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Endovascular revascularization of renal artery stenosis in the solitary functioning kidney
From the Eastern Vascular Society
Endovascular revascularization of renal artery stenosis in the solitary functioning kidney Mark G. Davies, MD, PhD, MBA, Wael E. Saad, MD, Jean X. Bismuth, MD, Joseph J. Naoum, MD, Eric K. Peden, MD, and Alan B. Lumsden, MD, Houston, Tex Background: Endovascular therapy for symptomatic atherosclerotic renal artery stenosis (ARAS) is considered effective. This study evaluates the factors that impact long term anatomic and functional outcomes of endovascular therapy of ARAS in patients with a solitary functioning kidney. Methods: We performed a retrospective analysis of records from patients who underwent endovascular intervention for ARAS and identified patients with a solitary functioning kidney (absent or nonfunctioning contralateral kidney) and patients with contralateral normal kidney (for comparison) between January 1990 and January 2008. Indications for intervention in the solitary functioning kidney were poorly controlled hypertension (diastolic blood pressure [BP] >90 mm Hg on >3 antihypertensive medications) and/or elevated creatinine (Cr >1.5 mg/dL). Clinical benefit was defined as freedom from composite recurrent symptoms (recurrent hypertension or renal-related morbidity-increase in persistent creatinine >20% of baseline, progression to hemodialysis, and death from renal-related causes), anatomic patency and patient survival were measured. Results: A total of 242 patients (56% male, average age 69 years, range, 45-90) underwent angioplasty (23%) or primary stenting (77%) of a single renal artery with a normal contralateral renal vessel and kidney and 73 patients (58% male, average age 70 years, range, 52-89) underwent angioplasty (37%) or primary stenting (63%) for a solitary functioning kidney. There were no significant differences in mortality or morbidity between the groups. There was a significant difference in the long-term survival with 55 ⴞ 8% patients with a normal contralateral kidney vs 27 ⴞ 7% patients with a solitary functioning kidney alive at 10 years. Clinical benefit was 67 ⴞ 6% and 67 ⴞ 4% at 5 years and 63 ⴞ 8% and 62 ⴞ 4% at 10 years for solitary functioning kidney and normal contralateral groups, respectively. Using proportional hazard analysis, the predictors of long-term clinical benefit were ipsilateral kidney size (>9 cm), no immediate deterioration in function, and an estimated Glomerular Filtration Rate (eGFR) >30 mL/min/1.73m2. Neither control of diabetes nor the administration of statins was shown to influence outcomes in the solitary functioning kidney. Conclusion: Intervention in patients with a solitary functioning kidney is a safe procedure and improves or stabilizes renal function in 82% of patients. Clinical benefit is dictated by preoperative GFR, renal size, and the occurrence of acute functional injury after the procedure. ( J Vasc Surg 2009;49:953-60.)
While controversy remains on the endovascular therapy for symptomatic atherosclerotic renal artery stenosis (ARAS), it is considered effective and appears to have significant benefits in the well-selected patient.1-7 Acute functional injury associated with renal intervention for atherosclerotic disease is now recognized as an important clinical problem and has led to a growing realization that embolic protection devices may be required to protect the renal parenchyma during renal interventions.8-10 We have recently shown that acute functional renal injury occurs in approximately 20% of patients undergoing percutaneous renal artery intervention, is more likely in the presence of an unrepaired abdominal aortic aneurysm (AAA), diabetes, with preexisting renal disease, is a negative predictor of survival, is From the Department of Cardiovascular Surgery, Methodist DeBakey Heart and Vascular Center, The Methodist Hospital. Competition of interest: none. Presented at the Annual Meeting of the Easter Vascular Society, September, 2008 (Boston, Mass). Reprint requests: Mark G. Davies, MD, PhD, MBA, Methodist DeBakey Heart and Vascular Center, Department of Cardiovascular Surgery, The Methodist Hospital, 6550 Fannin Street, Smith Tower - Suite 1401, Houston, TX 77030 (e-mail: [email protected]). 0741-5214/$36.00 Copyright © 2009 by The Society for Vascular Surgery. doi:10.1016/j.jvs.2008.11.042
associated with subsequent renal failure, need for dialysis, and death.11 We did find that the status of the contralateral renal artery was important. Additionally, the advent of renal embolic devices and the proposed indication of intervention for use in atherosclerotic disease in a solitary kidney to prevent functional injury added impetus for us to address the outcomes of intervention in patients with a solitary kidney. Thus, this study evaluates the factors that impact long term anatomic and functional outcomes of endovascular therapy of ARAS in patients with a solitary functioning kidney. METHODS Study design. We performed a retrospective analysis of records from patients who underwent endovascular intervention for ARAS and identified patients with a solitary functioning kidney (definition: absent or nonfunctioning contralateral kidney) and patients with a contralateral normal kidney between January 1990 and January 2008. Patients with bilateral ARAS were excluded from the study. Indications for intervention were poorly controlled hypertension (diastolic blood pressure [BP] ⬎90 mm Hg on ⬎3 antihypertensive medications) and/or with elevated creatinine (ⱖ1.5 mg/dL). For each patient, demographics, 953
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existing comorbid conditions, and risk factors for atherosclerosis were identified. We evaluated the early and late outcomes of endovascular renal interventions in 73 patients with solitary kidneys and compared them with results of 169 patients with normal contralateral kidneys who underwent renal interventions during the same period. Treatment algorithm. Patients with hypertension and/or elevated serum creatinine levels had a diagnostic study to identify the presence of renal artery stenosis. This study consisted of standard angiography, magnetic resonance angiography, renal isotope scan, or duplex ultrasound scan. Duplex ultrasound scan criteria to identify renal artery stenosis have been previously described.12 In the presence of clinical criteria defined by Rundback et al13 and a ⬎60% stenosis on ultrasound scan or ⬎50% stenosis on magnetic resonance angiography/computerized tomographic angiography or a positive renal isotope scan, angiography was performed. Interventions were performed in patients with renal artery stenosis ⱖ50% by angiography regardless of comorbidities. The majority of these interventions were transfemoral and no distal protection devices were used. Patients not categorized into the clinical criteria referenced were managed medically. Occluded renal arteries and nonfunctioning kidneys were not treated. Patients with creatinine ⬎1.5 mg/mL were hydrated overnight with normal saline and in the last 5 years received Mucomyst (Acetylcysteine, Bristol-Myers Squibb Company, Princeton, NJ) 600 mg twice a day (BID) prescribed orally (PO) 24 hours preoperatively and 48 hours postoperatively. Patients were followed at 6-month intervals after the procedure. Blood pressure, serum creatinine, and the number of antihypertensive medications were identified during these intervals. Each patient had at least one duplex ultrasound scan within 6 months of the procedure and an ultrasound scan every 6 months thereafter to assess patency. If the duplex ultrasound scan showed ⱖ60% stenosis and the patient had recurrent symptoms, angiography was performed and restenosis was treated if the arterial diameter was ⱖ50%. Definitions. Coronary artery disease was defined as a history of angina pectoris, myocardial infarction, congestive heart disease, or prior coronary artery revascularizations. Cerebrovascular disease included a history of stroke, transient ischemic attack, or carotid artery revascularization. Hypercholesterolemia was defined as fasting cholesterol ⬎200 mg/dL. Diabetes was defined as a fasting plasma glucose ⬎110 mg/dL or an HbA1c ⬎7%. Diabetics were characterized as insulin dependent diabetes mellitus (IDDM) or non-insulin dependent diabetes mellitus (NIDDM). Hypertension was defined as diastolic BP greater than 90 mm Hg on ⬎3 antihypertensive medications. Metabolic syndrome was defined as previously described14 (insulin resistance or impaired glucose tolerance, hypertension, dyslipidemia, and abdominal obesity), with the exception of abdominal circumference, which was not routinely recorded. We substituted a body mass index score ⱖ30.0 as a positive score instead of an abdominal circumference ⬎102 cm or ⬎88 cm for male or female patients,
