- Email: [email protected]
Liver Cell Transplantation
16. LaBerge ]M, Ferrell LD, Ring E], et a1. Histopathologic study of transjugular intrahepatic portosystemic shunts. ]VIR 1991; 2:549-556. 17. Sanyal A], Freedman AM, Purdum PP, Luketic VA, Shiffman MI, Tisnado]. et al. Transjugular intrahepatic portosystemic shunt (TIPS) vs. sclerotherapy for prevention of recurrent variceal hemorrhage: a randomized prospective trial. Gastroenterology 1994; 106:A975. 18. Cabrera], Maynar M, Granados R, Gorriz E, Reyes R, Pulids-Duque ]M, et a1. Transjugular intrahepatic portosystemic shunt versus sclerotherapy in the elective treatment of variceal hemorrhage. Gastroenerology 1996; 110:832-839. 19. Merli M, Riggo 0, Capocaccia L, Rossi P, Salerno F, DeFranchis R, et al. TIPS vs. sclerotherapy for prevention of variceal rebleeding: results of a randomized controlled trial. Gastroenterology 1996; 110:A1265. 20. Sauer P, Theilmann L, Benz C, Roeren T, Richterr G, Stremmel W, et al. Transjugular intrahepatic portosystemic stent shunt (TIPS) vs. sclerotherapy in the prevention of variceal rebleeding: a randomized study. Gastroenterology 1996; 110:A1313. 21. Cello], Ring E, Olcott E, Koch], Gordon R, Sandhu F, et al. Endoscopic Sclerotherapy versus Percutaneous Transjugular Intahepatic Protosystemic Shunt (TIPS) in Patients with Massive Acure Varicela Hemorrhage. Gastorenterology. (In press) 11:10 am
Health Care Policy Speaker to be Announced 11:40 am liver Cell Transplantation
Andrew S. Kerr, MD Learning objective: To review the recent experimental progress toward hepatocyte transplantation as an intervention procedure. CHRONIC liver disease has two important manifestations. Mechanical reorganization of liver manifests with portal hypertension and related complications. Decreased liver cell mass manifests with encephalopathy, coagulopathy, or progressive liver failure. Transjugular intrahepatic portosystemic shunt (TIPS) placement is one of the various interventions that helps to effectively control variceal hemorrhage. However, the rate of longterm survival of patients with chronic liver disease treated with TIPS is only 74% to 89% after 1 year and 62% after 2 years; these findings are similar to those for patients treated with sclerotherapy or shunt surgery. Poor long-term survival in this group of patients must depend on the effective hepatocyte mass available, because
treatment of variceal bleeding alone would not improve liver function. Although orthotopic liver transplantation can cure liver failure, there is a severe shortage of liver donors. Many patients with liver failure are also poor surgical candidates and the procedure is extremely complex. Consequently, in the United States, only a small fraction of patients with liver failure undergo orthotopic liver transplantation. Therefore, potential alternatives such as the use of bioartificialliver-support devices and the transplantation of liver cells have gained attention as methods of supplementing the function of diseased liver. Widespread application would require the development of a technique to augment the liver mass that is minimally invasive, is not limited by the shortage of donors, and is inexpensive. One possibility is the use of enzymes to break down donor livers into constituent cells; the hepatocytes would then be isolated and cryopreserved, just as erythrocytes are preserved by blood banks. Such a capability would allow use of isolated hepatocytes at short notice. A suitable candidate would undergo placement of percutaneous catheter with the distal tip in the portal circulation. Thawed hepatocytes would be infused into the portal vein and delivered to the hepatic sinusoids. A strategically placed occlusion balloon would prevent reflux of hepatocytes into portosystemic collateral vessels. Eventually, transplanted cells would integrate into the liver parenchyma and could potentially multiply to substantially repopulate the diseased liver. Further advances may one day make transcatheter liver cell transplantation useful for the treatment of acute or chronic hepatic failure and hepatic enzyme deficiency states. Cell transplantation could be beneficial in multiple ways. At its simplest, cells could be transplanted without any genetic or other manipulations. More complex strategies involved removal of cell from a patient, replacement of a missing gene, and retransplantation into the same host (ex vivo gene therapy). Such an approach that involves cells from the same individual obviates problems related to rejection caused by mismatched tissues. Although hepatocytes are believed to be weakly immunogenic, survival of allogenic cells in hosts requires immunosuppression. Cells could be transplanted to replace metabolic function, as has been demonstrated in animal models. States of genetic metabolic deficiency have been successfully ameliorated or corrected in Gunn rats with congenital hyperbilirubinemia, Nagase analbuminemic rats with low serum levels, and Watanabe heritable hypercholesterolemia. Hepatocyte transplantation has also been studied in animals with acute or chronic liver failure. The rationale for hepatocyte transplantation in patients with these disorders is as follows. First, a number of patients with acute liver failure are unsuitable for orthotopic liver transplantation while waiting for a suitable donor liver. It
