Search

Use of pediatric cadaver kidneys for transplantation is controversial; reports of outcome following pediatric donor transplantation have shown either similar results or worse results than when adult donors are used. Two techniques have been proposed for use of pediatric donor kidneys ‐ transplantation of a single kidney, or transplantation of both kidneys with a common aorta and cava to a single recipient. Single kidney transplants make optimum use of the donor pool; double transplants provide increased renal mass and therefore more functional reserve in the early posttransplant period. No study from a single institution has compared outcome after double versus single pediatric cadaver kidney transplantation. To investigate this issue, we reviewed our experience with 131 pediatric cadaver kidneys (donor age ≤ 10 years) transplanted between 1971 and 1988. We compared outcome of these transplants to outcome of adult donor kidney transplants. Of the group receiving pediatric kidneys, 33 (25%) received double and 98 (75%) received single pediatric kidney transplants. For double pediatric graft recipients, 5 and 10‐yr patient survival rates were 81% and 75%, respectively, whereas for single graft recipients, 5‐ and 10‐yr patient survival rates were 67% and 54% (NS). Graft survival was 78% (1 yr) and 48% (10 yr) in double kidney transplant recipients, but only 61% (1 yr) and 34% (10 yr) in single kidney transplant recipients (p = 0.07). When compared to adult cadaver kidney recipients, double graft recipients had similar short‐ and long‐term outcome (p = 0.6), whereas single pediatric kidney recipients had significantly decreased graft survival (p = 0.03). Pathogenesis for graft loss was similar in double and single pediatric kidney transplants. However, early graft loss (within first 3 months posttransplant) due to rejection was more frequent in single (16%) than in double (3%) pediatric allograft recipients (NS). We conclude that double pediatric cadaver kidneys provide an overall higher patient and graft survival. However, optimal use of the donor pool may be made by the use of single pediatric kidney transplants.

Our prospective, randomized trial comparing cyclosporine (CSA) and prednisone (P) with azathioprine (AZA)‐P‐antilymphoblast globulin (ALG) in cadaveric renal transplant patients from 1980 to 1984 demonstrated that CSA‐P treatment produced slightly higher graft survival rates, fewer acute rejection episodes, less infectious complications, and shorter hospital stays while the AZA‐P‐ALG treatment produced lower serum creatinine levels and a shorter duration of delayed graft function. In an attempt to capture the benefits of each protocol, we began evaluating a CSA‐P‐AZA‐ALG regimen in cadaveric renal allograft recipients. In this report, we compared the 1st year results of this new four‐drug protocol given to 78 patients with the 1st yr results of the two‐drug regimens previously studied (CSA‐P, n = 81 and AZA‐P‐ALG, n = 75). The three groups were matched for age, sex, number of retransplants, and diabetic status, and all patients were followed for at least 1 yr posttransplant. The overall 1‐yr actual patient survival rates were 94% for CSA‐P‐AZA‐ALG, 90% for CSA‐P, and 88% for AZA‐P‐ALG. Actual graft survival rates at 1 yr were 87% for CSA‐P‐AZA‐ALG, 80% for CSA‐P, and 73% for AZA‐P‐ALG. The incidence of acute rejection in the 1st yr was similar for CSA‐P‐AZA‐ALG ‐ and CSA‐P‐treated patients (40% vs33%), but was lower in both of these groups than in the AZA‐P‐ALG‐treated patients (55%). The 1‐yr incidence of infectious complications was 38% for CSA‐P‐AZA‐ALG patients, 30% for CSA‐P patients, and 55% for AZA‐P‐ALG patients. Although the incidence of acute tubular necrosis was not significantly different among the three groups, the duration of oliguria and number of dialyses required were significantly less in the CSA‐P‐AZA‐ALG patients than in the CSA‐P patients. Serum creatinine levels at 1 yr posttransplant were lowest in the AZA‐P‐ALG patients (1.5 ± 0.2 mg/dl), 1.7 ± 0.2 mg/dl for CSA‐P‐AZA‐ALG patients, and 2.0 ± 0.2 mg/dl for CSA‐P patients. In summary, our CSA‐P‐AZA‐ALG immunosuppressive protocol for use in cadaveric renal transplantation has achieved its original goal of reducing the adverse consequences of CSA nephrotoxicity by decreasing the duration of acute tubular necrosis and improving creatinine levels while maintaining high patient and graft survival rates.

Between January 1971 and February 1988, 1121 cadaver donor kidney transplants were performed at the University of Minnesota. Of these, 873 (77.9%) were from adult (> 15 years of age) donors, 117 (10.4%) from adolescents (> 10, < = 15) and 131 (11.7%) from pediatric (< = 10) donors. Of the last group, 25% of the patients received double and 75% single pediatric cadaver kidney transplants. We compared outcome of pediatric, adolescent and adult donor transplants. There was no difference in patient survival between recipient groups. One‐ and 5‐yr graft survival was 74% and 54% for recipients of adult kidneys, 68% and 53% for recipients of adolescent kidney, and 65% and 46% for recipients of pediatric cadaver kidneys (p = 0.03). Interestingly, the entire difference could be explained by a subgroup – adult or adolescent retransplant recipients of single pediatric kidneys. There was no statistical difference between any groups when primary transplants alone were considered. For pediatric retransplant recipients, there was no difference in outcome if the graft came from a pediatric or adult donor. For the adult or adolescent retransplant recipient most of the difference in graft survival occurred within the first 3 months after transplantation and this difference was maintained throughout the entire follow‐up. Analysis of graft loss within the first 3 months revealed that both acute and chronic rejection were more frequent in recipients of pediatric donor kidneys (p = 0.008). We conclude that the single pediatric kidney is associated with significantly worse graft survival in the adult retransplant recipient.

