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.     

Is incidental renal arteriography justified in a population of patients with symptomatic peripheral arterial disease?

Renal artery stenosis is a consequence of generalized atherosclerosis and many specialists perform routine selective renal angiography to detect and treat renal artery stenosis. The incidence of clinically important renal artery stenosis is not well defined in patients with symptomatic peripheral arterial disease. The purpose of this study was to better delineate the incidence of and the risk factors associated with renal artery stenosis, renovascular hypertension, and ischemic nephropathy incidentally discovered during angiography for symptomatic peripheral arterial disease. Two hundred consecutive patients undergoing angiographic evaluation of symptomatic lower extremity peripheral arterial disease were studied retrospectively. Angiograms were reviewed for the presence of renal artery stenosis (defined as >or= 25% diameter reduction in either renal artery) and findings were then correlated to the clinical diagnosis of renovascular hypertension (> 50% renal artery stenosis and >or= 3-drug resistive hypertension) and ischemic nephropathy (defined as > 50% bilateral renal artery stenosis, 3-drug hypertension, and creatinine >or= 1.5). Angiographic findings were also correlated with risk factors to determine if a relationship correlated to the presence of and degree of renal artery stenosis. Data were analyzed using the Student's t test, Chi-square model, and multiple logistic regression analysis. The overall incidence of any degree of renal artery stenosis in this study population was 26% (52 patients). Only 24 (12%) patients had an incidental finding of >or= 50% stenosis in either renal artery. Six (3%) of these patients were found to have associated renovascular hypertension. Additionally, 9 (4.5%) patients had coexistent renal insufficiency and significant renal artery stenosis; five with end-stage renal disease on chronic hemodialysis. Only one patient with end-stage renal disease had poorly controlled 3-drug hypertension. Thus definitive ischemic nephropathy was present in only one (0.5%) patient. Statistically significant risk factors associated with the presence of renal artery stenosis include hypertension (P < .001), coronary disease (P = .024), female gender (P = .010), diabetes (P = .039), aorto-iliac disease (P = .031), multiple levels of peripheral arterial disease (P < .001), and age over 60 ( P < .001). While the incidence of renal artery stenosis in patients being evaluated for symptomatic peripheral arterial disease is similar to that reported in the cardiology literature, the incidence of renovascular hypertension and ischemic nephropathy is exceedingly low (3% and 0.5%, respectively)-findings similar to data reported in the general hypertensive population. These data suggest that incidental selective renal angiography is not justified in patients with symptomatic peripheral arterial disease.     

Analgesic nephropathy: etiology, clinical syndrome, and clinicopathologic correlations in Australia.

Analgesic abuse is a major public health hazard in Australia, and analgesic nephropathy with consequent terminal renal failure is the underlying cause in 20% of the patients requiring dialysis and transplantation. Analgesics are invariably taken in the form of compounds and mixtures. In the aspirin-phenacetin-caffeine (APC) mixture, aspirin appears to be the major nephrotoxic agent and phenacetin appears to play a secondary and synergistic role. The renal disease associated with abuse of analgesics is characteristic and is part of a much wider clinical syndrome, the analgesic syndrome, which includes peptic ulcer disease (35%), anemia (60 to 90%), hypertension (15 to 70%), ischemic heart disease (35%), psychological and psychiatric manifestations, pigmentation, and possible gonadal- and pregnancy-related effects. The primary lesion in analgesic nephropathy is renal papillary necrosis (RPN), and this is a nephrotoxic effect common to all nonsteroid antiinflammatory agents. The most important factor in the management of patients with analgesic nephropathy is the cessation of analgesic abuse, and this leads to improvement and stabilization of renal function. A small proportion of patients will, however, deteriorate in relation to accelerated hypertension, persistent proteinuria, ischemic heart disease, and complications leading to nephrectomy. Patients with analgesic nephropathy are poor risk patients and have a poor prognosis, even after dialysis and transplantation.     

