Peripheral artery disease in chronic kidney disease
- Ann M O'Hare, MD
Ann M O'Hare, MD
- Associate Professor of Medicine
- University of Washington School of Medicine
- Section Editors
- Gary C Curhan, MD, ScD
Gary C Curhan, MD, ScD
- Section Editor — Chronic Kidney Disease
- Professor of Medicine
- Harvard Medical School
- John F Eidt, MD
John F Eidt, MD
- Section Editor — Vascular and Endovascular Surgery
- Professor of Surgery, Texas A&M Health Science Center
- Vice Chair of Vascular Surgical Services, Baylor Heart and Vascular Hospital at Dallas
- Joseph L Mills, Sr, MD
Joseph L Mills, Sr, MD
- Section Editor — Vascular and Endovascular Surgery
- Professor and Chief
- Division of Vascular Surgery and Endovascular Therapy
- Baylor College of Medicine
It is increasingly recognized that chronic kidney disease (CKD) is an independent risk factor for the development of generalized atherosclerosis and coronary artery disease, and is associated with a worse prognosis following cardiovascular events. Most patients with CKD have only moderate reductions in eGFR and are at a much higher risk of morbidity and death related to cardiovascular disease than of eventually requiring renal replacement therapy. (See "Chronic kidney disease and coronary heart disease".)
Lower extremity peripheral artery disease (PAD) is a significant clinical issue among patients with CKD. Traditionally, most studies of the epidemiology of cardiovascular disease did not report subgroup analyses among patients with CKD [1-5], and epidemiologic studies of PAD have generally not included CKD as a potential risk factor [6-10]. However, a growing number of studies have now described an association between PAD and CKD.
This topic will focus on aspects of the epidemiology, diagnosis, and treatment of PAD relevant to individuals with CKD. CKD will refer to individuals with decreased kidney function, excluding dialysis patients and kidney transplant recipients. A review of this issue among patients with end-stage renal disease, and more detailed management recommendations for PAD in the general population are presented separately. (See "Lower extremity peripheral artery disease in end-stage renal disease" and "Noninvasive diagnosis of arterial disease" and "Management of claudication" and "Clinical features and diagnosis of lower extremity peripheral artery disease" and "Surgical management of claudication" and "Treatment of chronic lower extremity critical limb ischemia".)
The 2005 American College of Cardiology/American Heart Association (ACC/AHA) guidelines on peripheral artery disease (PAD), which were produced in collaboration with major vascular medicine, vascular surgery, and interventional radiology societies do not specifically identify chronic kidney disease (CKD) as being a risk factor for PAD . The Inter-Society Consensus for the Management of Peripheral Artery Disease (TASC-II) notes the association of renal insufficiency and PAD, suggesting it may be causal, but provides little supporting evidence.
Prevalence — PAD appears to be more prevalent among patients with CKD than in the general population. To some extent, this may reflect the older age and higher prevalence of known risk factors for PAD such as dyslipidemias, diabetes, hypertension, and other forms of vascular disease among those with CKD; however, even after adjustment for these potential confounders, CKD is independently associated with an increased prevalence of PAD, and with the future risk for developing clinically significant PAD [12-14]. Risk factors for PAD are reviewed elsewhere.
- Fried LF, Shlipak MG, Crump C, et al. Renal insufficiency as a predictor of cardiovascular outcomes and mortality in elderly individuals. J Am Coll Cardiol 2003; 41:1364.
- Garg AX, Clark WF, Haynes RB, House AA. Moderate renal insufficiency and the risk of cardiovascular mortality: results from the NHANES I. Kidney Int 2002; 61:1486.
- Manjunath G, Tighiouart H, Coresh J, et al. Level of kidney function as a risk factor for cardiovascular outcomes in the elderly. Kidney Int 2003; 63:1121.
- Muntner P, He J, Hamm L, et al. Renal insufficiency and subsequent death resulting from cardiovascular disease in the United States. J Am Soc Nephrol 2002; 13:745.
