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Part 6: Cardiovascular Complications in PD |
Department of Medicine,1 Tampere University Hospital, Tampere; Medical School,2 Tampere University, Tampere; Satakunta Central Hospital,3 Pori; and Division of Vascular Surgery,4 Tampere University Hospital, Tampere, Finland
Correspondence to: H. Saha, Tampere University Hospital, PO Box 2000, Tampere FIN-33521 Finland. heikki.saha{at}uta.fi
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ABSTRACT |
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 TOP ABSTRACT DIAGNOSIS OF PVDEPIDEMIOLOGY OF PVDRISK FACTORSOUTCOME OF PVDTREATMENT OF EARLY DISEASE...MEDICAL TREATMENT OF PVDTREATMENT OF CRITICAL ISCHEMIACONCLUSIONSREFERENCES |
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In the present article, we review current knowledge of the epidemiology,
diagnosis, and treatment of peripheral vascular disease in patients with
end-stage renal disease. The main focus is placed on diabetic patients
receiving peritoneal dialysis, but studies on patients receiving hemodialysis
are also reviewed, because most reports involve this patient group, and the
number of reports on peripheral vascular disease in PD patients alone is
limited.
KEY WORDS: Peripheral vascular disease; diabetes.
The risk of cardiovascular disease in patients with chronic renal disease is far greater than that in the general population, and cardiovascular mortality in dialysis patients is 10–20 times that in the general population. As with other atherosclerotic diseases, peripheral vascular disease (PVD) is common in end-stage renal disease (1). However, compared with reports on coronary or cerebrovascular disease, reports on lower-extremity vascular disease in a dialysis population and data on PVD among peritoneal dialysis (PD) patients in particular are scarce. Therefore, because of a lack of evidence, recommendations for screening for and treating PVD lag behind those for other forms of cardiovascular disease (1). For example, the recent guidelines on PVD from the Kidney Disease Outcomes Quality Initiative (K/DOQI) are completely opinion-based (2).
Foot problems attributable to neurologic or vascular causes are frequent in patients suffering from diabetes with or without chronic kidney disease. In diabetic patients on dialysis, vascular disease is often combined with neuropathy, and loss of protective sensation is a major component of those problems. Patients may therefore ignore early lesions, use damaging footwear, and fail to report foot problems at an early stage when they could still heal. In addition to increased morbidity and mortality, foot ulcers in diabetic patients impair quality of life, generate substantial treatment costs, and represent the most important factor in foot amputation (3).
In the present article, we review current knowledge of the epidemiology, screening, diagnosis, and treatment of PVD in diabetic patients with chronic kidney disease. Our main scope is diabetic patients on PD, but studies on hemodialysis (HD) and transplantation patients are also reviewed, because most reports on PVD involve these patient groups and because data on PVD in PD patients alone are limited.
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DIAGNOSIS OF PVD |
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TOPABSTRACTDIAGNOSIS OF PVDEPIDEMIOLOGY OF PVDRISK FACTORSOUTCOME OF PVDTREATMENT OF EARLY DISEASE...MEDICAL TREATMENT OF PVDTREATMENT OF CRITICAL ISCHEMIACONCLUSIONSREFERENCES |
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In the general population, the sensitivity of using claudication to detect large-vessel disease is remarkably low. Among diabetic patients, the symptoms of claudication may be masked by neuropathy. The reproducibility of the palpation of pulses in clinical examination is poor.
A 19% prevalence of claudication was reported in a cohort of 325 patients
on renal replacement therapy
(4). In our recent study, the
prevalence of claudication was particularly low (6.8% and 2.8%, respectively)
in predialysis patients with chronic kidney disease and in dialysis patients
despite a high prevalence of PVD (22.0% and 30.6%, respectively) as assessed
by ankle–brachial index [ABI (
0.90)] and toe–brachial index
[TBI (0.60)] measurements
(5). Furthermore, one third of
the patients with claudication did not meet the criteria for PVD. Accordingly,
claudication is an insensitive and late sign of vascular disease, and in a
high-risk population such as diabetic PD patients, noninvasive methods that
are more sensitive and reliable are needed.
