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A new perfusate developed in the animal laboratory has been used in our clinical transplantation program in the last year. This perfusate provides excellent clinical results even with less-than-ideal kidneys, as manifested by an 83% immediate function rate and a 96.5% one-month graft survival. Optimum utilization of all donors referred to a transplant center may lessen the problem of insufficient donor organs. Continued basic research in the laboratory to optimize perfusion preservation may produce even better perfusates that can be adapted to the clinical situation and further improve graft survival.

Kidney transplantation for the treatment of end-stage renal disease has been limited by an inadequate number of donor organs. Because of the enormous impact kidney transplantation can have for patients, the authors have performed 40 living-unrelated donor renal transplantations using a donor-specific transfusion protocol since 1981. Ten additional patients were entered but became sensitized. Donors included 23 wives, seven husbands, six friends, and four individuals related by marriage. Type I diabetes was the most common indication for transplantation (45%). Despite 36 rejections in 24 patients (27 of 36 [75%] in the early postoperative period), only two grafts failed because of rejection. Twenty-one of these rejections responded to high-dose prednisone alone; the remainder required antilymphocyte globulin therapy or plasmapheresis. Sixteen patients had no acute rejections. Three other grafts were lost, including two deaths: one myocardial infarction (with a functioning graft), and one death secondary to a postoperative cecal perforation. One graft was lost from infarction after percutaneous nephrostomy placement. Of 40 grafts, 34 were functioning with a mean serum creatinine of 1.7 mg/dL (at a mean follow-up time of 27 months). Actuarial patient and graft survival were 94% and 89%, respectively, at 3 years. Living-unrelated renal transplants are an acceptable alternative to cadaver transplants, with excellent graft and patient survival.

With refinements in surgical techniques and increased clinical experience, there has been a resurgence of interest in vascularized pancreas transplantation. From December 1986 to April 1988, 30 whole-organ vascularized pancreas transplants with pancreatico duodenocystostomy were performed simultaneously with renal transplantation. The recipient population consisted of 20 men and ten women, with a mean age of 34.7 years (range of 25-53 years). The mean duration of insulin-dependent diabetes mellitus (IDDM) was 22.6 years (range of 10-37 years). The mean pancreas preservation time was 8.7 hours (range 3-19 years). All patients were immediately insulin-independent. Simultaneous pancreas-kidney engraftment was performed to both iliac fossae via a lower midline incision (n = 28) or through a bilateral lower abdominal incision (n = 2). The mean operating time was 5.9 hours, and packed cell transfusion requirement was 1.3 units. The mean length of hospital stay was 27.4 days. Recipients averaged 2.3 admissions (1-7), with ten patients (34.4%) requiring only one hospital admission. Postoperative immunosuppression consisted of cyclosporine, prednisone, azathioprine, and Minnesota antilymphoblast globulin (MALG). A total of 49 episodes of rejection occurred in 26 patients. Actuarial patient survival rate at two years is 96.3%. The kidney and pancreas survival rates for the same time interval is 94.0% and 84.0%, respectively. Mean serum creatinine at present is 1.75 mg/dl. In conclusion, renal transplantation in concert with pancreas transplantation has a dramatic positive impact on pancreas allograft survival. Combined engraftment does not appear to jeopardize renal allograft functional survival. In view of these results, simultaneous pancreas-kidney transplantation appears to be the treatment of choice for Type I diabetic patients.

A combined 51Cr-release/MTT dye method is described for accurately measuring cytolytic activity and colony size in the same set of culture microwells. The method was applied to the study of cell-mediated lympholysis (CML) in limiting dilution analysis (LDA) cultures of human PBL from a renal transplant recipient and a healthy control. The results showed that the combined CML/MTT method could detect differences in lytic activity per cell in LDA cultures, and thus is a useful adjunct to standard precursor frequency analysis.

A new solution (UW solution) was used for flushing and storage of 17 livers before transplantation. In 9 cases the preservation times exceeded 10 hours (mean 12.7, range 11-20) but all left hospital with good liver function.

