Editorial Arteriovenous Fistula Patency: Some Answers but Questions Remain Related Article, p. 464
I
t has been nearly 50 years since Brescia, Cimino, Appel, and Hurwich1 first described the technique of using a patient’s own radial artery and cephalic vein to construct an arteriovenous fistula (AVF), thereby enabling frequent venipuncture for longterm hemodialysis. In the original description, the AVF was constructed by performing a side-to-side anastomosis of the cephalic vein to the radial artery in the forearm, with dialysis performed the day after the surgical procedure, facilitated by the use of a tourniquet. The initial report detailed 13 patients who received dialysis for a total of 100 months with no reported episodes of AVF thrombosis. In the years following the initial description, others reported the successful use of AVFs for hemodialysis.2,3 However, there remained a subset of patients for whom it was difficult to establish a functioning AVF. This led to modifications to the technique, such as performing an end-to-side anastomosis and using other vessels, such as the cephalic vein to brachial artery (the brachiocephalic AVF)4 or the basilic vein to brachial artery (the brachiobasilic AVF).5 As clinical experience grew, it became clear that there was a significant number of patients with vessels deemed inadequate for constructing an AVF. This problem provided the impetus for using an expanded polytetrafluoroethylene arteriovenous graft (AVG) as a conduit for hemodialysis, and AVGs subsequently became the predominant form of vascular access used in the United States by the mid to late 1980s.6 It is apparent that the AVG was not the panacea it was first thought to be, having higher thrombosis and intervention rates compared to the AVF.6 Further data demonstrating lower infectious complications and improved patient survival in individuals using an AVF compared to either an AVG or central venous catheter7,8 convinced national clinical practice guideline groups to universally recommend the AVF as the vascular access of first choice for hemodialysis patients.9-11 However, the demographic and clinical characteristics of patients with end stage kidney failure requiring hemodialysis have changed. Patients are Address correspondence to Kevan R. Polkinghorne, FRACP, PhD, Department of Nephrology, Monash Medical Centre, 246 Clayton Road, Clayton, Melbourne, Victoria 3168, Australia. E-mail: [email protected] Ó 2014 by the National Kidney Foundation, Inc. 0272-6386/$36.00 http://dx.doi.org/10.1053/j.ajkd.2013.11.021 384
older, are more likely to have diabetes as the cause of their kidney failure, and have a greater burden of medical comorbid conditions. These changing characteristics have led some investigators to question the present dogma of fistula first,12 especially in its relationship to vascular patency advantages compared with AVGs. Against this background of uncertainties surrounding AVF patency in the so called “modern era” of hemodialysis, the systematic review and metaanalysis of AVF patency by Al-Jaishi et al13 appearing in this issue of AJKD is important and timely. The review examines patency rates for AVFs in 62 unique cohorts published from 2000 to 2012, covering a recruiting period from 1985 to 2008. This study provides important new data for 2 major outcomes that influence vascular access planning in predialysis patients with stage 5 chronic kidney disease: the rate (or risk) of primary AVF failure and primary (and secondary) patency rates in the 2 years after AVF creation. The review has been performed rigorously, with prespecified inclusion and exclusion criteria and, perhaps most importantly, reporting outcomes that are predefined and accepted in the literature.14,15 Primary failure of an AVF is a major clinical problem leading to lower prevalence rates of AVFs and the need for central venous catheters at the start of hemodialysis therapy. Al-Jaishi et al13 report an overall primary AVF failure rate of 23% determined from 37 studies assessing 7,393 fistulas, a rate considerably higher than the 15% seen in a previous meta-analysis assessing studies largely performed in the 1970s and 1980s.16 However, as might be expected, there was evidence of marked heterogeneity among the studies, with primary failure rates ranging from as low as 5% and up to the 60% seen in the Dialysis Access Consortium clopidogrel randomized trial.17 Failure rates were higher in forearm AVFs and among elderly individuals. Interestingly, neither diabetes mellitus nor peripheral vascular disease was associated with an increased risk of primary failure on metaregression, although the analysis is limited because it could include only studies with enough detail to assess these factors. Although it may appear counterintuitive that diabetes or peripheral vascular disease did not appear to be important for AVF patency, it is perhaps too simplistic to expect these variables to predict patency across studies in which there is marked heterogeneity, notwithstanding the known (and also unknown) complex biology surrounding AVF maturation and failure.18 Am J Kidney Dis. 2014;63(3):384-386