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is possible that cell transplantation in these patients might prolong survival and thus serve as a "bridge" toward orthotopic liver transportation. On the other hand, if transplanted hepatocytes could proliferate in the host liver or induce regeneration of host cells themselves, then perhaps orthotopic liver transplantation could be avoided all together. In patients with chronic liver failure and serious complications such as refractory encephalopathy or coagulopathy, it is possible that hepatocyte transplantation may improve liver function and patient survival or quality of life. Highly provocative results have been reported from a variety of animal studies that concern the value of hepatocyte transplantation in chemically or otherwise induced acute liver failure. A common finding in all these studies is that hepatocyte transplantation (into portal vein, spleen, or peritoneal cavity) leads to decreased mortality. For example, administration of Dgalactosamine or dimethylnitrosamine can induce acute liver failure; the mortality rate in rodents has been reported to approach 90%, which is similar to the mortality rate associated with fulminant liver failure in humans. This rate can be decreased to approximately 40% when hepatocytes are transplanted once after the onset of liver injury. Studies have also shown that in animals with hepatic encephalopathy, cell transplantation can ameliorate disease, a finding that is highly encouraging. In animal models of hepatic encephalopathy induced by either acute liver ischemia or portacaval shunts, hepatocyte transplantation caused improvement in biochemical parameters and in spontaneous and exploratory motor activities. Also, recent experiments have shown that when normal hepatocytes are transplanted into animals subjected to carcinogen treatments, substantial improvements occur. These changes include a decrease in morphologic alterations in host hepatocytes and in number of precancerous nodules that formed as a result of carcinogen treatment. These findings are exciting and indicate that cellular changes related to chronic liver disease might indeed be reversible. These findings should add impetus to the analysis of hepatocyte transplantation in patients with chronic liver disease. Hepatocyte transplantation has begun to be tested in patients; in vivo gene therapy has been used in patients with familial hypercholesterolemia. These studies resulted from experiments in Watanabe heritable hyperlipidemic rabbits. The deficient low-denSity lipoprotein receptor gene was introduced into hepatocytes isolated from an excised rabbit liver lobe in vitro. Grossman et al used this technique to ameliorate familial hypercholesterolemia in a young woman. Early results suggested that the approach has great merit, although creation of a large transplanted hepatocyte mass requires additional strategies. Limited uncontrolled studies have begun to examine the value hepatocyte transplantation in the treatment of chronic liver disease, as well as acute liver failure, with mixed results. Mito et al resected the left
lateral segment of the liver of each of 10 cirrhotic patients with liver failure; then autotransplanted these cells into each patient's spleen. One patient showed clinical improvement. Type I diabetics have been treated with islet cell transplantation into the liver by the injection of cells into the portal vein. Most islet cells are rejected, but occasionally patients remain insulin independent. Only limited conclusions can be drawn from these early clinical studies because the fate of transplanted hepatocytes either was not demonstrated or was demonstrated by indirect methods. However, the results of these early studies are encouraging, and fundamental insights into transplanted hepatocyte biology should accelerate additional process. Insights into cell cryopreservation, liver growth control, development of liver cell lines, and prevention of allograft rejection should also facilitate progress. These considerations indicate that percutaneous transcatheter hepatocyte transplantation may well be a routine clinical procedure in the foreseeable future, with exciting applications. Transplantation of hepatocytes rather than a whole organ has several major advantages: it is minimally invasive and less expensive; and it is not as vulnerable to difficulties caused by donor shortages. Transplantation of cells could be performed by intervention radiologists using a variety of transcatheter approaches. Initial results in various animal models suggest that hepatic cell engraftrnent with this technique may reverse induced hepatic failure and metabolic deficiencies. Prevention of hepatocyte pulmonary emboli is of major concern and may be circumvented by using intervention techniques.
