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.

• 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 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.

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.