commentary
of such an approach, and larger multicenter clinical trials are needed. Still, Bestard and colleagues should be credited for pointing us in the right direction with this timely publication. Finally, the authors showed that most of the repopulating T cells are of the effector memory phenotype rather than the central memory phenotype. The timing of such reappearance may correlate with waning effects of potent induction therapy, leading to the reaccumulation of memory cells in circulation, which may eventually injure the allograft via direct and indirect antigen presentation pathways. Also, interestingly, there was an increase in markers of regulatory T cells in those with donor hyporesponsiveness, perhaps suggesting that the detection of these cells could also be used as a marker to guide therapy. In summary, this interventional study is novel in several ways. First, it alters the paradigm for selection of immunosuppressive therapy, basing it not only on perceived risk and the absence or presence of alloantibodies, but also on the detection of donor-reactive T cells. This is logical as most immunosuppression is specific to T cell inhibition (rabbit anti-thymoglobulin, interleukin-2 receptor blockers, CNIs, mTOR inhibitors, and so on). Second, a negative ELISPOT assay suggesting the absence of circulating donor-reactive T cells at 6 months after transplantation has a high negative predictive value for graft injury. Third, we learn that despite relative control of preformed donor-reactive T cells with potent immunosuppression, the reappearance or de novo generation of effector memory T cells after transplantation is a risk factor for allograft injury. This suggests that any future approach should include serial monitoring of cellular alloreactivity with adjustment of immunosuppression accordingly. Although the findings of the present study are interesting and encouraging, shortcomings related to study design preclude immediate clinical implementation of the investigators’ approach. The ELISPOT assay could potentially be used as a risk-stratification tool before or at the time of transplantation in order to decide the type of induction therapy, and at various times after transplantation so as to further individualize immunosuppression. 1076
Therefore, multicenter clinical trials are needed that use assays to assess donor T cell activity (by measuring donor-specific T cell alloreactivity, chemokines, microarray analysis, and so on), followed by randomization to specific immunosuppressive interventions tailored to the individual cellular response. As the fellow Catalan Salvador Dalı´ made clear in his famous painting, the transplant community needs to gain further insight into the impact of ‘the persistence of memory’ before time melts away.
3.
4.
5.
6.
DISCLOSURE
The authors declared no competing interests.
7.
REFERENCES 1.
2.
Heeger PS. T-cell allorecognition and transplant rejection: a summary and update. Am J Transplant 2003; 3: 525–533. Jameson SC, Masopust D. Diversity in T cell memory: an embarrassment of riches. Immunity 2009; 31: 859–871.
8.
Augustine JJ, Siu DS, Clemente MJ et al. Pretransplant IFN-gamma ELISPOTs are associated with post-transplant renal function in African American renal transplant recipients. Am J Transplant 2005; 5: 1971–1975. Poggio ED, Clemente M, Hricik DE, Heeger PS. Panel of reactive T cells as a measurement of primed cellular alloimmunity in kidney transplant candidates. J Am Soc Nephrol 2006; 17: 564–572. Bestard O, Cruzado JM, Lucia M et al. Prospective assessment of antidonor cellular alloreactivity is a tool for guidance of immunosuppression in kidney transplantation. Kidney Int 2013; 84: 1226–1236. Cherkassky L, Lanning M, Lalli PN et al. Evaluation of alloreactivity in kidney transplant recipients treated with antithymocyte globulin versus IL-2 receptor blocker. Am J Transplant 2011; 11: 1388–1396. Augustine JJ, Poggio ED, Heeger PS, Hricik DE. Preferential benefit of antibody induction therapy in kidney recipients with high pretransplant frequencies of donor-reactive interferon-gamma enzyme-linked immunosorbent spots. Transplantation 2008; 86: 529–534. Cravedi P, Heeger PS. Immunologic monitoring in transplantation revisited. Curr Opin Organ Transplant 2012; 17: 26–32.