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respectively. An elevated creatinine was defined as ⱖ1.5 mg/dL on two consecutive values during a 3-month period. Chronic renal insufficiency was defined as a persistent serum creatinine ⬎1.5 mg/dL for greater than 6 months. Estimated glomerular filtration rate (eGFR) was defined as 186.3 * serum creatinine⫺1.154 * age⫺0.203 * 0.742 (if female) *1.212 (if African American). The baseline serum creatinine was the value recorded closest to the procedure. Patients were considered to have a “nonfunctioning kidney” if any two of the following local criteria used at our institution over the time of the study were met: (1) a duplex ultrasound scan identified a pole-to-pole length of less than 9 cm with no renal flow in the main renal artery and parenchymal peak systolic velocity ⬍10 cm/second; (2) surgically or congenitally absent kidney; (3) no visible nephrogram on contrast arteriogram. A normal contralateral kidney was considered a kidney without evidence of ⬎50% renal artery stenosis and not fulfilling criteria for a “nonfunctioning kidney”. Renal Resistive Index was defined from duplex scan imaging as 1-end-diastolic velocity/ peak systolic velocity (1-EDV/PSV)*100. Nephrosclerosis was defined as grade 1: normal intrarenal vessels, orderly progression of branching patterns (no pruning), normal nephrogram with distinct corticomedullary junction; grade 2: ectasia of arcuate and distal interlobular arteries, peripheral pruning, reduced arterial volume with normal renal mass, normal nephrogram; grade 3: marked ectasia extending centrally, total pruning with abrupt interlobar artery terminations, marked reduced arterial volume with decreased renal mass, and faint absent nephrogram. An endoluminal procedural success was a residual stenosis of ⬍30%; failures were residual stenosis ⱖ30%, by angiographic measurement, including lesions unable to be dilated or crossed, and occlusion within 30 days. A death within 30 days of the procedure was considered procedure-related. Acute functional renal injury was defined as a persistent increase in the serum creatinine of ⱖ0.5 mg/dL at 1 month after the procedure. Acute anatomic renal injury was defined as renal artery dissection, perforation, acute occlusion, renal parenchymal infarction, and renal parenchymal perforation. Access site complication was defined as hematoma, pseudoaneurysms, arteriovenous fistula, or a vessel injury requiring either percutaneous or open intervention. Systemic complications were any new cardiac pulmonary infectious or non-renal systemic complication that required intervention or halted discharge within 24 hours of the procedure. Response in the hypertensive patient was defined as follows: “cured” patients were normotensive (diastolic BP ⬍90 mm Hg and systolic BP ⬍140 mm Hg) without medications; “improved” patients were normotensive (diastolic BP ⬍90 mm Hg and/or systolic BP ⬍140 mm Hg) on the same (or reduced) number of medications, or had a diastolic BP 15 mm Hg below baseline with the same or reduced number of medications. “No effect” patients had no change or inability to meet these criteria for cure or improvement and were considered a treatment failure. Early renal function responses to angioplasty were defined as follows: “cured” renal function required a serum creatinine concentration
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⬍1.5 mg/dL; “improvement” in renal function required a ⬎20% reduction in the serum creatinine concentration; “stable” renal function required a ⬍20% increase or reduction in the serum creatinine concentration; “deterioration” in renal function required a ⬎20% increase in the serum creatinine concentration.13 Stable renal function and deterioration were considered treatment failures. Freedom from renal-related morbidity was defined as a persistent increase in creatinine ⬎20% of baseline, progression to hemodialysis, and death from renal-related causes.13 Statistical analysis. We performed our analysis on an “intention-to-treat” basis. Measured values are reported as percentages or means ⫾ 1 standard deviation. Mann-Whitney tests were used to test the difference between means. Fischer’s or 2 tests were performed to test the significance between proportions in each group. Survival and clinical benefit rates are calculated using life table analysis and reported using the Society for Vascular Surgery (SVS) criteria. Standard errors are reported in actuarial analyses. The log rank test was used to determine differences between life tables. Analyses were performed using JMP software version 7.0 (SAS Institute, Cary, NC). Cox proportional hazards models were employed for time-dependent outcomes by preprocedural variables and periprocedural variables. RESULTS Patient population. Over the time period, 242 patients (56% male, average age 69 years, range, 45-90) underwent angioplasty (23%) or primary stenting (77%) of a single renal artery with a normal contralateral renal vessel and kidney, and 73 patients (58% male, average age 70 years, range, 52-89) underwent angioplasty (37%) or primary stenting (63%) for a solitary functioning kidney. One hundred thirty-two patients with bilateral ARAS were excluded from the analysis. Hypertension was a much more common presentation in the normal group compared to the solitary functioning group where presentation with renal insufficiency predominated (Table I). There was no significant difference in the majority of the co-morbidities between the two groups except that there were significantly more patients with congestive heart failure and a history of cerebrovascular disease in the solitary functioning kidney group (Table I). When the status of renal insufficiency is specifically examined, there was no significant difference in the mean serum creatinine concentration and eGFR between the groups. However, the distribution of patients with an eGFR ⬍30 mL/min/1.73m2 was significantly greater in the group with a solitary functioning kidney (Table II). The intrinsic measures of the treated kidney (size, resistive index, and nephrosclerosis grade) were equivalent in both groups (Table II). The range of kidney size in the solitary group was 13.7 to 7.0 cm pole-to-pole length. Immediate outcomes (<3 months). Of the 242 planned interventions for a single renal artery with a normal contralateral renal vessel, there was a 5% technical failure rate (⬎30% residual stenosis) but no periprocedural or 90-day mortalities. The procedure-related complication
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Table I. Patients’ characteristics, presenting symptoms, and co-morbidities
Demographics Patients Kidneys treated Male Average age (mean ⫾ SD, years) Symptoms Hypertension Elevated creatinine Hypertension with elevated creatinine Co-morbidities Smoking history Coronary artery disease Congestive heart failure Diabetes mellitus Hyperlipidemia Metabolic syndrome Cerebrovascular
Normal
Solitary
P value
242 242 56%
73 73 58%
— — .88
69 ⫾ 11
70 ⫾ 9
.47
70% 12%
38% 21%
.001
18%
41%
60% 46% 24% 28% 65% 70% 23%
64% 53% 44% 23% 67% 74% 33%
.56 .32 .003 .41 .77 .52 .12
SD, Standard deviation.
rate for this group was 9% (all minor). Of the 73 planned interventions for solitary functioning kidney, there was a 4% technical failure rate (⬎30% residual stenosis). There were no periprocedural or 90-day mortalities. The procedurerelated complication rate (access and anatomic related) was 12% (all minor). There were no significant differences between the two groups. The nature of the renal interventions and categories of complications in both groups are shown in Table III. Immediate renal clinical benefit was superior in the solitary kidney group compared to the normal contralateral group (Table IV). In the presence of a normal contralateral kidney, only 6% of patients treated demonstrated immediate clinical benefit of improved or cured renal dysfunction and 86% showed no change within 3 months of procedure. In comparison, in the presence of a solitary functioning kidney, 12% of patients treated demonstrated immediate clinical benefit of improved or cured renal dysfunction and 69% showed no change within 3 months of procedure (Table IV). However, there was a significant difference in acute functional injury in the solitary functioning kidney group (Table III) which was translated into a greater number of patients who were considered to have had a deterioration in their renal function at 3 months (Table IV). A preprocedure eGFR ⬎30 mL/min/ 1.73m2 was associated with immediate clinical benefit in those patients with a solitary kidney (relative risk [RR] 0.66, 95% confidence interval [CI] 0.45 to 0.95, P ⬎ .0094). With respect to hypertension, there was a significant clinical benefit in 60% of the normal contralateral kidney group and 20% of the solitary functioning kidney group (Table IV). The differences in the respective clinical benefits achieved likely reflect the differences in presenting symptoms between the groups. Outcomes (>3 months). There was a significant difference in the long-term survival between the normal con-
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Table II. Kidney disease, creatinine levels, estimated GFR, ipsilateral and contralateral hemodynamic, and anatomy parameters
Kidney disease stage 1 2 3 4 5 Functional parameters Creatinine (mg/dL) Mean eGFR mL/ min/1.73m2 eGFR ⬍30mL/ min/1.73m2 eGFR 30-60mL/ min/1.73m2 eGFR ⬎60mL/ min/1.73m2 Ipsilateral kidney anatomy Kidney size Resistive index Nephrosclerosis Contralateral kidney anatomy Normal Stenosis (⬎60%) Nonfunctioning Surgically absent Atrophy Occlusion Contralateral kidney parameters Kidney size Resistive index Nephrosclerosis
Table IV. Outcomes
Normal
Solitary
P value
8% 27% 51% 11% 3%
0% 12% 53% 29% 5%
.05 .05 .1 .05 .09
1.5 ⫾ 1.0
1.9 ⫾ 1.0
.5
55 ⫾ 24
40 ⫾ 18
.5
13%
35%
.05
51%
53%
.1
36%
12%
.05
10.1 ⫾ 0.1 0.73 ⫾ 0.1 1.30 ⫾ 0.47
11.0 ⫾ 1.5 0.75 ⫾ 0.11 1.42 ⫾ 0.02
.1 .2 .3
100% 0% 0% 0% 0% 0%
0% 0% 23% 15% 21% 42%
— — — — — —
10.2 ⫾ 1.1 0.73 ⫾ 0.09 1.23 ⫾ 0.42
7.4 ⫾ 1.4 — 2.67 ⫾ 0.70
.05 — .01
eGFR, Estimated glomerular filtration rate.