Long-term outcome of surgical revascularization in ischemic nephropathy: normalization of average decline in renal function

OBJECTIVE: Renovascular disease may lead to ischemia of the nephrons and to fibrosis, which is generally considered to be irreversible and progressive. We investigated the potential of revascularization to recover and stabilize renal function in patients with ischemic nephropathy. METHODS: In a retrospective analysis of all our 61 patients with ischemic nephropathy who underwent treatment with surgical revascularization, we determined the long-term course of renal function decline with an estimated glomerular filtration rate (EGFR; Cockcroft and Gault formula). With the assumption of normal renal function at age 25 years, the preoperative slope of EGFR and the postoperative slope of EGFR were determined from the EGFR before surgery, at the short-term follow-up examination (on average, 8 months after surgery), and at the long-term follow-up examination (on average, at 47 months after surgery). These declines in renal function were compared with EGFR values in age-matched and sex-matched samples from a large cross-sectional population study. RESULTS: The overall surgical mortality rate amounted to 13.1%. Five patients became dialysis dependent-two with preexisting end-stage renal disease and three at later follow-up examination-and two patients, who before surgery were dialysis dependent, could be withdrawn from dialysis treatment. Shortly after the operation, the mean EGFR level had increased from 28.3 to 43.1 mL/min/1.73 m2 ( P <. 01). The rate of decline in renal function had decreased from an estimated -2.57 mL/min/1.73 m2/year before surgery (weighted mean: interquartile range, -2.71 to -1.98) to -0.66 mL/min/1.73 m2/year (weighted mean: interquartile range, -2.00 to -0.18) in the short-term interval to the long-term interval, which was even slightly better than the slope of -0.84 mL/min/1.73 m 2/year in the age-matched and sex-matched control population. CONCLUSION: Surgical revascularization in selected patients with renovascular disease and ischemic nephropathy restores renal function and makes the average long-term rate of decline in renal function equal to that of the general population. This indicates that in most patients a "point-of-no-return" has not yet been passed even though their renal function is already markedly impaired before surgery. Therefore, in well-selected patients with ischemic nephropathy, considerable improvement of renal function can be realized.     

Renal involvement in subjects with peripheral atherosclerosis

BACKGROUND: Ischemic nephropathy is an important cause of renal failure in western countries. Subclinical renal function abnormalities may exist in patients with extrarenal atherosclerosis, and may precede the onset of overt ischemic nephropathy. METHODS: To assess the impact of extrarenal atherosclerosis on the kidney, we evaluated renal function in 89 subjects with differing degrees of peripheral atherosclerosis, without manifest clinical or laboratory signs of ischemic nephropathy and renovascular hypertension. All laboratory testing, ultrasonography with Doppler analysis for the localization of peripheral vascular disease (carotid and lower limb arteries), and non-invasive evaluation of renal function by radionuclide studies of renal plasma flow (MAG3 clearance) and glomerular filtration (DTPA clearance), as well as total, LDL and HDL cholesterol, and triglycerides were determined; smoking habit was recorded. By combining sonographic data on arterial tree stenosis (ATS), the subjects were grouped according to the atherosclerotic vascular damage (ATS involvement). RESULTS: Despite no change in plasma creatinine and DTPA clearance (from 91.58+/-26.53 mL/min/1.73 m2 to 93.47+/-24.82), MAG3 clearance progressively declined with the severity of vascular damage (from 244.86+/-60.60 mL/min/1.73 m2 to 173.59+/-58.74). Stepwise multiple regression analysis indicated that MAG3 clearance was best explained by ATS involvement (standardized beta coefficient -0.40; p<0.001), smoking habit (-0.34; p= 0.004), and serum LDL-cholesterol (-0.24; p<0.035). CONCLUSIONS: The renal hemodynamic profile in atherosclerotic patients might constitute functional evidence of the silent phase of ischemic renal disease. The findings suggest that renal function should be carefully assessed in patients with extrarenal atherosclerosis, particularly in those with classic cardiovascular risk factors.     

Is duplex scanning the best screening test for renal artery stenosis?

