Long-Term Effects of Arterial Stenting on Kidney Functionfor Patients with Ostial Atherosclerotic Renal Artery Stenosis and Renal Insufficiency

Patients

Between September 1992 and August 1997, we treated a total of 63 patients with ostial atherosclerotic renal artery stenosis and compromised renal function (serum creatinine concentration of >120 μmol/L) and hypertension (BP of > 160/95 mmHg, with or without medication) with renal artery stents. Twenty-nine patients had been previously treated with percutaneous angioplasty. Ostial renal artery stenosis was defined as a ≥50% reduction in the luminal diameter within the first 10 mm of the aortic lumen. Patients were selected on the basis of the finding that stenosis contributed to their renal dysfunction. This was established by positive captopril renographic findings or by a ≥20% increase in plasma creatinine levels with the standardized use of an angiotensin-converting enzyme (ACE) inhibitor (12). Exclusion criteria were a history of cholesterol embolism, contraindications for anticoagulant medication, small size of the affected kidney (pole-to-pole distance of <8 cm), <25% function detected by renography, or a renal artery diameter of <4 mm. Informed consent was obtained, and the studies was approved by the hospital committee for studies in humans.

Protocol

BP and serum creatinine levels were measured before the intervention. The patients continued to receive their regular medications, but ACE inhibitor administration was discontinued at least 2 wk before this assessment. Stent placement was performed as described by Rees (10). Heparin was administered (5000 IU, intravenously) during this procedure, and treatment was continued until adequate anticoagulation was achieved with the use of orally administered warfarin. Bilateral stenoses were treated in one session. After 3 mo, warfarin was replaced by aspirin (100 mg daily). Beginning in March 1997, warfarin was deleted from this regimen and patients received only 100 mg of aspirin daily, starting the day before the procedure, with heparin administration during the procedure. The procedure was considered successful if the residual stenosis was <50% of the luminal diameter.

The patients attended the outpatient clinic at 1, 3, and 6 mo and every 6 mo thereafter, for measurement of BP and serum creatinine concentrations. For patients receiving an ACE inhibitor, administration was discontinued at least 2 wk before the 6-mo follow-up visit. At the other time points, ACE inhibitors were withheld only for patients with deterioration of renal function and serum creatinine concentrations measured without ACE inhibition were used for evaluation. Renal angiography was repeated at 6, 18, and 30 mo. When cholesterol embolism was suspected, angiography was replaced by spiral computed tomographic angiography. Angiography was also repeated if restenosis was suspected on a clinical basis, i.e., in cases with an increase in diastolic BP of at least 15 mmHg with unchanged antihypertensive medication or an increase in serum creatinine levels of at least 20% that developed spontaneously or after the start of treatment with ACE inhibitors. Restenosis, defined as a reduction in the luminal diameter of >50%, was treated by angioplasty in the stent.

Definitions

The results of angiography were assessed in consensus readings by two experienced vascular radiologists. The diameter of the first normal segment distal to the stenosis was used for reference. Clinical success, as assessed during the most recent follow-up examination, was classified according to the guidelines of the Standards of Practice Committee of the Society of Cardiovascular and Interventional Radiology (13). In those guidelines, cure of hypertension is defined as a diastolic pressure of ≤90 mmHg without antihypertensive medication. Improvement is defined as a diastolic pressure that decreases below 90 mmHg or decreases by at least 15 mmHg with unchanged antihypertensive medication. Any other result is classified as a failure. Improvement in renal function is defined as a decrease in the serum creatinine concentration of at least 20%, and deterioration is defined as an increase in the serum creatinine concentration of at least 20%. Any other result is defined as unchanged renal function.

Kidney Function before Treatment

For assessment of kidney function changes before stent placement, serum creatinine concentrations in the 1 yr preceding the procedure were compared. Only values measured without the use of ACE inhibitors were considered. Patients were considered to have declining renal function if serum creatinine levels had increased by at least 20% in the previous 12 mo. If serum creatinine measurements for 1 yr before the intervention were not available, increases in serum creatinine levels of ≥10% in the previous 6 mo or ≥15% in the previous 9 mo were considered to indicate deteriorating renal function. Patients with smaller increases or no changes in serum creatinine levels were considered to have stable function.