The activation of an alloantigen reactive T cell requires alloantigen recognition and additional external signals provided by antigen presenting cells of host or donor antigen. Graft passenger leukocytes are capable of presenting alloantigen directly to recipient T cells and providing interleukin-1. Alternatively, shed alloantigen may be presented passively by recipient antigen presenting cells. Nearly all attempts to alter graft tissue immunogenicity prior to transplantation have focused on removing passenger cells. Attempts to modulate islet graft immunogenicity include conventional organ culture, high oxygen/high pressure culture, interim hosting, and treatment with ultraviolet irradiation, monoclonal antibodies and complement, and immunotoxins. While these techniques have been successful in rodent models, attempts to apply these methods to human islet transplants have been unsuccessful.

Recent studies have documented the efficacy of quadruple immunotherapy with sequential ALG/cyclosporine in cadaveric renal transplantation. However, the exact role of ALG in this regimen is controversial. Over a four-year period, we performed 429 cadaveric renal transplants (367 primary, 62 retransplants) with prednisone, azathioprine, and the sequential use of Minnesota antilymphoblast globulin (MALG) and CsA. ALG therapy was divided into three protocols: true sequential (n = 259, mean no. days of ALG = 8.2); extended (defined as sequential MALG/CsA continued for 14 days irrespective of renal function or CsA level, n = 103, mean no. days of ALG = 14.1); and therapeutic (continued MALG therapy for early breakthrough rejection, n = 67 [15.6%], mean no. days of ALG = 17.2). The study groups were comparable and retrospectively analyzed in multivariate fashion for 15 variables. Requirement for postoperative dialysis was equivalent (14%) in both sequential and extended ALG groups. Extended ALG therapy failed to reduce the incidence of acute rejection (46.5% vs. 40.4% with true sequential therapy). Prolonging the duration of ALG treatment (greater than 10 days) was associated with a higher risk of infection. Logistic regression analysis revealed that the use of OKT3 after ALG accounted for the higher infection rate. Duration of ALG therapy had no impact on patient or graft survival after a mean follow-up interval of 20 months. We recommended a quadruple immunosuppressive strategy in cadaveric renal transplantation with sequential MALG/CsA to minimize early allograft dysfunction and to achieve excellent patient and graft survival. MALG therapy should be stopped after renal function is documented and CsA levels are therapeutic. Further ALG therapy offers no immunologic advantage and may place the patient at high risk for infection if OKT3 rescue therapy is required.

Based upon encouraging experimental results, we began employing a synthetic perfusate for cadaver kidney preservation. The new perfusate contains hydroxyethyl starch (HES) as the sole colloid for oncotic support; 107 cadaver kidneys were preserved and transplanted (93 primary, 14 nonprimary) using the HES solution and were compared with our previous experience of 180 cadaver kidneys (161 primary, 19 nonprimary) preserved and transplanted utilizing an albumin-based perfusate. All cadaver kidneys were locally harvested and preserved by machine perfusion. Donor and preservation characteristics in the HES (n = 61) and the albumin (n = 101) groups were comparable, with a mean preservation time of 30.9 hr. Cold storage in combination with hypothermic pulsatile perfusion (HPP) preservation was performed more often in the HES group (68.2% vs. 31.1%, P less than 0.001). Recipient characteristics were also comparable, and all received quadruple immunosuppressive therapy with sequential/Minnesota antilymphoblast globulin/(MALG)/cyclosporine. After primary transplantation, the incidence of immediate function (82.6% vs. 89.2%), preservation-related dialysis (14.9% vs. 8.6%), and primary nonfunction (2.5% vs. 0) were similar between the 2 groups, with trends favoring the latter HES data. One-month serum creatinine (1.8 vs. 1.7 mg/dl) and graft survival (95% vs. 97.8%) also were comparable. Similar trends were present in the retransplant group, including a significantly lower 1-month serum creatinine in the HES group (2.2 vs. 1.5 mg/dl; P less than 0.05). The preservation-related dialysis rate did not differ between primary and nonprimary transplants. Primary nonfunction has not occurred with our new perfusate. Combined cold-storage-HPP preservation with HES perfusate offers advantages over standard retrieval technology and provides excellent immediate allograft function.