Table III. Interventions and periprocedural complications
Interventions Angioplasty Stent placement Predilation Contralateral intervention Complications Acute functional injury Anatomic injury Access site Systemic
Normal
Solitary
P value
23% 77% 45% 0%
27% 73% 44% 0%
.51 — .88 —
14% 4% 5% 0%
30% 4% 8% 0%
.006 1.0 .38 —
tralateral kidney and solitary functioning kidney groups with patients with a solitary functioning kidney having a lower life expectancy (Fig, A). In patients with a normal contralateral kidney, survival was 76 ⫾ 4% and 55 ⫾ 8% at 5 and 10 years, while in patients with a solitary functioning kidney survival was 62 ⫾ 6% and 27 ⫾ 7% at 5 and 10 years. The eGFR ⬍30 (hazard ratio [HR] 8.18, 2.61-20.4;
Immediate hypertension outcomes Deterioration No change Improved Cured Long-term hypertension outcomes Deterioration No change Immediate renal outcomes Deterioration No change Improved Cured Long Term Renal Outcomes Increase in creatinine Progression to hemodialysis Death from renal cause
Normal
Solitary
P value
1% 39% 52% 8%
0% 80% 17% 3%
.0001
10% 90%
7% 93%
.44
8% 86% 5% 1%
19% 69% 11% 1%
.03
21% 7% 2%
22% 15% 3%
.86 .07 .65
95% CI; P ⬍ .03), dialysis dependency (HR 4.1, 1.92-8.65; P ⬍ .003) and smoking (HR 2.5, 1.15-5.38; P ⬍ .02) were associated with decreased survival in the solitary functioning kidney group. Cumulative patency rates determined by serial duplex scan imaging were 81 ⫾ 5% vs 87 ⫾ 6% at 5 years and 68% vs 83% at 10 years for normal contralateral and solitary functioning kidney groups respectively (Fig, B). By Cox proportional hazard analysis, hyperlipidemia (HR 5.16, 1.40-20.1, P ⬍ .012) and metabolic syndrome (HR 3.62, 1.74-7.43, P ⬍ .014) were associated with decreased patency. Restenosis rates were equivalent at 5 years (85 ⫾ 4% vs 87 ⫾ 6%, normal contralateral vs solitary functioning) and 10 years (78 ⫾ 9% vs 84 ⫾ 10%, normal contralateral vs solitary functioning) (Fig, C). Hyperlipidemia (HR 10.4, 2.1-64.7, P ⬍ .003) and an elevated fasting blood sugar (HR 7.3, 1.9-30.8, P ⬍ .004) were associated with increased rate of restenosis in solitary functioning kidneys. Freedom from renal-related morbidity (persistent increase in creatinine ⬎20% of baseline, progression to hemodialysis, and death from renal-related causes) was 59 ⫾ 10% and 73 ⫾ 7% at 5 years for solitary functioning kidney and normal contralateral groups, respectively (Fig, D). Recurrent symptoms and restenosis were highly correlated. Clinical benefit from hypertension (84 ⫾ 9% at 10 years) was superior to clinical benefit from renal-related morbidity (59 ⫾ 9% at 10 years) (Fig, E). Using proportional hazard analysis, the predictors of long-term clinical benefit were ipsilateral kidney size (⬎9 cm) (HR ⫺0.24, ⫺0.36 to ⫺0.12, P ⬍ .001), no immediate deterioration in function (HR 0.47, 0.01 to 0.88, P ⬍ .004) and a eGFR ⬎30 mL/ min/1.73m2 (HR ⫺0.44, ⫺0.72 to ⫺0.14, P ⬍ .02). Neither control of diabetes (HR 1.2, 0.88 to 1.94, P ⬍ .41) nor the administration of statins (HR 1.34, 0.86 to 2.14, P ⬍ .30) was shown to influence outcomes in the solitary functioning kidney.
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Fig. A, Survival: Kaplan-Meier analysis of survival of the patients with a solitary kidney or a normal contralateral kidney. The number at risk at each time interval is shown below each panel. Values are mean ⫾ standard error of the mean. Standard errors exceeding 10% are not shown. B, Patency: Kaplan-Meier analysis of cumulative patency with a solitary kidney or a normal contralateral kidney. The number at risk at each time interval is shown below each panel. Values are mean ⫾ standard error of the mean. Standard errors exceeding 10% are not shown. C, Restenosis: Kaplan-Meier analysis of freedom from restenosis of the patients with a solitary kidney or a normal contralateral kidney. The number at risk at each time interval is shown below each panel. Values are mean ⫾ standard error of the mean. Standard errors exceeding 10% are not shown. D, Recurrent symptoms: Kaplan-Meier analysis of freedom from renal-related morbidity (persistent increase in creatinine ⬎20% of baseline, progression to hemodialysis, death from renal-related causes) of the patients with a solitary kidney or a normal contralateral kidney. The number at risk at each time interval is shown below each panel. Values are mean ⫾ standard error of the mean. Standard errors exceeding 10% are not shown. E, Retained clinical benefit from recurrent hypertension and renal-related morbidity in the solitary kidney: Kaplan-Meier analysis of freedom from recurrent hypertension and renalrelated morbidity (increase in persistent creatinine ⬎20% of baseline, progression to hemodialysis, death from renal-related causes) of the patients with a solitary kidney. The number at risk at each time interval is shown below each panel. Values are mean ⫾ standard error of the mean. Standard errors exceeding 10% are not shown.
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DISCUSSION This series represents one of the largest reports on treatment of ARAS in the solitary functioning kidney. Intervention in patients with a solitary functioning kidney and appropriate symptoms is a safe procedure and compares favorably with those interventions performed for ARAS and a normal contralateral kidney. Intervention did improve or stabilize renal function in 82% of the patients presenting with ARAS in a solitary kidney. Although overall survival in these patients is much lower than if a normal contralateral kidney were present, the recurrence of symptoms was equivalent (59 ⫾ 10% and 73 ⫾ 7%) at 5 years supporting the longer term clinical efficacy of interventions in these patients. Clinical benefit appeared to be dictated by preoperative eGFR, renal size, and the occurrence of acute functional injury after the procedure. At the present time, there are no unique established criteria for endovascular treatment of renal artery stenosis in a solitary functioning kidney. One criterion suggested has been kidney size, as it is reported that a pole-to-pole length of less than 8 cm is a significant predictor that revascularization will not help in improving renal function.15 This was also taken into consideration in our patient selection with a mean kidney size of 11 cm, but we did perform procedures in kidneys with a minimum renal size of 7 cm during the early part of the series. A second criterion often employed is the anatomic location of the stenosis, as an ostial localization has a more favorable outcome than a peripheral lesion.16,17 A third criterion is the degree of stenosis present. While it has been shown that stenosis less than 60% have a 48% chance of progressing into significant stenosis in 3 years.12 A stenosis greater than 75% becomes an occlusion in 13 months in 39% of cases.18 A final criterion is the state and rate of decline of the renal insufficiency. Hanson et al have clearly demonstrated that intervening in a patient who is in the declining phase of renal insufficiency is far superior than intervening in the patient where the deterioration is established and long standing.19-22 Renal artery stenosis is an independent predictor of mortality. At 7 years, 73% of patients with renal artery stenosis are dead.23 The 7-year mortality in this study for patients with a solitary kidney was 66%, which is equivalent to untreated disease and was significantly higher than those patients with two kidneys (32% at 7 years). Similar to the current study, immediate and long-term postprocedure creatinine deterioration and dialysis-dependency have been associated with increased mortality.1,2,24 We have also shown that acute functional injury (ie, a rise in creatinine ⬎0.5 mg/dL) also has a significant impact on survival.11 There was a significant incidence in acute functional injury in the solitary kidney group that likely impacted the survival. Elevated creatinine has already been shown to affect survival after therapy for renal artery stenosis despite adequate revascularization.1,2,24 Intervention in the solitary kidney did not appear to influence survival. Technical success defined as ⬍30% residual stenosis at the end of the procedure has been reported to be between