Screening for renal artery stenosis is indicated in patients with suspected renovascular hypertension or ischemic nephropathy to identify those who could benefit from renal artery interventions. The critical requirements for a clinically useful screening test include safety, low cost, and a high sensitivity or low false-negative rate. Arteriography remains the "gold standard" for the anatomic diagnosis of renal artery disease, but it is unsuitable for screening because of its high cost and invasive nature. Although renal duplex scanning technically is difficult, experienced laboratories have been able to achieve sensitivities and specificities in the range of 93% to 98% for identification of stenoses in the main renal arteries. Renal duplex scanning also provides a method for assessing the renal parenchyma and predicting the clinical outcome of renal revascularization. The principal limitation of renal duplex scanning is failure to identify accessory renal arteries. The finding of one or more widely patent main renal arteries makes ischemic nephropathy unlikely, because this condition results from "total" renal ischemia. However, renovascular hypertension can be present with normal main renal arteries when there are isolated stenoses involving accessory renal arteries, so further testing may be indicated in selected hypertensive patients with normal main renal arteries by duplex scanning. Currently, duplex scanning in a qualified vascular laboratory arguably is the best screening test for renal artery stenosis. Other methods for assessing the renal arteries, particularly spiral computed tomography and magnetic resonance angiography, are evolving rapidly and also may play a role in screening of selected patients.     

Surgery of the renal arteries

Hypertension is a pervasive disease affecting between 10% and 15% of the population. Hypertension is manifested silently by an accelerated rate of atherosclerosis leading to increased incidence of cardiovascular, cerebrovascular, and peripheral vascular morbidities and deaths. Through activation of the renin-angiotensin axis, renovascular disease (RVD) accounts for approximately 5% of this hypertensive population. Recently, the relationship between renovascular occlusive disease and progressive renal insufficiency has been delineated and termed ischemic nephropathy. Patients with ischemic nephropathy present with hypertension in conjunction with elevated serum creatinine. It has been estimated that 15% of patients initiating dialysis each year have renovascular disease as the origin of their renal dysfunction. Renal dysfunction is due to a global reduction in renal perfusion, most often as a result of bilateral renal artery occlusive disease, although a mild form of renal insufficiency can be brought on by unilateral occlusive disease due to the effects of the renin-angiotensin system on the contralateral kidney. Historically, treatment of RVD has been centered on interrupting the renin-angiotensin axis and curing the resultant hypertension and its associated morbid disease. Currently, repair efficacy has been realized with concurrent retrieval of excretory renal function and cure of renovascular hypertension.      

Vascular reconstruction in urology

Vascular reconstructive surgery in urology includes techniques of revascularization of the renal artery for renovascular hypertension or ischemic nephropathy in situ or extracorporeal renal artery reconstruction. The indications for aortorenal bypass, extra-anatomic bypass, or simultaneous aortic substitution and renal revascularization are based on the cause, location, and extent of the vascular lesion. Techniques of bench surgery mainly depend on location of the renal artery disease and availability of autologous graft material.     

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.     

Kidney disease in cardiology.

Focusing on the convergence of cardiology and nephrology, this article marks the second year of NDT's section on Kidney Diseases beyond Nephrology. The clinical themes highlighted by the articles chosen for review include risk stratification and diagnosis of ischemic heart disease in severe chronic kidney disease and endstage renal disease patients, trials to reduce the risk of acute kidney injury (particularly contrast nephropathy) occurring with the invasive diagnosis and treatment of ischemic heart disease, and new data on the special clinical characteristics of dialysis patients with acute myocardial infarction. Finally, two clinical trials focusing on cardiovascular disease in severe kidney disease patients will be briefly highlighted.     

Value, limitations, and techniques of renal artery stenting

Percutaneous therapy for renovascular occlusive disease has become the preferred alternative to open renal artery revascularization. Angioplasty and stenting of renal artery stenoses has been shown to be a safe and effective option for severe hypertension and ischemic nephropathy. Catheter-based treatment, especially when performed with lower-profile systems can be performed with minimal morbidity and a reliably high degree of initial technical success. The long-term beneficial effects on blood pressure control and renal function, while debated, appear to be valid. In this article, data supporting the value and limitations of renal artery stenting are reviewed, and our technique for renal artery stenting using a lower-profile platform of balloons and stents is described.     

Comprehensive renal artery stenosis management by nephrology: a more selective approach

The impact of renal artery stenosis (RAS) and resulting ischemic nephropathy on kidney function has been well described. Based on several recent randomized, multicenter trials that revealed limitations to the utility of nonselective renal artery intervention, the general nephrology community has recently taken a conservative stance on this disease state. The purpose of this report is to summarize some recent contributions to our understanding of renal artery stenosis, which may cast RAS intervention in a new light.     