Statistical Analyses

Values are presented as medians and interquartile ranges (25 to 75%). Changes in serum creatinine concentrations before and after procedures were analyzed by comparisons of the slopes of plots of reciprocal serum creatinine concentrations versus time (in months). Statistical analyses were performed by using the Wilcoxon signed-rank test and Kaplan-Meier analysis (for survival times and renal function preservation). P < 0.05 was considered to indicate statistical significance.

Patients

There was a propensity for the male gender (Table 1). Hypercholesterolemia, extrarenal atherosclerotic disease, and smoking were common. Unilateral artery stenosis, with a normal contralateral renal artery, was observed for only 24% of patients. The other patients had bilateral renal artery stenosis or contralateral occlusion. Thirty-six patients had hypercholesterolemia (serum cholesterol levels of >6.5 mmol/L); 25 of these patients used a lipid-lowering drug and eight began using a statin soon after inclusion. During the course of the study, the national recommended cholesterol level above which statins are indicated for secondary prevention was decreased to 5.0 mmol/L, and eventually 10 more patients received lipid-lowering drug therapy.

Immediate Effects and Complications of Stent Placement

Sixty-one of the 63 patients underwent successful stenting of at least one renal artery. In one patient with unilateral disease, the stent was placed too distally and a second stent failed, leaving >50% stenosis. In one patient with bilateral stenoses, an occlusion occurred during catheterization of the first kidney addressed, which required a surgical bypass. For three patients with bilateral ostial stenoses, stenting failed on one side. For the other 17 patients with bilateral disease, the procedure was effective on both sides. For seven of these patients, one of the arteries could be treated by conventional angioplasty because the stenosis was truncal rather than ostial.

The most common complication was local bleeding at the puncture site (Table 2). One patient required a blood transfusion. Immediate thrombosis of the stent occurred once and was successfully resolved by selective intra-arterial streptokinase administration. Seven patients (11%) exhibited clinical signs of cholesterol embolism; for five of those patients (6%), plasma creatinine levels increased by at least 20% for > 1 mo after the procedure. One patient became dialysis-dependent.

Long-Term Patency

Repeat angiography was performed for most available patients at 6 mo (54 of 56 patients, 96%), 18 mo (36 of 42 patients, 86%), and 30 mo (12 of 18 patients, 67%). The numbers of patients with newly detected restenosis (≥50%) at these time points were ten (19%), seven (19%), and two (17%), respectively. Cumulatively, restenosis occurred in 19 cases. In 11 cases, the restenosis was successfully treated with conventional percutaneous transluminal angioplasty or with a second stent (n = 1). For one patient with a patent contralateral renal artery, nephrectomy was performed because of an aneurysm that had developed behind the stent. No action was taken in the other seven cases, because BP was well controlled and kidney function seemed stable, without deterioration, during standardized exposure to an ACE inhibitor.

Follow-up angiography was complicated by a temporary loss of renal function because of a cholesterol embolism in one patient. No permanent loss of renal function attributable to the angiography was observed.

Renal Function

Twenty-eight patients were classified as having stable renal dysfunction before stenting. Nine of those patients had unilateral disease. One became dialysis-dependent after 5 mo. One patient died at 6 mo, with end-stage renal failure. Of the remaining patients in this group, renal function improved for two, remained unchanged for 18, and declined for six. Serum creatinine levels were, by definition, stable in the period before the stent procedure and did not change in the 1 yr after the treatment (Table 3). The change in renal function, expressed as the change in 1/serum creatinine concentration per month, was -2.3 (-5.3 to 1.6) × 10^-5 L/μmol per mo before stent placement and -3.3 (-6.7 to 4.9) × 10^-5 L/μmol per mo in the subsequent 1 yr (P = 0.20, Wilcoxon signed-rank test) (Figure 1). At 12 mo, ACE inhibitors were used by 11 patients (42%) (for evaluation of kidney function during ACE inhibition, see above). During additional follow-up monitoring [median, 26 (14 to 42) mo], serum creatinine levels remained unchanged (Table 3).