Selected Bibliography Grossman M, Raper SE, Kozarsky K, et al. Successful ex-vivo gene therapy directed to liver in a patient with familial hypercholesterolemia. Nature Genet 1994; 6:335-341. Gupta S, Rajvanshi P, Lee CD. Integration of transplanted hepotocytes in host liver plates demonstrated with dipeptidyl peptidase N deficient rats. Proc Nad Acad Sci USA 1995; 92:5860-5864. Gupta S, Roy Chowdhury R, Jagtiani R, et al. A novel system for transplantation of isolated hepatocytes utiliZing HBsAg producing transgenic donor cells. Transplantation 1990; 50:472--475. Gupta S, Yemeni P, Vemum RP, Lee CD, Yellin EL, Bhargava KK. Studies on the safety of intrasplenic hepatocyte transplantation: relevance to ex-vivo gene therapy and liver repopulation in acute hepatic failure. Hum Gene Ther 1993; 4:249-257. Kerlan RK, LaBerge JM, Gordon RL, Ring EJ. Transjugular intrahepatic portosystemic shunts: current status. AJR 1995; 164:1059-1066 Kerr A, Rajvanshi P, Bhargava KK, Burk RD, Gupta S. Transcatheter hepatocyte transplantation: preclinical studies of anatomic consequences in the portal venous system. Acad Radiol 1994; 1:229-236. Kerr A, Rajvanshi P, Gupta S. Percutaneous transcath-
eter liver cell transplantation: an emerging modality and its clinical implications. ]VIR 1996; 7: 169-176 Mito M, Kusano M, Kauwara Y. Hepatocyte transplantation in man. Transplant Proc 1992; 24:3052-3053. Rajvanshi P, Kerr A, Bhargava KK, Burk RD, Gupta S. Studies of liver repopulation using the dipeptidyl peptidase IV deficient rat and other rodent recipients: cell size and structure relationships regulate capacity for increased transplanted hepatocyte mass in the liver lobule. Hepatology 1996; 23:482---496. Roy Chowdhury J, Grossman M, Gupta S, Roy Chowdhury N, Baker JR, Wilson JM. Long-term improvement of hypercholesterolemia after ex vivo gene therapy in LDL receptor deficient rabbits. Science 1991; 254:1802-1805. Sutherlan DE, Gores PF, Farney AC, et al. Evolution of kidney, pancreas, and islet transplantation for patients with diabetes at the University of Minnesota. Am J Surg 1993; 166:456---491. Wilson JM, Johnston DE, Jefferson DM, Mulligan RC. Correction of the genetic defect in hepatocytes from the Watanabe heritable hyperlipidemic rabbit. Proc Natl Acad Sci USA 1988; 85:4421---4425.
Wednesday, March 12, 1997 8:00 am-12:15 pm Plenary Sessions-Access for Hemodialysis Moderator: Matthew A. Mauro, MD 8:00 am
Temporary Access for Hemodialysis and Problem Solving to Maintain It Ziv j. Haskal, MD Learning objectives: As a results of attending the plenary session, the attendee will be able to: (1) list the appropriate indications for dialysis catheter placement; (2) enumerate the differences between existing venous catheters for hemodialysis; (3) place temporary and permanent hemodialysis catheters; and (4) assess and manage failing dialysis catheters caused by either infection or thrombosis. IN 1991, approximately 200,000 Americans were treated for end stage renal disease, 60% with hemodialysis (1). In 1993, over 160,000 patients with chronic renal failure underwent hemodialysis (2). The yearly incidence of patients with end stage renal disease treated nearly doubled during the last decade. Although renal transplantation is the preferred treatment for most renal failure patients, the availability of donor organs continues to limit growth in the number of transplants. Thus, most patients are maintained with hemodialysis as the primary mode of renal replacement. As the average age of the United States population continues to rise, the needs of this population will continue to increase, as both the prevalence of dialysis and associated comorbid conditions increase.