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93-100% for endovascular interventions in the solitary kidney. Cumulative patency rates in this series determined by serial duplex scan imaging were 81 ⫾ 5% vs 87 ⫾ 6% at 5 years and 68% vs 83% at 10 years for normal and solitary kidney groups. In a series of 15 patients by Sahin et al,25 primary patency rates were 100% for 6 months, 92.3% for 12 months, and 69.2% for 24 months. The secondary patency rate at 24 months was 100%. In another series of 16 patients by Cioni et al,26 cumulative primary patency rate was 81% at 12 months and 75% at 24 months. We had a 0% mortality rate and an all-cause morbidity rate of 12%, all of which were minor. Other reports have shown mortality rates ranging from 0% to 4% and all-cause morbidity rates ranging from 27% to 43%.25-27 These data compared very favorably to open surgery where perioperative mortality was 6%, and major morbidity was 43%, including the need for permanent (9%) and temporary (9%) dialysis.28 It thus appears that intervention in the solitary kidney has a relatively low mortality and morbidity compared to historical data on endoluminal intervention and open surgery. After simple angioplasty in all comers, improvement or cure of BP has been reported as 66-100%, and improvement or stabilization of the renal functions was reported as 38-100%.29-32 In contrast, after primary stent placement, improvement or cure of BP was reported as 44-100% and improvement or stabilization of the renal functions was reported as 24-100%.17,26,33-37 While the immediate clinical outcomes in patients with a normal contralateral kidney demonstrated numbers in these ranges (hypertension 60% and renal 92%) those with a solitary kidney were much less likely for hypertension (20%) and equivalent for renal (81%). Bush et al27 reported improvement in renal function in 46% of patients, no change in 28%, and deterioration in 25% while Shannon et al38 reported 43%, 29%, and 29%, respectively. In comparison, only 12% of patients treated in this study demonstrated immediate clinical benefit of improved or cured renal dysfunction and 69% showed no change within 3 months of procedure. This data was equivalent to the control group except we saw a greater proportion of patients showing deterioration in renal function. While the improvement rates were lower than previous reports, a lower proportion of deterioration than in those previous reports balanced this. Only 19% of patients showed deterioration in their renal function with 3 months of intervention lower than the reports by Bush (25%) and Shannon (29%), however, twofold greater than our control group. We did find that a preprocedure eGFR ⬎30 mL/ min/1.73m2 was associated with immediate renal benefit in those patients with a solitary kidney. Long-term clinical benefit from renal-related morbidity was 59% at 5 years and was predicted by ipsilateral kidney size (⬎9 cm), no immediate deterioration in renal function and a eGFR ⬎30 mL/min/1.73m2. In contrast to these percutaneous results, Reilly et al28 reported the outcomes of open surgical interventions in 35 patients and showed that 91% of patients had stable or improved renal function and that hypertension was cured or improved in 85%. The current data suggests that a quantification of residual function through
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both biochemical and functional assessments in the solitary kidney will predict success and will allow better stratification of indications for intervention. CONCLUSION Intervention in patients with a solitary functioning kidney is a safe procedure and in the short term improves or stabilizes renal function in 82% of patients. Clinical benefit is dictated by preoperative eGFR, renal size, and the occurrence of acute functional injury after the procedure. AUTHOR CONTRIBUTIONS Conception and design: MD Analysis and interpretation: WS, MD Data collection: EP, JB, JN, WS, AL, MD Writing the article: WS, AL, MD Critical revision of the article: EP, JB, JN, WS, AL, MD Final approval of the article: EP, JB, JN, WS, AL, MD Statistical analysis: WS, MD Obtained funding: MD Overall responsibility: MD REFERENCES 1. Sivamurthy N, Suroweic SM, Culakova E, Rhodes JM, Lee D, Sternbach Y, et al. Divergent outcomes after percutaneous therapy for symptomatic renal artery stenosis. J Vasc Surg 2004;39:565-74. 2. Yutan E, Glickerman DJ, Caps MT, Hatsukami T, Harley JD, Kohler TR, Davies MG. Percutaneous transluminal revascularization for renal artery stenosis: Veterans Affairs Puget Sound Health Care System experience. J Vasc Surg 2001;34:685-93. 3. Dejani H, Eisen TD, Finkelstein FO. Revascularization of renal artery stenosis in patients with renal insufficiency. Am J Kidney Dis 2000;36: 752-8. 4. Martin LG, Rundback JH, Sacks D, Cardella JF, Rees CR, Matsumoto AH, et al. Quality improvement guidelines for angiography, angioplasty, and stent placement in the diagnosis and treatment of renal artery stenosis in adults. J Vasc Interv Radiol 2003;14(9 Pt 2):S297-310. 5. Beek FJ, Kaatee R, Beutler JJ, van der Ven PJ, Mali WP. Complications during renal artery stent placement for atherosclerotic ostial stenosis. Cardiovasc Intervent Radiol 1997;20:184-90. 6. Boisclair C, Therasse E, Oliva VL, Soulez G, Bui BT, Quérin S, Robillard P. Treatment of renal angioplasty failure by percutaneous renal artery stenting with Palmaz stents: midterm technical and clinical results. AJR Am J Roentgenol 1997;168:245-51. 7. White CJ. Catheter-based therapy for atherosclerotic renal artery stenosis. Circulation 2006;113:1464-73. 8. Holden A, Hill A. Renal angioplasty and stenting with distal protection of the main renal artery in ischemic nephropathy: early experience. J Vasc Surg 2003;38:962-8. 9. Holden A, Hill A, Jaff MR, Pilmore H. Renal artery stent revascularization with embolic protection in patients with ischemic nephropathy. Kidney Int 2006;70:948-55; comment 830-2. 10. Edwards MS, Corriere MA, Craven TE, Pan XM, Rapp JH, Pearce JD, et al. Atheroembolism during percutaneous renal artery revascularization. J Vasc Surg 2007;46:55-61. 11. Davies MG, Saad WE, Peden EK, Mohiuddin IT, Naoum JJ, Lumsden AB. Implications of acute renal injury following percutaneous renal artery intervention. Ann Vasc Surg 2008;22:783-9. 12. Caps MT, Perissinotto C, Zierler RE, Polissar NL, Bergelin RO, Tullis MJ, et al. Prospective study of atherosclerotic disease progression in the renal artery. Circulation 1998;98:2866-72. 13. Rundback JH, Sacks D, Kent KC, Cooper C, Jones C, Murphy TP, et al. Guidelines for the reporting of renal artery revascularization in clinical trials. American Heart Association. Circulation 2002;106:1572-85.
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14. Grundy SM, Brewer HB Jr, Cleeman JI, Smith SC Jr, Lenfant C, American Heart Association, et al. Definition of metabolic syndrome: report of the National Heart, Lung, and Blood Institute/American Heart Association conference on scientific issues related to definition. Circulation 2004;109:433– 8. 15. Rees CR, Palmaz JC, Becker GJ, Ehrman KO, Richter GM, Noeldge G, et al. Palmaz stent in atherosclerotic stenoses involving the ostia of the renal arteries: preliminary report of a multicenter study. Radiology 1991;181:507-14. 16. Baumgartner I, von Aesch K, Do DD, Triller J, Birrer M, Mahler F. Stent placement in ostial and nonostial atherosclerotic renal arterial stenoses: a prospective follow-up study. Radiology 2000;216:498-505. 17. Chatziioannou A, Mourikis D, Agroyannis B, Katsenis K, Pneumaticos S, Antoniou A, et al. Renal artery stenting for renal insufficiency in solitary kidney in 26 patients. Eur J Vasc Endovasc Surg 2002;23:49-54. 18. Schreiber MJ, Pohl MA, Novick AC. The natural history of atherosclerotic and fibrous renal artery disease. Urol Clin North Am 1984;11: 383-92. 19. Pearce JD, Craven BL, Craven TE, Piercy KT, Stafford JM, Edwards MS, Hansen KJ. Progression of atherosclerotic renovascular disease: a prospective population-based study. J Vasc Surg 2006;44:955-62; discussion 962-3. 20. Cherr GS, Hansen KJ, Craven TE, Edwards MS, Ligush J Jr, Levy PJ, et al. Surgical management of atherosclerotic renovascular disease. J Vasc Surg 2002;35:236-45. 21. Hansen KJ, Cherr GS, Craven TE, Motew SJ, Travis JA, Wong JM, et al. Management of ischemic nephropathy: dialysis-free survival after surgical repair. J Vasc Surg 2000;32:472-81; discussion 481-2. 22. Oskin TC, Hansen KJ, Deitch JS, Craven TE, Dean RH. Chronic renal artery occlusion: nephrectomy versus revascularization. J Vasc Surg 1999;29:140-9. 23. Zierler RE, Bergelin RO, Davidson RC, Cantwell-Gab K, Polissar NL, Strandness DE Jr. A prospective study of disease progression in patients with atherosclerotic renal artery stenosis. Am J Hypertens 1996;9: 1055-61. 24. Galaria II, Surowiec SM, Rhodes JM, Illig KA, Shortell CK, Sternbach Y, et al. Percutaneous and open renal revascularizations have equivalent longterm functional outcomes. Ann Vasc Surg 2005;19:218-28. 25. Sahin S, Cims¸it C, Andaç N, Baltaciog˘lu F, Tug˘lular S, Akog˘lu E. Renal artery stenting in solitary functioning kidneys: technical and clinical results. Eur J Radiol 2006;57:131-7. 26. Cioni R, Vignali C, Petruzzi P, Neri E, Caramella D, Vagli P, et al. Renal artery stenting in patients with a solitary functioning kidney. Cardiovasc Intervent Radiol 2001;24:372-7. 27. Bush RL, Martin LG, Lin PH, MacDonald MJ, Chaikof EL, Lumsden AB, Weiss VJ. Endovascular revascularization of renal artery stenosis in the solitary functioning kidney. Ann Vasc Surg 2001;15:60-6. 28. Reilly JM, Rubin BG, Thompson RW, Allen BT, Flye MW, Anderson CB, Sicard GA. Revascularization of the solitary kidney: a challenging problem in a high risk population. Surgery 1996;120:732-6; discussion 736-7. 29. Leertouwer TC, Gussenhoven EJ, Bosch JL, van Jaarsveld BC, van Dijk LC, Deinum J, Man In ’t Veld AJ. Stent placement for renal arterial stenosis: where do we stand? A meta-analysis. Radiology 2000;216:78-85. 30. Plouin PF, Chatellier G, Darné B, Raynaud A. Blood pressure outcome of angioplasty in atherosclerotic renal artery stenosis: a randomized trial. Essai Multicentrique Medicaments vs Angioplastie (EMMA) Study Group. Hypertension 1998;31:823-9. 31. Hoffman O, Carreres T, Sapoval MR, Auguste MC, Beyssen BM, Raynaud AC, Gaux JC. Ostial renal artery stenosis angioplasty: immediate and mid-term angiographic and clinical results. J Vasc Interv Radiol 1998;9(1 Pt 1):65-73. 32. Jensen G, Zachrisson BF, Delin K, Volkmann R, Aurell M. Treatment of renovascular hypertension: one year results of renal angioplasty. Kidney Int 1995;48:1936-45. 33. Taylor A, Sheppard D, Macleod MJ, Harden P, Baxter GM, Edwards RD, Moss JG. Renal artery stent placement in renal artery stenosis: technical and early clinical results. Clin Radiol 1997;52:451-7.