During the 25‐year period from 1963 to 1988, 127 patients with end‐stage renal failure (ESRF) secondary to autosomal dominant polycystic kidney disease (ADPKD) received a total of 143 renal transplants. The average follow‐up time was 116 months (range 3 to 300 months). Mean age (45.8 yr) was significantly higher than the average age in our transplant population (31 yr) (p< 0.001). No correlation was found between ADPKD and HLA‐A or ‐B antigen frequency among the patients. Overall patient and graft survival was 90% and 73% at 1 yr, 74% and 53% at 5 yr, 55% and 36% at 10 yr, and 37% and 28% at 15 yr, respectively. When death with a functioning graft was excluded as a cause of graft loss, 15‐yr graft survival was 57%. The most common causes of death were cardiovascular complications (46%) and infections (34%), while graft loss was mainly due to patient death (50%), or rejection (38%). Multivariable analysis showed patient survival to be influenced by the level of panel reacting antibodies at the time of transplantation (PRA) (p = 0.002), while graft survival was affected primarily by the donor status (living related vs. cadaver) (p = 0.02). Outcome in transplant patients with ADPKD was compared to outcome in two matched control groups: diabetic and nondiabctic transplant recipients. There was a lower patient survival rate for the diabetic group (p = 0.0003). Graft survival, however, was similar among the three groups, with the exception of diabetics treated with azathioprine, , ALG and prednisone who appeared to have a lower graft survival rate (p = 0.0002). The cause of patient death and graft loss overall did not differ among the three groups studied; however, ADPKD and diabetic patients showed an increased death rate due to cardiovascular episodes for the time period between the 1st and 5th posttransplant years (p = 0.02). We conclude that, although ADPKD patients are older at the time of transplantation, they are excellent transplant candidates.

The results of 182 primary renal transplants in patients over 50 yr old were analyzed by two eras: 123 patients received standard therapy (antilymphocyte globulin, azathioprine and prednisone) during Era 1 (January 1968‐July 1979); while 25 patients received standard immunosuppression, and 34 received cyclosporine (cyclosporine plus prednisone) during Era 2 (August 1979‐April 1984). Our results indicate: (1) older patients during Era 1 did significantly poorer than younger patients (p < 0.03), (2) results in older patients receiving cyclosporine improved during Era 2, (3) the greatest improvement was seen in recipients of cadaveric grafts, (4) the incidence of acute rejection episodes was slightly higher (NS) in the standard treatment groups during Era 2; however, the cyclopsorine group had easily reversed rejections while the standard therapy group developed lethal infectious complications, and (5) results in older and younger patients receiving cyclopsorine are comparable. We conclude that cyclosporine allows older patients to be transplanted safely and with excellent results.

Despite the superior patient and allograft survival rates of HLA‐identical sibling renal transplantation, a substantial incidence of acute rejection still occurs with the conventional azathioprine‐prednisone (AZA‐P) or AZA‐P‐antilymphocyte globulin (ALG) immunosuppressive regimens. In an attempt to further improve these results, we compared a cyclosporine (CSA)‐AZA‐P combination with AZA‐P‐ALG in 60 consecutive HLA‐identical sibling renal allograft recipients. The distribution of gender, age and proportion of diabetics was almost identical between the two groups. There was no significant difference (p = 0.51) between the CSA‐AZA‐P versus AZA‐P‐ALG groups in patient or graft survival at 1 year (100% versus 93%). Renal function was also similar when comparing the best (1.0 ± 0.7 vs 1.0 ± 0.3 mg/dl, p = 0.46) and current serum creatinine concentrations (1.4 ± 0.7 vs 1.4 ± 0.3 mg/dl, p = 0.45). The AZA‐P‐ALG treated group had a 40% incidence of rejections at 6 months, while rejections were totally eliminated in the CSA‐AZA‐P group (p < 0.001). Patients who received CSA‐AZA‐P also had a lower incidence of infections at 6 months posttransplant (3% vs 27%, p = 0.05), and shorter mean hospitalization time posttransplant (7.4 ± 4.3 days vs 12.4 ± 7.7 d, p < 0.001). Our results suggest that the CSA‐AZA‐P combination is safe and extremely effective for immunosuppression in HLA‐identical sibling renal transplantation.