Editorial
Similar to primary failure, 1- and 2-year patency rates appear inferior to those reported previously19: pooled primary patency (with primary failure included) was only 60% at 1 year and 51% at 2 years. The key issue here is the inclusion of primary failure in the patency calculations, albeit this is limited because only 14 studies included primary failure in their assessment of primary patency. In the previous systematic review,19 primary failure was not specifically collected or included in the patency calculations. Overall, 40% of all fistulas failed or needed at least one intervention within the first year of creation. The secondary patency rate was 71% at 1 year and 64% at 2 years; although these are improved compared with the earlier findings, nearly one-third of patients lost their AVFs despite procedures attempting to maintain patency. Overall, these figures suggest poorer patency rates with a higher need for interventions to maintain patency than older studies had suggested. One limitation of the pooled estimates reported in the study relates to the quality of the included studies themselves. The majority of the studies were assessed to be at moderate or high risk of bias, with inadequate reporting of methodology and inconsistent outcome definitions across the studies. For example, reporting of patient follow-up (attrition bias) was particularly poor. Perhaps most concerning was that .30% of the studies failed to use standardized definitions for the AVF outcomes and 50% of studies failed to consider or report important sources of confounding, such as sex, age, diabetes mellitus, or peripheral vascular disease. Finally, the review assessed studies addressing AVF patency alone and did not make comparisons to AVGs. That, of course, is a separate question and would require a separate study. However, a metaanalysis of studies comparing AVF and AVG patency in the same study population would be interesting, especially when accounting for primary AVF failure. Where do we go now in AVF research? A clear understanding of AVF biology and epidemiology remains a significant goal. The Hemodialysis Fistula Maturation prospective cohort study,20 sponsored by the National Institute of Diabetes and Digestive and Kidney Diseases, hopefully will provide important insights into the defining predictors and underlying mechanisms of fistula maturation success and failure. However, it appears that now more than ever there is uncertainty regarding the stated superiority of the AVF over the AVG, especially in selected subpopulations such as the elderly or individuals with peripheral vascular disease.21 Although the recent update to the Australasian vascular access guidelines22 still recommends the AVF as first choice, additional comment is provided regarding the uncertainty in the comparison between AVFs and AVGs and emphasizes the need for a catheter-last instead of Am J Kidney Dis. 2014;63(3):384-386
fistula-first approach.12 Like others,23 I believe there is a clear need to perform adequately powered randomized controlled trials comparing AVFs with AVGs in subpopulations in which we believe there is clinical equipoise. Such studies should assess standardized vascular access outcomes, including not just vascular access patency, but also other outcomes such as, for example, the use of central venous catheters. Although performing such trials likely will be logistically difficult, they are possible24 and ultimately necessary in order for us to confidently assess the best approach to improve the lives and outcomes for the patients initiating hemodialysis therapy now and into the future. Kevan R. Polkinghorne, FRACP, PhD Monash University Clayton, Australia
ACKNOWLEDGEMENTS Support: None. Financial Disclosure: The author declares that he has no relevant financial interests.