三维对比剂增强MR血管成像诊断慢性缺血性肾病的临床价值

目的：探讨三维对比剂增强MR血管成像（3DCE-MRA）在诊断慢性缺血性肾病中的临床价值.方法：选择一组疑有慢性缺血性肾病的患者,应用Siemens公司Sonata型1.5T超导型磁共振成像系统,对肾动脉进行3DCE-MRA扫描,对比剂为钆喷替酸葡甲胺（Gd-DTPA）;在MRA扫描后2 d内进行肾动脉彩色多普勒超声检查;对比观察肾动脉图像;同时观察血肌酐与肾动脉狭窄程度的关系.结果：在18例患者中,3DCE-MRA显示：6例肾动脉无异常,5例肾动脉狭窄（其中1例为双侧狭窄）,7例肾动脉显著狭窄（其中1例为双侧狭窄）;彩色多普勒超声：7例肾动脉无异常,4例肾动脉狭窄,7例肾动脉显著狭窄（其中1例为双侧狭窄）.18例患者均有血肌酐升高,明显升高的则肾动脉显著狭窄或双侧狭窄.结论：3DCE-MRA检查有无创、安全血管图像清晰准确等优点,可以做为筛选肾动脉狭窄,诊断慢性缺血性肾病的重要方法.     

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.     

Pathogenesis and management of renovascular hypertension and ischemic nephropathy

Renovascular disease is an important cause of secondary hypertension and renal impairment. Atherosclerotic renal artery stenosis (ARAS) is the most important cause of renal artery stenosis (RAS), and has been linked to increased cardiovascular risk. The pathogenesis of renovascular hypertension is complex, but is mainly due to the over-activation of Renin-Angiotensin-Aldosterone system. A major consequence of untreated RAS is ischemic nephropathy, which is due to the sustained reduction in renal perfusion leading to derangement of microvascular function, and eventual development of interstitial fibrosis. Diagnosis of these conditions can be complex, sometimes needing invasive testing. Aggressive medical management is key to preventing progression of disease, as the role of revascularization in the management of ARAS is still not well defined.     

End-stage renal disease in North Africa

There are many similarities in the profile of chronic renal disease in the five North African countries, reflecting their close resemblance in ethnic background, bioecology and socioeconomic standards. The incidence of renal disease is much higher than that in the West, yet the prevalence is relatively lower, which mirrors the inadequacy of medical care facilities. The principal causes of end-stage chronic renal disease (ESRD) are interstitial nephritis (14 to 32%), often attributed to environmental pollution and inadvertent use of medications; glomerulonephritis (11 to 24%), mostly mesangioproliferative and focal segmental sclerosis; diabetes (5 to 20%) and nephrosclerosis (5 to 21%). Obstructive/reflux nephropathy, attributed to urinary schistosomiasis, is common in Egypt (7%), Libya and Southern Algeria. Primary urolithiasis is a frequent cause of obstructive nephropathy in the western (hyperoxaluria) and middle (cystinuria) regions. The incidence of tuberculosis is increasing, particularly the diffuse interstitial and hematogenous forms. It is responsible also for 10 to 40% of renal amyloidosis. The latter is also frequently associated with familial Mediterranean fever. Sickle cell anemia is an important health problem in the west, leading to a wide range of glomerular and tubulointerstitial nephropathies. Takayasu disease is increasingly recognized as a cause of ischemic nephropathy and renovascular hypertension. The management of ESRD is largely influenced by late referral, co-morbidities and lack of dialysis facilities. Hemodialysis is the most frequent modality of renal replacement therapy (RRT). CAPD is used sporadically. Renal transplantation, largely from live (often unrelated) donors, is offered to less than 5% of patients with ESRD. The reported outcome of RRT generally conforms with international standards.     

The management of atherosclerotic renovascular disease

Atherosclerotic renovascular disease (ARVD) seems to be a common clinical condition. ARVD is clinically presented as: 'silent' renal artery stenosis, renovascular hypertension, ischemic nephropathy leading to deterioration of renal function and recurrent 'flash' pulmonary edema. Management of ARVD involves both revascularization and medical treatment. However, the impact of revascularization on kidney function and blood pressure control is a matter of great controversy in view of the results of recent randomized clinical trials. At present, concerted medical management (includes lifestyle modifications, such as smoking cessation) remains the main treatment option for patients with ARVD. However, there is a need to accurately identify individuals who may benefit from renal revascularization.     

The diabetic patient: renal insufficiency like other kidney failures?