A retrospective analysis of our renal transplant population between 1981 and 1987 was undertaken to study the natural history of posttransplant hypercalcemia and to review indications and recommendations regarding the timing of parathyroidectomy. During this period, 1158 renal transplant procedures were performed in 1025 patients, with 819 allografts (71%) functioning currently. Posttransplant hypercalcemia greater than 10.5 mg/dl was associated with a longer duration of dialysis and developed in 227 patients, with onset of hypercalcemia occurring in 90% of these patients by 1 year. In 69% of these patients, spontaneous resolution of the hypercalcemia occurred between 6 months and 7 years after transplantation. A total of 42 patients with asymptomatic hypercalcemia are currently being followed up, with a mean serum calcium level of 11.0 +/- 0.41 mg/dl and a mean follow-up interval of 3.3 +/- 1.6 years since transplantation. Nine symptom-free patients with moderate hypercalcemia (12.0 to 12.4 mg/dl) more than 1 year after transplantation were identified. Five of these patients had spontaneous resolution of the hypercalcemia between 2 and 7 years. Fifteen patients with posttransplant hyperparathyroidism (6.6%) required parathyroidectomy--11 for symptomatic and four for asymptomatic hyperparathyroidism. One patient had symptomatic hyperparathyroidism despite the presence of normocalcemia. One symptom-free patient with significant hypercalcemia (serum calcium level, 14.7 mg/dl) underwent parathyroidectomy 3 months after transplantation. The remaining three symptom-free patients had serum calcium determinations of greater than or equal to 12.5 mg/dl more than 1 year after renal transplantation. Patients with pretransplant and posttransplant hypercalcemia required parathyroidectomy more frequently than did patients with only posttransplant hypercalcemia (18% versus 3.0%; p less than 0.001). An unusual finding was the occurrence of a single adenoma in two patients, which represents sporadic primary hyperparathyroidism in the patient undergoing renal transplantation rather than tertiary hyperparathyroidism. We recommend a conservative approach to posttransplant hypercalcemia, with surgery reserved for patients with symptomatic disease and patients with asymptomatic persistent hypercalcemia greater than or equal to 12.5 mg/dl more than 1 year after transplantation.

We have done a comparative analysis of two consecutive clinical trials at our center: the first in 56 patients who received blood transfusions from their prospective donors (DST group), and the second in 36 patients who received such transfusions while they were taking Imuran in an attempt to reduce the incidence of sensitization against the donor (IM + DST group). The major findings of our study are: (1) Imuran significantly (P less than .05) reduced the rate of sensitization from 27% to 11%; (2) Patients who had prolonged dialysis before entering one of these protocols were significantly more likely to become sensitized against their living donors, and had significantly higher sensitization against the leukocyte panel, although panel-reactive antibodies were not significantly changed by transfusions from the live donor; (3) MLC reactivity against the living donor was not significantly altered by donor transfusions, and was also not different for sensitized and transplanted patients; (4) Results of transplantation were excellent in both patient groups, with only two grafts and two patients lost in 68 transplants (actuarial one-year survival of 97% and 93% of patients alive and with functional grafts at one year in the DST and IM + DST groups, respectively); (5) Rejection episodes occurred in about 50% of each group, but were of a special type (DST-type rejection) in about 30% of the DST patients and 10% of the IM + DST patients (P = .07); (6) The probability of transplantation, and the results of transplantation after unsuccessful entry into one of these protocols was not adversely affected. We think that primarily because of the low rate of sensitization the IM + DST protocol is superior to the DST protocol. Both, however, are established clinical tools that have increased our clinical transplant volume by a large number of highly successful transplants.

Fox kidney and skin grafts were transplanted into dog recipients. Fox kidneys, transplanted en bloc into untreated dogs, survived 6.2 +/- 0.4 days. The skin transplants survived 5.9 +/- 1.4 days. The grafted kidneys showed almost normal function before rejection. Both skin and kidney rejection were mediated through a cellular mechansim. Performed natural antibodies against donor tissue were not present in the serum of the recipients. These results combined with absorption studies suggested a close relationship between fox and dog, but different number and morphology of chromosomes, immunoelectrophoretic patterns of serum proteins, and disparities of the transplantation antigens proved that the fox is a species quite separate from the dog. It was concluded that the fox-dog system, with its similarity to the chimpanzeeman relationship, offers a unique model to study clinically applicable methods of managing xenografts between closely related species.

This paper describes the Madison experience in pancreas transplantation. With the use of pancreaticocystostomy, overall mortality could be decreased to a level similar to the results reported for kidney transplantation in diabetic patients. Particularly encouraging are the results obtained in combined kidney and pancreas transplantation, with current actuarial graft survival rates for kidneys of 95% and pancreatic grafts of 85%. Overall, the quality of life for patients receiving a pancreatic transplant has been good, and in cases where no postoperative complications were encountered, a tremendous feeling of well-being from a physiological and psychological standpoint was achieved. It is our conclusion that pancreatic transplantation should be pursued as a viable form of therapy in selected patients and centers with large experience in the transplantation of diabetic patients.

