International Urology and Nephrology 43 (1), pp. 95-- 104 (1981)

The Use of Pediatric Cadaver Kidneys in Renal Transplantation (Experience with 97 Cases and Comparison with Adult Kidneys) L. G. MANAGADZE, H. OESTERWITZ, D. SCHOLZ, G. MAY, M. MEBEL Kidney Transplantation Center, Berlin-Friedrichshain, Department of Urology, Division of Experimental Organ Transplantation, Humboldt-University (Charit6), Berlin, GDR (Received September 30, 1980)

Pediatric cadaver donors are an important pool of kidneys for human allotransplantation. Experiences with 97 transplantations of pediatric cadaveric kidneys (age: 4 months to 15 years) and comparison with 230 transplantations of adult kidneys (age: 16-25 and 40-68 years) are presented. The cumulative patient survival was similar in both groups, however, the graft survival was significantly lower in the pediatric donor group (p < 0.05). This difference was established almost exclusively within the first 3 months after transplantation. In this group the percentage of technical complications in the first month was higher (13.4 ~) than in the adult kidney group (6.5 %). The analysis of the whole pool of harvested kidneys shows a significantly higher rate of transplanted kidneys in the pediatric group (61 ~) as compared with the adult group (44.7 %). In both groups the mode of arterial vascular anastomosis (end-to-end or end-to-side) does not influence the graft survival. Further investigations on pediatric donor kidneys are necessary. The utilization of pediatric cadaveric kidneys for transplantation should be increased because 20-25 of all potential kidney donors are younger than 15 years.

Introduction Renal transplantation has become a powerful tool for the treatment of chronic renal failure with more than 50,000 transplantations having been done up to date [1, 14]. One of the main problems in renal transplantation is the shortage o f a sufficient number o f suitable cadaver donor kidneys. Since the first use of a pediatric cadaver kidney in clinical transplantation [20], in the last decade more and more single cases of transplantations in pediatric [5, 9, 15-17, 21-25, 28-32, 34, 37, 41, 45, 48] and adult recipients [2, 6, 7, 10, 12, 19, 23, 26, 33, 36, 40, 42, 44, 47] have been reported, and the possibility and necessity of increasing the potential source o f suitable grafts by the use of pediatric cadaver kidneys have been stressed [7, 12, 19, 40, 47]. However, there are only few publications that report on experiences with 10 or more cases of pediatric kidneys transplanted into adult recipients [7, 19, 26, 36, 44]. The lack of information and comparative analyses in this field of clinical renal transplantation stimulated us to undertake this study. International Urology and Nephrology 13, 1981

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Material and methods

Among 535 human cadaver kidney transplantations performed from January 1971 to August 1979 in the three Kidney Transplantation Centers of the Uni-versity Departments of Urology in Berlin, 1 Rostock2 and Halle, a 97 recipients received donor kidneys harvested from children aged up to 15 years, and 230 received kidneys harvested from adults aged 16 to 25 and 40 to 68 years, respectively. The pediatric donor group was divided into 3 subgroups according to age: 11 to 15 years (52 recipients), 6 to 15 years (39 recipients) and younger than 6 years (6 recipients). The adult donor control group was divided into the 2 subgroups as mentioned above (Fig. 1). The age distribution in the control group was therefore selected in order to have a low-risk (16 to 25 years) and a high-risk (above 40 years) adult donor group for comparative analyses with the pediatric groups. The methods of organ procurement and preservation and the criteria of organ viability and selection for the use as donor kidneys in transplantation were similar in all groups. Suitable recipients were selected on the basis of HLA typing and final cross matching for cytotoxic antibodies. Furthermore, standard operative techniques were used. The transplanted kidney was placed retroperitoneally in the iliac fossa. Vascular anastomoses were accomplished between the renal and iliac vessels. In adult donor kidney transplantation the standard arterial anasto-

2~176 t 171

z 100

52

50-

iiiiii 6

ehO

16-25

11-15 6-10 <6 Donor Qge (yectrs)

2Fig. 1. N u m b e r of transplantations performed at three Transplantation Centers in the 5 donor age groups ([~ Berlin, [ ] Rostock, [ ~ Halle) 1 Director: Prof. M. Mebel. Director: Prof. Th. Erdmann. Director: Prof. H. Rockstroch. International Urology and Nephrology 13, 1981