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34. Lederman RJ, Mendelsohn FO, Santos R, Phillips HR, Stack RS, Crowley JJ. Primary renal artery stenting: characteristics and outcomes after 363 procedures. Am Heart J 2001;142:314-23. 35. Dorros G, Jaff M, Mathiak L, Dorros II, Lowe A, Murphy K, He T. Four-year follow-up of Palmaz-Schatz stent revascularization as treatment for atherosclerotic renal artery stenosis. Circulation 1998;98: 642-7. 36. Rocha-Singh KJ, Ahuja RK, Sung CH, Rutherford J. Long-term renal function preservation after renal artery stenting in patients with progressive ischemic nephropathy. Catheter Cardiovasc Interv 2002;57:135-41.
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37. Hennequin LM, Joffre FG, Rousseau HP, Aziza R, Tregant P, Bernadet P, et al. Renal artery stent placement: long-term results with the Wallstent endoprosthesis. Radiology 1994;191:713-9. 38. Shannon HM, Gillespie IN, Moss JG. Salvage of the solitary kidney by insertion of a renal artery stent. AJR Am J Roentgenol 1998;171:21722.
Submitted Sep 19, 2008; accepted Nov 11, 2008.
Endovascular revascularization of renal artery stenosis in the solitary functioning kidney Mark G. Davies, MD, PhD, MBA, Wael E. Saad, MD, Jean X. Bismuth, MD, Joseph J. Naoum, MD, Eric K. Peden, MD, and Alan B. Lumsden, MD, Houston, Tex Background: Endovascular therapy for symptomatic atherosclerotic renal artery stenosis (ARAS) is considered effective. This study evaluates the factors that impact long term anatomic and functional outcomes of endovascular therapy of ARAS in patients with a solitary functioning kidney. Methods: We performed a retrospective analysis of records from patients who underwent endovascular intervention for ARAS and identified patients with a solitary functioning kidney (absent or nonfunctioning contralateral kidney) and patients with contralateral normal kidney (for comparison) between January 1990 and January 2008. Indications for intervention in the solitary functioning kidney were poorly controlled hypertension (diastolic blood pressure [BP] >90 mm Hg on >3 antihypertensive medications) and/or elevated creatinine (Cr >1.5 mg/dL). Clinical benefit was defined as freedom from composite recurrent symptoms (recurrent hypertension or renal-related morbidity-increase in persistent creatinine >20% of baseline, progression to hemodialysis, and death from renal-related causes), anatomic patency and patient survival were measured. Results: A total of 242 patients (56% male, average age 69 years, range, 45-90) underwent angioplasty (23%) or primary stenting (77%) of a single renal artery with a normal contralateral renal vessel and kidney and 73 patients (58% male, average age 70 years, range, 52-89) underwent angioplasty (37%) or primary stenting (63%) for a solitary functioning kidney. There were no significant differences in mortality or morbidity between the groups. There was a significant difference in the long-term survival with 55 ⴞ 8% patients with a normal contralateral kidney vs 27 ⴞ 7% patients with a solitary functioning kidney alive at 10 years. Clinical benefit was 67 ⴞ 6% and 67 ⴞ 4% at 5 years and 63 ⴞ 8% and 62 ⴞ 4% at 10 years for solitary functioning kidney and normal contralateral groups, respectively. Using proportional hazard analysis, the predictors of long-term clinical benefit were ipsilateral kidney size (>9 cm), no immediate deterioration in function, and an estimated Glomerular Filtration Rate (eGFR) >30 mL/min/1.73m2. Neither control of diabetes nor the administration of statins was shown to influence outcomes in the solitary functioning kidney. Conclusion: Intervention in patients with a solitary functioning kidney is a safe procedure and improves or stabilizes renal function in 82% of patients. Clinical benefit is dictated by preoperative GFR, renal size, and the occurrence of acute functional injury after the procedure. ( J Vasc Surg 2009;49:953-60.)
While controversy remains on the endovascular therapy for symptomatic atherosclerotic renal artery stenosis (ARAS), it is considered effective and appears to have significant benefits in the well-selected patient.1-7 Acute functional injury associated with renal intervention for atherosclerotic disease is now recognized as an important clinical problem and has led to a growing realization that embolic protection devices may be required to protect the renal parenchyma during renal interventions.8-10 We have recently shown that acute functional renal injury occurs in approximately 20% of patients undergoing percutaneous renal artery intervention, is more likely in the presence of an unrepaired abdominal aortic aneurysm (AAA), diabetes, with preexisting renal disease, is a negative predictor of survival, is From the Department of Cardiovascular Surgery, Methodist DeBakey Heart and Vascular Center, The Methodist Hospital. Competition of interest: none. Presented at the Annual Meeting of the Easter Vascular Society, September, 2008 (Boston, Mass). Reprint requests: Mark G. Davies, MD, PhD, MBA, Methodist DeBakey Heart and Vascular Center, Department of Cardiovascular Surgery, The Methodist Hospital, 6550 Fannin Street, Smith Tower - Suite 1401, Houston, TX 77030 (e-mail: [email protected]). 0741-5214/$36.00 Copyright © 2009 by The Society for Vascular Surgery. doi:10.1016/j.jvs.2008.11.042
associated with subsequent renal failure, need for dialysis, and death.11 We did find that the status of the contralateral renal artery was important. Additionally, the advent of renal embolic devices and the proposed indication of intervention for use in atherosclerotic disease in a solitary kidney to prevent functional injury added impetus for us to address the outcomes of intervention in patients with a solitary kidney. Thus, this study evaluates the factors that impact long term anatomic and functional outcomes of endovascular therapy of ARAS in patients with a solitary functioning kidney. METHODS Study design. We performed a retrospective analysis of records from patients who underwent endovascular intervention for ARAS and identified patients with a solitary functioning kidney (definition: absent or nonfunctioning contralateral kidney) and patients with a contralateral normal kidney between January 1990 and January 2008. Patients with bilateral ARAS were excluded from the study. Indications for intervention were poorly controlled hypertension (diastolic blood pressure [BP] ⬎90 mm Hg on ⬎3 antihypertensive medications) and/or with elevated creatinine (ⱖ1.5 mg/dL). For each patient, demographics, 953
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existing comorbid conditions, and risk factors for atherosclerosis were identified. We evaluated the early and late outcomes of endovascular renal interventions in 73 patients with solitary kidneys and compared them with results of 169 patients with normal contralateral kidneys who underwent renal interventions during the same period. Treatment algorithm. Patients with hypertension and/or elevated serum creatinine levels had a diagnostic study to identify the presence of renal artery stenosis. This study consisted of standard angiography, magnetic resonance angiography, renal isotope scan, or duplex ultrasound scan. Duplex ultrasound scan criteria to identify renal artery stenosis have been previously described.12 In the presence of clinical criteria defined by Rundback et al13 and a ⬎60% stenosis on ultrasound scan or ⬎50% stenosis on magnetic resonance angiography/computerized tomographic angiography or a positive renal isotope scan, angiography was performed. Interventions were performed in patients with renal artery stenosis ⱖ50% by angiography regardless of comorbidities. The majority of these interventions were transfemoral and no distal protection devices were used. Patients not categorized into the clinical criteria referenced were managed medically. Occluded renal arteries and nonfunctioning kidneys were not treated. Patients with creatinine ⬎1.5 mg/mL were hydrated overnight with normal saline and in the last 5 years received Mucomyst (Acetylcysteine, Bristol-Myers Squibb Company, Princeton, NJ) 600 mg twice a day (BID) prescribed orally (PO) 24 hours preoperatively and 48 hours postoperatively. Patients were followed at 6-month intervals after the procedure. Blood pressure, serum creatinine, and the number of antihypertensive medications were identified during these intervals. Each patient had at least one duplex ultrasound scan within 