- Shlipak MG, Simon JA, Grady D, et al. Renal insufficiency and cardiovascular events in postmenopausal women with coronary heart disease. J Am Coll Cardiol 2001; 38:705.
- Criqui MH, Langer RD, Fronek A, et al. Mortality over a period of 10 years in patients with peripheral arterial disease. N Engl J Med 1992; 326:381.
- Fowkes FG, Housley E, Cawood EH, et al. Edinburgh Artery Study: prevalence of asymptomatic and symptomatic peripheral arterial disease in the general population. Int J Epidemiol 1991; 20:384.
- Murabito JM, D'Agostino RB, Silbershatz H, Wilson WF. Intermittent claudication. A risk profile from The Framingham Heart Study. Circulation 1997; 96:44.
- Murabito JM, Evans JC, Nieto K, et al. Prevalence and clinical correlates of peripheral arterial disease in the Framingham Offspring Study. Am Heart J 2002; 143:961.
- Ridker PM, Stampfer MJ, Rifai N. Novel risk factors for systemic atherosclerosis: a comparison of C-reactive protein, fibrinogen, homocysteine, lipoprotein(a), and standard cholesterol screening as predictors of peripheral arterial disease. JAMA 2001; 285:2481.
- Hirsch AT, Haskal ZJ, Hertzer NR, et al. ACC/AHA 2005 Practice Guidelines for the management of patients with peripheral arterial disease (lower extremity, renal, mesenteric, and abdominal aortic): a collaborative report from the American Association for Vascular Surgery/Society for Vascular Surgery, Society for Cardiovascular Angiography and Interventions, Society for Vascular Medicine and Biology, Society of Interventional Radiology, and the ACC/AHA Task Force on Practice Guidelines (Writing Committee to Develop Guidelines for the Management of Patients With Peripheral Arterial Disease): endorsed by the American Association of Cardiovascular and Pulmonary Rehabilitation; National Heart, Lung, and Blood Institute; Society for Vascular Nursing; TransAtlantic Inter-Society Consensus; and Vascular Disease Foundation. Circulation 2006; 113:e463.
- O'Hare AM, Glidden DV, Fox CS, Hsu CY. High prevalence of peripheral arterial disease in persons with renal insufficiency: results from the National Health and Nutrition Examination Survey 1999-2000. Circulation 2004; 109:320.
- O'Hare AM, Vittinghoff E, Hsia J, Shlipak MG. Renal insufficiency and the risk of lower extremity peripheral arterial disease: results from the Heart and Estrogen/Progestin Replacement Study (HERS). J Am Soc Nephrol 2004; 15:1046.
- Wattanakit K, Folsom AR, Selvin E, et al. Kidney function and risk of peripheral arterial disease: results from the Atherosclerosis Risk in Communities (ARIC) Study. J Am Soc Nephrol 2007; 18:629.
- Carter SA. Indirect systolic pressures and pulse waves in arterial occlusive diseases of the lower extremities. Circulation 1968; 37:624.
- Zheng ZJ, Sharrett AR, Chambless LE, et al. Associations of ankle-brachial index with clinical coronary heart disease, stroke and preclinical carotid and popliteal atherosclerosis: the Atherosclerosis Risk in Communities (ARIC) Study. Atherosclerosis 1997; 131:115.
- Newman AB, Shemanski L, Manolio TA, et al. Ankle-arm index as a predictor of cardiovascular disease and mortality in the Cardiovascular Health Study. The Cardiovascular Health Study Group. Arterioscler Thromb Vasc Biol 1999; 19:538.
- Leskinen Y, Salenius JP, Lehtimäki T, et al. The prevalence of peripheral arterial disease and medial arterial calcification in patients with chronic renal failure: requirements for diagnostics. Am J Kidney Dis 2002; 40:472.
- Shlipak MG, Fried LF, Crump C, et al. Cardiovascular disease risk status in elderly persons with renal insufficiency. Kidney Int 2002; 62:997.
