Reports of serial aortography have spanned the past 35 years. These retrospective observations include patients with clinical indication for repeated aortograms and thus describe carefully selected patient groups. Table 39-1 summarizes the results of these studies.

A 1968 report by Wollenweber and colleagues at the Mayo Clinic noted the clinical course of 109 patients with atherosclerotic RVD. The majority of these angiographic studies were performed to evaluate secondary hypertension. Of these patients, 30 required serial angiography for worsening clinical disease. Over a mean interval of 28 months, 13 of 22 patients (59%) without operative correction of their renovascular lesion had progression, including the development of some occlusive disease in three previously normal renal arteries.

In that same year, Meaney and colleagues reported on a cohort of patients with renovascular hypertension who had undergone serial angiography. Of 39 patients with atherosclerotic disease, 14 (36%) were found to have lesion progression between 6-month and 7-year follow up. Three (8%) developed renal artery occlusion. A 1984 report by Schreiber et al. updated this experience. All medically managed patients with documented RVD and serial angiograms between 1960 and 1979 were reviewed. Of 85 patients with atherosclerosis, 37 (44%) had lesion progression over a mean of 52 months, and 14 of 126 arteries (11%) progressed to occlusion. On mean follow up of 13 months, half of the occluded arteries had demonstrated >75% stenosis on the preceding angiogram. Anatomic progression of RVD from one category of disease to a higher category was frequently associated with decreased kidney function and kidney size. A significantly greater proportion of patients with disease progression demonstrated a decrease in both kidney function (54% vs. 25%; P < 0.02) and kidney size (70% vs. 27%; P < 0.001), compared with patients without progressive disease.

These early studies report a dramatic progression of disease. However, the applicability of these observations to the population at large is probably flawed. These studies reported on selected groups of patients with significant clinical disease that demonstrated clinical progression leading to serial invasive studies. Renovascular hypertension was suspected in nearly all these subjects, and worsening hypertension was the most frequent indication for a repeat study. It is doubtful whether the same rate of progression would apply to all individuals with renovascular lesions.

A 1991 report by Tollefson and Ernst reviewed 48 patients without suspected renovascular hypertension who were evaluated with serial angiography. Of these, 63% of arteries with <50% stenosis remained stable over a mean interval of 7 years. Overall, disease progressed in 53% of arteries. The authors observed an average annual stenosis increase of 4.6%. Seven arteries progressed to occlusion. Of these, five renal arteries had >80% stenosis on the preceding angiogram, and two had 60% to 79% stenosis. Interestingly, of patients who went on to occlusion, four out of seven demonstrated good blood pressure control, and only two out of seven had an increase in serum creatinine. Although RVD was not initially suspected in these patients, the study was biased by the selection of patients who required serial angiography for evaluation of clinically significant systemic atherosclerosis. Moreover, a variable interval existed between angiograms, making an accurate estimation of progression rate difficult. Like earlier studies, measurement of renal function was not consistently performed, and information regarding antihypertensive agents was not provided.

Chabova and colleagues reported on the clinical course of 68 patients with a mean age of 72 years who had >70% angiographic stenosis managed without intervention. Ninety-seven percent of patients demonstrated diffuse atherosclerosis with significant disease in extrarenal locations. Over an average 39 months of follow up, no significant change in mean blood pressure was observed, although the average number of medications increased from 1.6 to 1.9. Despite the use of angiotensinconverting enzyme inhibitors in 32% and loop diuretics in 47%, 85% of patients had stable serum creatinine over 36 months of follow up, while 8.8% (six patients) developed end-stage renal disease (ESRD). Of these six patients with eventual ESRD, five had diabetic nephropathy or acute renal failure. Although the prevalence of diabetes mellitus was 35% in the cohort, diabetics accounted for a disproportionate percentage of those with declining renal function. Half of patients with a >50% increase in serum creatinine and two thirds who progressed to ESRD were diabetic. Of 21 patients with bilateral RVD or disease to a solitary kidney, only four (19%) had a decline in renal function over 36 months. These patients demonstrated a trend toward older age and higher baseline serum creatinine than those with unilateral disease. In addition, follow-up mortality was twice as high in patients with bilateral disease (43% vs. 21%; P = 0.07). Of 47 patients with unilateral disease, six (13%) had an increase in serum creatinine over 40 months. This study suggests that hypertension can be adequately controlled without renal artery intervention despite high-grade unilateral or bilateral RVD. Adverse outcomes were most often due to co-existent coronary disease and diabetes mellitus. Mortality and ESRD, respectively, were not due to RVD in most instances. Without serial imaging, the rate of anatomic lesion progression during this relatively benign clinical course was not determined.

Crowley and colleagues reported on a large series of patients with serial aortography that was performed in patients selected for coronary catheterization. Between 1989 and 1996, more than 14,000 aortograms were performed simultaneously at the time of more than 32,000 cardiac catheterizations. Of these, 1,178 patients with two studies separated by at least 6 months were analyzed for disease progression over an average of 2.6 years. Of these, ≤50% stenosis was present in 2.4% of patients at baseline and 13.5% at follow up. Independent predictors of progression included female sex, increased age, coronary disease at baseline, and increased time interval between studies. Of the 1,090 patients with normal renal arteries at baseline, none with ≤50% progression demonstrated a rise in serum creatinine. Among the group with disease progression to ≥75% stenosis, serum creatinine increased significantly from 97 ± 44 µmol/L to 141 ± 114 µmol/L. The authors concluded that in this highly selected patient cohort, a significant percentage of patients developed renal artery stenosis over time. Moreover, progression of disease appeared to be associated with deterioration in renal function. These data demonstrated that renal artery stenosis can be identified in 2% to 13% of patients submitted to cardiac catheterization. However, a causal relationship between the presence of renal artery lesions and increasing creatinine was not proved. Despite the retrospective nature of this study and its inherent flaws, these data have been interpreted by some as a justification for “prophylactic” intervention for asymptomatic renal artery lesions.

Several randomized trials have compared renal artery intervention to medical management. Analysis of the medical treatment arms of these studies provides an indication of disease progression. Table 39-2 summarizes the results of these trials.

More than 25 years ago, Dean and colleagues reported on patients with renovascular hypertension randomized to medical management or surgical revascularization. Forty-one patients with significant atherosclerotic renal artery stenosis and renovascular hypertension proven by renal vein renin assay and/or split renal function studies were randomized to medical management. These patients were followed for an average of 44 months, during which 17 patients (41%) crossed over to the surgical arm. Despite the fact that 15 of the 17 patients had controlled hypertension, each patient had declining renal function as defined by a 10% loss of renal length, a 100% increase in serum creatinine, or a 50% reduction in measured glomerular filtration rate (GFR) or creatinine clearance (CrCl). Among the patients treated medically, 22 (54%) had no increase in serum creatinine and 47% of those who underwent isotopic
measurement of GFR or CrCl had no significant change. In addition, 37% had a <50% decline in GFR and one patient (2%) experienced a >50% decline. Interestingly, four patients (13%) demonstrated improvement in measured CrCl or GFR when measured serially. Despite the severity of RVD, the decline in renal function was variable, with 97% of patients losing <50% of measured GFR.