral vascular disease have coincident renal artery stenosis. The present study characterized the natural history of the condition. METHODS: Some 98 patients (71 men) with more than 50 per cent atherosclerotic renal artery stenosis (unilateral 64, bilateral 34) were recruited prospectively. Measurements of serum creatinine, blood pressure and renal size were recorded at baseline and every 6 months, for a minimum of 2 years. RESULTS: Data were available for 85 patients with a minimum follow-up of 2 years. The mean age was 71 (range 51-87) years. All 52 patients with unilateral renal artery stenosis were managed conservatively (group 1); 21 of the 33 patients with bilateral disease had no intervention (group 2) and the remaining 12 had angioplasty or reconstruction (group 3). The overall mortality rate was 32 per cent at 2 years (27 patients) and this was similar in all three groups. In only three patients was death related directly to renovascular disease; coronary disease accounted for the majority of deaths. All three patients who needed dialysis died within 1 year. In survivors from groups 1 and 3 there was a significant increase in serum creatinine concentration at follow-up. Blood pressure did not increase significantly. CONCLUSION: Patients with renal artery stenosis and peripheral vascular disease had a poor prognosis, but this was not directly attributable to renal failure.     

Results of surgical treatment of renovascular hypertension.

We have used a comprehensive protocol to identify secondary forms of hypertension and operated upon 77 patients with functionally significant renovascular disease. The population included 52 patients with atherosclerotic renal arterial lesions (31 unilateral and 21 bilateral) and 25 patients with fibrodysplasia (19 unilateral and 6 bilateral). In the entire population there was a 90% cured-improved rate, a 5% failure rate and a 5% postoperative mortality. The cure rate was highest in the unilateral fibrodysplasia group and lowest in those with bilateral atherosclerotic disease. The choice of initial operative approach was based on an attempt to preserve renal mass; in 11 patients vascular reconstruction was attempted and these required secondary nephrectomy because of early or late failure. All 11 patients had a good result after nephrectomy. Our observations indicate that a vigorous operative approach to renovascular hypertension is beneficial once accurate demonstration of a functionally significant lesion is made.     

Late results after surgical treatment of renovascular hypertension. A follow-up study of 122 patients 2-18 years after surgery.

During the period 1963-1980, 122 patients were operated on for renovascular hypertension at surgical department D, vascular section, Rigshospitalet, Copenhagen. Seventeen patients, with a median age of 24 years, had fibromuscular hyperplasia and 95 patients, with a median age of 48 years, had atherosclerosis. Twenty-four of the latter had bilateral renal artery lesions and 71 had unilateral disease. Ten patients had various other causes of renovascular hypertension. Operative mortality was 4.9%, decreasing to two per cent in the last 8 years. At discharge, 71% of the patients were normotensive without medication, 18% were improved, and 11% were unimproved. At follow-up in 1982, the actuarial 10-year survival rates for patients with unilateral and bilateral atherosclerotic disease were 65% and 48%, respectively. There was no difference between survival rates for patients with fibromuscular hyperplasia and an age- and sex-matched, population. Sixty-nine patients were reexamined with a median follow-up of 9 years. Of the survivors with atherosclerosis, 87% benefitted from the operation: 50% were normotensive without medication and 37% were improved. Of patients with fibromuscular hyperplasia, 93% benefitted from operation: 79% were normotensive and 14% were improved. The results support the value of surgery in patients with renal fibromuscular hyperplasia and to the long-term benefits of surgical treatment of patients with atherosclerotic renovascular disease.     

Ischemic nephropathy: where are we now?

Identification and reversing the loss of kidney function beyond occlusive disease of the renal arteries poses a major clinical challenge. Recent studies indicate that atherosclerotic renal artery stenosis develops as a function of age and is commonly associated with other microvascular disease, including nephrosclerosis and diabetic nephropathy. The risks of renal artery stenosis are related both to declining kidney function and to accelerated cardiovascular disease, with increased morbidity and mortality. Newer drugs, including agents that block the renin-angiotensin system, have improved the level of BP control for renovascular hypertension. Progressive renovascular disease during medical therapy can produce refractory hypertension, congestive heart failure, and renal failure with tubulointerstitial fibrosis. Recent studies indicate a complex interplay of oxidative stress, endothelial dysfunction, and activation of fibrogenic cytokines as a result of experimental atherosclerosis and renal hypoperfusion. Advances in imaging and interventional devices offer major new opportunities to prevent progressive loss of kidney function. Recent series indicate that although 25 to 30% of patients with impaired renal function can recover glomerular filtration after revascularization, many have no apparent change in kidney function and 19 to 25% experience a significant loss of kidney function, in some cases as a result of atheroemboli. To select patients who are most likely to benefit from vascular intervention, clinicians should understand the pathophysiology of developing ischemic nephropathy and the potential hazards of revascularization in the setting of diffuse atherosclerotic disease. Further research should be directed toward identification of critical disease, regulation of fibrogenesis, and the interaction with other atherosclerotic processes.     

Chronic mesenteric ischemia in childhood and adolescence

Chronic mesenteric ischemia is uncommon in the atherosclerotic age group but is particularly rare in childhood. Because of the nonspecific nature of symptoms produced and absence of pathognomonic findings by physical examination or by routine laboratory testing, its recognition is difficult and its true incidence is unknown. Four children treated for chronic mesenteric ischemia in our center demonstrated the spectrum of clinical presentations and operative considerations important in the management of this uncommon malady. Ages at presentation ranged from 30 months to 17 years. These presentations ranged from clinically silent ischemia in the 30-month-old child to evolving gastrointestinal infarction in the 17-year-old adolescent. Coexistence of abdominal aortic coarctation and/or renal artery stenoses was present in three of the four children. Successful bowel revascularization was achieved by superior mesenteric artery revascularization alone in three children (reimplantation in two and a bypass in one) and by multiple celiac and superior mesenteric artery bypasses in one. Delayed distal small bowel and proximal colonic resection was required in one child. This experience increases awareness that mesenteric ischemia does occur in childhood and is a rare but potentially lethal cause of abdominal complaints in children. Finally, the finding of both renal and visceral artery disease in three of the four patients underscores the need for adequate evaluation of mesenteric vessels before renovascular procedures are undertaken in this age group.