- Wattanakit K, Folsom AR, Criqui MH, et al. Albuminuria and peripheral arterial disease: results from the multi-ethnic study of atherosclerosis (MESA). Atherosclerosis 2008; 201:212.
- O'Hare AM, Bertenthal D, Sidawy AN, et al. Renal insufficiency and use of revascularization among a national cohort of men with advanced lower extremity peripheral arterial disease. Clin J Am Soc Nephrol 2006; 1:297.
- DeLoach SS, Mohler ER 3rd. Peripheral arterial disease: a guide for nephrologists. Clin J Am Soc Nephrol 2007; 2:839.
- Wu CK, Yang CY, Tsai CT, et al. Association of low glomerular filtration rate and albuminuria with peripheral arterial disease: the National Health and Nutrition Examination Survey, 1999-2004. Atherosclerosis 2010; 209:230.
- Mostaza JM, Suarez C, Manzano L, et al. Relationship between ankle-brachial index and chronic kidney disease in hypertensive patients with no known cardiovascular disease. J Am Soc Nephrol 2006; 17:S201.
- Baber U, Mann D, Shimbo D, et al. Combined role of reduced estimated glomerular filtration rate and microalbuminuria on the prevalence of peripheral arterial disease. Am J Cardiol 2009; 104:1446.
- Liew YP, Bartholomew JR, Demirjian S, et al. Combined effect of chronic kidney disease and peripheral arterial disease on all-cause mortality in a high-risk population. Clin J Am Soc Nephrol 2008; 3:1084.
- Belch JJ, Topol EJ, Agnelli G, et al. Critical issues in peripheral arterial disease detection and management: a call to action. Arch Intern Med 2003; 163:884.
- Collins TC, Petersen NJ, Suarez-Almazor M, Ashton CM. The prevalence of peripheral arterial disease in a racially diverse population. Arch Intern Med 2003; 163:1469.
- Diehm C, Schuster A, Allenberg JR, et al. High prevalence of peripheral arterial disease and co-morbidity in 6880 primary care patients: cross-sectional study. Atherosclerosis 2004; 172:95.
- Newman AB, Naydeck BL, Sutton-Tyrrell K, et al. The role of comorbidity in the assessment of intermittent claudication in older adults. J Clin Epidemiol 2001; 54:294.
- Kannel WB, Skinner JJ Jr, Schwartz MJ, Shurtleff D. Intermittent claudication. Incidence in the Framingham Study. Circulation 1970; 41:875.
- Kannel WB, McGee DL. Update on some epidemiologic features of intermittent claudication: the Framingham Study. J Am Geriatr Soc 1985; 33:13.
- O'Hare AM, Bertenthal D, Shlipak MG, et al. Impact of renal insufficiency on mortality in advanced lower extremity peripheral arterial disease. J Am Soc Nephrol 2005; 16:514.
- O'Hare AM, Sidawy AN, Feinglass J, et al. Influence of renal insufficiency on limb loss and mortality after initial lower extremity surgical revascularization. J Vasc Surg 2004; 39:709.
- O'Hare AM, Feinglass J, Reiber GE, et al. Postoperative mortality after nontraumatic lower extremity amputation in patients with renal insufficiency. J Am Soc Nephrol 2004; 15:427.
- Weitz JI, Byrne J, Clagett GP, et al. Diagnosis and treatment of chronic arterial insufficiency of the lower extremities: a critical review. Circulation 1996; 94:3026.
- Koelemay MJ, Lijmer JG, Stoker J, et al. Magnetic resonance angiography for the evaluation of lower extremity arterial disease: a meta-analysis. JAMA 2001; 285:1338.
- Smith SC Jr, Benjamin EJ, Bonow RO, et al. AHA/ACCF Secondary Prevention and Risk Reduction Therapy for Patients with Coronary and other Atherosclerotic Vascular Disease: 2011 update: a guideline from the American Heart Association and American College of Cardiology Foundation. Circulation 2011; 124:2458.