6 months of the procedure and an ultrasound scan every 6 months thereafter to assess patency. If the duplex ultrasound scan showed ⱖ60% stenosis and the patient had recurrent symptoms, angiography was performed and restenosis was treated if the arterial diameter was ⱖ50%. Definitions. Coronary artery disease was defined as a history of angina pectoris, myocardial infarction, congestive heart disease, or prior coronary artery revascularizations. Cerebrovascular disease included a history of stroke, transient ischemic attack, or carotid artery revascularization. Hypercholesterolemia was defined as fasting cholesterol ⬎200 mg/dL. Diabetes was defined as a fasting plasma glucose ⬎110 mg/dL or an HbA1c ⬎7%. Diabetics were characterized as insulin dependent diabetes mellitus (IDDM) or non-insulin dependent diabetes mellitus (NIDDM). Hypertension was defined as diastolic BP greater than 90 mm Hg on ⬎3 antihypertensive medications. Metabolic syndrome was defined as previously described14 (insulin resistance or impaired glucose tolerance, hypertension, dyslipidemia, and abdominal obesity), with the exception of abdominal circumference, which was not routinely recorded. We substituted a body mass index score ⱖ30.0 as a positive score instead of an abdominal circumference ⬎102 cm or ⬎88 cm for male or female patients,
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respectively. An elevated creatinine was defined as ⱖ1.5 mg/dL on two consecutive values during a 3-month period. Chronic renal insufficiency was defined as a persistent serum creatinine ⬎1.5 mg/dL for greater than 6 months. Estimated glomerular filtration rate (eGFR) was defined as 186.3 * serum creatinine⫺1.154 * age⫺0.203 * 0.742 (if female) *1.212 (if African American). The baseline serum creatinine was the value recorded closest to the procedure. Patients were considered to have a “nonfunctioning kidney” if any two of the following local criteria used at our institution over the time of the study were met: (1) a duplex ultrasound scan identified a pole-to-pole length of less than 9 cm with no renal flow in the main renal artery and parenchymal peak systolic velocity ⬍10 cm/second; (2) surgically or congenitally absent kidney; (3) no visible nephrogram on contrast arteriogram. A normal contralateral kidney was considered a kidney without evidence of ⬎50% renal artery stenosis and not fulfilling criteria for a “nonfunctioning kidney”. Renal Resistive Index was defined from duplex scan imaging as 1-end-diastolic velocity/ peak systolic velocity (1-EDV/PSV)*100. Nephrosclerosis was defined as grade 1: normal intrarenal vessels, orderly progression of branching patterns (no pruning), normal nephrogram with distinct corticomedullary junction; grade 2: ectasia of arcuate and distal interlobular arteries, peripheral pruning, reduced arterial volume with normal renal mass, normal nephrogram; grade 3: marked ectasia extending centrally, total pruning with abrupt interlobar artery terminations, marked reduced arterial volume with decreased renal mass, and faint absent nephrogram. An endoluminal procedural success was a residual stenosis of ⬍30%; failures were residual stenosis ⱖ30%, by angiographic measurement, including lesions unable to be dilated or crossed, and occlusion within 30 days. A death within 30 days of the procedure was considered procedure-related. Acute functional renal injury was defined as a persistent increase in the serum creatinine of ⱖ0.5 mg/dL at 1 month after the procedure. Acute anatomic renal injury was defined as renal artery dissection, perforation, acute occlusion, renal parenchymal infarction, and renal parenchymal perforation. Access site complication was defined as hematoma, pseudoaneurysms, arteriovenous fistula, or a vessel injury requiring either percutaneous or open intervention. Systemic complications were any new cardiac pulmonary infectious or non-renal systemic complication that required intervention or halted discharge within 24 hours of the procedure. Response in the hypertensive patient was defined as follows: “cured” patients were normotensive (diastolic BP ⬍90 mm Hg and systolic BP ⬍140 mm Hg) without medications; “improved” patients were normotensive (diastolic BP ⬍90 mm Hg and/or systolic BP ⬍140 mm Hg) on the same (or reduced) number of medications, or had a diastolic BP 15 mm Hg below baseline with the same or reduced number of medications. “No effect” patients had no change or inability to meet these criteria for cure or improvement and were considered a treatment failure. Early renal function responses to angioplasty were defined as follows: “cured” renal function required a serum creatinine concentration
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⬍1.5 mg/dL; “improvement” in renal function required a ⬎20% reduction in the serum creatinine concentration; “stable” renal function required a ⬍20% increase or reduction in the serum creatinine concentration; “deterioration” in renal function required a ⬎20% increase in the serum creatinine concentration.13 Stable renal function and deterioration were considered treatment failures. Freedom from renal-related morbidity was defined as a persistent increase in creatinine ⬎20% of baseline, progression to hemodialysis, and death from renal-related causes.13 Statistical analysis. We performed our analysis on an “intention-to-treat” basis. Measured values are reported as percentages or means ⫾ 1 standard deviation. Mann-Whitney tests were used to test the difference between means. Fischer’s or 2 tests were performed to test the significance between proportions in each group. Survival and clinical benefit rates are calculated using life table analysis and reported using the Society for Vascular Surgery (SVS) criteria. Standard errors are reported in actuarial analyses. The log rank test was used to determine differences between life tables. Analyses were performed using JMP software version 7.0 (SAS Institute, Cary, NC). Cox proportional hazards models were employed for time-dependent outcomes by preprocedural variables and periprocedural variables. RESULTS Patient population. Over the time period, 242 patients (56% male, average age 69 years, range, 45-90) underwent angioplasty (23%) or primary stenting (77%) of a single renal artery with a normal contralateral renal vessel and kidney, and 73 patients (58% male, average age 70 years, range, 52-89) underwent angioplasty (37%) or primary stenting (63%) for a solitary functioning kidney. One hundred thirty-two patients with bilateral ARAS were excluded from the analysis. Hypertension was a much more common presentation in the normal group compared to the solitary functioning group where presentation with renal insufficiency predominated (Table I). There was no significant difference in the majority of the co-morbidities between the two groups except that there were significantly more patients with congestive heart failure and a history of cerebrovascular disease in the solitary functioning kidney group (Table I). When the status of renal insufficiency is specifically examined, there was no significant difference in the mean serum creatinine concentration and eGFR between the groups. However, the distribution of patients with an eGFR ⬍30 mL/min/1.73m2 was significantly greater in the group with a solitary functioning kidney (Table II). The intrinsic measures of the treated kidney (size, resistive index, and nephrosclerosis grade) were equivalent in both groups (Table II). The range of kidney size in the solitary group was 13.7 to 7.0 cm pole-to-pole length. Immediate outcomes (<3 months). Of the 242 planned interventions for a single renal artery with a normal contralateral renal vessel, there was a 5% technical failure rate (⬎30% residual stenosis) but no periprocedural or 90-day mortalities. The procedure-related complication
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Table I. Patients’ characteristics, presenting symptoms, and co-morbidities
Demographics Patients Kidneys treated Male Average age (mean ⫾ SD, years) Symptoms Hypertension Elevated creatinine Hypertension with elevated creatinine Co-morbidities Smoking history Coronary artery disease Congestive heart failure Diabetes mellitus Hyperlipidemia Metabolic syndrome Cerebrovascular
Normal
Solitary
P value
242 242 56%
73 73 58%
— — .88
69 ⫾ 11
70 ⫾ 9
.47
70% 12%
38% 21%
.001
18%
41%
60% 46% 24% 28% 65% 70% 23%
64% 53% 44% 23% 67% 74% 33%
.56 .32 .003 .41 .77 .52 .12
SD, Standard deviation.