To determine whether renal allograft recipients with sustained or transient elevation in hemoglobin (Hgb) level are at increased risk for thromboembolism, we examined the incidence of arterial and venous thromboembolic events in various subgroups of 224 patients who were prospectively randomized and stratified by risk to treatment with either cyclosporine‐prednisone (CSA‐P) (n = 117) or azathioprine‐prednisone‐antilymphocyte globulin (AZA‐P‐ALG) (n = 107). Eleven CSA patients (9.4%) and 4 AZA patients (3.7%) developed posttransplant erythrocytosis (PTE) (p = 0.08). There were no significant differences in the incidence of thromboembolic events among subgroups of phlebotomized or nonphlebotomized, CSA‐ or AZA‐treated, PTE patients, nor did these incidence rates differ significantly from those for the entire AZA and CSA groups. There was no significant increase in the incidence of thromboembolism in any of the CSA‐treated subgroups with “sustained” (≥ 1 year) or transient elevation in Hgb level when compared with the CSA‐P group as a whole or with CSA subgroups with lower Hgb levels. The percentage of AZA‐treated patients with thromboses increased in parallel with sustained Hgb levels, reaching statistical significance when patients with Hgb ≥ 16 g/dl for at least 1 yr were compared to the AZA‐P‐ALG group as a whole (p = 0.02), to AZA subgroups with lower Hgb levels (Hgb ≥ 14 g/dl for at least 1 yr, Hgb never > 17 g/dl, and Hgb never > 14 g/dl; p = 0.02, 0.02, and 0.05, respectively), and to their CSA‐treated counterparts (p = 0.03). Under both immunosuppressive regimens, however, Hgb levels tended to be low precisely at the time when patients in all subgroups had their complications. We conclude that neither transient marked elevations nor modest sustained elevations of Hgb level per seis directly associated with an increased incidence of thromboembolic complications in renal transplant recipients. PTE can be successfully managed without an increase in thromboses if therapeutic phlebotomy is utilized to maintain the hematocrit (HCT) < 50–55% and/or to treat symptoms attributable to polycythemia.

We studied the long‐term morbidity and mortality of 123 consecutive HLA‐ID living‐related kidney transplants performed at a single institution more than 10 years ago. Type I diabetes was the cause of renal failure in 39% of patients; mean age at transplant was 32 ± 12 yr (range 2–64). Immunosuppression consisted of prednisone and Imuran; most patients received ALG perioperatively. For nondiabetics, 10‐, 15‐, and 20‐yr actuarial patient survival was 85%, 75%, and 68%; for diabetics. 10‐ and 15‐yr survival was 65% and 34% (p = 0.0015). Cardiovascular complications were the main cause of death in diabetics, affecting mostly males; sepsis, malignancy, and graft loss were the main cause of death in nondiabetics. Graft survival paralleled patient survival; 76% of grafts lost were due to patient death. Graft survival at 10 and 15 yr was 81% and 73% for nondiabetics; for diabetics, it was 63% and 24%, respectively (p = 0.0031). When death as a cause of graft loss was excluded, there was no difference between diabetics and nondiabetics. Mean serum creatinine at 10 yr was 1.4 ± 0.5. Thirty‐two patients (26%) had one or more acute rejection episodes, most of them occurring within the 1st yr posttransplant. Only 7 grafts have been lost either to acute (4) or chronic (3) rejection. Twenty‐four percent of the patients had no complications. Cardiovascular complications (28%) were the major cause of morbidity and mortality, affecting mostly diabetic males. Sepsis was also a significant problem (19.5%), CMV being the most common pathogen. Malignancy occurred in 12.2% of cases, affecting most frequently the skin. Liver dysfunction, mainly of viral etiology, was the cause of 2 deaths and contributed to several others. Nontraumatic osteonecrosis occurred in 4.9% of the patients; it tended to present in young patients soon after their transplant. We conclude that the long‐term results of HLA‐ID transplantation are excellent when compared to other options in patients with ESRD. Mortality due to the underlying disease (diabetes) and morbidity due to the immunosuppression remain as major obstacles to the long‐term survival and successful rehabilitation of these patients.

One hundred and two consecutive first kidney transplants were performed in children 10 years old and younger (47 ≤ 5 years old) at the University of Minnesota between June 1963 and April 1981. Five infants under 1-year old received transplants, two of whom are alive and well. The mean age was 6 years and mean weight was 16 kg. The most common primary renal diseases were congenital hypoplastic-dysplastic kidneys (25.5), congenital nephrosis (20), and glomerulonephritis (16.5). Statistical analyses of cumulative patient and graft survival were based on the results of 88 first kidney transplants performed in children 1 to 10 years old since 1968 when medical management, patient selection criteria, surgical technique, and immunosuppression protocols were standardized. Patient survival was 72. Twenty-six percent received transplants at least twice (23 of 88), one-half of whom still have functioning second grafts. Mean intraoperative systolic blood pressures were significantly lower in children who received intraperitoneal versus extraperitoneal grafts. No differences in central venous pressure were observed. The mean blood pressure drop at the time of revascularizing the kidney did not appear to be directly related to the incidence of postoperative acute tubular necrosis (ATN). Most patients underwent splenectomy prior to or at the time of transplantation. With the use of prophylactic antibiotics, splenectomy was not a single determining factor in deaths from sepsis. Technical complications were few (four renal artery stenosis and six ureteral revisions). Results of parent to child kidney transplants in the child under 10 did not differ significantly from those results seen in an older (17 to 49) parent to child group who received transplants at this same center.

