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Editorial: Renal Transplantation--Salvage Surgery and Suppression
0022-534719511536-1811$03.00/0
Vol. 153,1811,June 1995 Printed in U.S.A.
T H E J O I I R N A L OF UROLOGY
Copyright 0 1995 by AMERICANUKOLOCICAL ASSOCIATION, INC.
EDITORIAL: RENAL TRANSPLANTATION-SALVAGE SUPPRESSION Two articles in this issue of the Journal deal with aspects a t either end of the process of renal transplantation. Barry and Lemmers (page 1803) describe techniques for the salvage of renal veins damaged during a multi-organ recovery operation. Such articles assume added importance, since the increasing need for all transplantable organs has simultaneously increased the frequency of multi-organ recovery operations and the need to avoid waste of kidneys from any cause. The particular injury to which they address themselves is amputation of the cephalad portion of the renal vein during division of the inferior vena cava in donor hepatectomy. When vena caval division occurs, the vena cava is frequently placed on tension and as a result an illusion is created suggesting that the insertion of the renal veins into the inferior vena cava is more caudad than is actually the fact. When this illusion has not been recognized, then the injury described can easily occur. The vein injury can usually be prevented by collaboration between the donor nephrectomy and hepatectomy surgeons a t division of the vena cava. When the injury occurs the manner of reconstruction of the right renal vein is dictated by the extent of injury and material available for repair. The methods described by Barry and Lemmers illustrate 2 successful approaches. I have usually used the approach similar to the flap technique. I have generally reserved the use of patch g r a f t s to such injuries involving pediatric en bloc kidneys. The principles underlying the repair are the avoidance of outright stenosis and, I believe, a fastidious avoidance of trauma to the vessels. The diagrams of Barry and Lemmers show a streamlined repair but my experience has been that even extraordinarily ugly and irregular closures work without fault if manipulation. instrumentation, irrigation and other gratuitous insults to the vena cava and vein are avoided. In determining how much of the vena caval extension to remove before anastomosis, care should be taken to achieve or replicate a certain amount of the normal physiological tension such that redundant vena cava is not left after anastomosis. Cyclosporine has profoundly altered almost every aspect of transplantation for the better. However, cyclosporinetoxicity and, in particular, its nephrotoxicity have led some to delay its use until renal function has been established and/or to use the drug a t lower doses. Khauli et a1 (page 1805) describe their experience with cyclosporine, azathioprine and steroid triple therapy immunosuppression in a single center study of 61 consecutive cadaveric transplants between 1987 and 1990. They add support to the concept that aggressive administration of cyclosporine can result in a lower incidence of early
SURGERY AND
rejection, an increased short-term and long-term graft survival, as well as an increased incidence of nephrotoxicity. Nephrotoxicity was reversible in their experience and was not associated with detrimental effects to the graft or patient survival rate during the course of the study. As others have demonstrated, patients with early episodes of rejection are less likely to have long-term graft survival than those without such episodes. The initial protocol used by Khauli et al aimed to maintain a cyclosporinelevel of 150 ng./ml. (by high performance liquid chromatography) for the first 3 months after transplantation. As a result of their analyses, they conclude that the induction phase cyclosporine target level should be increased to greater than 200 ng./ml. The authors report an incidence of acute tubular necrosis or delayed initiation of renal function of 6.6%,which is an enviably low incidence and they speculate that vigorous hydration and calcium channel blockers may be contributory. All of the patients received the calcium channel blocker nifedipine. Without controls, the effect of nifedipine upon acute tubular necrosis or cyclosporine nephrotoxicity in this series cannot be evaluated. Cold ischemia time of the kidneys is an important factor in acute tubular necrosis but this was not reported. There is no doubt that acute and chronic administration of cyclosporine can result in mild to extreme nephrotoxicity, which is clearly demonstrated in some heart transplant patients when cyclosporine immunosuppression cannot be arbitrarily lowered to protect native kidneys. In renal transplantation, however, early nephrotoxicity in some instances is an acceptable trade-off for subsequent prolonged graft survival, particularly in the highly sensitized patient and in those who have rejected prior grafts. Khauli et a1 report that 7 of 70 patients (10%)had a percent reactive antibody level of more than 20%and 4 of the 70 had undergone repeat transplantation. Both patient characteristics are associated with poor graft survival. The observed actuarial graft survival rate of 93.4% at 1year and 78.5% a t 5 years attests to the power of cyclosporineimmunosuppression and the increasing skill with which it is being administered. Of equal importance is that fact that such gains in graft survival occur with less of the devastation caused by the higher steroid doses previously required.
