Booth, A

Corman, J

Groth, C

Halgrimson, CG

Penn, I

Putnam, CW

Starzl, TE

English

PubMed

D-Scholarship@Pitt

Eight- to Ten-Year Follow-up in Early Cases of Renal Homotransplantation By C. G. Halgrimson, I. Penn, A. Booth, C. Groth, C. W. Putnam, J. Corman, and T. E. Starzl l 1H1S report will be concerned with a medicat social, and psychiatric follow-up on a group of patients treated by renal homotransplantation from 81/2 to 10 yr ago at the Denver Veterans Administration and Colorado General Hospitals. CASE MATERIAL The 64 patients who underwent trans-plantation between November, 1962 and March, 1964 have been extensively de-scribed in journals and in a book based almost entirely on these cases.1.2 There were 46 recipients of consanguineous kid-neys from 23 siblings, 20 parents, one aunt, one uncle, and one cousin, and 18 recip-ients of nonrelated kidneys donated by healthy volunteers. Immunosuppression was with azathioprine and prednisone, using two regimens. In 45 cases azathio-prine was started alone; prednisone was added in 43 of these 45 patients with the appearance of clinically obvious rejection. In the other 19 recipients both drugs were administered from the outset. Typing procedures were not available when this series was compiled. Conse-quently, the donor-recipient matching was not by any kind of immunologic guidelines except for the avoidance in all cases after case 23 of the kind of red blood cell type incompatibility that can lead to hyperacute From the Department of Surgery, University of Colorado School of Medicine and the Veterans Administration Hospital, Denver, Colorado. Supported by research Grants from the Veterans Administration, by Grants RR-00051 and RR-0069 from the general clinical research centers program of the Division of Research Resources, National Institutes of Health, and by USPHS Grants AI-I0176-01, AI-AM-08898, and AM-07772. rejection. l Parenthetically, one of our earli-est recipients is still alive with perfect graft function 9 yr 8 mo after transplantation from a B+ type donor to A+ type recip-ient, a combination which would no longer ever be used. All of the recipients had splenectomy. The first eight (of whom four are still living) had pretransplantation thymectomy. Nine additional patients had thymectomy 81/2 to 17 mo after transplantation in the hope of being able to reduce immunosup-pression. Five of the nine recipients are still alive but three of them have under-gone retransplantation. Although thymec-tomy may have a beneficial effect in humans2, it is no longer performed in our center. SURVIVAL The 46 Related Cases After a heavy mortality (33%) in the first 6 mo, subsequent deaths have been uncommon (Fig. 1). Of the 31 recipients who survived for a half year, 29 and 28 lived for 3 and 5 yr, respectively, and 24 are still alive after 81/2 to almost 10 yr. No one is now on dialysis and 21 of the 24 have function of their original grafts; the other three had retransplantations 51/2,5%, and 7 yr after the first procedure and the secondary kidneys have subsequently func-tioned for 41/3, 3%, and 11/2 yr. The outcome was not strikingly influ-enced by the nature of the relationship whether this be parental, sibling, or other (Table 1). The parent-to-offspring results were amazingly stable in terms of recipient survival. At the end of 6 mo, 14 of 20 recipients (70%) were alive. By 81/2-10 yr Transplantation Proceedings, Vol. V, No.1 (March), 1973 787 788 FRACTION SURVIVIM; , , R.Jalld_46Po".ot. Unr.loIlcI- __ 18 Pall..,U "l ___ , ___________ ". . , , TIME IN YEARS Fig. 1. Life survival curves of 64 patients treated from November, 1962 to March, 1964. The denominators in the related and non related curves refer to patient survival and the numerators to survival of the orig-inal homograft. Thus, 22 of the 26 living recipients still bear primary grafts; the other four have had successful retransplants. there were still 13 (65%) alive, although three of these were by virtue of retrans-plantation. Also of interest was the fact that all of the three distantly related renal grafts (aunt, uncle, and cousin) were pro-viding superb function, nearly a decade after their insertion (Table 1). The causes of mortality in the first 5-yr follow-up of this series have been exhaus-tively reportedL2 for which reason only the four deaths in the second 5 yr will be mentioned. Two patients with adequate renal function 81/4 and 9 yr posttransplan-tation died of chronic aggressive hepatitis of several years' duration; one was Aus-tralia-antigen positive. A third patient had HALGRIMSON ET AL. a fatal myocardial infarction after 71/3 yr. The fourth patient had a technically