see clinical investigation on page 1237
Predicting dialysis vascular access blood flow and diameter: too much, too little, or just right Prabir Roy-Chaudhury1,2, Timmy C. Lee1,2 and Rino Munda3 Arteriovenous fistula (AVF) maturation continues to cause significant morbidity and mortality. Despite the magnitude of the clinical problem, however, there are no effective clinical or biological predictors of AVF success or failure. Caroli et al. describe an innovative technology that may be successful in predicting AVF flow and diameter using standardof-care preoperative inputs. Pending additional longer-term validation, the use of this technology could help us get the right access into the right patient at the right time. Kidney International (2013) 84, 1076–1078. doi:10.1038/ki.2013.307
1 Dialysis Vascular Access Research Group, Division of Nephrology, University of Cincinnati, Cincinnati, Ohio, USA; 2Cincinnati Veterans Affairs Medical Center, Cincinnati, Ohio, USA and 3 Division of Transplant Surgery, University of Cincinnati, Cincinnati, Ohio, USA Correspondence: Prabir Roy-Chaudhury, Division of Nephrology, University of Cincinnati, MSB G-251, 231 Albert Sabin Way, Cincinnati, Ohio 45267-0585, USA. E-mail: [email protected]
Dialysis vascular access continues to have the dubious distinction of being both the lifeline and the Achilles’ heel of hemodialysis. This dichotomy is emphasized by the fact that even though arteriovenous fistulae (AVFs) are the preferred mode of dialysis vascular access, their primary patency at 1 year is only 50%1 (possibly even Kidney International (2013) 84
commentary
less if assessed in terms of suitability for dialysis2). Paradoxically, as many as 20% of created AVFs suffer from the obverse, in that the problem is too much flow resulting in vascular steal or contributing to hyperdynamic heart failure. Perhaps even more concerning is the fact that there are very few tested clinical and biological predictors that could help us to identify the best site (radiocephalic versus brachiocephalic versus brachiobasilic) for surgical placement of an AVF (the ongoing National Institutes of Health-funded Hemodialysis Fistula Maturation Consortium may provide more information on this when complete); or alternatively guide us in deciding on the best sort of access (AVF versus arteriovenous graft versus tunneled dialysis catheter) for a particular patient. In this context, the paper by Caroli et al.3 (this issue), which attempts to validate a patient-specific hemodynamic computational model for the surgical placement of AVFs, is a welcome breath of fresh air. Specifically, Caroli et al.3 describe the use of a previously developed computational network model of the forearm arteries and vein (with many analogies to an electrical circuit),4,5 wherein they use a pulse propagation model for the prediction of vascular blood flow and diameter on postoperative days 1 and 40. Input data for this study included preoperative arterial and venous diameters, pulse rate, hemoglobin and plasma protein concentrations, the presence or absence of diabetes and hypertension, and last but not least the preoperative blood flow volume in the brachial and radial arteries prior to surgery. These input data were then fed into a computational model, which provided a predicted estimate of future postoperative blood flow volume and venous and arterial diameters of the AVF. Interestingly, the correlations between predicted and actual blood flow and diameter at different sites were excellent, hence the importance of this study to the field of dialysis vascular access, especially in the context of the clinical decision making around which type of AVF to create. Kidney International (2013) 84
At a more practical level, this particular study has far greater clinical relevance than previous work by the same group,6 in that this appears to be the first time that successful predictions have been made without the need for preoperative magnetic resonance imaging or angiography. The ability to predict blood flow and diameter accurately, using preoperative tests that are, in essence, standard of care (duplex Doppler ultrasound), could allow surgeons to use this technique to identify the best site for placement of an AVF—one that will result in just the right amount of flow, not too much and not too little. This technology could also potentially help to guide surgeons in creating an arteriovenous graft in situations in which the 40-day predicted flow is less than 400 ml at all potential AVF sites; or alternatively drive surgeons toward the use of a more distal site for AVF creation in the event of a very high predicted flow rate (greater than 1.5–2 liters per minute), for an upper-arm AVF. As is always the case with novel and innovative research, however, the current study by Caroli et al.3 brings to the forefront a host of unanswered questions that will probably require further investigation. In particular, as the authors themselves note, we do not have complete information about whether the predicted AVF flow and diameter correlated with important clinical end points such as successful real-time cannulation, the time to successful cannulation, or the occurrence of vascular steal. There are also no data on the correlation of long-term patency and complications with predicted flow and diameter. This is important, because although the described pulse propagation model is clinically friendly in terms of time and resources, it is possible that more complex threedimensional modeling programs would be able to better identify regions of non-laminar flow and flow separation, which in the longer term could predispose to vascular stenosis. Finally, it is important to point out that the clinical decision about the site of AVF placement, or even the decision