Creation and maintenance of vascular access for hemodialysis continues to present a complex challenge for nephrologists, surgeons, and interventional radiologists. Present methods of dialysis access include surgically created arteriovenous fistula (eg, Brescia-Cimino fistulae (3)), prosthetic arteriovenous grafts, and dual lumen central venous catheters. Many physicians consider the autogenous radiocephalic fistula to be the most desired option because of the high long-term patency and low rate of associated complications. Disadvantages include a long maturation process and a moderate rate of primary failure to reach maturation. Most failed fistulae thrombose within the first month because of the insufficient size of the venous outflow (4). Despite the relatively trouble-free nature of mature arteriovenous fistulae, the majority of US patients have dialysis through prosthetic grafts; results from the Medicare End Stage Renal Disease program revealed that 83% of patients who were on dialysis for more than 3 months were treated with prosthetic grafts (5). These grafts carry a set of complications including pseudoaneurysms, infection, ipsilateral extremity edema caused by venous hypertension, and above all, graft thrombosis. Graft failure most commonly results from smooth muscle cell proliferation at and just beyond the venous anastomosis and often requires repeated angioplasty, stents, or surgical revisions to preserve patency. Central venous catheter placement for dialysis has replaced the original Scribner external arteriovenous shunt (6). It may be indicated for patients with acute renal failure who require temporary dialysis, and patients awaiting renal transplantation or maturation of surgical prosthetic grafts or fistulae. In some cases, these catheters must provide lifelong dialysis access because all potential fistula sites are depleted. In 1979, Uldall et al emphasized the advantages and convenience of transvenous subclavian access using a double lumen catheter (7). Since then, many centers have reported results using similar catheters for temporary and permanent hemodialysis access (7-33).
Temporary Hemodialysis Catheters These devices are noncuffed, semi-stiff, tapered, dual lumen catheters designed for short-term hemodialysis, plasmapheresis, or photopheresis. They are available in a variety of lengths and are placed using the standard percutaneous techniques used to place other central venous catheters. Typically, a 15 cm long catheter is suitable for right internal or external jugular catheters, whereas 20 cm long devices are necessary for left-sided catheters. Although some investigators have reported satisfactory long-term success using these catheters (32,33), most practitioners agree that tunneled-access catheters provide improved stability and lower infection rates when used for long-term access. In our experience, the steps required to tunnel and place a cuffed long-term catheter add little additional time to catheter insertion. Accordingly, we now place tunneled catheters in all patients in whom more than 2
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Health Care Policy Speaker to be Announced 11:40 am liver Cell Transplantation
Andrew S. Kerr, MD Learning objective: To review the recent experimental progress toward hepatocyte transplantation as an intervention procedure. CHRONIC liver disease has two important manifestations. Mechanical reorganization of liver manifests with portal hypertension and related complications. Decreased liver cell mass manifests with encephalopathy, coagulopathy, or progressive liver failure. Transjugular intrahepatic portosystemic shunt (TIPS) placement is one of the various interventions that helps to effectively control variceal hemorrhage. However, the rate of longterm survival of patients with chronic liver disease treated with TIPS is only 74% to 89% after 1 year and 62% after 2 years; these findings are similar to those for patients treated with sclerotherapy or shunt surgery. Poor long-term survival in this group of patients must depend on the effective hepatocyte mass available, because