A new method for the take-down of Cimino-Brescia fistulas is described. Instead of ligating the venous runoff vessels individually, the fistula is opened over the area of the arteriovenous anastomosis and the connection between vein and artery is closed with a running Prolene suture. The advantages of this new method are described.

Since the introduction of OKT3 at our center in January 1986, we have performed 246 cadaveric renal transplants (220 primary, 26 nonprimary). All patients received quadruple immunosuppression consisting of prednisone, azathioprine, and the sequential use of Minnesota antilymphoblast globulin (MALG) and cyclosporine. OKT3 (Orthoclone OKT3) therapy was reserved for corticosteroid- and/or ALG-resistant rejection. Of the 246 patients, 138 developed one or more rejection episodes (56.1%). Ninety-seven (70.3%) were successfully reversed with prednisone and/or ALG, whereas 41 (29.7%) required additional treatment with OKT3. Initial graft salvage occurred in 34 (82.9%) patients treated with OKT3, but rejection recurred in 18 (52.9%) and was successfully reversed in only 6 patients. However, the rate of recurrent rejection was much lower in patients given OKT3 early (14%), shortly after it was apparent that high-dose corticosteroid therapy was proving ineffective, than in patients who received OKT3 after a prolonged or second course of corticosteroids (64%) or ALG (60%). Graft survival after a mean follow-up interval of 11 months in all OKT3-treated patients was 54%. One or more infections occurred in 19 (46%) patients treated with OKT3. Patients developing infections following OKT3 therapy received significantly larger total doses of prednisone during graft rejection (46.3 mg/kg vs. 27.9 mg/kg, P less than .05) than OKT3-treated patients who did not develop infectious complications. Our experience shows that use of OKT3 for treatment of corticosteroid- and/or ALG-resistant rejection is associated with a high rate of recurrent rejection, except when given early, as soon as it is clear that high-dose corticosteroid therapy is not reversing the rejection episode. It further suggests that prolonged administration of high-dose corticosteroids and possibly ALG for the treatment of rejection prior to beginning OKT3 greatly increases the rate of infection following OKT3 therapy.

The toxic effects of FK-506 (FK), a newly discovered immunosuppressive agent isolated from Streptomyces tsukubaensis, were studied in the human fetal pancreas (HFP) system. Human fetal pancreas explants (14-21 wk gestation) were cultured up to 72 h with either 10(-10) to 10(-7) M FK or 10(-8) to 10(-5) M cyclosporin A (CsA), then examined histologically and functionally with a stimulated insulin-release assay. Additionally, FK and CsA were tested for the ability to suppress cell-mediated immunity with a human mixed-lymphocyte reaction (MLR). Previous studies have demonstrated that near-complete immunosuppression is obtained with FK at 10(-8) M and CsA at 10(-6) M. When cultured up to 72 h throughout the concentration range, neither FK nor CsA altered HFP cellular architecture, and indirect immunoperoxidase staining for insulin demonstrated no change in quantity or distribution of insulin-producing beta-cells compared with control tissue. Drug-cultured HFP also retained the ability to release insulin in response to a glucose/theophylline challenge. Finally, 50% inhibition of a human MLR was achieved with FK at 2 x 10(-9) M and CsA at 2 x 10(-7) M, demonstrating the 100-fold greater potency of FK. Our results suggest that further work with FK will show that this immunosuppressive agent can be used with HFP transplantation into diabetic patients without toxicity to HFP.

