The results of transplantation survival for 70 consecutive cadaver kidneys preserved under hypothermic pulsatile perfusion at Henry Ford Hospital are reviewed. Pulsatile perfusion for up to 30 hours did not adversely alter the survival rate following transplantation. Thus, kidneys perfused for prolonged periods of time (\u3e 20 hours) can be used for transplantation, if the basic rules for organ retrieval and preservation have been followed. Hypothermic pulsatile perfusion of cadaver kidneys has been demonstrated to be an adequate system for ex-vivo preservation for transplantation

Cerny, Joseph C.

Cortes, Pedro

Cruz, Cosme

Dienst, Stanley G.

Farah, Riad

Levin, Nathan W.

Santiago, Godofredo

Toledo-Pereyra, Luis H.

Valjee, Krishna D.

Henry Ford Health System Scholarly Commons

Henry Ford Hospital Medical Journal Volume 26 Number 2 Article 9 6-1978 Length of Perfusion Time in Cadaver Kidney Transplantation Krishna D. Valjee Luis H. Toledo-Pereyra Stanley G. Dienst Cosme Cruz Pedro Cortes See next page for additional authors Follow this and additional works at: https://scholarlycommons.henryford.com/hfhmedjournal  Part of the Life Sciences Commons, Medical Specialties Commons, and the Public Health Commons Recommended Citation Valjee, Krishna D.; Toledo-Pereyra, Luis H.; Dienst, Stanley G.; Cruz, Cosme; Cortes, Pedro; Santiago, Godofredo; Levin, Nathan W.; Farah, Riad; and Cerny, Joseph C. (1978) "Length of Perfusion Time in Cadaver Kidney Transplantation," Henry Ford Hospital Medical Journal : Vol. 26 : No. 2 , 47-52. Available at: https://scholarlycommons.henryford.com/hfhmedjournal/vol26/iss2/9 This Article is brought to you for free and open access by Henry Ford Health System Scholarly Commons. It has been accepted for inclusion in Henry Ford Hospital Medical Journal by an authorized editor of Henry Ford Health System Scholarly Commons. Length of Perfusion Time in Cadaver Kidney Transplantation Authors Krishna D. Valjee, Luis H. Toledo-Pereyra, Stanley G. Dienst, Cosme Cruz, Pedro Cortes, Godofredo Santiago, Nathan W. Levin, Riad Farah, and Joseph C. Cerny This article is available in Henry Ford Hospital Medical Journal: https://scholarlycommons.henryford.com/hfhmedjournal/vol26/iss2/9 Henry Ford Hosp Medjournal Vol 26, No 2, 1978 Length of Perfusion Time in Cadaver Kidney Transplantation Krishna D. Valjee, MD,* Luis H. Toledo-Pereyra, MD, PhD,* Stanley G. Dienst, MD,* Cosme Cruz, MD,** Pedro Cortes, MD,** Godofedro Santiago, MD,** Nathan W. Levin, MD,** Riad Farah, MD,*** and Joseph C. Cerny, MD*** The results of transplantation survival for 70 consecutive cadaver kidneys preserved under hypothermic pulsatile perfusion at Henry Ford Hospital are reviewed. Pulsatile perfusion for up to 30 hours did not adversely alter the survival rate following transplantation. Thus, kidneys per-fused for prolonged periods of time (> 20 hours) can be used for transplantation, if the basic rules for organ retrieval and preservation have been followed. Hypothermic pulsatile perfusion of cadaver kidneys has been demonstrated to be an adequate system for ex-vivo preservation for transplantation. Introduction A controversy exists as to whether or not cadaver kidney preservation by hypothermic pulsatile perfusion diminishes the long-term function of transplanted kidneys.