An ABI using the Doppler technique is a simple, noninvasive, and
inexpensive method of confirming PVD for epidemiologic or clinical purposes.
Systolic blood pressure is measured by a Doppler probe at the brachial artery
and at the posterior tibial or dorsal pedal artery of each ankle. The ABI is
determined by dividing the blood pressure in the ankle by that in the brachial
artery. An ABI of 0.90 indicates PVD, normal range being 0.91–1.30,
and an ABI of >1.30 or a non-compressible ankle artery suggests a calcified
vessel.
An ABI of <0.90 has 95% sensitivity and almost 100% specificity in detecting angiogram-positive PVD in apparently healthy individuals. Compared with the claudication questionnaire, ABI measurement identifies large numbers of patients with previously unrecognized PVD in both the general and dialysis populations (5).
A finding of falsely elevated pressure (ABI of >1.30) or non-compressible artery at ankle level is common in diabetic patients. It is caused by medial arterial calcification (MAC), which is common among patients with diabetes and has been shown to be associated with male sex, nephropathy, and neuropathy. Diabetic patients with MAC are at high risk for developing both macrovascular and microvascular complications; their cardiovascular mortality is also increased (6).
Typical radiology findings of MAC in plain X-ray images are "railroad-track" calcifications, which can be distinguished from the discrete, plaque-like intimal calcifications. The medium-to-small muscular arteries in the lower limbs are the ones usually affected by MAC. An ABI value of >1.30 suggests the presence of MAC, which renders a diagnosis of PVD by ABI measurement unreliable. Under such circumstances, a TBI is recommended for the diagnosis of PVD in both diabetes and CKD, because MAC does not interfere with toe-pressure measurement (5). However, TBI measurement is technically more demanding than ABI measurement is, and it requires additional equipment.
For detailed or preoperative lower extremity vascular mapping, contrast arteriography is still the "gold standard." However, at some centers, magnetic resonance angiography is used as the first-line imaging technique in CKD patients, because this technique uses lesser quantities of less-nephrotoxic contrast agents.
The recent K/DOQI guidelines (2) specify that all patients should be evaluated for the presence of PVD at the time of dialysis initiation. Checking arterial pulses and assessing skin integrity is recommended, particularly in diabetic dialysis patients. Accordingly, the recommendations may be considered quite conservative. Assessments of ABI and TBI were discussed, but further studies were deemed warranted to determine whether using these tests in the screening of asymptomatic patients would improve limb survival.
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EPIDEMIOLOGY OF PVD |
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TOPABSTRACTDIAGNOSIS OF PVDEPIDEMIOLOGY OF PVDRISK FACTORSOUTCOME OF PVDTREATMENT OF EARLY DISEASE...MEDICAL TREATMENT OF PVDTREATMENT OF CRITICAL ISCHEMIACONCLUSIONSREFERENCES |
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The U.S. Renal Data System reported a 15% prevalence of PVD in 2000 among incident dialysis patients when clinical criteria were used. A recent exceptionally large Japanese study (1010 HD patients) observed an ABI of <0.90 in 16.9% of the subjects (7). Other studies have reported a low ABI in 30%–35% of HD patients (5,8). In a Finnish study that used both ABI and TBI, the prevalence of PVD was 30.6% in dialysis patients, one third of whom were on PD; the prevalence among pre-dialysis patients was 22.0% and among transplantation recipients, 14.6% (5).
Martin et al. (9) reported a PVD prevalence of 29.4% in PD patients when claudication, gangrene, or amputation were used as criteria for diagnosis. In that study, PVD was highly significantly related to diabetes: 12 of 15 diabetic patients as compared with 3 of 36 nondiabetic patients developed vascular lesions. Webb et al. (4) reported claudication in 30% of 70 PD patients and in 16% each of HD and transplantation patients. Webb and Brown (10) showed that symptomatic PVD was more common than coronary or cerebrovascular disease among PD patients, especially women, in whom PVD tended to be the only sign of atherosclerosis (10).