about whether to place an AVF versus an arteriovenous graft, needs to be a holistic decision that looks at the patient as a whole, not one that is dependent only on a prediction of flow or diameter. Thus, for patients with small veins in whom distal AVF maturation may take a prolonged period of time, and who already have an incident tunneled dialysis catheter (TDC), it may be more appropriate to create a proximal AVF or even place an arteriovenous graft in order to be able to remove the TDC as quickly as possible. Such a plan may be indicated in certain patient subgroups, even if the predicted blood flow and diameter with a distal AVF are at the lower end of the range thought to be adequate to support dialysis. Finally, even though it is not the focus of the study by Caroli et al.,3 one cannot ignore processof-care issues such as appropriate cannulation expertise, the lack of which can ruin the most carefully crafted AVFs, as also the reputation of the most elegant predictive models. At a more biological level, it is somewhat surprising that the prediction of blood flow and diameter was so accurate even without incorporating vascular function tests such as flowmediated dilatation and venous plethysmography7 into the predictive equations. In addition, a vein wall thickness of 10% of overall diameter was used as a default input into the model, although work performed by us and others has clearly documented that there is a wide variation in the thickness of venous segment samples obtained from the actual site of surgery.8 There is also no mention of whether the presence of calcification needs to be included in this model. Despite these theoretical arguments, however, the data presented suggest that biological parameters may have to take a back seat with regard to being important predictors of AVF flow and diameter. Although this could be good for the field of dialysis vascular access and for our patients (biological tests are time consuming and expensive), the one caveat that remains is that biological systems tend to hit back over the long 1077
commentary
Technology
Biology
Clinical need and setting
Innovation sandbox
perately need to develop approaches that combine biology, technology, and the clinical setting (within the innovation sandbox; Figure 1) as was done by Caroli et al.,3 in order to develop innovative techniques and technologies to reduce the clinical and economic burden of dialysis vascular access dysfunction. DISCLOSURE
Innovative therapies for dialysis vascular access dysfunction
Figure 1 | Combining biology, technology, and the clinical setting to develop innovative therapies for dialysis vascular access.
term. This makes it even more important to follow this cohort (and others like it) over a longer duration, and also to keep an open mind about the possible future inclusion of vascular function testing into the described predictive computational network analysis. Finally, we believe that two aspects of this work need special emphasis. INDIVIDUALIZATION OF VASCULAR ACCESS PARADIGMS
Over and above its ability to help support surgical decision making, this work is particularly significant because it represents the first small steps toward the individualization of vascular access. Looking to the future, it is possible that more refined predictive algorithms would allow us to move away from the one-size-fits-all paradigm that we currently operate under, toward a more patient-centered approach by which we could get the right access into the right patient at the right time. MAKING AN IMPACT WITH A MULTIDISCIPLINARY AND TRANSLATIONAL RESEARCH PROGRAM
Dialysis vascular access dysfunction is a multidisciplinary problem that can be solved only through a multidisciplinary approach. Yet all too often as health
1078
professionals involved in the care of vascular access in hemodialysis patients we operate in predetermined silos ordained by our specialty—which could well be why vascular access in many cases enjoys an orphan status at best. In this context, the research team involved in the current study3 is a fine example of a multidisciplinary team that includes surgeons, nephrologists, vascular biologists, and engineers involved in high-quality translational research that could reduce dialysis vascular access dysfunction. We desperately need more such collaborative groups in order to make an impact on dialysis vascular access dysfunction. In summary, the paper by Caroli et al.3 is an outstanding example of an integrated, multidisciplinary, translational research team taking that all-important first step toward the development of preoperative predictors of AVF success or failure. The described technologies could also allow us to move toward individualization of vascular access care, which would likely reduce the huge clinical (morbidity and mortality) and economic costs associated with dialysis vascular access dysfunction. Most importantly, this work emphasizes the fact that we des-
Prabir Roy-Chaudhury is a consultant/advisory board member for W.L. Gore, Medtronic, Bioconnect, Vascular Therapeutics, Abbott Vascular, and Bard Peripheral Vascular. ACKNOWLEDGMENTS
Dr. Roy-Chaudhury is supported by National Institutes of Health (NIH) grants 5U01DK82218, 1R21-DK089280-01, 1R01DK088777 (MPI), and 1R21-EB016150; a Veterans Affairs Merit Review; a University of Cincinnati NIH/National Center for Research Resources UL1-RR026314 Clinical and Translational Science Award grant; and industry grants from W.L. Gore, Shire, and Bard Peripheral Vascular. REFERENCES 1. 2.