REFERENCES 1. Brescia M, Cimino J, Appel K, Hurwich B. Chronic hemodialysis using venipuncture and a surgically created arteriovenous fistula. N Engl J Med. 1966;275(20):1089-1092. 2. Hanson J, Carmody M, Keogh B, O’Dwyer W. Access to circulation by permanent arteriovenous fistula in regular dialysis treatment. Br Med J. 1967;4(579):586-589. 3. Cohen S, Lidksy I, Kest L, Kastagir B, Vertes V. Experiences with arteriovenous fistulas. Trans Am Soc Artif Intern Organs. 1968;14:421-425. 4. Cascardo S, Acchiardo S, Beven E, Popowniak K, Nakamoto S. Proximal arteriovenous fistulae for haemodialysis when radial arteries are unavailable. Proc Eur Dial Transplant Assoc. 1970;7:42-46. 5. Dagher F, Gelber R, Ramos E, Sadler J. Basilic vein to brachial artery fistula: a new access for chronic hemodialysis. South Med J. 1976;69(11):1438-1440. 6. Kapoian T, Sherman RA. A brief history of vascular access for hemodialysis: an unfinished story. Semin Nephrol. 1997;17(3): 239-245. 7. Polkinghorne KR, McDonald SP, Atkins RC, Kerr PG. Vascular access and all-cause mortality: a propensity score analysis. J Am Soc Nephrol. 2004;15(2):477-486. 8. Pisoni RL, Arrington CJ, Albert JM, et al. Facility hemodialysis vascular access use and mortality in countries participating in DOPPS: an instrumental variable analysis. Am J Kidney Dis. 2009;53(3):475-491. 9. Jindal K, Chan C, Deziel C, et al. Chapter 4: vascular access. J Am Soc Nephrol. 2006;17(suppl 1):S16-S23. 10. National Kidney Foundation. KDOQI clinical practice guidelines and clinical practice recommendations for 2006 updates: hemodialysis adequacy, peritoneal dialysis adequacy and vascular access. Am J Kidney Dis. 2006;48(1)(suppl 1):S1-S322. 11. Tordoir JH, Canaud BJ, Haage P, et al. EBPG on vascular access. Nephrol Dial Transplant. 2007;22(suppl 2):ii88-ii117. 12. Lok CE. Fistula first initiative: advantages and pitfalls. Clin J Am Soc Nephrol. 2007;2(5):1043-1053. 385
Kevan R. Polkinghorne 13. Al-Jaishi AA, Oliver MJ, Thomas SM, et al. Patency rates of the arteriovenous fistula for hemodialysis: a systematic review and meta-analysis. Am J Kidney Dis. 2014;63(3):464-478. 14. Lee T, Mokrzycki M, Moist L, et al. Standardized definitions for hemodialysis vascular access. Semin Dial. 2011;24(5):515-524. 15. Sidawy A, Gray R, Besarab A, et al. Recommended standards for reports dealing with arteriovenous hemodialysis accesses. J Vasc Surg. 2002;35(3):603-610. 16. Rooijens P, Tordoir J, Stijnen T, Burgmans J, Smetde A, Yo T. Radiocephalic wrist arteriovenous fistula for hemodialysis: meta-analysis indicates a high primary failure rate. Eur J Vasc Surg. 2004;28(6):583-589. 17. Dember L, Beck G, Allon M, et al. Effect of clopidogrel on early failure of arteriovenous fistulas for hemodialysis: a randomized controlled trial. JAMA. 2008;299(18):2164-2171. 18. Roy-Chaudhury P, Spergel LM, Besarab A, Asif A, Ravani P. Biology of arteriovenous fistula failure. J Nephrol. 2007;20(2):150-163. 19. Huber T, Carter J, Carter R, Seeger J. Patency of autogenous and polytetrafluoroethylene upper extremity arteriovenous
386
hemodialysis accesses: a systematic review. J Vasc Surg. 2003;38(5):1005-1011. 20. Dember LM, Imrey PB, Beck GJ, et al. Objectives and design of the Hemodialysis Fistula Maturation Study. Am J Kidney Dis. 2013;63(1):104-112. 21. Lok CE, Sontrop JM, Tomlinson G, et al. Cumulative patency of contemporary fistulas versus grafts (2000-2010). Clin J Am Soc Nephrol. 2013;8:810-818. 22. Polkinghorne KR, Chin GK, MacGinley RJ, et al. KHACARI guideline: vascular access—central venous catheters, arteriovenous fistulae and arteriovenous grafts. Nephrology. 2013; 18(11):701-705. 23. Allon M, Lok CE. Dialysis fistula or graft: the role for randomized clinical trials. Clin J Am Soc Nephrol. 2010;5(12): 2348-2354. 24. Rooijens PPGM, Burgmans JPJ, Yo TI, et al. Autogenous radial-cephalic or prosthetic brachial-antecubital forearm loop AVF in patients with compromised vessels? A randomized, multicenter study of the patency of primary hemodialysis access. J Vasc Surg. 2005;42(3):481-486.