treatment of variceal bleeding alone would not improve liver function. Although orthotopic liver transplantation can cure liver failure, there is a severe shortage of liver donors. Many patients with liver failure are also poor surgical candidates and the procedure is extremely complex. Consequently, in the United States, only a small fraction of patients with liver failure undergo orthotopic liver transplantation. Therefore, potential alternatives such as the use of bioartificialliver-support devices and the transplantation of liver cells have gained attention as methods of supplementing the function of diseased liver. Widespread application would require the development of a technique to augment the liver mass that is minimally invasive, is not limited by the shortage of donors, and is inexpensive. One possibility is the use of enzymes to break down donor livers into constituent cells; the hepatocytes would then be isolated and cryopreserved, just as erythrocytes are preserved by blood banks. Such a capability would allow use of isolated hepatocytes at short notice. A suitable candidate would undergo placement of percutaneous catheter with the distal tip in the portal circulation. Thawed hepatocytes would be infused into the portal vein and delivered to the hepatic sinusoids. A strategically placed occlusion balloon would prevent reflux of hepatocytes into portosystemic collateral vessels. Eventually, transplanted cells would integrate into the liver parenchyma and could potentially multiply to substantially repopulate the diseased liver. Further advances may one day make transcatheter liver cell transplantation useful for the treatment of acute or chronic hepatic failure and hepatic enzyme deficiency states. Cell transplantation could be beneficial in multiple ways. At its simplest, cells could be transplanted without any genetic or other manipulations. More complex strategies involved removal of cell from a patient, replacement of a missing gene, and retransplantation into the same host (ex vivo gene therapy). Such an approach that involves cells from the same individual obviates problems related to rejection caused by mismatched tissues. Although hepatocytes are believed to be weakly immunogenic, survival of allogenic cells in hosts requires immunosuppression. Cells could be transplanted to replace metabolic function, as has been demonstrated in animal models. States of genetic metabolic deficiency have been successfully ameliorated or corrected in Gunn rats with congenital hyperbilirubinemia, Nagase analbuminemic rats with low serum levels, and Watanabe heritable hypercholesterolemia. Hepatocyte transplantation has also been studied in animals with acute or chronic liver failure. The rationale for hepatocyte transplantation in patients with these disorders is as follows. First, a number of patients with acute liver failure are unsuitable for orthotopic liver transplantation while waiting for a suitable donor liver. It
111
112
is possible that cell transplantation in these patients might prolong survival and thus serve as a "bridge" toward orthotopic liver transportation. On the other hand, if transplanted hepatocytes could proliferate in the host liver or induce regeneration of host cells themselves, then perhaps orthotopic liver transplantation could be avoided all together. In patients with chronic liver failure and serious complications such as refractory encephalopathy or coagulopathy, it is possible that hepatocyte transplantation may improve liver function and patient survival or quality of life. Highly provocative results have been reported from a variety of animal studies that concern the value of hepatocyte transplantation in chemically or otherwise induced acute liver failure. A common finding in all these studies is that hepatocyte transplantation (into portal vein, spleen, or peritoneal cavity) leads to decreased mortality. For example, administration of Dgalactosamine or dimethylnitrosamine can induce acute liver failure; the mortality rate in rodents has been reported to approach 90%, which is similar to the mortality rate associated with fulminant liver failure in humans. This rate can be decreased to approximately 40% when hepatocytes are transplanted once after the onset of liver injury. Studies have also shown that in animals with hepatic encephalopathy, cell transplantation can ameliorate disease, a finding that is highly encouraging. In animal models of hepatic encephalopathy induced by either acute liver ischemia or portacaval shunts, hepatocyte transplantation caused improvement in biochemical parameters and in spontaneous and exploratory motor activities. Also, recent experiments have shown that when normal hepatocytes are transplanted into animals subjected to carcinogen treatments, substantial improvements occur. These changes include a decrease in morphologic alterations in host hepatocytes and in number of precancerous nodules that formed as a result of carcinogen treatment. These findings are exciting and indicate that cellular changes related to chronic liver disease might indeed be reversible. These findings should add impetus to the analysis of hepatocyte transplantation in patients with chronic liver disease. Hepatocyte transplantation has begun to be tested in patients; in vivo gene therapy has been used