unsuc-cessful retransplantation in the sixth year, and then committed suicide by refusing to be placed back on hemodialysis. The 18 Nonrelated Cases Two-thirds of the recipients died in the first year with a mortality that continued until only two patients were left at the 5-yr mark (Fig. 1). These two are still alive after 81/2 and 82/3 yr but in the second instance a second homograft from a mother has supported life for the last 6 yr of the total survival. GRAFT FUNCTION AND IMMUNOSUPPRESSION In Table 2 are shown the average cur-rent renal functions of the 26 survivors, these values representing 22 primary kid-neys that have functioned for 81/2 to nearly 10 yr and four retransplants that have functioned for 11/2-41/3 yr. On the average, the older grafts are performing better than the more recent ones. The chronic immuno-suppression being given those patients is also listed. The average daily doses of prednisone are small enough so that only one patient (the most recent retransplant) has a Cushing's facies. Arterial hypertension is an almost uni-versal finding in the immediate posttrans-plantation period and even for several years afterwards.1.2 This problem has tended to become less with longer follow-up. Only Table 1. The Influence of Consanguinity upon Present Survival in 46 Cases After 8-1 /2 to 9-5/6 Yr 1 Yr 3 Yr 5 Yr Now Donor Patient Graft Patient Graft Patient Graft Patient Graft 20 Parents 14 14 14 14 14 (70%) 14 (70%) 13 (65%)* 10 (50%) 23 Siblings 14 14 12 12 11 (48%) 11 (48%) 8 (35%) 8 (35%) 3 Aunt, uncle. or cousin 3 3 3 3 3 (100%) 3 (100%) 3 (100%) 3 (100%) *Retransplantation was carried out after 5'12, 53/4, and 7 yr. RENAL HOMOTRANSPLANTATION one of the survivors (and this the retrans-plant of 11/2 yr ago) has severe hyperten-sion. Five other patients receive small daily doses of a combination of antihyperten-sives. Fourteen recipients require no anti-hypertensive therapy, and six are receiving only chlorothiazide. With the generally low steroid doses, there are no examples of steroid-induced diabetes. THE QUESTION OF CANCER Six of the 64 recipients (9%) including four who are still alive developed carcin-789 omas, the features of which are summarized in Table 3. All were skin cancers and treat-ment was by standard surgical measures. 50 far cancer has not been a cause of death in this original group of patients although we have had two deaths from de novo reticulum cell sarcomas in patients treated since 1964.2 THE QUALITY OF LIFE The degree of rehabilitation in this group has been truly remarkable. All those who were adults at the time of transplantation Table 2. Average Current Renal Function and Immunosuppression in 26 Recipients of Renal Homografts Surviving 81/2-10 Yr Posttransplantation Serum Creatinine BUN Creatinine Clearance Azathioprine Prednisone Patient (mg 100 mil (mg 100 ml) (ml/min) (mg/day) (mg/day) LD 1- 22 1.6 90 125 15 LD 2 16 1.7 70 100 0 LD 3 11 1.1 130 150 0 LD 6 20 1.3 105 200 10 LD 12 18 1.4 70 100 15 LD 13 19 1.4 90 87.5 7.5 LD 14 10 0.9 120 200 0 LD 17 9 0.8 70 100 2.5 LD 22 17 0.8 90 137.5 10 LD 25 22 1.6 80 50 10 LD 33 12 1.2 90 125 0 LD 34 31 1.5 60 50 0 LD 37 11 1.0 94 150 15 LD 39 17 1.0 80 125 10 LD 41- 60 3.0 20 5 30 LD 42 18 1.1 75 125 7.5 LD 49 25 1.1 70 87.5 5 LD 50- 49 2.0 45 75 20 LD 51 21 1.3 85 125 10 LD 52 17 0.8 110 150 5 LD 53 25 1.6 55 100 5 LD 54* + 25 1.1 85 125 15 LD 55 27 1.4 40 150 20 LD 58 16 1.4 65 137.5 10 LD 60 46 3.3 40 87.5 20 LD 63+ 27 1.4 80 125 15 Mean ± SD 22 Original grafts 19.8 ± 8.3 1.3 ± 0.5 80.4 ± 22.9 121.0 ± 38.8 8.1 ± 6.3 Four retransplantation 39.0 ± 18.5 1.9 ± 0.8 60.0 ± 33.4 82.5 ± 56.8 20.0 ± 7.1 All 36 patients 22.7 ± 12.2 1.4 ± 0.6 77.3 ± 25.2 115.1 ± 43.1 9.9 ±7.7 'Patients surviving after retransplantation (LD 1, 4112 yr, LD 41,1 3/ 4 yr, LD 50, 3 yr, LD 54, 6 yr). tSurviving recipients of living unrelated renal homografts. 790 heave returned to some kind of full time work ranging from menial through tech-nical to highly intellectual. Twelve of the survivors were younger than 18 yr (3-17) at the time of the original operation. They all returned to school, half graduated from college, eight now support themselves fully in adult work, and nine have married. The only one who has spent an excessive amount of time in the hospital is a child originally treated at the age of 3, whose original homograft failed, and who subsequently required retransplantation. He is now 12 years old and is stunted in growth. His prognosis to reach emotional and physical maturity is doubtful. At the time of this original series, poten-tial recipients were screened with great care to rule out those with possible important psychiatric