Am J Kidney Dis. 2014;63(3):384-386
I
t has been nearly 50 years since Brescia, Cimino, Appel, and Hurwich1 first described the technique of using a patient’s own radial artery and cephalic vein to construct an arteriovenous fistula (AVF), thereby enabling frequent venipuncture for longterm hemodialysis. In the original description, the AVF was constructed by performing a side-to-side anastomosis of the cephalic vein to the radial artery in the forearm, with dialysis performed the day after the surgical procedure, facilitated by the use of a tourniquet. The initial report detailed 13 patients who received dialysis for a total of 100 months with no reported episodes of AVF thrombosis. In the years following the initial description, others reported the successful use of AVFs for hemodialysis.2,3 However, there remained a subset of patients for whom it was difficult to establish a functioning AVF. This led to modifications to the technique, such as performing an end-to-side anastomosis and using other vessels, such as the cephalic vein to brachial artery (the brachiocephalic AVF)4 or the basilic vein to brachial artery (the brachiobasilic AVF).5 As clinical experience grew, it became clear that there was a significant number of patients with vessels deemed inadequate for constructing an AVF. This problem provided the impetus for using an expanded polytetrafluoroethylene arteriovenous graft (AVG) as a conduit for hemodialysis, and AVGs subsequently became the predominant form of vascular access used in the United States by the mid to late 1980s.6 It is apparent that the AVG was not the panacea it was first thought to be, having higher thrombosis and intervention rates compared to the AVF.6 Further data demonstrating lower infectious complications and improved patient survival in individuals using an AVF compared to either an AVG or central venous catheter7,8 convinced national clinical practice guideline groups to universally recommend the AVF as the vascular access of first choice for hemodialysis patients.9-11 However, the demographic and clinical characteristics of patients with end stage kidney failure requiring hemodialysis have changed. Patients are Address correspondence to Kevan R. Polkinghorne, FRACP, PhD, Department of Nephrology, Monash Medical Centre, 246 Clayton Road, Clayton, Melbourne, Victoria 3168, Australia. E-mail: [email protected] Ó 2014 by the National Kidney Foundation, Inc. 0272-6386/$36.00 http://dx.doi.org/10.1053/j.ajkd.2013.11.021 384
older, are more likely to have diabetes as the cause of their kidney failure, and have a greater burden of medical comorbid conditions. These changing characteristics have led some investigators to question the present dogma of fistula first,12 especially in its relationship to vascular patency advantages compared with AVGs. Against this background of uncertainties surrounding AVF patency in the so called “modern era” of hemodialysis, the systematic review and metaanalysis of AVF patency by Al-Jaishi et al13 appearing in this issue of AJKD is important and timely. The review examines patency rates for AVFs in 62 unique cohorts published from 2000 to 2012, covering a recruiting period from 1985 to 2008. This study provides important new data for 2 major outcomes that influence vascular access planning in predialysis patients with stage 5 chronic kidney disease: the rate (or risk) of primary AVF failure and primary (and secondary) patency rates in the 2 years after AVF creation. The review has been performed rigorously, with prespecified inclusion and exclusion criteria and, perhaps most importantly, reporting outcomes that are predefined and accepted in the literature.14,15 Primary failure of an AVF is a major clinical problem leading to lower prevalence rates of AVFs and the need for central venous catheters at the start of hemodialysis therapy. Al-Jaishi et al13 report an overall primary AVF failure rate of 23% determined from 37 studies assessing 7,393 fistulas, a rate considerably higher than the 15% seen in a previous meta-analysis assessing studies largely performed in the 1970s and 1980s.16 However, as might be expected, there was evidence of marked heterogeneity among the studies, with primary failure rates ranging from as low as 5% and up to the 60% seen in the Dialysis Access Consortium clopidogrel randomized trial.17 Failure rates were higher in forearm AVFs and among elderly individuals. Interestingly, neither diabetes mellitus nor peripheral vascular disease was associated with an increased risk of primary failure on metaregression, although the analysis is limited because it could include only studies with enough detail to assess these factors. Although it may appear counterintuitive that diabetes or peripheral vascular disease did not appear to be important for AVF patency, it is perhaps too simplistic to expect these variables to predict patency across studies in which there is marked heterogeneity, notwithstanding the known (and also unknown) complex biology surrounding AVF maturation and failure.18 Am J Kidney Dis. 2014;63(3):384-386