^"^ Recently Toledo-Pereyra and his colleagues^ reported that perfusion of cadaver kidneys for morethan 30 hours did not adversely affect either their long-term function after transplantation or the onset of rejection. These findings have been confirmed by Seim and his associates." This paper presents the results ofa study of cadaver kidneys harvested at several different hospitals and preserved under hypothermic pulsatile perfusion by the Henry Ford Hospital Preservation Team. All kidneys were transplanted at this institution. Our study was designed to determine the influ-ence of perfusion time on the short- and long-term funcfion of 70 consecutive, perfused cadaver kidneys transplanted at a single center. Submitted for publication: February 15, 1978 Accepted for publication: March 24, 1978 * Department of Surgery, Section ofTransplantation, Henry Ford Hospital ** Department of Medicine, Division of Nephrology, Henry Ford Hospital * * * Department of Urology, Henry Ford Hospital Address reprint requests to Dr. Toledo-Pereyra, Department of Surgery, Section of Transplantation and Surgical Research, Henry Ford Hospital, 2799 W Crand Blvd, Detroit, Ml 48202 Material and Methods From July, 1973 to June, 1977, 70 cadaver kidneys were perfused and transplanted to patients in end-stage renal failure at Henry Ford Hospital. After transplantation, patients were followed for a minimum of six months. All kidneys in this study were preserved by hypothermic pulsatile perfu-sion for variable periodsof time. The actuarial survival of all kidney transplants was calculated bythe method of Merrell and Shulman.= All different variables among groups were compared using 2 x 2 chi square statistical analysis. Standard methods were employed for harvesting all cadaver kidneys. After nephrectomy, cold (4°C) Ringer's lactate containing 10,000 U/L of heparin was usedto wash out the blood in all kidneys until the venous effluent was clear. The kidneys were then placed in the perfusion system at a systolic perfusion pressure of 60 mm Hg, PO2 of 200 mm Hg, pH of 7.4, and temperature of 7°C. The perfusate was cryoprecipitated plasma, which contained the normal con-centration of extracel I u lar electrolytes and osmolarity of 290 47 Valjee, Toledo-Pereyra, Dienst, et al mOsm/L. Routinely added tothe perfusate were ampicillin (1.0 gm/L ) , methylprednisolone (500 mg /L ) , phe-nolsulphonphthalein (PSP) (2ml/L), magnesium sulfate 50% (2 ml/L), and regular insulin (80 U/L). We discarded all kidneys wfth a flow of less than 0.3 m l /m in /gm, a perfusion pressure of morethan 60 mm Hg, and/orsevere vascular or ureteral abnormalities. The warm ischemic time rarely exceeded five minutes. Cold ischemic time from the time of cold flushing until the kidney was placed in the perfusion machine rarely exceeded 15 min-utes. Donor peripheral blood and lymph nodes removed at the time of nephrectomy were used for histocompatability testing. Recipient cytotoxic antibodies directed against donor cells were studied by the microlymphocytotoxicity method developed at the National Institute of Health.'' The surgical transplant technique, immunosuppression, and postoperative treatment remained relatively constant throughout the study. The recipient immunosuppressive dosage consisted of azathioprine 5.0 mg/ K/day foroneday, 2.5 mg/K/day for 14 days, then 1.0-2.5 mg/K/day as the whi te blood count indicated. Patients received pred-nisolone at a dose of 1.2 mg/K/day on the day of surgery, then reduced by 2.0 mg each day to a maintenance dose of 10 to 30 mgdaily. As outpatients, they were randomized for daily or alternate doses. Satisfactory renal function was defined as that sufficient to sustain life without requiring dialysis. Signs of graft failure were permanent restoration of dialysis, graft removal, or patient death. Results Figure 1 shows that the actuarial survival rate of all perfused cadaver kidneys wfthout exclusions. Fifty-three per cent of the entire group of grafted kidneys were functioning at six months. Thereafter, the loss of graft function was minimal up to threeyears after transplantation. There were no significant differences (p>0.08-0.5) among kidneys perfused for dif-ferent intervals. Six renal grafts were lost due to technical errors within the first month after transplantation. When these kidneys were eliminated from the total group (Figure 2), data for short-term and long-term function were improved, and the basic pattern of survival among the different groups of perfused kidneys for varying periods was maintained. It has been reported that diabetic patients do not survive as well as nondiabetic patients after transplantation.' When they were excluded from the study (Figure 3), there was a tendency toward improved function from six months to three years, although this improvement was not significant (p>0.1-0.5). Figure 4 shows the actuarial survival rate of first cadaver transplants only. The results followed a trend similar to that observed in the entire transplant population. < > > cr 3 00 < CL O 100 80 60 40 • 20 2 1 - 3 0 HRS (14) ^ 0 - 1 0 HRS (10) O <3.7 ^ 1 1-20 H R S ( 4 6 ) ^ T O T A L ( 7 0 ) • - 0 - < j 12 18 24 3C 36 MONTHS POST-TRANSPLANTATION Fig.1 Actuarial functional survival curves in 70 pertused cadaver kidney transplants divided according to the length of perfusion. All causes of kidney loss and death are included. In parentheses is the number of transplants per group. There is an apparent trend for better survival wi th kidneys perfused for 21-30 hours than for those perfused for 11-20 hours, although this is not statistically significant. < > > CC 00 < cc too -80 60 40 20 2 1 - 3 0 HRS (13) 0 - 1 0 HRS (10) TOTAL (64) ••O O 1 1-20 HRS (41) 12 18 24 30 36 MONTHS POST-TRANSPLANTATION Fig. 2 Actuarial functional survival curves in 64 perfused cadaver kidney transplants divided according to the length of perfusion. Failures due to technical factors were eliminated. A slight improvement over those in Figure 1 is evident. In parentheses is the number of transplants in each group. As expected, patients under 40 years of age and with two or more antigen matches did better than older patients and those wfth fewer than two antigen matches (Figures 5,6). Women in this study, contrary to other repor ts ,showed better long-term function than men (Figure 7). 4B Perfusion Time in Kidney Transplantation < > > GC ZD 00 < CC o 100 -80 • 60 • 40 20 J ^ \ ^ 2 1 - 3 0 H R S d l ) " ^ 0 - 1 0 HRStS) 1 1-20 HRS (29) TOTAL (48) 12 18 24 3 0 36 MONTHS POST-TRANSPLANTATION Fig. 3 Actuarial functional survival curves of cadaver kidney transplants, exclud-ing transplants of diabetic patients. In parentheses is the number of transplants per group. In our search for the ideal risk patient, we eliminated diabetic recipients, patients over 40, and those who had received multiple transplants (Figure 8). The overall survival was improved. Again, the length of perfusion did not adversely affect the perfused kidneys. Perfused kidneys that did not function immediately after transplantation did not survive as well over the long term as those that had immediate function (Figure 9). However, kidneys that recovered function after dialysis had excellent long-term survival. The main causes of graft failure were rejection (30%), infection (28%), and other causes associated with delayed kidney function after transplantation (26%), such as acute posttransplant renal failure and/or associated rejection. The main causes of patient death were infecfion (73%), cardiac (17%), and gastrointestinal bleeding (10%). Discussion In this study, we confirm the data from other institu-tions^""'^'^" that prolonged perfusion does not hinder long-term renal function after transplantation, nordoes it result in an increased rate of rejection. In fact, cadaver kidneys perfused for more than 20 hours had slightly better survival rates than those