3.
4.
5.
6.
7.
8.
Dember LM. Fistulas first—but can they last? Clin J Am Soc Nephrol 2011; 6: 463–464. Dember LM, Beck GJ, Allon M et al. Effect of clopidogrel on early failure of arteriovenous fistulas for hemodialysis: a randomized controlled trial. JAMA 2008; 299: 2164–2171. Caroli A, Manini S, Antiga L et al. Validation of a patient-specific hemodynamic computational model for surgical planning of vascular access in hemodialysis patients. Kidney Int 2013; 84: 1237–1245. Bode A, Caroli A, Huberts W et al. Clinical study protocol for the ARCH project—computational modeling for improvement of outcome after vascular access creation. J Vasc Access 2011; 12: 369–376. Huberts W, Bode AS, Kroon W et al. A pulse wave propagation model to support decisionmaking in vascular access planning in the clinic. Med Eng Phys 2012; 34: 233–248. Bode AS, Huberts W, Bosboom EM et al. Patient-specific computational modeling of upper extremity arteriovenous fistula creation: its feasibility to support clinical decisionmaking. PLoS One (online) 2012; 7: e34491. van der Linden J, Lameris TW, van den Meiracker AH et al. Forearm venous distensibility predicts successful arteriovenous fistula. Am J Kidney Dis 2006; 47: 1013–1019. Lee T, Chauhan V, Krishnamoorthy M et al. Severe venous neointimal hyperplasia prior to dialysis access surgery. Nephrol Dial Transplant 2011; 26: 2264–2270.
Kidney International (2013) 84
of such an approach, and larger multicenter clinical trials are needed. Still, Bestard and colleagues should be credited for pointing us in the right direction with this timely publication. Finally, the authors showed that most of the repopulating T cells are of the effector memory phenotype rather than the central memory phenotype. The timing of such reappearance may correlate with waning effects of potent induction therapy, leading to the reaccumulation of memory cells in circulation, which may eventually injure the allograft via direct and indirect antigen presentation pathways. Also, interestingly, there was an increase in markers of regulatory T cells in those with donor hyporesponsiveness, perhaps suggesting that the detection of these cells could also be used as a marker to guide therapy. In summary, this interventional study is novel in several ways. First, it alters the paradigm for selection of immunosuppressive therapy, basing it not only on perceived risk and the absence or presence of alloantibodies, but also on the detection of donor-reactive T cells. This is logical as most immunosuppression is specific to T cell inhibition (rabbit anti-thymoglobulin, interleukin-2 receptor blockers, CNIs, mTOR inhibitors, and so on). Second, a negative ELISPOT assay suggesting the absence of circulating donor-reactive T cells at 6 months after transplantation has a high negative predictive value for graft injury. Third, we learn that despite relative control of preformed donor-reactive T cells with potent immunosuppression, the reappearance or de novo generation of effector memory T cells after transplantation is a risk factor for allograft injury. This suggests that any future approach should include serial monitoring of cellular alloreactivity with adjustment of immunosuppression accordingly. Although the findings of the present study are interesting and encouraging, shortcomings related to study design preclude immediate clinical implementation of the investigators’ approach. The ELISPOT assay could potentially be used as a risk-stratification tool before or at the time of transplantation in order to decide the type of induction therapy, and at various times after transplantation so as to further individualize immunosuppression. 1076
Therefore, multicenter clinical trials are needed that use assays to assess donor T cell activity (by measuring donor-specific T cell alloreactivity, chemokines, microarray analysis, and so on), followed by randomization to specific immunosuppressive interventions tailored to the individual cellular response. As the fellow Catalan Salvador Dalı´ made clear in his famous painting, the transplant community needs to gain further insight into the impact of ‘the persistence of memory’ before time melts away.