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moses were performed end-to-end with the internal iliac artery (70~o); however, if two or more renal arteries occurred, the anastomoses were end-to-side (30 ~), if possible with a patch. In pediatric kidney transplantation the arterial anastomoses Were performed end-to-side (50 ~ ) as well as end-to-end (50 ~o). The venous anastomoses were accomplished end-to-side with the external iliac vein. The anastomoses in the 3 en bloc transplantations were performed end-to-end between the donor aorta and the internal iliac artery and end-to-side between the donor vena cava and the external iliac vein. Ureterocystoneostomy was performed extravesically with submucosal tunnel as described by Braun [8]. Immunosuppressive therapy did not differ between the adult and pediatric kidney groups and consisted of Azathioprine and Prednisolone in various dosage related to the body weight of the recipient. .... The pediatric and adult donor age groups were compared statistically with regard to the recipients' age and weight; degree of histocompatibility antigen identity; time of dialysis before transplantation; warm and cold ischemic time; cumulative patient and graft survival; rate of technical Complications - that resulted within the first month after transplantation in graft failure or within the first week in the death of the recipient - and the mode of arterial vascular anastomosis and their influence on graft survival. Statistical data were compared using Student's t-test. The cumulative patient and graft survival was icalctdated according to the E D T A guidelines [ 13]. Furthermore, in the pediatric and adult donor age groups the whole pool of harvested kidneys was analysed with respect to the percentage of not viable and therefore not transplanted kidneys. Here statistical data were compared using the z2-test. Results

Table 1 shows the data of the donors' and recipients' age, antigen matching, time of dialysis before renal transplantation and warm and cold ischemic time. The two groups are comparable to each other without any significant difference. Table 1 Data of donors and recipients in the five donor age groups Donor age group (years)

>40 16-25 11--15 6-10 <6 7

Donor age (years)

No. of transplants

Recipient age (years)

Antigen matching (average number of identical antigens)

Time of dialysis before transplantation (months)

Warm ischemic time (rain)

44.3+ 4.7 19.3--2.8 13.2-- 1.6 8.2--1.3 2.9--2

59 171 52 39 6

35.4__+10 31.4_+ 9.9 33.9__+ 9 28.8-- 9.7 26 -t-11.9

2.24 2.15 2.08 2.16 2.17

19.5-t- 14.3 19.2--15.4 19.6-- 12.2 23.6__+15.4 20.1+20.6

6.2-- 9.8 7.7+ 10 7.2__+ 12.2 9.0-t- 9.8 8.8__13.7

Cold ischemie time (hour)

15.9+5.7 15.0__+5.8 13.5__+3.6 12.8-I-4.3 11.5+6.1

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Figure 2 shows the cumulative patient survival of recipients with pediatric or adult donor kidneys. There was no significant difference. In Fig. 3 a comparison of cumulative graft survival between the two subgroups of the adult donor control group was made. There appears to be very little difference in graft survival between these groups indicating that donor age in the adult group is not important with respect to graft survival. We therefore decided in the following calculations to pool the two subgroups. Figure 4 shows the cumulative graft survival in the pediatric and adult donor kidney group. At 3 and 6 months and 1, 2 and 4 years there were significant differences (p < 0.05). Figure 5 shows the cumulative graft survival in the adult and the 3 single pediatric groups and indicates, with t w o exceptions, no significant difference. At 3 months and 2 years the difference was significant between groups I and III % 100

1

2

3

4

5 Yeors

80

60

20,,

Fig. 2. Cumulative patient survival (no significant difference). I = d o n o r s aged 16-25 years and over 40 (n = 230); II = d o n o r s aged less t h a n 16 years (n = 97) % 100

36

1

2

3

/,,

5 Years

80

60-

-'-..~ ~ , ~ . ~

20 Fig. 3. Cumulative graft survival (no significant difference). I = d o n o r s aged 16-25 years (n----- 171); II---- d o n o r s aged over 40 years (n = 59) International Urology and Nephrology 13, 1981

Manayadze et al. : Pediatric cadaver kidney in transplantation % 100

2

99

5 Yeors

3

80-

60-

I

I

Fig. 4. Cumulative graft survival (the difference is significant at 3 and 6 month~and 1, 2 g* and 4 years). I = donors aged 16-25 and over 40 years (n = 230); 1I = donors2aged less than 16 years (n = 97) % lo0

3

&

5 Yeors

-

80

60

~0-

-"-4,.