From January 1968 to December 1981, 470 uremic diabetic patients received primary renal allografts at the University of Minnesota. Until 1979, the patient and graft survival rates were less good in diabetic than in nondiabetic recipients. Since 1979, the results in diabetics have been at least equal to those achieved in nondiabetic patients. Two-year actuarial patient and graft survival rates in diabetic renal allograft recipients were, respectively, 71 and 66 from 1968 to 1976 (n = 156), 78 and 64 from 1976 to 1979 (n = 187), and 88 and 82 from 1979 to 1981 (n = 127). Improved survival rates were seen in all donor source and recipient age categories. For comparison, the 2-year patient and graft survival rates in nondiabetic renal allograft recipients who received transplants between 1979 and 1981 (n = 162) were 92 and 79. Changes associated with improved survival rates included performance of pretransplant splenectomy on all patients except those receiving grafts from HLA-identical siblings, deliberate transfusions of blood from ≥5 random donors at least 1 month before transplantation, intensive insulin therapy for diabetic management post-transplant, and less vigorous treatment of repetitive rejection episodes. The current results show that diabetic recipients are no longer at higher risk than nondiabetics for graft or patient loss, at least during the first 2 years after transplantation.

Summary: A prospective and randomized clinical trial of an inception cohort of diabetic kidney recipients to test the hypothesis that maximized metabolic control of diabetes prevents or delays diabetic nephropathy in the renal allografts was initiated approximately three years ago. Notwithstanding the fact that all our diabetic patients were on prednisone and therefore metabolically unstable, we achieved and maintained a clear difference between the standard control (group A) and the maximized control patients (group B). At 13 months of study, the mean fasting blood glucose mg% (A: 24222, B: 1309, p<0.001), nonfasting blood glucose (A: 27640, B: 13510, p<0.001), 24 hour urine glucose (A: 8516, B: 51, p<0.001), and glycosylated hemoglobin % (A: 130.9, B: 100.8, p<0.01) were all clearly and statistically significantly higher for the group A patients. These results show the feasibility of such a trial using the tools available today to treat diabetes.

We were concerned that clinical manifestations of rejection (R) might be subtle in small children transplanted with adult kidneys. We retrospectively analyzed the first rejection episode (biopsy proven) in 22 children (R group) under age 4 years [mean age, 23.7±2.2 months (±SEM); mean weight, 9.4±0.4 kg] receiving an adult-related donor kidney. We matched these patients for age, date of transplant, donor source and immunosuppression with 36 children without R (control or C group). We compared both groups at similar intervals from transplantation, based on the time of R (5.38±1.2 months) in the R group and analyzed the immediate 8-week period prior to R and the corresponding interval in the C group. Hypertension occurred in 82% (18/22) of the R versus 8% (3/36) of the C group (P<0.01). Fever longer than 7 days occurred in 45% (10/22) of the R versus 0% (0/36) of the C group (P<0.01). Increased creatinine occurred in only 45% (10/22) of the R versus 3% (1/30) of the C group (P<0.01). Cyclosporine did not influence these manifestations of R. The clinical manifestations did not predict the R grades on biopsy, which were moderate to severe in 13 and mild in 9 of the R patients. Graft survival was higher at 3 years in the C (95%) than in the R patients (65%), (P<0.004). Thus, clinical manifestations of acute R can be subtle in small children with adult renal allografts. Renal biopsy should not be delayed until the creatinine is elevated in these patients.

We compared the efficacy of continuous intraarterial versus intravenous 6-mercaptopurine (6-MP) infusion in a mongrel canine renal allograft model with regard to overall survival, incidence of systemic and renal toxicity, and systemic drug exposure. Arterial anastomoses were done end-to-end, and infusion catheters were placed in the iliac artery or vena cava and connected to a subcutaneously placed programmable pump. A dose of 0.5 mg/kg/day 6-MP did not prolong survival over heparin-treated or untreated controls (MST 7 days for both groups) when administered either locally or systemically. However, 0.75 mg/kg/day 6-MP i.a. (MST 20 days) significantly prolonged survival over both un treated (P0.007) and heparin-treated controls (P 0.02), with all dogs eventually dying of rejection. In contrast, 0.75 mg/kg/day i.v. (MST 7 days) failed to prolong survival over controls (P< 0.1) and produced death from systemic toxicity in 3 of 7 animals. Six of 7 dogs receiving 2.0 mg/kg/day 6-MP i.a. (MST 12 days) developed azotemia secondary to drug-induced nephrotoxicity. Identical renal histologic changes occurred in the same time frame in autotransplants treated similarly. Of 7 animals receiving 2.0 mg/kg/day i.v. (MST 12 days), 5 died from early, severe systemic drug toxicity and 2 from early rejection. During 6-MP infusion at 0.5 mg/kg/day, systemic exposure was significantly less in the locally treated than in the systemically treated dogs when Cr concentrations were normal or moderately elevated (P< 0.0005 and P0.01, respectively) but not when renal function became severely impaired (P0.34). In contrast to i.v. infusion, i.a. 6-MP delivery dissociated immunosuppressive efficacy from systemic toxicity, supporting previous work demonstrating high first-pass renal elimination of 6-MP. We conclude that tightly controlled local delivery of an immunosuppressive agent can effectively prolong graft survival with reduced systemic toxicity in a large animal model employing a pump/catheter system applicable to man.