perfused for 11 to 20 hours. Perfusion for minimal periods (0-10 hrs) did not appear to be detrimental for transplantation either. Although there has been considerable controversy about the effect on cadaver kidney transplantation of hypothermic pulsatile perfusion as opposed to hypothermic storage,^'^ the data of Toledo-Pereyra and his associates,^ as well as that from the Human Renal Transplant Registry," showed no significant differences in graft function between perfused and cold-stored kidneys. Toledo-Pereyra and his groups indicated in a prospective and controlled comparative study that perfused kidneys did better than cold-stored kidneys. Other studies carried out by Payne et a l " demonstrated clinically and experimentally that kidneys perfused by hypothermic pulsatile perfusion for 24 to 48 hours had equal or better survival than unperfused grafts or those preserved by cold storage. In this paper, we can say only that < > > cc 00 < cc o 100 FIRST CADAVER KIDNEY TRANSPLANTS 21-30 HRS (11) 1 1-20 HRS (35) 6 12 18 24 30 36 MONTHS POST.TRANSPLANTATION MULTIPLE CADAVER KIDNEY TRANSPLANTS 100 TOTAL (9) 6 12 18 24 30 36 MONTHS POST-TRANSPLANTATION Fig. 4 Actuarial functional survival curves of all first cadaver kidney transplants. In parentheses is the number of transplants per group. When multiple transplants are excluded, slight improvement over those in Figure 2 is evident. 49 Valjee, Toledo-Pereyra, Dienst, et al AGE < 4 0 YEARS 21 -30 HRS (5) / 11-20 HRS (15) 0-10 HRS (6) TOTAL (26) 6 12 18 24 30 36 MONTHS POST-TRANSPLANTATION 100 AGE > 4 0 YEARS 21-30 HRS (8) 0-10 HRS (4) 6 12 18 24 30 36 MONTHS POST-TRANSPLANTATION Fig. 5 Actuarial functional curves of perfused cadaver kidney transplants comparing age and length of perfusion. Patients over 40 do less wel l than those under 40. Prolonged perfusion does not adversely affect long-term transplant function. In parentheses is the number of transplants per group. < > > tr CO < CC o too 80 -60 4 0 20 > 2 ANTIGEN MATCHES 21-30 HRS (1 ) - ^ o o. 0-10 HRS (3) .-TOTAL (9) A 1-20 HRS (5) 6 12 18 24 30 36 MONTHS POST-TRANSPLANTATION < 2 ANTIGEN MATCHES 100 a: 40 2 0 21 -30 HRS (12) 11-20 HRS (36) 0-10 HRS (7) TOTAL (55) 6 12 18 24 30 36 MONTHS POST-TRANSPLANTATION Fig. 6 Actuarial functional survival curves of cadaver kidney transplants comparing antigen matching in perfused kidneys. Kidneys wi th two or more antigen matches did better than those wi th one or fewer antigen match. In parentheses is the number of transplants per group. the length of perfusion is not an adverse factor in cadaver kidney transplantation. In general, our data corroborate the detrimental effect of high-risk factors in cadaver transplantation, such as age, diabetes mellitus, and multiple transplantation. Antigen matching also correlated wel l w i th long-term kidney function. Contrary to the reports of others,^'^^ our data indicate that kidneys which did not function promptly after transplanta-tion did not do as well as those kidneys that began to function immediately. If kidney function did return, com-plete recovery was observed. Prolonged preservation under the conditions described had no detrimental effect on immediate kidney function. There was a similar incidence of 50 Perfusion Time in Kidney Transplantation MALES too < > > cc 3 CO < CC o FEMALES 100 \ 21-30 HRS (4) 6 12 18 24 30 36 MONTHS POST-TRANSPLANTATION 6 12 18 24 30 36 MONTHS POST-TRANSPLANTATION Fig. 7 Actuarial functional curves of cadaver kidney transplants in men and women. Women did better than men. Kidneys perfused for 21-30 hours had a better trend of survival in women than in the other groups. < > > CC 3 00 < CC o 100 80 60 40 20 2 1 - 3 0 HRS (5) ,11-20 HRS (7) 0 -10 HRS (5) 6 12 18 24 3 0 36 MONTHS POST-TRANSPLANTATION Fig. 8 Actuarial functional curves of first cadaver kidney transplants after diabetics and patients over 40 years old are eliminated. When compared to those in Figure 2, there is overall improvement in long-term function, in parentheses is the number of transplants per group. nonfunction in all groups of perfused kidneys, regardless of the length of perfusion. In short, in this study we demonstrate that hypothermic pulsatile perfusion of kidneys is an adequate means of ex-vivo preservation for transplantation. 