1811
Thomas R. Hakala Division of Urologic Surgery University of Pittsburgh Medical Center Pittsburgh, Pennsylvania
Vol. 153,1811,June 1995 Printed in U.S.A.
T H E J O I I R N A L OF UROLOGY
Copyright 0 1995 by AMERICANUKOLOCICAL ASSOCIATION, INC.
EDITORIAL: RENAL TRANSPLANTATION-SALVAGE SUPPRESSION Two articles in this issue of the Journal deal with aspects a t either end of the process of renal transplantation. Barry and Lemmers (page 1803) describe techniques for the salvage of renal veins damaged during a multi-organ recovery operation. Such articles assume added importance, since the increasing need for all transplantable organs has simultaneously increased the frequency of multi-organ recovery operations and the need to avoid waste of kidneys from any cause. The particular injury to which they address themselves is amputation of the cephalad portion of the renal vein during division of the inferior vena cava in donor hepatectomy. When vena caval division occurs, the vena cava is frequently placed on tension and as a result an illusion is created suggesting that the insertion of the renal veins into the inferior vena cava is more caudad than is actually the fact. When this illusion has not been recognized, then the injury described can easily occur. The vein injury can usually be prevented by collaboration between the donor nephrectomy and hepatectomy surgeons a t division of the vena cava. When the injury occurs the manner of reconstruction of the right renal vein is dictated by the extent of injury and material available for repair. The methods described by Barry and Lemmers illustrate 2 successful approaches. I have usually used the approach similar to the flap technique. I have generally reserved the use of patch g r a f t s to such injuries involving pediatric en bloc kidneys. The principles underlying the repair are the avoidance of outright stenosis and, I believe, a fastidious avoidance of trauma to the vessels. The diagrams of Barry and Lemmers show a streamlined repair but my experience has been that even extraordinarily ugly and irregular closures work without fault if manipulation. instrumentation, irrigation and other gratuitous insults to the vena cava and vein are avoided. In determining how much of the vena caval extension to remove before anastomosis, care should be taken to achieve or replicate a certain amount of the normal physiological tension such that redundant vena cava is not left after anastomosis. Cyclosporine has profoundly altered almost every aspect of transplantation for the better. However, cyclosporinetoxicity and, in particular, its nephrotoxicity have led some to delay its use until renal function has been established and/or to use the drug a t lower doses. Khauli et a1 (page 1805) describe their experience with cyclosporine, azathioprine and steroid triple therapy immunosuppression in a single center study of 61 consecutive cadaveric transplants between 1987 and 1990. They add support to the concept that aggressive administration of cyclosporine can result in a lower incidence of early
SURGERY AND
rejection, an increased short-term and long-term graft survival, as well as an increased incidence of nephrotoxicity. Nephrotoxicity was reversible in their experience and was not associated with detrimental effects to the graft or patient survival rate during the course of the study. As others have demonstrated, patients with early episodes of rejection are less likely to have long-term graft survival than those without such episodes. The initial protocol used by Khauli et al aimed to maintain a cyclosporinelevel of 150 ng./ml. (by high performance liquid chromatography) for the first 3 months after transplantation. As a result of their analyses, they conclude that the induction phase cyclosporine target level should be increased to greater than 200 ng./ml. The authors report an incidence of acute tubular necrosis or delayed initiation of renal function of 6.6%,which is an enviably low incidence and they speculate that vigorous hydration and calcium channel blockers may be contributory. All of the patients received the calcium channel blocker nifedipine. Without controls, the effect of nifedipine upon acute tubular necrosis or cyclosporine nephrotoxicity in this series cannot be evaluated. Cold ischemia time of the kidneys is an important factor in acute tubular necrosis but this was not reported. There is no doubt that acute and chronic administration of cyclosporine can result in mild to extreme nephrotoxicity, which is clearly demonstrated in some heart transplant patients when cyclosporine immunosuppression cannot be arbitrarily lowered to protect native kidneys. In renal transplantation, however, early nephrotoxicity in some instances is an acceptable trade-off for subsequent prolonged graft survival, particularly in the highly sensitized patient and in those who have rejected prior grafts. Khauli et a1 report that 7 of 70 patients (10%)had a percent reactive antibody level of more than 20%and 4 of the 70 had undergone repeat transplantation. Both patient characteristics are associated with poor graft survival. The observed actuarial graft survival rate of 93.4% at 1year and 78.5% a t 5 years attests to the power of cyclosporineimmunosuppression and the increasing skill with which it is being administered. Of equal importance is that fact that such gains in graft survival occur with less of the devastation caused by the higher steroid doses previously required.
1811
Thomas R. Hakala Division of Urologic Surgery University of Pittsburgh Medical Center Pittsburgh, Pennsylvania