20-

Fig. 5. Cumulative graft survival (the difference is not significant, with two exceptions at 3 months and 2 years between groups I and III). I = donors aged 16-25 and over 40 years (n = 230); II = donors aged 11-15 years (n = 52); III = donors aged 6-10 years (n = 39); IV = donors aged less than 6 years (n = 6) (p < 0.05). The n u m b e r o f cases in g r o u p IV was t o o small for statistical analysis at 4 and 5 years. The percentage o f technical complications was 6.5 ~ in the adult and 13.4 in the pediatric d o n o r group. This difference is significant (p < 0.05). Figure 6 shows the percentage o f useless, respectively not viable and therefore not transplanted d o n o r kidneys in each d o n o r age group indicating the highest rate (67.8 ~o)in the age g r o u p over 40 years. In the pediatric groups the percentage is markedly lower and ranges f r o m 32.1 to 5 4 ~ . A n explanation for this p h e n o m e n o n is the possibly m o r e rigorous d o n o r kidney selection and/or judgement o f the organ viability in the age g r o u p over 40 because o f an increased frequency o f arteriosclerosis, high b l o o d pressure and other age-related diseases. 7*

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Managadze et al.: Pediatric cadaver kidney in transplantation % 100

248

9/.0

548

139

81

26

16-25

11-15

6-10

<6

Donor kidneys

Donor Qge (years)

Fig. 6. Percentage of not viable and therefore not transplanted kidneys in relation to the whole pool of harvested donor kidneys (the difference between the adult and the pediatric donor groups is significant) To summarize, in the adult group 55.3 % of the harvested kidneys were not used for transplantation, in contrast to only 39% in the pediatric group. The difference was significant (p < 0.01). The mode of arterial vascular anastomosis does not significantly influence the cumulative graft survival. Discussion

The limited availability of cadaveric kidneys has resulted in an increased utilization of pediatric kidneys and their use in adult recipients [7]. However, there are only few reports presenting comparative analyses between recipients with pediatric or adult donor kidneys [7, 19, 36]. Pediatric age has been suggested as a proper criterion for donor exclusion [18]. Statistically significant improvement in graft survival with decreasing donor age has been reported [11, 35] and denied [46]. Opelz and Terasaki [38] found that between 11 and 60 years the age of the recipient appeared to be more impor= rant than that of the donor, contrary to the results of Morling et al. [35]. Donor organ supply and demand were studied by Fox et al. [18] who concluded that donor age was the most restrictive criterion for selection. Inclusion of pediatric donors might have doubled the number of otherwise suitable candidates in that study. In our whole series of 535 cadaveric transplants, 97 (18%) were from pediatric donors, indeed a substantial proportion as compared with 21.8 % in the series of Glass et al. [19]. These numbers also agree with the study of cadaveric organ availability by Roloff et al. [43], in which 23 % of the cases were excluded because they were younger than 16 years. Our results regarding the graft survival are similar to those of Boczko et al. [7] and Salvatierra and Belzer [44] in 45 recipients of the younger than 10-year-old donor kidneys. They are also similar to those of Glass et al. [19], however, markedly better than those of Munda et al. [36] in all of the 97 recipients of pediatric donor kidneys (Table 2). In the 230 recipients of adult donor kidneys our results are better than those International Urology and Nephrology 13, 1981

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Table 2 Graft survival at 6 months, 1 and 2 years in the pediatric donor group (less than 16 years) G r a f t survival ( ~ ) Authors

Glass et al. [19] Munda et al. [36] Present series

6 months

I year

2 years

33-- 45

33-- 45 22 49

33- 45

55

47

figuring in the comparative analyses~ of all authors (Table 3), Contrary to the results ofo~her authors [7, 19], our analysis demonstrated that there is a significant difference between pediatric and adult donor kidneys with respect to the graft survival. This difference is established almost exclusively within the first 3 months after transplantation. Figures 4 arld 5 show an apparent inverse relationship between early graft loss and donor age, and correlates with the results of Glass et al. [19]. This could be attributed to the significantly higher rate of technical problems and complications in the pediatric donor group. A similar observation was made by Munda et al. [36]. In comparison with the literature, our results with pediatric and adult donor kidneys are excellent [1, 14]. Therefore, it does not seem necessary to decrease the use of pediatric kidneys in transplantation. However, further investigations on the problems of pediatric donor kidney, as described also by Owens et al. [39], are necessary to explain our results and to increase the utilization of pediatric cadaver donor kidneys, since the persistent shortage of cadaveric kidneys is a limiting factor for the frequency of transplantation. In a retrospective study Bart et al. [3, 4] showed that in a defined geographic area only 8.9 ~o of the potential kidneys were harvested for use in transplantation, and 24.9 of the potential kidney donors were under the age of 15 years. These numbers represent the importance of pediatric cadavers as potential kidney donors and the necessity of making a potential donor an actual donor.