• Nineteen of 224 renal allograft recipients who were prospectively randomized to receive either cyclosporine (n = 117) or azathioprine sodium—antilymphocyte globulin (n = 107) for immunosuppression suffered from one period of pneumonia (14 azathioprine and five cyclosporine recipients); two recipients of azathioprine had two episodes. Four patients in the azathioprine group and one in the cyclosporine group died, for mortalities of 3.7% and 0.85%, respectively. The percentage of pneumonia-free patients at one year was 96.3% in the cyclosporine group while it was 90.8% in the azathioprine group. Nondiabetics, women, and recipients of grafts from living related donors were at a statistically lower risk of developing pneumonia when treated with cyclosporine. Viral (cytomegalovirus), fungal (Candida, Aspergillus), and multibacterial causes of pneumonia each occurred with a similar incidence.(Arch Surg 1986;121:1056-1060)

• We compared early (&lt;70 days) cumulative survival, cause of death, and morbidity (defined as the number of organ system failures and reoperations) of 236 patients who needed dialysis for acute tubular necrosis (ATN) after transplantation with that of a control group of 215 transplant patients who had immediate renal function after transplantation. The patients were matched for age, number of transplants, time of transplantation, diabetic status, living-related vs cadaveric donor, and number of HLA matches. There were no differences in cumulative survival after transplantation, causes of death, organ system failure, or surgical complications as evident from the number of reoperations. The ATN patients' overall clinical course was similar to that described for other postsurgical patients with ATN in their native kidneys. We conclude that the poor survival and the surgical complications in patients with postoperative ATN are due to the basic disease and not to acute renal failure or to dialysis. To improve survival, research should be focused on the basic disease and the surgical procedures rather than on dialysis technique.(Arch Surg 1985;120:907-910)

The complications, cost, and inconvenience associated with pretransplant hemodialysis and peritoneal dialysis would be minimized if transplantation were instituted without prior dialysis. That preuremic transplantation is safe and efficacious in patients with immanent end-stage renal disease has not been established. All 1742 consecutive primary renal transplants performed at the University of Minnesota during the 16.5 year period from January 1968 through July 1984 were reviewed to determine whether graft and patient survival were adversely affected by transplantation prior to dialytic therapy. In the overall group of primary renal transplants, no differences in actuarial graft or patient survival were noted with or without prior dialysis. Likewise, outcome was not affected by the pretransplant dialysis status in recipients of allografts from HLA-identical or mismatched living-related donors. However, in cadaveric transplantation graft function appeared to be adversely affected by transplantation prior to dialysis, with 52 vs. 66 two-year graft function for nondialyzed vs. chronically dialyzed recipients, respectively (P =0.15). Patient survival was significantly (P=.04) decreased in the nondialyzed group, with 66 vs. 80 two-year survival in the chronic dialysis group. However, nearly all of the nondialyzed, cadaveric recipients were diabetic. The outcome of transplantation was found to be identical in these patients, as compared with chronically dialyzed diabetic recipients of cadaveric grafts. Thus, the apparent detrimental effect of predialytic transplantation in the cadaver group was due to the preponderance of diabetics in the nondialyzed group. Since July 1984, a single-armed therapeutic trial of combination therapy with azathioprine, prednisone, antilymphoblast globulin (ALG), and cyclosporine has been undertaken. Since that time, 36 primary graft recipients were transplanted prior to dialysis. Of these 36, 35 currently have a functioning graft. Thus, transplantation prior to chronic dialysis is safe irrespective of donor source, or choice of immunosuppressive agents.

The beneficial effects of pretransplant blood transfusions on the success rate of renal transplantation have been so overwhelmingly emphasized that there is virtually no information on the fate of grafts in nontransfused patients transplanted during the last decade. Since 1979, all patients who have undergone renal transplantation at the University of Minnesota have routinely received random blood transfusions except Jehovah's Witnesses. Jehovah's Witnesses refuse transfusions but will accept renal allografts. From 1979 to May 30, 1987, primary renal allografts were placed in thirteen nontransfused Jehovah's Witnesses; six patients received kidneys from mismatched living-related donors, two patients received HLA-identical sibling grafts, and five patients received cadaveric renal allografts. The range of follow-up of the thirteen patients was 3–93 months, with a mean of 45 months and a median of 50 months. The outcomes after renal transplantation in Jehovah's Witnesses were compared with those of a paired control group (n=25) matched for age, date of transplant, donor source, and diabetic status. The overall three-year actuarial patient and graft survival rates of the Jehovah's Witnesses were 83 per cent and 66 per cent, versus 80 per cent and 77 per cent for the controls. Although the outcomes after renal transplantation in Jehovah's Witnesses were similar to those of the control group, the Jehovah's Witnesses had an increased susceptibility to rejection episodes. The cumulative percentage of incidence of primary rejection episodes was 77 per cent at three months in the Jehovah's Witnesses versus 44 per cent at 21 months in the matched control group. The consequence of early allograft dysfunction from rejection was particularly detrimental to Jehovah's Witnesses who developed severe anemia (hemoglobin (Hgb) 4.5 g per cent)—two early deaths occurred in the subgroup with this combination of problems. The overall results suggest that renal transplantation can be safely and efficaciously applied to most Jehovah's Witnesses but those with anemia who undergo early rejection episodes are a high-risk group relative to other transplant patients.