rate for this group was 9% (all minor). Of the 73 planned interventions for solitary functioning kidney, there was a 4% technical failure rate (⬎30% residual stenosis). There were no periprocedural or 90-day mortalities. The procedurerelated complication rate (access and anatomic related) was 12% (all minor). There were no significant differences between the two groups. The nature of the renal interventions and categories of complications in both groups are shown in Table III. Immediate renal clinical benefit was superior in the solitary kidney group compared to the normal contralateral group (Table IV). In the presence of a normal contralateral kidney, only 6% of patients treated demonstrated immediate clinical benefit of improved or cured renal dysfunction and 86% showed no change within 3 months of procedure. In comparison, in the presence of a solitary functioning kidney, 12% of patients treated demonstrated immediate clinical benefit of improved or cured renal dysfunction and 69% showed no change within 3 months of procedure (Table IV). However, there was a significant difference in acute functional injury in the solitary functioning kidney group (Table III) which was translated into a greater number of patients who were considered to have had a deterioration in their renal function at 3 months (Table IV). A preprocedure eGFR ⬎30 mL/min/ 1.73m2 was associated with immediate clinical benefit in those patients with a solitary kidney (relative risk [RR] 0.66, 95% confidence interval [CI] 0.45 to 0.95, P ⬎ .0094). With respect to hypertension, there was a significant clinical benefit in 60% of the normal contralateral kidney group and 20% of the solitary functioning kidney group (Table IV). The differences in the respective clinical benefits achieved likely reflect the differences in presenting symptoms between the groups. Outcomes (>3 months). There was a significant difference in the long-term survival between the normal con-
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Table II. Kidney disease, creatinine levels, estimated GFR, ipsilateral and contralateral hemodynamic, and anatomy parameters
Kidney disease stage 1 2 3 4 5 Functional parameters Creatinine (mg/dL) Mean eGFR mL/ min/1.73m2 eGFR ⬍30mL/ min/1.73m2 eGFR 30-60mL/ min/1.73m2 eGFR ⬎60mL/ min/1.73m2 Ipsilateral kidney anatomy Kidney size Resistive index Nephrosclerosis Contralateral kidney anatomy Normal Stenosis (⬎60%) Nonfunctioning Surgically absent Atrophy Occlusion Contralateral kidney parameters Kidney size Resistive index Nephrosclerosis
Table IV. Outcomes
Normal
Solitary
P value
8% 27% 51% 11% 3%
0% 12% 53% 29% 5%
.05 .05 .1 .05 .09
1.5 ⫾ 1.0
1.9 ⫾ 1.0
.5
55 ⫾ 24
40 ⫾ 18
.5
13%
35%
.05
51%
53%
.1
36%
12%
.05
10.1 ⫾ 0.1 0.73 ⫾ 0.1 1.30 ⫾ 0.47
11.0 ⫾ 1.5 0.75 ⫾ 0.11 1.42 ⫾ 0.02
.1 .2 .3
100% 0% 0% 0% 0% 0%
0% 0% 23% 15% 21% 42%
— — — — — —
10.2 ⫾ 1.1 0.73 ⫾ 0.09 1.23 ⫾ 0.42
7.4 ⫾ 1.4 — 2.67 ⫾ 0.70
.05 — .01
eGFR, Estimated glomerular filtration rate.
Table III. Interventions and periprocedural complications
Interventions Angioplasty Stent placement Predilation Contralateral intervention Complications Acute functional injury Anatomic injury Access site Systemic
Normal
Solitary
P value
23% 77% 45% 0%
27% 73% 44% 0%
.51 — .88 —
14% 4% 5% 0%
30% 4% 8% 0%
.006 1.0 .38 —
tralateral kidney and solitary functioning kidney groups with patients with a solitary functioning kidney having a lower life expectancy (Fig, A). In patients with a normal contralateral kidney, survival was 76 ⫾ 4% and 55 ⫾ 8% at 5 and 10 years, while in patients with a solitary functioning kidney survival was 62 ⫾ 6% and 27 ⫾ 7% at 5 and 10 years. The eGFR ⬍30 (hazard ratio [HR] 8.18, 2.61-20.4;
Immediate hypertension outcomes Deterioration No change Improved Cured Long-term hypertension outcomes Deterioration No change Immediate renal outcomes Deterioration No change Improved Cured Long Term Renal Outcomes Increase in creatinine Progression to hemodialysis Death from renal cause
Normal
Solitary
P value
1% 39% 52% 8%
0% 80% 17% 3%
.0001
10% 90%
7% 93%
.44
8% 86% 5% 1%
19% 69% 11% 1%
.03
21% 7% 2%
22% 15% 3%
.86 .07 .65
95% CI; P ⬍ .03), dialysis dependency (HR 4.1, 1.92-8.65; P ⬍ .003) and smoking (HR 2.5, 1.15-5.38; P ⬍ .02) were associated with decreased survival in the solitary functioning kidney group. Cumulative patency rates determined by serial duplex scan imaging were 81 ⫾ 5% vs 87 ⫾ 6% at 5 years and 68% vs 83% at 10 years for normal contralateral and solitary functioning kidney groups respectively (Fig, B). By Cox proportional hazard analysis, hyperlipidemia (HR 5.16, 1.40-20.1, P ⬍ .012) and metabolic syndrome (HR 3.62, 1.74-7.43, P ⬍ .014) were associated with decreased patency. Restenosis rates were equivalent at 5 years (85 ⫾ 4% vs 87 ⫾ 6%, normal contralateral vs solitary functioning) and 10 years (78 ⫾ 9% vs 84 ⫾ 10%, normal contralateral vs solitary functioning) (Fig, C). Hyperlipidemia (HR 10.4, 2.1-64.7, P ⬍ .003) and an elevated fasting blood sugar (HR 7.3, 1.9-30.8, P ⬍ .004) were associated with increased rate of restenosis in solitary functioning kidneys. Freedom from renal-related morbidity (persistent increase in creatinine ⬎20% of baseline, progression to hemodialysis, and death from renal-related causes) was 59 ⫾ 10% and 73 ⫾ 7% at 5 years for solitary functioning kidney and normal contralateral groups, respectively (Fig, D). Recurrent symptoms and restenosis were highly correlated. Clinical benefit from hypertension (84 ⫾ 9% at 10 years) was superior to clinical benefit from renal-related morbidity (59 ⫾ 9% at 10 years) (Fig, E). Using proportional hazard analysis, the predictors of long-term clinical benefit were ipsilateral kidney size (⬎9 cm) (HR ⫺0.24, ⫺0.36 to ⫺0.12, P ⬍ .001), no immediate deterioration in function (HR 0.47, 0.01 to 0.88, P ⬍ .004) and a eGFR ⬎30 mL/ min/1.73m2 (HR ⫺0.44, ⫺0.72 to ⫺0.14, P ⬍ .02). Neither control of diabetes (HR 1.2, 0.88 to 1.94, P ⬍ .41) nor the administration of statins (HR 1.34, 0.86 to 2.14, P ⬍ .30) was shown to influence outcomes in the solitary functioning kidney.
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Fig. A, Survival: Kaplan-Meier analysis of survival of the patients with a solitary kidney or a normal contralateral kidney. The number at risk at each time interval is shown below each panel. Values are mean ⫾ standard error of the mean. Standard errors exceeding 10% are not shown. B, Patency: Kaplan-Meier analysis of cumulative patency with a solitary kidney or a normal contralateral kidney. The number at risk at each time interval is shown below each panel. Values are mean ⫾ standard error of the mean. Standard errors exceeding 10% are not shown. C, Restenosis: Kaplan-Meier analysis of freedom from restenosis of the patients with a solitary kidney or a normal contralateral kidney. The number at risk at each time interval is shown below each panel. Values are mean ⫾ standard error of the mean. Standard errors exceeding 10% are not shown. D, Recurrent symptoms: Kaplan-Meier analysis of freedom from renal-related morbidity (persistent increase in creatinine ⬎20% of baseline, progression to hemodialysis, death from renal-related causes) of the patients with a solitary kidney or a normal contralateral kidney. The number at risk at each time interval is shown below each panel. Values are mean ⫾ standard error of the mean. Standard errors exceeding 10% are not shown. E, Retained clinical benefit from recurrent hypertension and renal-related morbidity in the solitary kidney: Kaplan-Meier analysis of freedom from recurrent hypertension and renalrelated morbidity (increase in persistent creatinine ⬎20% of baseline, progression to hemodialysis, death from renal-related causes) of the patients with a solitary kidney. The number at risk at each time interval is shown below each panel. Values are mean ⫾ standard error of the mean. Standard errors exceeding 10% are not shown.