problems. Because of this, it has not been surprising to find exceptional HALGRIMSON ET AL. emotional stability among those who were accepted and who are still surviving. Excel-lent adjustments have been made in spite of such serious early postoperative compli-cations as aseptic necrosis of one or both of the femoral heads in three of the adoles-cents. These latter patients have learned to walk adequately in spite of their handicaps. Many of the young patients were stunted in growth before and after transplantations and have had catch-up growth spurts late in their teens. Nine of the 64 patients of the original series have had children of their own, in-cluding three by two female and 10 by seven male recipients. One of these off-spring had a meningomyelocele which re-quired surgical correction. It is of interest that all the children issuing from this trans-plant population came from those 26 still surviving. Thus, no orphans have so far Table 3. Features of Cancers in Original Colorado Transplant ReCipients Time of Onset Follow-up After After Initial Trans- Diagnosis of Patient plant Tumor Number (Mo) Type of Tumor Treatment Outcome (Mo) LD 63 66 Squamous cell Wide excision No recurrence 35 carcinoma lower lip LD 30 32 Squamous cell Wide excision No recurrence; 20 carcinoma skin died of perforated of ear dive rticu litis LD 6 75 Basal cell carcinoma Wide excision No recurrence 38 nasolabial fold LD 48 74 Squamous cell Multiple Died of myocardial 14 carcinomas excisions infarction forearms, right arm, and scalp LD 60 78 Squamous cell Excisions and No recurrence 24 carcinomas-two skin graft of of left hand and hand one of face LD 55 87 Squamous cell Wide excision Eight months later 15 carcinoma face and skin graft had radical neck dissection for lymph node metastases RENAL HOMOTRANSPLANTATION been created by the premature death of a transplant patient. DISCUSSION It is axiomatic that some degree of immu-nologic weakening must be accepted as the price of success after whole organ trans-plantation under immunosuppression. Be-cause of this, it was once feared that a real margin of safety might not exist which would permit effective graft protection without killing the host. The fallacy of this assumption as it applies to the early post-operative course has long since been proved. Now, there is evidence that immu-nosuppression may be tolerated for inter-vals that will extend beyond a decade in many instances. In the early days of transplantation, the feared specter with chronic immunosup-pressive therapy was infection particularly with opportunistic organisms for which ef-fective treatment is not available. A second concern has more recently derived from the well-documented increased incidence of de novo cancer in the transplant population. Both anxieties have a real basis as the ob-servations in this early series have shown. Yet, the incidence and severity of late infec-tion or tumors has by no means cancelled 791 the effectiveness of treatment by trans-plantation. Instead, with each passing year the case is strengthened that transplantation repre-sents one of the greatest, although as yet incompletely exploited, therapeutic achieve-ments of modern medicine. It has become clear that about half of the original series of related kidney recipients are going to move into the second decade of their con-valescence. The poorer results in non-related transplantation would have been discouraging if it were not for the great progress made in many centers including our own with cadaver transplantation since the spring of 1964, when the presently re-ported series was completed. SUMMARY Sixty-four consecutive patients under-went renal homotransplantation 81/2 to al-most 10 yr ago, 46 from related and 18 from nonrelated living donors. Twenty-four (52 %) of the 46 consanguineous recip-ients survive to date, in 21 cases with func-tion of the original grafts. Only two of the 18 recipients of nonrelated kidneys survive and one of these patients has undergone retransplantation. The patients who are alive have had a high and continuing de-gree of rehabilitation. REFERENCES 1. Starzl, T. E.: Experience in Renal Trans-plantation, Philadelphia, Saunders, 1964. 2. Starzl, T. E., Porter, K. A., Andres, G., Halgrimson, C. G., Hurwitz, R., Giles, G., Tera-saki, P. I., Penn, I., Schroter, G. T., Lilly, J., Starkie, S. J., and Putnam, C. W.: Ann. Surg. 172:437, 1970. 

Eight- to ten-year follow-up in early cases of renal homotransplantation.

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Eight- to ten-year follow-up in early cases of renal homotransplantation.

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