The effects of mismatching for DR antigens on renal allograft survival rates have largely been restricted to analyses of cadaver transplant results. Analyses of HLA matching in recipients of transplants from related donors have focused on the number of haplotypes shared between the recipients without regard to DR, or on the total number of HLA antigens mismatched, or on the degree of MLC responsiveness of the recipient to the donor. Most related donorrecipient pairs sharing only one HLA haplotype will be mismatched for DR at the other haplotype, but because there are a limited number of DR alleles, sharing of DR antigens on the mismatched haplotypes occurs relatively frequently. To determine the influence of mismatching for DR on the fate of renal allografts from related donors, we analyzed the results of 172 kidney transplants from related donors who shared one HLAABC haplotype with the recipient. There were 156 primary grafts and 16 retransplants 147 donorrecipient pairs were satisfactory typed for DR antigens. Because genotyping was not usually done, we performed two analyses under two different assumptions. The first assumption was that individuals expressing ≤1 DR antigen had null antigens, or were homozygous for DR the alternative assumption was that blanks were true antigens and individuals with blanks were heterozygous. The first assumption is more likely to be correct, and is the assumption used in most analyses of the effect of DR antigen mismatches on the results of cadaveric transplantation. Under the first assumption, of the 147 related donorrecipient pairs in whom DR typing was satisfactory, 33 were mismatched for 0, 64 for 1, and 3 for 2 DR antigens. The oneyear absolute graft survival rates in recipients of kidneys from donors with 0 mismatches for DR was 92 n49 in those with one mismatch for DR it was 82 n94 and from those with two mismatches it was 50 n4. The oneyear graft survival rate in 25 donorrecipient pairs in which one or both members could not be satisfactorily DR typed was 76. Differences in graft survival rates between the 0 and 1 and the 1 and 2 DRmismatched groups were not statistically significant. However, there was a difference in the number of recipients who required treatment for at least one rejection episode 24 of those who were 0 mismatched, 43 with 1 mismatch, 75 with two mismatches, and 44 of those not typed required antirejection treatment—and the difference between the 0 and the 1 mismatched groups was statistically significant P<.05. The demographic features of the four groups with regard to age, diabetes, splenectomy, transfusions, method of immunosuppression, and donor source were similar. Thus, we conclude that avoiding DR mismatches in recipients of renal allografts from livingrelated donors sharing one HLAABC haplotype may provide only a slight improvement in graft survival rates, but the need for antirejection treatment is significantly reduced.

• Herpes simplex virus (HSV) and cytomegalovirus (CMV) infections occur frequently after renal transplantation. To determine the effect of these infections on long-term prognosis, we reviewed the charts of 558 patients who underwent primary renal transplantation between Jan 1, 1974 and Dec 31, 1978, at the University of Minnesota Hospitals, Minneapolis, for cultural evidence of these infections. The presence of HSV alone appeared to have a minimal effect on either patient or allograft survival. Positive CMV cultures were associated with decreased patient and allograft survival. Patients with HSV and CMV infections had further reduced patient and allograft survival. Lethal CMV syndrome and associated severe bacterial and fungal infections were common and frequently were the immediate cause of death in patients who had concomitant positive HSV and CMV cultures. Concurrent HSV and CMV infections in renal transplant patients may be a grave prognostic Indicator, being associated with enhanced mortality and renal allograft loss.(Arch Surg 1984;119:812-817)

The effect of HLA matching on the success of cadaver renal allografts was examined utilizing computerized multifactoral analysis in a large single renal transplant center. One hundred ninety-one consecutive cadaver transplant recipients (from January 1968 to August 1975) were followed from 21/2to 9 years. During the period surveyed we had not utilized the tissue typing results in a prospective manner to select recipients. The data presented attest to the beneficial effect of utilizing well matched cadaver grafts. HLA matching of two or more antigens results in significantly superior 2− and 4-year patient survival and graft function compared to results for cadaver kidneys matched for zero and one HLA antigen. The results are not greatly influenced when age, sex, or time of transplant are controlled. The importance of tissue typing is particularly clear if higher doses of antilymphoblast globulin (ALG) are administered. The risk inherent in advancing recipient age is markedly reduced by better transplant matches. Graft function is also superior in the diabetic patients receiving good HLA matches, but there are too few patients to make these results statistically significant.

A prospective study of 276 patients that were greater than 12 years old and received transplants between October 1,1977 and September 30, 1979 has been undertaken. Any patient with clinical findings compatible with overt cytomegalovirus (CMV) disease was placed on a “CMV disease diagnostic protocol.” All diagnosed cases of CMV occurring before November 15, 1979 have been analyzed. Eighty patients (29) had overt CMV disease. Seventy-two (90) of them contracted CMV within the first 3 months post-transplant. The incidence of overt CMV varied with donor type. Eight percent (4 of 49), 17 (8 of 48), 20 (5 of 25), 40 (46 of 115) and 43 (15 of 35) of HLA-identical (ID) siblings, non-ID siblings, child donor, cadaveric donor, and parental donor, respectively, contracted CMV disease. Overt clinical CMV disease influenced the graft function and patient survival rates significantly (P< 0.01).