Diagnosis of MAC is frequent in the dialysis population, which most likely weakens the sensitivity of ABI in detecting PVD in diabetic PD patients. Leskinen et al. reported an ABI of >1.30 in 41.7% of dialysis patients (5), which is a much higher proportion than that found in the sample of 1010 Japanese dialysis patients, in whom the prevalence of MAC was 10.9% (7). In the Finnish study, 58% of diabetic CKD patients had MAC, the corresponding prevalence in nondiabetic patients being 17%. Those authors suggested that MAC is an entity of its own, because 3 of 4 patients with MAC had no PVD as assessed by TBI.
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RISK FACTORS |
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TOPABSTRACTDIAGNOSIS OF PVDEPIDEMIOLOGY OF PVDRISK FACTORSOUTCOME OF PVDTREATMENT OF EARLY DISEASE...MEDICAL TREATMENT OF PVDTREATMENT OF CRITICAL ISCHEMIACONCLUSIONSREFERENCES |
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Recently, Foley et al. (13) studied the association between smoking and new-onset cardiovascular outcomes in a cohort of 3941 patients starting dialysis. In that cohort, 48.8% of the patients initiated PD. Current smoking was associated with an increased rate of new-onset PVD. Former smokers had an adjusted event-risk similar to that of lifelong nonsmokers, which may suggest that smoking cessation can reduce the cardiovascular risk in dialysis patients as well as in the general population.
In a few small studies concerning PD patients, the risk factors for PVD have been reported to include diabetes (8), high systolic blood pressure and hypercholesterolemia (4), and smoking and erythropoietin (EPO) use or dose (14,15). Wakeen and Zimmerman (14) reported more severe PVD and an increased requirement for amputation in diabetic PD patients allocated to EPO therapy as compared with those not receiving EPO, and in the study by Lipscombe et al. (15), the rate of foot amputations was related to the average weekly EPO dose. Whether the association between EPO and vascular events in these studies reflects other differences between the groups (overall wellbeing, chronic inflammation) or whether it is related to the EPO use itself is impossible to determine. However, the revised European best practice guidelines for the management of anemia recommend a cautious approach to raising blood hemoglobin concentration in diabetic patients to levels higher than 12 g/dL.
Vascular calcification has been shown to be associated with age, duration on dialysis, hyperphosphatemia, dose of calcium-containing phosphate binder, and markers of chronic inflammation (16). The relationship between vascular calcification and atherosclerosis or PVD is incompletely understood, but some evidence suggests that hyperphosphatemia or its effective therapy may affect the pathogenesis or course of PVD in dialysis patients (12,17,18).
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OUTCOME OF PVD |
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TOPABSTRACTDIAGNOSIS OF PVDEPIDEMIOLOGY OF PVDRISK FACTORSOUTCOME OF PVDTREATMENT OF EARLY DISEASE...MEDICAL TREATMENT OF PVDTREATMENT OF CRITICAL ISCHEMIACONCLUSIONSREFERENCES |
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In the report on lower extremity amputations in an ESRD population covered by the Medicare program in the United States, the amputation rate among diabetic dialysis patients was 5 times that of other dialysis patients and up to 10 times that of diabetic patients not on dialysis (19). Survival after lower extremity amputation was 49.3% at 1 year and 32.7% at 2 years.
A recent study examined postoperative morbidity and mortality in connection with surgical revascularization or amputation attributable to PVD in a large cohort of Medicare-covered dialysis patients (20). In the revascularization group, the death rate was 8.7% within 30 days and 49.7% within 1 year as compared with 16.0% and 62.3% respectively in the amputation group. The presence of gangrene was the strongest indication for choosing amputation over revascularization, but diabetes as a cause of ESRD and PD as the modality of dialysis were also both associated with amputation. The very high postoperative mortality and poor survival emphasize the importance of preventing and slowing the development of PVD and of detecting foot problems early, before surgical intervention is needed, especially in diabetic dialysis patients.