The number of patients requiring renal replacement therapy because of diabetic nephropathy has been relentlessly increasing, and diabetes mellitus is now the leading cause of end stage renal disease in most Western Countries. Diabetic nephropathy has specificities. First, it tends to progress rapidly toward end stage renal disease. Second, patients with diabetic nephropathy are at increased risk of cardiovascular disease, when compared to patients with non diabetic nephropathy; similarly to what has been shown for diabetic patients on dialysis. Third, patients with diabetic nephropathy tend to be more severely anemic than patients with non-diabetic chronic kidney disease. Finally, small studies suggest that patients with diabetic nephropathy could have lower serum concentrations of parathyroid hormone than patients with non-diabetic nephropathy and similar glomerular filtration rate.     

Sickle cell nephropathy: an update on pathophysiology,diagnosis, and treatment

Sickle cell nephropathy is a major complication of sickle cell disease. It manifests in different forms, including glomerulopathy, proteinuria, hematuria, and tubular defects, and frequently results in end-stage renal disease (ESRD). Different pathophysiologic mechanisms have been proposed to explain the development of nephropathy in SCD, where hemolysis and vascular occlusion are the main contributors in the manifestations of this disease. Markers of renal injury, such as proteinuria and tubular dysfunction, have been associated with outcomes among patients with sickle cell nephropathy and provide means for early detection of nephropathy and screening prior to progression to renal failure. In small-sized clinical trials, hydroxyurea has demonstrated to be effective in slowing the progression to ESRD. Dialysis and renal transplantation represent the last resort for patients with sickle cell nephropathy. Nevertheless, despite the availability of diagnostic and therapeutic strategies, sickle cell nephropathy remains a challenging and under-recognized complication for patients with sickle cell disease.     

Management of ischemic nephropathy: dialysis-free survival after surgical repair

PURPOSE: This retrospective review describes the surgical management of consecutive patients with severe hypertension and ischemic nephropathy due to atherosclerotic renovascular disease. METHODS: From January 1987 through December 1998, a total of 590 patients underwent operative renal artery repair at our center. A subgroup of 232 hypertensive patients (97 women, 135 men; mean age, 66 +/- 8 years) with atherosclerotic renovascular disease and preoperative serum creatinine levels of 1.8 mg/dL or more forms the basis of this report. Change in renal function was determined from glomerular filtration rates estimated from preoperative and postoperative serum creatinine. The influence of selected preoperative parameters and renal function response on time to dialysis and dialysis-free survival was determined by a proportional hazards regression model. RESULTS: In all, 83 patients underwent unilateral renal artery repair and 149 patients underwent bilateral repair, including repair to a solitary kidney in 17 cases. A total of 332 renal arteries were reconstructed, and 32 nephrectomies were performed in these patients. After surgery, there were 17 deaths (7.3%) in the hospital or within 30 days of surgery. Advanced patient age (P =.001; hazard ratio, 1.1; 95% CI [1.1, 1.2]) and congestive heart failure (P =.04; hazard ratio, 2.9 CI [1.0, 8.6]) demonstrated significant and independent associations with perioperative mortality. With a change of 20% or more in EGFR being considered significant, 58% of patients had improved renal function, including 27 patients removed from dialysis dependence; function was unchanged in 35% and worsened in 7%. Follow-up death from all causes or progression to dialysis dependence demonstrated a significant and independent association with early renal function response. Both patients whose function was unchanged (P =.005; hazard ratio, 6.0; CI [2.2, 16.6]) and patients whose function was worsened (P =.03; hazard ratio, 2.2; CI [1.1, 4. 5]) remained at increased risk of death or dialysis dependence. For patients with unchanged renal function after operation, risk of death or dialysis demonstrated a significant interaction with preoperative renal function. In addition to severe preoperative renal dysfunction, diabetes mellitus demonstrated a significant and independent association with follow-up death or dialysis. CONCLUSION: Surgical correction of atherosclerotic renovascular disease can retrieve excretory renal function in selected hypertensive patients with ischemic nephropathy. Patients with improved renal function had a significant and independent increase in dialysis-free survival in comparison with patients whose function was unchanged and patients whose function was worsened after operation. These results add further evidence in support of a prospective, randomized trial designed to define the value of renal artery intervention in patients with ischemic nephropathy.