in patients with familial hypercholesterolemia. These studies resulted from experiments in Watanabe heritable hyperlipidemic rabbits. The deficient low-denSity lipoprotein receptor gene was introduced into hepatocytes isolated from an excised rabbit liver lobe in vitro. Grossman et al used this technique to ameliorate familial hypercholesterolemia in a young woman. Early results suggested that the approach has great merit, although creation of a large transplanted hepatocyte mass requires additional strategies. Limited uncontrolled studies have begun to examine the value hepatocyte transplantation in the treatment of chronic liver disease, as well as acute liver failure, with mixed results. Mito et al resected the left
lateral segment of the liver of each of 10 cirrhotic patients with liver failure; then autotransplanted these cells into each patient's spleen. One patient showed clinical improvement. Type I diabetics have been treated with islet cell transplantation into the liver by the injection of cells into the portal vein. Most islet cells are rejected, but occasionally patients remain insulin independent. Only limited conclusions can be drawn from these early clinical studies because the fate of transplanted hepatocytes either was not demonstrated or was demonstrated by indirect methods. However, the results of these early studies are encouraging, and fundamental insights into transplanted hepatocyte biology should accelerate additional process. Insights into cell cryopreservation, liver growth control, development of liver cell lines, and prevention of allograft rejection should also facilitate progress. These considerations indicate that percutaneous transcatheter hepatocyte transplantation may well be a routine clinical procedure in the foreseeable future, with exciting applications. Transplantation of hepatocytes rather than a whole organ has several major advantages: it is minimally invasive and less expensive; and it is not as vulnerable to difficulties caused by donor shortages. Transplantation of cells could be performed by intervention radiologists using a variety of transcatheter approaches. Initial results in various animal models suggest that hepatic cell engraftrnent with this technique may reverse induced hepatic failure and metabolic deficiencies. Prevention of hepatocyte pulmonary emboli is of major concern and may be circumvented by using intervention techniques.
Selected Bibliography Grossman M, Raper SE, Kozarsky K, et al. Successful ex-vivo gene therapy directed to liver in a patient with familial hypercholesterolemia. Nature Genet 1994; 6:335-341. Gupta S, Rajvanshi P, Lee CD. Integration of transplanted hepotocytes in host liver plates demonstrated with dipeptidyl peptidase N deficient rats. Proc Nad Acad Sci USA 1995; 92:5860-5864. Gupta S, Roy Chowdhury R, Jagtiani R, et al. A novel system for transplantation of isolated hepatocytes utiliZing HBsAg producing transgenic donor cells. Transplantation 1990; 50:472--475. Gupta S, Yemeni P, Vemum RP, Lee CD, Yellin EL, Bhargava KK. Studies on the safety of intrasplenic hepatocyte transplantation: relevance to ex-vivo gene therapy and liver repopulation in acute hepatic failure. Hum Gene Ther 1993; 4:249-257. Kerlan RK, LaBerge JM, Gordon RL, Ring EJ. Transjugular intrahepatic portosystemic shunts: current status. AJR 1995; 164:1059-1066 Kerr A, Rajvanshi P, Bhargava KK, Burk RD, Gupta S. Transcatheter hepatocyte transplantation: preclinical studies of anatomic consequences in the portal venous system. Acad Radiol 1994; 1:229-236. Kerr A, Rajvanshi P, Gupta S. Percutaneous transcath-
eter liver cell transplantation: an emerging modality and its clinical implications. ]VIR 1996; 7: 169-176 Mito M, Kusano M, Kauwara Y. Hepatocyte transplantation in man. Transplant Proc 1992; 24:3052-3053. Rajvanshi P, Kerr A, Bhargava KK, Burk RD, Gupta S. Studies of liver repopulation using the dipeptidyl peptidase IV deficient rat and other rodent recipients: cell size and structure relationships regulate capacity for increased transplanted hepatocyte mass in the liver lobule. Hepatology 1996; 23:482---496. Roy Chowdhury J, Grossman M, Gupta S, Roy Chowdhury N, Baker JR, Wilson JM. Long-term improvement of hypercholesterolemia after ex vivo gene therapy in LDL receptor deficient rabbits. Science 1991; 254:1802-1805. Sutherlan DE, Gores PF, Farney AC, et al. Evolution of kidney, pancreas, and islet transplantation for patients with diabetes at the University of Minnesota. Am J Surg 1993; 166:456---491. Wilson JM, Johnston DE, Jefferson DM, Mulligan RC. Correction of the genetic defect in hepatocytes from the Watanabe heritable hyperlipidemic rabbit. Proc Natl Acad Sci USA 1988; 85:4421---4425.