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DISCUSSION This series represents one of the largest reports on treatment of ARAS in the solitary functioning kidney. Intervention in patients with a solitary functioning kidney and appropriate symptoms is a safe procedure and compares favorably with those interventions performed for ARAS and a normal contralateral kidney. Intervention did improve or stabilize renal function in 82% of the patients presenting with ARAS in a solitary kidney. Although overall survival in these patients is much lower than if a normal contralateral kidney were present, the recurrence of symptoms was equivalent (59 ⫾ 10% and 73 ⫾ 7%) at 5 years supporting the longer term clinical efficacy of interventions in these patients. Clinical benefit appeared to be dictated by preoperative eGFR, renal size, and the occurrence of acute functional injury after the procedure. At the present time, there are no unique established criteria for endovascular treatment of renal artery stenosis in a solitary functioning kidney. One criterion suggested has been kidney size, as it is reported that a pole-to-pole length of less than 8 cm is a significant predictor that revascularization will not help in improving renal function.15 This was also taken into consideration in our patient selection with a mean kidney size of 11 cm, but we did perform procedures in kidneys with a minimum renal size of 7 cm during the early part of the series. A second criterion often employed is the anatomic location of the stenosis, as an ostial localization has a more favorable outcome than a peripheral lesion.16,17 A third criterion is the degree of stenosis present. While it has been shown that stenosis less than 60% have a 48% chance of progressing into significant stenosis in 3 years.12 A stenosis greater than 75% becomes an occlusion in 13 months in 39% of cases.18 A final criterion is the state and rate of decline of the renal insufficiency. Hanson et al have clearly demonstrated that intervening in a patient who is in the declining phase of renal insufficiency is far superior than intervening in the patient where the deterioration is established and long standing.19-22 Renal artery stenosis is an independent predictor of mortality. At 7 years, 73% of patients with renal artery stenosis are dead.23 The 7-year mortality in this study for patients with a solitary kidney was 66%, which is equivalent to untreated disease and was significantly higher than those patients with two kidneys (32% at 7 years). Similar to the current study, immediate and long-term postprocedure creatinine deterioration and dialysis-dependency have been associated with increased mortality.1,2,24 We have also shown that acute functional injury (ie, a rise in creatinine ⬎0.5 mg/dL) also has a significant impact on survival.11 There was a significant incidence in acute functional injury in the solitary kidney group that likely impacted the survival. Elevated creatinine has already been shown to affect survival after therapy for renal artery stenosis despite adequate revascularization.1,2,24 Intervention in the solitary kidney did not appear to influence survival. Technical success defined as ⬍30% residual stenosis at the end of the procedure has been reported to be between
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93-100% for endovascular interventions in the solitary kidney. Cumulative patency rates in this series determined by serial duplex scan imaging were 81 ⫾ 5% vs 87 ⫾ 6% at 5 years and 68% vs 83% at 10 years for normal and solitary kidney groups. In a series of 15 patients by Sahin et al,25 primary patency rates were 100% for 6 months, 92.3% for 12 months, and 69.2% for 24 months. The secondary patency rate at 24 months was 100%. In another series of 16 patients by Cioni et al,26 cumulative primary patency rate was 81% at 12 months and 75% at 24 months. We had a 0% mortality rate and an all-cause morbidity rate of 12%, all of which were minor. Other reports have shown mortality rates ranging from 0% to 4% and all-cause morbidity rates ranging from 27% to 43%.25-27 These data compared very favorably to open surgery where perioperative mortality was 6%, and major morbidity was 43%, including the need for permanent (9%) and temporary (9%) dialysis.28 It thus appears that intervention in the solitary kidney has a relatively low mortality and morbidity compared to historical data on endoluminal intervention and open surgery. After simple angioplasty in all comers, improvement or cure of BP has been reported as 66-100%, and improvement or stabilization of the renal functions was reported as 38-100%.29-32 In contrast, after primary stent placement, improvement or cure of BP was reported as 44-100% and improvement or stabilization of the renal functions was reported as 24-100%.17,26,33-37 While the immediate clinical outcomes in patients with a normal contralateral kidney demonstrated numbers in these ranges (hypertension 60% and renal 92%) those with a solitary kidney were much less likely for hypertension (20%) and equivalent for renal (81%). Bush et al27 reported improvement in renal function in 46% of patients, no change in 28%, and deterioration in 25% while Shannon et al38 reported 43%, 29%, and 29%, respectively. In comparison, only 12% of patients treated in this study demonstrated immediate clinical benefit of improved or cured renal dysfunction and 69% showed no change within 3 months of procedure. This data was equivalent to the control group except we saw a greater proportion of patients showing deterioration in renal function. While the improvement rates were lower than previous reports, a lower proportion of deterioration than in those previous reports balanced this. Only 19% of patients showed deterioration in their renal function with 3 months of intervention lower than the reports by Bush (25%) and Shannon (29%), however, twofold greater than our control group. We did find that a preprocedure eGFR ⬎30 mL/ min/1.73m2 was associated with immediate renal benefit in those patients with a solitary kidney. Long-term clinical benefit from renal-related morbidity was 59% at 5 years and was predicted by ipsilateral kidney size (⬎9 cm), no immediate deterioration in renal function and a eGFR ⬎30 mL/min/1.73m2. In contrast to these percutaneous results, Reilly et al28 reported the outcomes of open surgical interventions in 35 patients and showed that 91% of patients had stable or improved renal function and that hypertension was cured or improved in 85%. The current data suggests that a quantification of residual function through
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both biochemical and functional assessments in the solitary kidney will predict success and will allow better stratification of indications for intervention. CONCLUSION Intervention in patients with a solitary functioning kidney is a safe procedure and in the short term improves or stabilizes renal function in 82% of patients. Clinical benefit is dictated by preoperative eGFR, renal size, and the occurrence of acute functional injury after the procedure. AUTHOR CONTRIBUTIONS Conception and design: MD Analysis and interpretation: WS, MD Data collection: EP, JB, JN, WS, AL, MD Writing the article: WS, AL, MD Critical revision of the article: EP, JB, JN, WS, AL, MD Final approval of the article: EP, JB, JN, WS, AL, MD Statistical analysis: WS, MD Obtained funding: MD Overall responsibility: MD REFERENCES 1. Sivamurthy N, Suroweic SM, Culakova E, Rhodes JM, Lee D, Sternbach Y, et al. Divergent outcomes after percutaneous therapy for symptomatic renal artery stenosis. J Vasc Surg 2004;39:565-74. 2. Yutan E, Glickerman DJ, Caps MT, Hatsukami T, Harley JD, Kohler TR, Davies MG. Percutaneous transluminal revascularization for renal artery stenosis: Veterans Affairs Puget Sound Health Care System experience. J Vasc Surg 2001;34:685-93. 3. Dejani H, Eisen TD, Finkelstein FO. Revascularization of renal artery stenosis in patients with renal insufficiency. Am J Kidney Dis 2000;36: 752-8. 4. Martin LG, Rundback JH, Sacks D, Cardella JF, Rees CR, Matsumoto AH, et al. Quality improvement guidelines for angiography, angioplasty, and stent placement in the diagnosis and treatment of renal artery stenosis in adults. J Vasc Interv Radiol 2003;14(9 Pt 2):S297-310. 5. Beek FJ, Kaatee R, Beutler JJ, van der Ven PJ, Mali WP. Complications during renal artery stent placement for atherosclerotic ostial stenosis. Cardiovasc Intervent Radiol 1997;20:184-90. 6. Boisclair C, Therasse E, Oliva VL, Soulez G, Bui BT, Quérin S, Robillard P. Treatment of renal angioplasty failure by percutaneous renal artery stenting with Palmaz stents: midterm technical and clinical results. AJR Am J Roentgenol 1997;168:245-51. 7. White CJ. Catheter-based therapy for atherosclerotic renal artery stenosis. Circulation 2006;113:1464-73. 8. Holden A, Hill A. Renal angioplasty and stenting with distal protection of the main renal artery in ischemic nephropathy: early experience. J Vasc Surg 2003;38:962-8. 9. Holden A, Hill A, Jaff MR, Pilmore H. Renal artery stent revascularization with embolic protection in patients with ischemic nephropathy. Kidney Int 2006;70:948-55; comment 830-2. 10. Edwards MS, Corriere MA, Craven TE, Pan XM, Rapp JH, Pearce JD, et al. Atheroembolism during percutaneous renal artery revascularization. J Vasc Surg 2007;46:55-61. 11. Davies MG, Saad WE, Peden EK, Mohiuddin IT, Naoum JJ, Lumsden AB. Implications of acute renal injury following percutaneous renal artery intervention. Ann Vasc Surg 2008;22:783-9. 12. Caps MT, Perissinotto C, Zierler RE, Polissar NL, Bergelin RO, Tullis MJ, et al. Prospective study of atherosclerotic disease progression in the renal artery. Circulation 1998;98:2866-72. 13. Rundback JH, Sacks D, Kent KC, Cooper C, Jones C, Murphy TP, et al. Guidelines for the reporting of renal artery revascularization in clinical trials. American Heart Association. Circulation 2002;106:1572-85.
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Submitted Sep 19, 2008; accepted Nov 11, 2008.