Initially, poor long-term prognosis in patients with SLE and fear of recurrent disease dissuaded renal transplantation in this group of patients. However, in 1975 the Advisory Committee to the Renal Transplant Registry reported satisfactory 1–2-year results in 56 patients with SLE from 36 institutions. Subsequently, renal transplantation for SLE patients with end-stage renal disease has become more accepted, though it has been recommended that transplantation be postponed for at least one year after initiating dialysis. Five cases of recurrent lupus nephritis have been reported in the literature. However, since the long-term outcome after transplantation in this group of patients is not well established, we have examined the long-term outcome in SLE patients who underwent renal transplantation at the University of Minnesota.

Between September 23, 1968 and March 22, 1980, primary renal allografts were performed in 373 uremic patients with insulin-dependent diabetes. After transplantation 65 of the diabetic patients (17) underwent 151 amputations involving at least a digit or a limb. The lower extremity was involved in 72 of the amputations. Twenty-four patients had only one procedure, while 41 required multiple procedures. Mean interval from transplantation to first amputation was 25.2 × 2.4 (SE) months. Patient and graft loss (perioperative risk) in the first 3 months after amputation was 13.

In 1980 we determined the patient and renal allograft survival in 299 kidney transplants recipients who, between 1976 and 1979, were randomized to splenectomy (n=146) versus nonsplenectomy (n=152), and who were treated with antilymphocyte globulin-azathioprine-prednisone for immunosuppression. The preliminary analysis showed significantly (P<.05) better (10 overall, 12 for cadaver, 14 for non identical-related) graft survival rates at two years in splenectomized recipients. The splenectomized patients had higher white blood counts and received more azathioprine and less prednisone. We concluded that splenectomy had a beneficial effect for at least the first two years posttransplant without a detrimental effect on patient survival. Splenectomy, however, remains controversial. Thus, we reanalyzed the original cohort 7 years after the study began and 4 years after the last patient was entered. The reanalysis showed that the differences in graft survival rates between splenectomized and non splenectomized recipients were no longer significant. There were more late deaths from sepsis in the splenectomized group, although the overall patient survival rates were similar in splenectomized and non splenectomized recipients. Splenectomy modestly improved graft survival for the first few years, but the eventual fate of the graft was determined by other factors. The dominant influence on graft survival rates was the source of the kidney (at 6 years in splenectomized recipients the functional survival rate of grafts from HLA-identical siblings was 24 higher than that of grafts from HLA-mismatched relatives, which in turn was 24 higher than that of grafts from cadaver donors; in non splenectomized recipients the difference in 6-year function rates between HLA-identical and mismatched related grafts was 34, and between mismatched related and cadaver grafts was 16. Between 1979 and 1983, we performed pretrans-plant splenectomies in all recipients of renal allografts from HLA-mismatched related or cadaver donors. Two-year graft survival rates were 81 and 68, respectively, in azathioprine-treated recipients, 7 and 12 higher than in the splenectomized patients in the randomized trial. During the same period, splenectomized patients treated with cyclosporine had mismatched related and cadaveric graft survival rates of 86 and 78, respectively. Whether discontinuation of a splenectomypolicy will allow these graft survival rates to be maintained remains to be seen, but we have concluded that indiscriminate splenectomy should not be performed in all renal allograft recipients.

Between September 1980 and June 1984, 246 splenectomized, transfused renal allograft recipients were stratified according to presence of diabetes and donor source, and randomized to treatment with either cyclosporine (CsA)-prednisone (pred) or antilymphoblast-globulin (ALG—azathioprine (AZA)—prednisone. As of August 1986, mean follow-up is 47 months. Over all, actuarial patient survival is 84 and 83, respectively at 4 years. Corresponding graft survival is 70 and 63 for CsA-treated and ALG-AZA-treated patients (NS). Within the subgroup of diabetic recipients of cadaver grafts, graft survival is 70 for CsA-treated and 53 for ALG-AZA-treated recipients (P=.035). In the CsA group, 71 required either a significant reduction in CsA dosage with the addition of azathioprine or a complete switch to azathioprine, mainly because of CsA-associated nephrotoxicity. Of those CsA patients switched at a mean time of 21.3±16.4 months posttransplant with mean serum creatinine of 2.40 ± 0.67, current serum creatinine is 1.79±.63. Current mean serum creatinine values are significantly greater for patients randomized to CsA-pred (1.73±.60) vs. ALG-AZA-pred (1.49±.59), P= .014, even though most CsA-treated patients were eventually switched.

Six symptoms that occur during hemodialysis were investigated to determine their frequency and to define when a patient's condition becomes "stable." Three symptoms—nausea, hypotension, and muscle cramps—stabilized after 13 dialysis treatments (approximately one month). Two symptoms, hypertension and vomiting, stabilized after 17 and 20 dialyses, respectively. Headache showed little variation per dialysis. The changes in the frequency of these symptoms were detected through the use of the cumulative sum technique (CUSUM). This technique was found to be much more discriminating than the original data. Hemodialysis patients should not be considered "stable" for investigation of changes in techniques or therapy until after 1½ months of dialysis. Even then, symptoms will be found during each dialysis.(Arch Intern Med 140:804-807, 1980)

The incidence of arterial and venous thromboembolic complications was compared in 224 renal allograft recipients who were prospectively randomized and stratified by risk to treatment with either cyclosporine-prednisone (CsA-P) (n=117) or azathioprine-prednisone-antilymphocyte globulin (AZA-P-ALG) (n=107). Thirteen CsA patients (11) had 22 thromboembolic events, while 19 AZA patients (18) had 24 events (P= 0.22). There was no significant difference between the 2 regimens in the number of patients with each type of venous or arterial event or in the number of patients with multiple or lethal events. The incidence of “minor” complications (all except myocardial infarction and stroke) in the related donor subgroup (n=85) and the overall incidence of thromboembolism in the diabetic subgroup (n=125) were both significantly higher in AZA-treated patients (P= 0.008 and 0.045, respectively). Thus, CsA immunosuppression does not appear to be a risk factor for thromboembolic disease, and it may in fact lower the incidence of thromboembolism in diabetic renal allograft recipients.