Wednesday, March 12, 1997 8:00 am-12:15 pm Plenary Sessions-Access for Hemodialysis Moderator: Matthew A. Mauro, MD 8:00 am
Temporary Access for Hemodialysis and Problem Solving to Maintain It Ziv j. Haskal, MD Learning objectives: As a results of attending the plenary session, the attendee will be able to: (1) list the appropriate indications for dialysis catheter placement; (2) enumerate the differences between existing venous catheters for hemodialysis; (3) place temporary and permanent hemodialysis catheters; and (4) assess and manage failing dialysis catheters caused by either infection or thrombosis. IN 1991, approximately 200,000 Americans were treated for end stage renal disease, 60% with hemodialysis (1). In 1993, over 160,000 patients with chronic renal failure underwent hemodialysis (2). The yearly incidence of patients with end stage renal disease treated nearly doubled during the last decade. Although renal transplantation is the preferred treatment for most renal failure patients, the availability of donor organs continues to limit growth in the number of transplants. Thus, most patients are maintained with hemodialysis as the primary mode of renal replacement. As the average age of the United States population continues to rise, the needs of this population will continue to increase, as both the prevalence of dialysis and associated comorbid conditions increase.
Creation and maintenance of vascular access for hemodialysis continues to present a complex challenge for nephrologists, surgeons, and interventional radiologists. Present methods of dialysis access include surgically created arteriovenous fistula (eg, Brescia-Cimino fistulae (3)), prosthetic arteriovenous grafts, and dual lumen central venous catheters. Many physicians consider the autogenous radiocephalic fistula to be the most desired option because of the high long-term patency and low rate of associated complications. Disadvantages include a long maturation process and a moderate rate of primary failure to reach maturation. Most failed fistulae thrombose within the first month because of the insufficient size of the venous outflow (4). Despite the relatively trouble-free nature of mature arteriovenous fistulae, the majority of US patients have dialysis through prosthetic grafts; results from the Medicare End Stage Renal Disease program revealed that 83% of patients who were on dialysis for more than 3 months were treated with prosthetic grafts (5). These grafts carry a set of complications including pseudoaneurysms, infection, ipsilateral extremity edema caused by venous hypertension, and above all, graft thrombosis. Graft failure most commonly results from smooth muscle cell proliferation at and just beyond the venous anastomosis and often requires repeated angioplasty, stents, or surgical revisions to preserve patency. Central venous catheter placement for dialysis has replaced the original Scribner external arteriovenous shunt (6). It may be indicated for patients with acute renal failure who require temporary dialysis, and patients awaiting renal transplantation or maturation of surgical prosthetic grafts or fistulae. In some cases, these catheters must provide lifelong dialysis access because all potential fistula sites are depleted. In 1979, Uldall et al emphasized the advantages and convenience of transvenous subclavian access using a double lumen catheter (7). Since then, many centers have reported results using similar catheters for temporary and permanent hemodialysis access (7-33).
Temporary Hemodialysis Catheters These devices are noncuffed, semi-stiff, tapered, dual lumen catheters designed for short-term hemodialysis, plasmapheresis, or photopheresis. They are available in a variety of lengths and are placed using the standard percutaneous techniques used to place other central venous catheters. Typically, a 15 cm long catheter is suitable for right internal or external jugular catheters, whereas 20 cm long devices are necessary for left-sided catheters. Although some investigators have reported satisfactory long-term success using these catheters (32,33), most practitioners agree that tunneled-access catheters provide improved stability and lower infection rates when used for long-term access. In our experience, the steps required to tunnel and place a cuffed long-term catheter add little additional time to catheter insertion. Accordingly, we now place tunneled catheters in all patients in whom more than 2
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