Table 3 Graft survival at 1, 2 and 5 years in the adult donor group (more than 15 years) G r a f t survival ( % ) Authors 1 year

Boczko et al. [7] Glass et al. [19] Munda et al. [36J Present series

35 48 48 62

2 years

5 years

13 41 59

41

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Acknowledgements The authors wish to thank all the surgical teams for their continued support in the harvesting of donor kidneys. We are grateful to Drs. R. Templin and H. Schulze, and to Mrs. Wilia Franke for their invaluable assistance in data collection.

References 1. Advisory Committee ACS/NIH Renal Transplant Registry: The 13th report of the human renal transplant registry. Transplant. Proc., 9, 9 (1977). 2. Andersen, O. S., Jonasson, O., Merkel, F. K. : En bloc transplantation of pediatric kidneys into adult patients. Arch. Sur#., 108, 35 (1974). 3. Bart, K. J. : The prevalence of cadaveric kidneys for transplantation. Amer. Ass. Tissue Banks, Proc. 1977, p. 124. 4. Bart, K. J., Macon, E. J., Humphries, A. L.: A response to the shortage of cadaveric kidneys for transplantation. Transplant. Proc., 11, 455 (1979). 5. Belzer, F. O., Schweitzer, R. T., Holliday, M., Potter, D., Kountz, S. L.: Renal homotransplantation in children. Am. J. Sur#., 124, 270 (1972). 6. Belzer, F. O., Schweitzer, R. T., Kountz, S. L. : Management of multiple vessels in renal transplantation. Transplant. Proc., 4, 639 (1972). 7. Boczko, S., Tellis, V., Veith, F. J. : Transplantation of children's kidneys into adult recipients. Sur9. Gynec. Obstet., 146, 387 (1978). 8. Braun, E. : Eine einfache Methode der Ureteroneozystostomie mit extravesikaler submuk~ser Tunnelbildung. Zschr. Urol., 66, 765 (1973). 9. Chailley, J., Lanson, J., Gagnadouy, M.-F., Lenoir, G., Guespy, P., Beurton, D., Broyer, M., Cukier, J.: Les transplantation r6nales de l'enfant. J. Urol. N~phrol., 76, 173 (1978). 10. Chlepas, S., Sigel, A. : Einfache oder doppelte en-bloc-Transplantationvon Kindernieren auf Erwachsene? Aeta Urol., 10, 65 (1979). 11. Darmady, E. M. : Transplantation and the ageing kidney. Lancet, 11, 1046 (1974). 12. Dreikorn, K., R/Shl, L., Horsch, R. : The use of double renal transplants from pediatric cadaver donors. Brit. J. Urol., 49, 361 (1977). 13. EDTA Registration Committee: Combined report, including paediatrics, on regular dialysis and transplantation in Europe, IV, 1973. Proc. EDTA, 11, 2 (1974). 14. EDTA Registration Committee: Combined report on regular dialysis and transplantation in Europe, IX, 1978. Proc. EDTA, 16, 3 (1979). 15. Fine, R. N., Brennan, L. P., Edelbrock, H. H., Riddell, H., Stiles, Q., Lieberman, E. : Use of pediatric cadaver kidneys for homotransplantation in children. JAMA, 210, 477 (1969). 16. Fine, R. N., Korsch, B. M., Stiles, Q., Riddell, H., Edelbrock, H. H., Brennan, L. P., Grushkin, C. M., Lieberman, E. : Renal homotransplantation in children. J. Pediat., 76, 347 (1970). 17. Fine, R. N., Korsch, B. M., Brennan, L. P., Edelbrock, H. H., Stiles, Q., Riddell, H., Weitzman, J. J., Mickelson, J. C., Tucker, B. L., Grushkin, C. M. : Renal transplantation in young children. Am. J. Sur#., 125, 559 (1973). 18. Fox, P. S., Failla, J. P;, Kauffman, H.. M., Darin, J. C. : The cadaver donor: logistics of supply and demand in an urban population. JAMA, 222, 162 (1972). 19. Glass, N. R., Stillman, R. M., Butt, K. M. H., Kountz, S. L. : Results of renal transplantation using pediatric cadaver donors. Surgery, 85, 504 (1979).