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TREATMENT OF EARLY DISEASE AND NON-CRITICAL ISCHEMIA |
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TOPABSTRACTDIAGNOSIS OF PVDEPIDEMIOLOGY OF PVDRISK FACTORSOUTCOME OF PVDTREATMENT OF EARLY DISEASE...MEDICAL TREATMENT OF PVDTREATMENT OF CRITICAL ISCHEMIACONCLUSIONSREFERENCES |
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Smoking Cessation: Smoking cessation slows the progression of critical ischemia and reduces risk of death from vascular disease. Although approximately half of all dialysis patients are current or past smokers (5,13), no reports are available on smoking cessation programs in this population. However, smoking is linked not only to a higher incidence of PVD (13), but also to death in a population with enormous cardiovascular risk. Organized efforts to encourage and help dialysis patients to stop smoking are therefore required if morbidity and mortality are to be reduced, including the morbidity and mortality associated with PVD.
Exercise: In the general population, exercise appears to be an effective treatment for claudication. Exercise-induced increases in walking ability may exceed those attained with medication (22). No reports on exercise as treatment for claudication in PD or HD patients are available, and yet increased physical activity has been recommended for this population, because activity may improve outcomes through enhanced overall health and a better cardiovascular risk profile.
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MEDICAL TREATMENT OF PVD |
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TOPABSTRACTDIAGNOSIS OF PVDEPIDEMIOLOGY OF PVDRISK FACTORSOUTCOME OF PVDTREATMENT OF EARLY DISEASE...MEDICAL TREATMENT OF PVDTREATMENT OF CRITICAL ISCHEMIACONCLUSIONSREFERENCES |
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Treatment of Hyperlipidemia: Large studies of statins have shown that, in populations with high cardiovascular risk, statin therapy also reduces PVD events. Simvastatin and atorvastatin may both improve pain-free walking time, which appears to be related to the noncholesterol-lowering properties of statins (23). In patients with diabetes, target levels of <2.5 mmol/L (100 mg/dL) for low-density lipoprotein cholesterol and <1.7 mmol/L (150 mg/dL) for triglycerides have been recommended.
Treatment of Diabetes and Hypertension: Intensive control of blood glucose prevents the microvascular complications of diabetes, but a similar effect on PVD or other macrovascular complications is not as evident (23). The target level for HbA1c is <7%. In the general population, angiotensin converting-enzyme inhibitors as antihypertensive agents have been shown to reduce cardiovascular events in patients with or without PVD, and they are widely recommended as first-line blood pressure–lowering drugs in patients with PVD (1,2,23).
Antiplatelet Agents: A meta-analysis of clinical trials of antiplatelet agents demonstrated that application of any antiplatelet therapy reduced the risk of cardiovascular mortality or morbidity by 23% in patients with PVD (24).
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TREATMENT OF CRITICAL ISCHEMIA |
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TOPABSTRACTDIAGNOSIS OF PVDEPIDEMIOLOGY OF PVDRISK FACTORSOUTCOME OF PVDTREATMENT OF EARLY DISEASE...MEDICAL TREATMENT OF PVDTREATMENT OF CRITICAL ISCHEMIACONCLUSIONSREFERENCES |
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The amputation and mortality rates after lower extremity revascularization are high among dialysis patients. Mortality and limb salvage rates may be more favorable after percutaneous angioplasty than after surgical revascularization (1). On the other hand, as compared with revascularization, amputation is associated with higher mortality in dialysis patients (20). Nevertheless, these findings may reflect only selection bias (1).
Critical ischemia in PD patients should not automatically result in amputation. Revascularization (surgical or by angioplasty) and limb salvage (when feasible) may be preferable in comparison with amputation in selected diabetic PD patients (2,20).
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CONCLUSIONS |
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TOPABSTRACTDIAGNOSIS OF PVDEPIDEMIOLOGY OF PVDRISK FACTORSOUTCOME OF PVDTREATMENT OF EARLY DISEASE...MEDICAL TREATMENT OF PVDTREATMENT OF CRITICAL ISCHEMIACONCLUSIONSREFERENCES |
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REFERENCES |
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TOPABSTRACTDIAGNOSIS OF PVDEPIDEMIOLOGY OF PVDRISK FACTORSOUTCOME OF PVDTREATMENT OF EARLY DISEASE...MEDICAL TREATMENT OF PVDTREATMENT OF CRITICAL ISCHEMIACONCLUSIONSREFERENCES |
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| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