51 < > > cc 3 CO < CC o too -oG 40 -20 Valjee, Toledo-Pereyra, Dienst, et al NO IMMEDIATE FUNCTION 0-10HRS (5) TOTAL (16) / 21-30 HRS (4) o o •• / 11-20 HRS (7) 6 12 I f i ! 1 i 24 30 36 MONTHS POST -TRANSPLANTATION 100 80 -60 4 0 20 • Fig. 9 IMMEDIATE FUNCTION 1 1-20 HRS (34)' 21,-30 HRS (9) TOTAL (48) 12 24 30 3>6 MONTHS POST-TRANSPLANTATION Actuarial functional survival curves of perfused cadaver kidneys comparing immediate function after transplantation. Kidneys wi th immediate function did better than those that did not function immediately after transplantation. Acknowledgments The assistance of other members of the Transplant Team from the Department of Surgery (Dr. H. K. Oh), the Division of Nephrology (Dr. F Dumler), the Department of Urology (Dr. R. C. Klugo), and the Departmentof Pathology (Dr. H. Hayashi and Dr. D. J. PatO is greatly appreciated. They participated in various phases of the laboratory testing, clinical management, and treatment. The help of Louise Bernbeck and Jay Hunter is also appreciated. References 1. Clark EA, Terasaki PI, Opelz G, and Mickey MR: Cadaver kidney transplant fai I ures at one month. New Engl j Med 291:1099-1102,1974. 2. Toledo-Pereyra LH, Simmons RL, MobergAW, Olson LC, and Najarian JS: Organ preservation in success of cadaver transplants. Arch Surg 110:1031, 1975. 3. Toledo-Pereyra LH, Simmons RL, Olson LC, and Najarian JS: Perfusion time and survival of cadaver transplants. Surg 79:377, 1976. 4. Seim SK, Maisel KE, and Merkel FK: The effect of length of preservation on renal transplant survival. Surg Gynecol Obstet 145:709, 1977. 5. Merrell M and Shulman LE: Determination of prognosis in chronic disease illustrated by systemic lupus erythematosus. / Chronic Dis 1:12, 1955. 6. Terasaki PI and Park MS: Microdroplet lymphocyte microcytotoxicity. U.S. Dept Health, Education & Welfare, No. 76545, 1976. 7. Kjellstrand CM, Simmons RL, Goetz FC, Buselmeier TJ, Shideman JR, von Hartitzsch B, and Najarian JS: Renal transplantation in patients with insulin dependent diabetes. Lancet 2:4, 1973. 8. Najarian JS, Kjellstrand CM, and Simmons RL: High risk patients in renal transplantation. Transp/ Proc 9:107, 1977, 9. Merkel FK, Seim SK, and Maisel KE: Relevance of duration of preservation to renal transplant survival. Transp! Proc 9:1617, 1977, 10. Scott DF, Whiteside D, Rehead J, and Atkins RC: Ice storage versus perfusion for preservation of kidneys before transplantation. 6r/t Med / 4:76, 1974. 11. Advisory Comm ittee to the Renal Transplant Registry: The 12th report of the human renal transplant registry./AMA 233:787, 1975. 12. Payne W D , Michels LD, Toledo-Pereyra LH, Simmons RL, and Na-jarian JS: Effects of pulsatile perfusion on the immunogenicity of renal allografts. / Surg Res 22:380, 1977. 13. Toledo-Pereyra LH, Moberg AW, Callender CO, Simmons RL, and Najarian JS: Factors determining early kidney function fol lowing clinical preservation. Minn Med 58:446, 1975. 52 

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Length of Perfusion Time in Cadaver Kidney Transplantation

Length of Perfusion Time in Cadaver Kidney Transplantation

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