3.
4.
5.
6.
DISCLOSURE
The authors declared no competing interests.
7.
REFERENCES 1.
2.
Heeger PS. T-cell allorecognition and transplant rejection: a summary and update. Am J Transplant 2003; 3: 525–533. Jameson SC, Masopust D. Diversity in T cell memory: an embarrassment of riches. Immunity 2009; 31: 859–871.
8.
Augustine JJ, Siu DS, Clemente MJ et al. Pretransplant IFN-gamma ELISPOTs are associated with post-transplant renal function in African American renal transplant recipients. Am J Transplant 2005; 5: 1971–1975. Poggio ED, Clemente M, Hricik DE, Heeger PS. Panel of reactive T cells as a measurement of primed cellular alloimmunity in kidney transplant candidates. J Am Soc Nephrol 2006; 17: 564–572. Bestard O, Cruzado JM, Lucia M et al. Prospective assessment of antidonor cellular alloreactivity is a tool for guidance of immunosuppression in kidney transplantation. Kidney Int 2013; 84: 1226–1236. Cherkassky L, Lanning M, Lalli PN et al. Evaluation of alloreactivity in kidney transplant recipients treated with antithymocyte globulin versus IL-2 receptor blocker. Am J Transplant 2011; 11: 1388–1396. Augustine JJ, Poggio ED, Heeger PS, Hricik DE. Preferential benefit of antibody induction therapy in kidney recipients with high pretransplant frequencies of donor-reactive interferon-gamma enzyme-linked immunosorbent spots. Transplantation 2008; 86: 529–534. Cravedi P, Heeger PS. Immunologic monitoring in transplantation revisited. Curr Opin Organ Transplant 2012; 17: 26–32.
see clinical investigation on page 1237
Predicting dialysis vascular access blood flow and diameter: too much, too little, or just right Prabir Roy-Chaudhury1,2, Timmy C. Lee1,2 and Rino Munda3 Arteriovenous fistula (AVF) maturation continues to cause significant morbidity and mortality. Despite the magnitude of the clinical problem, however, there are no effective clinical or biological predictors of AVF success or failure. Caroli et al. describe an innovative technology that may be successful in predicting AVF flow and diameter using standardof-care preoperative inputs. Pending additional longer-term validation, the use of this technology could help us get the right access into the right patient at the right time. Kidney International (2013) 84, 1076–1078. doi:10.1038/ki.2013.307
1 Dialysis Vascular Access Research Group, Division of Nephrology, University of Cincinnati, Cincinnati, Ohio, USA; 2Cincinnati Veterans Affairs Medical Center, Cincinnati, Ohio, USA and 3 Division of Transplant Surgery, University of Cincinnati, Cincinnati, Ohio, USA Correspondence: Prabir Roy-Chaudhury, Division of Nephrology, University of Cincinnati, MSB G-251, 231 Albert Sabin Way, Cincinnati, Ohio 45267-0585, USA. E-mail: [email protected]
Dialysis vascular access continues to have the dubious distinction of being both the lifeline and the Achilles’ heel of hemodialysis. This dichotomy is emphasized by the fact that even though arteriovenous fistulae (AVFs) are the preferred mode of dialysis vascular access, their primary patency at 1 year is only 50%1 (possibly even Kidney International (2013) 84
commentary
less if assessed in terms of suitability for dialysis2). Paradoxically, as many as 20% of created AVFs suffer from the obverse, in that the problem is too much flow resulting in vascular steal or contributing to hyperdynamic heart failure. Perhaps even more concerning is the fact that there are very few tested clinical and biological predictors that could help us to identify the best site (radiocephalic versus brachiocephalic versus brachiobasilic) for surgical placement of an AVF (the ongoing National Institutes of Health-funded Hemodialysis Fistula Maturation Consortium may provide more information on this when complete); or alternatively guide us in deciding on the best sort of access (AVF versus arteriovenous graft versus tunneled dialysis catheter) for a particular patient. In this context, the paper by Caroli et al.3 (this issue), which attempts to validate a patient-specific hemodynamic computational model for the surgical placement of AVFs, is a welcome breath of fresh air. Specifically, Caroli et al.3 describe the use of a previously developed computational network model of the forearm arteries and vein (with many analogies to an electrical circuit),4,5 wherein they use a pulse propagation model for the prediction of vascular blood flow and diameter on postoperative days 1 and 40. Input data for this study included preoperative arterial and venous diameters, pulse rate, hemoglobin and plasma protein concentrations, the presence or absence of diabetes and hypertension, and last but not least the preoperative blood flow volume in the brachial and radial arteries prior to surgery. These input data were then fed into a computational model, which provided a predicted estimate of future postoperative blood flow volume and venous and arterial diameters of the AVF. Interestingly, the correlations between predicted and actual blood flow and diameter at different sites were excellent, hence the importance of this study to the field of dialysis vascular access, especially in the context of the clinical decision making around which type of AVF to create. Kidney International (2013) 84