Editorial
Similar to primary failure, 1- and 2-year patency rates appear inferior to those reported previously19: pooled primary patency (with primary failure included) was only 60% at 1 year and 51% at 2 years. The key issue here is the inclusion of primary failure in the patency calculations, albeit this is limited because only 14 studies included primary failure in their assessment of primary patency. In the previous systematic review,19 primary failure was not specifically collected or included in the patency calculations. Overall, 40% of all fistulas failed or needed at least one intervention within the first year of creation. The secondary patency rate was 71% at 1 year and 64% at 2 years; although these are improved compared with the earlier findings, nearly one-third of patients lost their AVFs despite procedures attempting to maintain patency. Overall, these figures suggest poorer patency rates with a higher need for interventions to maintain patency than older studies had suggested. One limitation of the pooled estimates reported in the study relates to the quality of the included studies themselves. The majority of the studies were assessed to be at moderate or high risk of bias, with inadequate reporting of methodology and inconsistent outcome definitions across the studies. For example, reporting of patient follow-up (attrition bias) was particularly poor. Perhaps most concerning was that .30% of the studies failed to use standardized definitions for the AVF outcomes and 50% of studies failed to consider or report important sources of confounding, such as sex, age, diabetes mellitus, or peripheral vascular disease. Finally, the review assessed studies addressing AVF patency alone and did not make comparisons to AVGs. That, of course, is a separate question and would require a separate study. However, a metaanalysis of studies comparing AVF and AVG patency in the same study population would be interesting, especially when accounting for primary AVF failure. Where do we go now in AVF research? A clear understanding of AVF biology and epidemiology remains a significant goal. The Hemodialysis Fistula Maturation prospective cohort study,20 sponsored by the National Institute of Diabetes and Digestive and Kidney Diseases, hopefully will provide important insights into the defining predictors and underlying mechanisms of fistula maturation success and failure. However, it appears that now more than ever there is uncertainty regarding the stated superiority of the AVF over the AVG, especially in selected subpopulations such as the elderly or individuals with peripheral vascular disease.21 Although the recent update to the Australasian vascular access guidelines22 still recommends the AVF as first choice, additional comment is provided regarding the uncertainty in the comparison between AVFs and AVGs and emphasizes the need for a catheter-last instead of Am J Kidney Dis. 2014;63(3):384-386
fistula-first approach.12 Like others,23 I believe there is a clear need to perform adequately powered randomized controlled trials comparing AVFs with AVGs in subpopulations in which we believe there is clinical equipoise. Such studies should assess standardized vascular access outcomes, including not just vascular access patency, but also other outcomes such as, for example, the use of central venous catheters. Although performing such trials likely will be logistically difficult, they are possible24 and ultimately necessary in order for us to confidently assess the best approach to improve the lives and outcomes for the patients initiating hemodialysis therapy now and into the future. Kevan R. Polkinghorne, FRACP, PhD Monash University Clayton, Australia
ACKNOWLEDGEMENTS Support: None. Financial Disclosure: The author declares that he has no relevant financial interests.