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20. Goodwin, W. E., Mims, H. M., Kaufman, J. J. : Human renal transplantation. IlL Technical problems encountered in six cases of kidney homotransplantation. J. UroL, 89, 349 (1963). 21. Henriksson, C., Sigstr6m, L., Gustafsson, A., Gelin, L.-E.: Renal transplantation in children. Scand. J. Urol. Nephrol., 38, 99 (1976). 22. Hume, D. M., Lee, H. M., Williams, G. M., White, H. J., Ferr6, J., Wolf, J. S., Prout, G. R., Slapak, M., O'Brien, J., Kilpatrick, S., Kauffman, H. M., Cleveland, R. J.: Comparative results of cadaver and related donor homografts in man, and immunologic implications of the outcome of second and paired transplants. Ann. Surg., 164, 352 (1966). 23. Iitaka, K., Martin, L. W., Cox, J. A., Mc Enery, P. T., West, C. C.: Transplantation of cadaver kidneys from anencephalic donors. J. Pediat., 93, 216 (1978). 24. Kelly, W. D., Lillehei, R. C., Aust, J. B., Varco, R. L., Leonhard, A. S., Griffin, W. J., Markland, C., Herdman, R. C., Vernier, R. L., Michael, A. F., Levitt, J.: Kidney transplantation: Experience at the University of Minnesota Hospitals. Surgery, 62, 704 (1967). 25. King, L., Gerbie, A. G., Idriss, F. S., Swensson, O., Sigel, A., Delgreco, F., Grayhack, J., Gross, M., Gonzales, E., Stolpe, Y. : Human renal transplantation with kidney grafts from the newborn. Inbest. Urol., 8, 622 (1971). 26. Kinne, D. W., Spanos, P. K., DeShazo, M. M., Simmons, R. L., Najarian, J. S. : Double renal transplants from pediatric donors to adult recipients. Am. J. Surg., 127, 292 (1974). 27. Krneta, A., Tscholl, R. : Transplantationsresultat 2 Jahre nach der Implantation zweier kindlicher Nieren en bloc mit Aorta und V. cava bei einem Erwachsenen. Helv. chir. Acta, 42, 143 (1975). 28. Ktiss, R., Carney, M., Poisson, J., Chatelain, C. : Aspects chirurgicaux de l'homotransplantation r6nale chez l'homme. M~m. Acad. Chir., 92, 624 (1966). 29. La Plante, M. P., Kaufman, J. J., Goldman, R., Gonick, H. C., Martin, D. C., Goodwin, W. E. : Kidney transplantation in children. Pediatrics, 46, 665 (1970). 30. Lawson, R. K., Campbell, R. A., Hodges, C. V. : Renal transplantation in infants and small children. Transplant. Proc., 3, 358 (1971). 31. Lawson, R. K., Bennett, W. M., Campbell, R. Q., Pirofsky, B., Hodges, C. V. : Hyperacute renal allograft rejection in the human neonate. Invest. UroL, 10, 444 (1973). 32. Martin, L. W., Gonzalez, L. L., West, C. D., Swartz, R. A., Sutorius, D. J.: Homotransplantation of both kidneys from art anencephalic monster to a 17-pound boy with Eagle-Barrett syndrome. Surgery, 66, 603 (1969). 33. Meakins, J. L., Smith, E. J., Alexander, J. W.: En bloc transplantation of both kidneys from pediatric donors into adult patients. Surgery, 71, 72 (1972). 34. Merkel, F. K., Ing, T. S., Ahmadian, Y., Lewy, P., Armbruster, K., Oyama, J., Sulieman, J. S., Belam, A. B., King, L. R. : Transplantation in the young. J. Urol., 111, 679 (1974). 35. Morling, N., Ladefoged, J., Lange, P., Nerstr/Sm, B., Nielsen, B., Staub Nielsen, L., S6rensen, B. L. : Kidney transplantation and the donor age. Tissue Antigens, 6, 163 (1975). 36. Munda, R., Alexander, J. W., First, M. R., Fidler, J. P. : Hypothermic pulsatile perfusion and transplantation of pediatric cadaveric kidneys into adults. Am. J. Surg., 44, 451 (1978). 37. Najarian, J. S., Simmons, R. L., Tallent, M. B., Kjellstrand, C. M., Buselmeier, T. J., Vernier, R. L., Michael, A. F.: Renal transplantation in infants and children. Ann. Surg., 174, 583 (1971). 38. Opelz, G., Terasaki, P. I.: Cadaver kidney transplant in North America: Analysis 1978. Dial. & Transplantation, 8, 167 (1979). 39. Owens, M. L., Pritchett, T. R., Robertson, T., Simmons, S. : The effect of insulation on warm ischemia during kidney transplantation. J. Surg. Res., 27, 100 (1979). International Urology and Nephrology 13, 1981

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