At a more practical level, this particular study has far greater clinical relevance than previous work by the same group,6 in that this appears to be the first time that successful predictions have been made without the need for preoperative magnetic resonance imaging or angiography. The ability to predict blood flow and diameter accurately, using preoperative tests that are, in essence, standard of care (duplex Doppler ultrasound), could allow surgeons to use this technique to identify the best site for placement of an AVF—one that will result in just the right amount of flow, not too much and not too little. This technology could also potentially help to guide surgeons in creating an arteriovenous graft in situations in which the 40-day predicted flow is less than 400 ml at all potential AVF sites; or alternatively drive surgeons toward the use of a more distal site for AVF creation in the event of a very high predicted flow rate (greater than 1.5–2 liters per minute), for an upper-arm AVF. As is always the case with novel and innovative research, however, the current study by Caroli et al.3 brings to the forefront a host of unanswered questions that will probably require further investigation. In particular, as the authors themselves note, we do not have complete information about whether the predicted AVF flow and diameter correlated with important clinical end points such as successful real-time cannulation, the time to successful cannulation, or the occurrence of vascular steal. There are also no data on the correlation of long-term patency and complications with predicted flow and diameter. This is important, because although the described pulse propagation model is clinically friendly in terms of time and resources, it is possible that more complex threedimensional modeling programs would be able to better identify regions of non-laminar flow and flow separation, which in the longer term could predispose to vascular stenosis. Finally, it is important to point out that the clinical decision about the site of AVF placement, or even the decision
about whether to place an AVF versus an arteriovenous graft, needs to be a holistic decision that looks at the patient as a whole, not one that is dependent only on a prediction of flow or diameter. Thus, for patients with small veins in whom distal AVF maturation may take a prolonged period of time, and who already have an incident tunneled dialysis catheter (TDC), it may be more appropriate to create a proximal AVF or even place an arteriovenous graft in order to be able to remove the TDC as quickly as possible. Such a plan may be indicated in certain patient subgroups, even if the predicted blood flow and diameter with a distal AVF are at the lower end of the range thought to be adequate to support dialysis. Finally, even though it is not the focus of the study by Caroli et al.,3 one cannot ignore processof-care issues such as appropriate cannulation expertise, the lack of which can ruin the most carefully crafted AVFs, as also the reputation of the most elegant predictive models. At a more biological level, it is somewhat surprising that the prediction of blood flow and diameter was so accurate even without incorporating vascular function tests such as flowmediated dilatation and venous plethysmography7 into the predictive equations. In addition, a vein wall thickness of 10% of overall diameter was used as a default input into the model, although work performed by us and others has clearly documented that there is a wide variation in the thickness of venous segment samples obtained from the actual site of surgery.8 There is also no mention of whether the presence of calcification needs to be included in this model. Despite these theoretical arguments, however, the data presented suggest that biological parameters may have to take a back seat with regard to being important predictors of AVF flow and diameter. Although this could be good for the field of dialysis vascular access and for our patients (biological tests are time consuming and expensive), the one caveat that remains is that biological systems tend to hit back over the long 1077
commentary
Technology
Biology
Clinical need and setting
Innovation sandbox
perately need to develop approaches that combine biology, technology, and the clinical setting (within the innovation sandbox; Figure 1) as was done by Caroli et al.,3 in order to develop innovative techniques and technologies to reduce the clinical and economic burden of dialysis vascular access dysfunction. DISCLOSURE
Innovative therapies for dialysis vascular access dysfunction
Figure 1 | Combining biology, technology, and the clinical setting to develop innovative therapies for dialysis vascular access.