A total of 17 patients with intestinal urinary diversion or enterocystoplasty underwent renal transplantation between 1970 and 1988. Patient age ranged from 4 to 35 years (mean age 20 years). The patients were divided into 2 groups. In group 1 (10 patients, 2 of whom required retransplantation) the ureter of the transplanted kidney was implanted into an ileal (7) or colonic (1) conduit or enterocystoplasty (2). In group 2 (7 patients, 1 of whom required a second transplant) the diversion was taken down and the transplanted ureter was implanted into the defunctionalized bladder. There were 14 living related and 6 cadaveric kidneys transplanted.

The effect of vesical dysfunction on the survival and function of renal transplants was evaluated by a retrospective study in which 18 children with posterior urethral valves and 18 children with vesicoureteral reflux were randomly matched with 36 children used as controls. There was no statistically significant difference in patient survival among the 3 groups. Five years after transplantation 50 per cent of the grafts in children with posterior urethral valves were functioning, while 73 and 75 per cent, respectively, of the grafts were functioning in children with vesicoureteral reflux and in the control group. Renal function during the 5 years was significantly better in children in the control group and in those with vesicoureteral reflux than in children with posterior urethral valves. We believe that the presence of an abnormal bladder may alter graft survival and adversely affect the function of the transplanted kidney.

To the Editor.—Peters et al1 concluded that splenectomy places renal transplant patients at a higher risk for infections, will decrease patient and graft survival rates, and is therefore contraindicated except for specific indications. They stated that each center has to evaluate its own results to determine the risk of splenectomy, but their overall conclusion was that splenectomy is detrimental. We disagree with their conclusion in general and believe their analysis is flawed for several reasons.First, between 1970 and 1974, renal transplant recipients at their institution (University of Tennessee, Memphis) had splenectomies. From 1974 to 1980, adjunctive operations, such as bilateral nephrectomies and/or splenectomies, were performed only for specific indications; for splenectomy, the indications were hypersplenism and leukopenia. There were many patients who had early transplants at a time when, in general, patients tended to be overimmunosuppressed and patient treatment was not as good as in recent years.

Children with the prune belly syndrome are at high risk for renal failure. The effect of the prune belly syndrome on the outcome of renal transplantation was evaluated in a retrospective study in which 8 transplant recipients with this syndrome were randomly matched with 13 control, nondi-abetic transplant patients. The parameters evaluated were patient and graft survival, renal function and interval until transplantation. The patients were matched by computer for age at transplantation, date of transplantation, immunosuppressive therapy used and type of donor. Data were analyzed by the Gehan test. There was no statistically significant difference in patient deaths (1 versus 3), graft survival (75 versus 69%) or graft function between patients with the prune belly syndrome and controls. Patients with the prune belly syndrome waited a shorter interval for transplantation than did controls (no statistically significant difference) because the distensible abdominal wall characteristic of the syndrome permits placement of an adult kidney in a young child. The prune belly syndrome did not adversely affect the outcome of renal transplantation in these patients.

Abstract: The authors measured the length of the surgical anal canal (anorectal ring to anal verge) in 108 men and 103 women; the age ranged from 18 to 90 years (average 59 years). The average length of the surgical anal canal was 4.2 cm (range 3.0–5.3 cm). In men the average length was 4.4 cm (range 3.2–5.3 cm) compared with the average length of 4.0 cm (range 3.0–5.0 cm) in women (P<0.001). The average length of the anatomic anal canal (dentate line to anal verge) was 2.2 cm (range 1.0–3.8 cm). In men, the average length was 2.2 cm (range 1.4–3.8 cm), whereas in women the average length was 2.0 cm (range 1.0–3.2 cm) (P<.01). The length of the anatomic and cnal has no relationship to the length of the surgical anal canal orvice versa (P<0.1). There was no statistically significant difference in the length of the surgical anal canal or the anatomic anal canal in persons below 60 years old versus those above in either sex (P>0.1).

To the Editor.—The Task Force on Organ Transplantation1 wanted to improve matching of donors and recipients as well as access to organs by groups at special disadvantage, and thereby improve the outcome of organ transplantation. Mandatory sharing of six-antigen matches will definitely improve matching. There is also no doubt that the point system recently described by Starzl et al,2 and adopted by the United Network for Organ Sharing as the basis for sharing organs, will improve access for disadvantaged groups and patients with medical emergencies. However, will the point system lower the national outcome results?One problem is that low-risk candidates waiting for kidneys may have to become higher risk before they have enough points to receive kidneys. Let us consider where the points come from in nationally shared kidneys. Since medical emergencies are rare, most persons are close to a transplant center, and all nationally shared