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Figure 1.

Reciprocals of serum creatinine levels before and after stent placement. Patients were divided on the basis of stable or deteriorating renal function in the 1 yr before stent placement. For patients with deteriorating renal function, the decreasing slope of the curve was reversed (P < 0.001) after stent placement. Seven patients who developed end-stage renal failure or were lost to follow-up monitoring within 6 mo were not included in this evaluation [UNK], deteriorating (n = 30); [UNK], stable (n = 26).

Thirty-five patients, of whom six had unilateral disease, were considered to have deteriorating renal function before stent placement. Of these, one required dialysis 3 mo after stent placement and two others died within 6 mo, with predialysis serum creatinine levels. The stent placement did not clearly alter the rate of renal function decline for these three patients. One more patient died within 6 mo, and another was lost to follow-up monitoring at 4 mo, after experiencing a cerebrovascular accident. For these two subjects, the stent placement stabilized renal function. Of the remaining 30 patients in this group, kidney function improved for six, remained unchanged for 20, and declined for four. Serum creatinine levels, which by definition were increasing in the period before stent placement, had improved after 1 yr (Table 3). The decrease in renal function, i.e., -29.0 (-41.2 to -17.1) × 10^-5 L/μmol per mo in the period before stenting, was reversed into improvement, 5.3 (-0.8 to 8.4) × 10^-5 L/μmol per mo (P < 0.001, Wilcoxon signed-rank test) (Figure 1). At 12 mo, ACE inhibitors were used by nine patients (30%), which was not significantly different from the percentage of patients using ACE inhibitors in the group with stable renal function [9 of 35 (30%) versus 11 of 28 (42%)]. During additional follow-up monitoring [median, 23 (19 to 29) mo], one patient became dialysis-dependent after 27 mo. For the other patients, plasma creatinine levels remained stable (Table 3).

The cumulative number of patients who developed at least 20% decreases in renal function is presented in Figure 2. In 23 (13 to 36) mo, 15 of the 63 patients (24%) exhibited deterioration, and six of those patients reached end-stage renal failure. These latter patients exhibited a median baseline serum creatinine concentration of 326 μmol/L (range, 199 to 450 μmol/L). For further analysis of whether increased baseline serum creatinine concentrations are associated with poor outcomes, patients were divided into two groups, i.e., patients with mild renal failure (serum creatinine concentration of ≤300 μmol/L) and patients with severe renal failure (serum creatinine concentration of >300 μmol/L). Baseline measurements indicated severe renal failure for ten patients, of whom five (50%) exhibited worsening of their renal function; this result was significantly different from the outcomes for patients with mild renal failure (10 of 53 patients [19%]; P < 0.05). None of the 15 patients with unilateral stenosis experienced deterioration of renal function after stent placement; renal function improved for two patients, and no change in serum creatinine levels was observed for the remaining patients.

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Figure 2.

Kaplan-Meier curves for maintained renal function in all patients with atherosclerotic ostial renal artery stenosis and renal dysfunction who were treated with stent placement. Maintained renal function was defined as serum creatinine concentrations that did not increase above 120% of the serum creatinine levels at the time of stent placement. ESRD, number of patients who developed end-stage renal disease.

BP

Median baseline and follow-up systolic and diastolic BP values and the number of antihypertensive medications for all patients are presented in Table 4. Systolic and diastolic BP had decreased significantly by 6 mo after stent placement (P < 0.001), and this gain seemed to be durable. At the latest follow-up examination (at least 6 mo, i.e., 56 patients), improvement or cure of hypertension was observed for 50% (28 of 56 patients) and 9% (5 of 56 patients) of patients, respectively.

Survival Rates

Twelve patients, one of whom was undergoing dialysis, died, after a median period of 9.5 mo (range, 4 to 42 mo). The Kaplan-Meyer survival curve is shown in Figure 3. In eight cases, death could be attributed to a cardiovascular cause. No procedure-related death or death within 30 d of stent placement was noted.

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Figure 3.

Kaplan-Meier survival curve for all patients with atherosclerotic ostial renal artery stenosis and renal dysfunction who were treated with stent placement.