term. This makes it even more important to follow this cohort (and others like it) over a longer duration, and also to keep an open mind about the possible future inclusion of vascular function testing into the described predictive computational network analysis. Finally, we believe that two aspects of this work need special emphasis. INDIVIDUALIZATION OF VASCULAR ACCESS PARADIGMS
Over and above its ability to help support surgical decision making, this work is particularly significant because it represents the first small steps toward the individualization of vascular access. Looking to the future, it is possible that more refined predictive algorithms would allow us to move away from the one-size-fits-all paradigm that we currently operate under, toward a more patient-centered approach by which we could get the right access into the right patient at the right time. MAKING AN IMPACT WITH A MULTIDISCIPLINARY AND TRANSLATIONAL RESEARCH PROGRAM
Dialysis vascular access dysfunction is a multidisciplinary problem that can be solved only through a multidisciplinary approach. Yet all too often as health
1078
professionals involved in the care of vascular access in hemodialysis patients we operate in predetermined silos ordained by our specialty—which could well be why vascular access in many cases enjoys an orphan status at best. In this context, the research team involved in the current study3 is a fine example of a multidisciplinary team that includes surgeons, nephrologists, vascular biologists, and engineers involved in high-quality translational research that could reduce dialysis vascular access dysfunction. We desperately need more such collaborative groups in order to make an impact on dialysis vascular access dysfunction. In summary, the paper by Caroli et al.3 is an outstanding example of an integrated, multidisciplinary, translational research team taking that all-important first step toward the development of preoperative predictors of AVF success or failure. The described technologies could also allow us to move toward individualization of vascular access care, which would likely reduce the huge clinical (morbidity and mortality) and economic costs associated with dialysis vascular access dysfunction. Most importantly, this work emphasizes the fact that we des-
Prabir Roy-Chaudhury is a consultant/advisory board member for W.L. Gore, Medtronic, Bioconnect, Vascular Therapeutics, Abbott Vascular, and Bard Peripheral Vascular. ACKNOWLEDGMENTS
Dr. Roy-Chaudhury is supported by National Institutes of Health (NIH) grants 5U01DK82218, 1R21-DK089280-01, 1R01DK088777 (MPI), and 1R21-EB016150; a Veterans Affairs Merit Review; a University of Cincinnati NIH/National Center for Research Resources UL1-RR026314 Clinical and Translational Science Award grant; and industry grants from W.L. Gore, Shire, and Bard Peripheral Vascular. REFERENCES 1. 2.
3.
4.
5.
6.
7.
8.
Dember LM. Fistulas first—but can they last? Clin J Am Soc Nephrol 2011; 6: 463–464. Dember LM, Beck GJ, Allon M et al. Effect of clopidogrel on early failure of arteriovenous fistulas for hemodialysis: a randomized controlled trial. JAMA 2008; 299: 2164–2171. Caroli A, Manini S, Antiga L et al. Validation of a patient-specific hemodynamic computational model for surgical planning of vascular access in hemodialysis patients. Kidney Int 2013; 84: 1237–1245. Bode A, Caroli A, Huberts W et al. Clinical study protocol for the ARCH project—computational modeling for improvement of outcome after vascular access creation. J Vasc Access 2011; 12: 369–376. Huberts W, Bode AS, Kroon W et al. A pulse wave propagation model to support decisionmaking in vascular access planning in the clinic. Med Eng Phys 2012; 34: 233–248. Bode AS, Huberts W, Bosboom EM et al. Patient-specific computational modeling of upper extremity arteriovenous fistula creation: its feasibility to support clinical decisionmaking. PLoS One (online) 2012; 7: e34491. van der Linden J, Lameris TW, van den Meiracker AH et al. Forearm venous distensibility predicts successful arteriovenous fistula. Am J Kidney Dis 2006; 47: 1013–1019. Lee T, Chauhan V, Krishnamoorthy M et al. Severe venous neointimal hyperplasia prior to dialysis access surgery. Nephrol Dial Transplant 2011; 26: 2264–2270.
Kidney International (2013) 84