- Baigent C, Landray MJ, Reith C, et al. The effects of lowering LDL cholesterol with simvastatin plus ezetimibe in patients with chronic kidney disease (Study of Heart and Renal Protection): a randomised placebo-controlled trial. Lancet 2011; 377:2181.
- Feringa HH, Karagiannis SE, Chonchol M, et al. Lower progression rate of end-stage renal disease in patients with peripheral arterial disease using statins or Angiotensin-converting enzyme inhibitors. J Am Soc Nephrol 2007; 18:1872.
- Alonso-Coello P, Bellmunt S, McGorrian C, et al. Antithrombotic therapy in peripheral artery disease: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012; 141:e669S.
- Rooke TW, Hirsch AT, Misra S, et al. 2011 ACCF/AHA focused update of the guideline for the management of patients with peripheral artery disease (updating the 2005 guideline): a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines: developed in collaboration with the Society for Cardiovascular Angiography and Interventions, Society of Interventional Radiology, Society for Vascular Medicine, and Society for Vascular Surgery. Catheter Cardiovasc Interv 2012; 79:501.
- Clagett GP, Sobel M, Jackson MR, et al. Antithrombotic therapy in peripheral arterial occlusive disease: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest 2004; 126:609S.
- CAPRIE Steering Committee. A randomised, blinded, trial of clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE). CAPRIE Steering Committee. Lancet 1996; 348:1329.
- Beebe HG, Dawson DL, Cutler BS, et al. A new pharmacological treatment for intermittent claudication: results of a randomized, multicenter trial. Arch Intern Med 1999; 159:2041.
- Money SR, Herd JA, Isaacsohn JL, et al. Effect of cilostazol on walking distances in patients with intermittent claudication caused by peripheral vascular disease. J Vasc Surg 1998; 27:267.
- Dawson DL, Cutler BS, Meissner MH, Strandness DE Jr. Cilostazol has beneficial effects in treatment of intermittent claudication: results from a multicenter, randomized, prospective, double-blind trial. Circulation 1998; 98:678.
- Owens CD, Ho KJ, Kim S, et al. Refinement of survival prediction in patients undergoing lower extremity bypass surgery: stratification by chronic kidney disease classification. J Vasc Surg 2007; 45:944.
- Lüders F, Bunzemeier H, Engelbertz C, et al. CKD and Acute and Long-Term Outcome of Patients with Peripheral Artery Disease and Critical Limb Ischemia. Clin J Am Soc Nephrol 2016; 11:216.
- Harrington EB, Harrington ME, Schanzer H, Haimov M. End-stage renal disease--is infrainguinal limb revascularization justified? J Vasc Surg 1990; 12:691.
- Johnson BL, Glickman MH, Bandyk DF, Esses GE. Failure of foot salvage in patients with end-stage renal disease after surgical revascularization. J Vasc Surg 1995; 22:280.
- Korn P, Hoenig SJ, Skillman JJ, Kent KC. Is lower extremity revascularization worthwhile in patients with end-stage renal disease? Surgery 2000; 128:472.
- Lantis JC 2nd, Conte MS, Belkin M, et al. Infrainguinal bypass grafting in patients with end-stage renal disease: improving outcomes? J Vasc Surg 2001; 33:1171.
- Lumsden AB, Besman A, Jaffe M, et al. Infrainguinal revascularization in end-stage renal disease. Ann Vasc Surg 1994; 8:107.
- Wassermann RJ, Saroyan RM, Rice JC, Kerstein MD. Infrainguinal revascularization for limb salvage in patients with end-stage renal disease. South Med J 1991; 84:190.
- Whittemore AD, Donaldson MC, Mannick JA. Infrainguinal reconstruction for patients with chronic renal insufficiency. J Vasc Surg 1993; 17:32.
- O'Hare AM, Feinglass J, Sidawy AN, et al. Impact of renal insufficiency on short-term morbidity and mortality after lower extremity revascularization: data from the Department of Veterans Affairs' National Surgical Quality Improvement Program. J Am Soc Nephrol 2003; 14:1287.