REFERENCES 1. Brescia M, Cimino J, Appel K, Hurwich B. Chronic hemodialysis using venipuncture and a surgically created arteriovenous fistula. N Engl J Med. 1966;275(20):1089-1092. 2. Hanson J, Carmody M, Keogh B, O’Dwyer W. Access to circulation by permanent arteriovenous fistula in regular dialysis treatment. Br Med J. 1967;4(579):586-589. 3. Cohen S, Lidksy I, Kest L, Kastagir B, Vertes V. Experiences with arteriovenous fistulas. Trans Am Soc Artif Intern Organs. 1968;14:421-425. 4. Cascardo S, Acchiardo S, Beven E, Popowniak K, Nakamoto S. Proximal arteriovenous fistulae for haemodialysis when radial arteries are unavailable. Proc Eur Dial Transplant Assoc. 1970;7:42-46. 5. Dagher F, Gelber R, Ramos E, Sadler J. Basilic vein to brachial artery fistula: a new access for chronic hemodialysis. South Med J. 1976;69(11):1438-1440. 6. Kapoian T, Sherman RA. A brief history of vascular access for hemodialysis: an unfinished story. Semin Nephrol. 1997;17(3): 239-245. 7. Polkinghorne KR, McDonald SP, Atkins RC, Kerr PG. Vascular access and all-cause mortality: a propensity score analysis. J Am Soc Nephrol. 2004;15(2):477-486. 8. Pisoni RL, Arrington CJ, Albert JM, et al. Facility hemodialysis vascular access use and mortality in countries participating in DOPPS: an instrumental variable analysis. Am J Kidney Dis. 2009;53(3):475-491. 9. Jindal K, Chan C, Deziel C, et al. Chapter 4: vascular access. J Am Soc Nephrol. 2006;17(suppl 1):S16-S23. 10. National Kidney Foundation. KDOQI clinical practice guidelines and clinical practice recommendations for 2006 updates: hemodialysis adequacy, peritoneal dialysis adequacy and vascular access. Am J Kidney Dis. 2006;48(1)(suppl 1):S1-S322. 11. Tordoir JH, Canaud BJ, Haage P, et al. EBPG on vascular access. Nephrol Dial Transplant. 2007;22(suppl 2):ii88-ii117. 12. Lok CE. Fistula first initiative: advantages and pitfalls. Clin J Am Soc Nephrol. 2007;2(5):1043-1053. 385
Kevan R. Polkinghorne 13. Al-Jaishi AA, Oliver MJ, Thomas SM, et al. Patency rates of the arteriovenous fistula for hemodialysis: a systematic review and meta-analysis. Am J Kidney Dis. 2014;63(3):464-478. 14. Lee T, Mokrzycki M, Moist L, et al. Standardized definitions for hemodialysis vascular access. Semin Dial. 2011;24(5):515-524. 15. Sidawy A, Gray R, Besarab A, et al. Recommended standards for reports dealing with arteriovenous hemodialysis accesses. J Vasc Surg. 2002;35(3):603-610. 16. Rooijens P, Tordoir J, Stijnen T, Burgmans J, Smetde A, Yo T. Radiocephalic wrist arteriovenous fistula for hemodialysis: meta-analysis indicates a high primary failure rate. Eur J Vasc Surg. 2004;28(6):583-589. 17. Dember L, Beck G, Allon M, et al. Effect of clopidogrel on early failure of arteriovenous fistulas for hemodialysis: a randomized controlled trial. JAMA. 2008;299(18):2164-2171. 18. Roy-Chaudhury P, Spergel LM, Besarab A, Asif A, Ravani P. Biology of arteriovenous fistula failure. J Nephrol. 2007;20(2):150-163. 19. Huber T, Carter J, Carter R, Seeger J. Patency of autogenous and polytetrafluoroethylene upper extremity arteriovenous
386
hemodialysis accesses: a systematic review. J Vasc Surg. 2003;38(5):1005-1011. 20. Dember LM, Imrey PB, Beck GJ, et al. Objectives and design of the Hemodialysis Fistula Maturation Study. Am J Kidney Dis. 2013;63(1):104-112. 21. Lok CE, Sontrop JM, Tomlinson G, et al. Cumulative patency of contemporary fistulas versus grafts (2000-2010). Clin J Am Soc Nephrol. 2013;8:810-818. 22. Polkinghorne KR, Chin GK, MacGinley RJ, et al. KHACARI guideline: vascular access—central venous catheters, arteriovenous fistulae and arteriovenous grafts. Nephrology. 2013; 18(11):701-705. 23. Allon M, Lok CE. Dialysis fistula or graft: the role for randomized clinical trials. Clin J Am Soc Nephrol. 2010;5(12): 2348-2354. 24. Rooijens PPGM, Burgmans JPJ, Yo TI, et al. Autogenous radial-cephalic or prosthetic brachial-antecubital forearm loop AVF in patients with compromised vessels? A randomized, multicenter study of the patency of primary hemodialysis access. J Vasc Surg. 2005;42(3):481-486.
Am J Kidney Dis. 2014;63(3):384-386
