Zeller and colleagues (page 13) prospectively studied 215 consecutive patients with angiographically confirmed ostial atherosclero- tic renal artery stenosis of 70% or greater who underwent percutaneous stent placement and were followed up for 1 year. These subjects also had hypertension or impaired renal function (serum creatinine concentration of > 1.1 mg/dL for women and > 1.2 mg/dL for men), or both, but the initial clinical indications for suspecting the presence of renal artery stenosis were not defined. The primary end point was improvement in renal function at the end of 1 year, as defined by a reduction in serum creatinine concentration. Over the 1-year follow-up period, 52% of patients achieved a meager reduction in median serum creatinine concentration of 0.02 mg/dL that was equivalent to a mean increase in creatinine clearance of 2.3 mL/min. Patients with a baseline serum creatinine concentration of 1.5 mg/dL or less had no benefit from the procedure, compared with those with a baseline serum creatinine concentration greater than 1.5 mg/dL, who had the greatest benefit, with a median reduction of 0.33 mg/dL. Others, however, found a serum creatinine of 1.5 mg/dL or more to be a negative prognostic indicator.1 In the study by Zeller and colleagues, there was an overall procedural complication rate of 6.9%. Two percent of patients required long-term dialysis from acute postprocedure complications secondary to either contrast nephropathy or atheroembolic disease. In those patients without improvement in serum creatinine, the median creatinine increased by 0.11 mg/dL. Although there were no immediate procedure-related deaths, the 1-year mortality rate was 7.4%. Based on routine duplex sonographic screening at 6 and 12 months of the study, there was angiographic evidence of restenosis at the end of 1 year in 11.2% of patients, of which 85% occurred in the first 6 months.
The secondary end point of blood pressure response to stenting of renal artery stenosis showed a reduction in blood pressure in 76% of patients, but the precise blood pressure values and medications were not delineated. Interestingly, Dorros and colleagues also showed a significant improvement in blood pressure and reduction in the number of medications required 4 years after stent placement.1 After stenting, hypertension is generally categorized as cured, improved, or unchanged, and reduced need for antihyper-
tensive medications. Comparisons among studies have been difficult because of nonstandardized criteria, different target blood pressures, and variations in the medical regimen.2 In general, the reduction in blood pressure has been moderate, and resolution of hypertension has been the exception rather than the rule, suggesting the presence of an underlying essential hypertension rather than a primary renovascular etiology.1,2
As mentioned by the authors, the lack of a control group is a sig-
nificant limitation to the study. Chabova and colleagues followed 68 patients with atherosclerotic renal artery stenosis over an average of
3 years and found that 85% had stable renal function and less than
10% advanced to end-stage renal disease.3 The mortality rate was 29% over the 3 years, primarily due to cardiovascular disease.3 These data suggest that renal function remains stable for extended periods of time, despite the presence of atherosclerotic renal artery stenosis, and there is a relatively high mortality rate due to cardiovascular disease compared with end-stage renal disease.2 Yet, atherosclerotic renal artery stenosis is currently responsible for 5% to 15% of incident end-stage renal disease patients and is expected to increase as mean age increases, thus creating an unsolved dilemma for diagnosis and treatment.2
The primary goal of renal artery stenting is preservation of renal function weighed against the risk of adverse events, particularly contrast nephropathy and atheroemboli.2 But the appropriate timing of any in-
tervention is controversial. Most studies evaluate renal function by monitoring the serum creatinine concentration. Serum creatinine is an inaccurate marker in the early stages of renal dysfunction, how-ever, as changes may not be seen until 50% of total renal mass is lost. In the initial stages of atherosclerotic renal artery stenosis, the reduction in glomerular filtration of the affected kidney is often offset by increased glomerular filtration in the contralateral kidney that maintains a “normal” serum creatinine value.2 This might, in part, explain the absence of improved renal function after stenting in patients with a baseline creatinine concentration of 1.5 mg/dL or less. Moreover, an increased serum creatinine in unilateral atherosclerotic renal artery stenosis suggests the possibility of severe undetected bilateral renal artery stenosis, a nonfunctioning contralateral kidney, or parenchymal disease in the contralateral kidney. Determination of split renal function by nuclear imaging may detect hyperfiltration or reduced function of the contralateral kidney.2 Baseline proteinuria should be determined in diabetic patients because high-grade proteinuria indicates the presence
of glomerular disease, which, along with a resistive index of 0.8 or greater by duplex Doppler, is considered a negative predictor of a favorable renal outcome.4
With advances in noninvasive technologies, the diagnosis of renal artery stenosis has been made with greater regularity. The diagnosis should be entertained if there is deteriorating renal function, especially in elderly patients with coronary, peripheral, and cerebral vascular disease. Suspicion may also be raised in the presence of “flash” pulmonary edema, asymmetrical kidney sizes, or worsening blood pressure control. Depending on specific local expertise, user-dependent Doppler sonography or magnetic resonance angiography appear to be the studies of choice for initial screening. The indications for routine renal angiography or “drive-by” renal angiography have yet to be established. After the diagnosis of renal artery stenosis has been established, it is reasonable to consider stenting if the stenosis is 70% or more. Currently accepted indications for renal artery angioplasty with stenting include progressive azotemia, solitary kidney (functional or anatomical) with high-grade stenosis, flash pulmonary edema, and resistant hypertension. In the absence of accepted indications for intervention, the decision to stent a high-grade stenosis remains controversial. Caution should be exercised in the presence of severe atherosclerotic changes of contiguous arteries, advanced comorbid conditions, and short life expectancy. Future efforts should focus on prevention of atherosclerosis and improved methods of treatment of atherosclerotic renal artery stenosis with regard to prevention of contrast nephropathy and atheroemboli to the kidneys or periphery.