The significance of the antiglobulin crossmatch in the cyclosporine era remains controversial. Over an 11-month period, 124 recipients of cadaveric renal allografts (109 primary, 15 nonprimary) were retrospectively crossmatched via the antiglobulin technique. Criteria for recipient selection for transplantation included a negative T lymphocytotoxic (CDC) crossmatch for current and historical sera. Fourteen patients (11.3%) underwent transplantation in the setting of a negative T and positive antiglobulin crossmatch. The patient group included 10 female and 4 male patients with a mean age of 43.8 years. All but one patient received a primary transplant, and current sera were positive in the antiglobulin crossmatch in all cases. The mean HLA-ABDR match was 1.4 (range 0-4). Preoperative PRA titers ranged from 0 to 80% (mean 18.3%). All patients underwent successful renal transplantation with quadruple immunosuppression consisting of prednisone, azathioprine, and the sequential use of MALG/cyclosporine. There were no episodes of hyperacute rejection. However, 10 patients (71.4%) experienced acute rejection, including 7 episodes within 4 days of transplant. Early rejection was significantly more common in patients with a positive antiglobulin test (50% vs. 20.9%, P less than 0.05). The mean one-month serum creatinine was 1.7 mg/dl. Actual patient and allograft survival are 92.9% and 85.7%, respectively. Risk factors for a positive antiglobulin crossmatch included female sex and prior sensitization as measured by PRA. Although these patients represent a high-risk group for early rejection, no adverse effect on patient or graft survival was noted with quadruple immunotherapy. In conclusion, a positive antiglobulin crossmatch is no longer a contraindication to renal transplantation with current immunosuppressive strategies.

Our experience over the last 4 years with HLA-identical, donor-specific transfusion (DST), and Imuran (IM) + DST living-donor transplants in 206 patients is presented. Transplants from 8 completely incompatible sibling donors, 4 distantly related donors, and 7 unrelated donors are included. Except for a slightly higher average serum creatinine, and a markedly reduced rate of donor-specific sensitization in the IM + DST group when compared with the DST group (14% vs. 31%, P less than .005), the results of transplantation using these 3 protocols have been equivalent. Actuarial one-year survival was 97% for patients and 93% for grafts for the combined group of 206 patients. Of the 44 patients who entered the DST or IM + DST protocols but were not transplanted, 31 patients (70%) have subsequently been transplanted, and all 5 recipients of living-donor kidneys and 20 of 26 recipients of cadaveric kidneys (77%) have functioning grafts. Because it optimizes the availability of transplantable living-donor kidneys, gives results equivalent to those obtained with HLA-identical donors and the DST protocol, and is not associated with clinically apparent adverse effects, we now use the IM + DST protocol for all living-donor transplants except those between HLA-identical donor-recipient pairs.

OKT3 has emerged as a highly effective antirejection therapy, but its efficacy in pancreas transplantation remains to be determined. During a 26-mo period, 46 vascularized pancreas transplants were performed with pancreaticoduodenocystostomy. Twenty-one patients (45.7%) were treated with OKT3. Indications for OKT3 use included steroid- and/or antilymphoblast globulin-resistant rejection in isolated-pancreas transplant (n = 8) or simultaneous pancreas-kidney-transplant (n = 13) recipients. A total of 46 rejection episodes occurred (mean 2.2). OKT3 was administered for a 14-day course concomitant with pulsed corticosteroids, azathioprine, and cyclosporin. OKT3 rescue therapy was successful in 13 cases (61.9%). The mean time to rejection reversal was 8.8 days (range 5-14 days). In isolated-pancreas transplants, OKT3 reversed only 1 episode of rejection (12.5%). In contrast, 12 episodes (92.3%) of allograft rejection were responsive to OKT3 in simultaneous pancreas-kidney recipients (P less than .05). Graft loss from rejection occurred at a mean 5.5 mo posttransplantation. OKT3 therapy was more successful in the setting of early rejection, rejection in combined pancreas-kidney transplants, and rejection not associated with hyperglycemia. No graft loss due to infection or patient death has occurred after OKT3 therapy. After a mean follow-up of 17.3 mo, patient survival was 89.1%, and allograft survival was 26.3% in isolated-pancreas and 85.2% in simultaneous pancreas-kidney transplants (P less than .05). Salvage therapy with OKT3 is a safe and effective means of reversing rejection in pancreas-allograft recipients. OKT3 is more effective in simultaneous pancreas-kidney recipients due to the earlier diagnosis of rejection.

The results of kidney retransplantation in the cyclosporine era remain to be determined. Over a 42-month period, 76 nonprimary renal transplants (66 second, 7 third, 3 fourth allografts) were performed in 73 recipients under cyclosporine immunosuppression. The patient population was predominantly white (90.4%) with a mean age of 32.3 years. Twenty-one recipients (28.8%) were diabetic, and 36 (49.3%) were highly sensitized (panel-reactive antibody [PRA] greater than 50%). Sixty-two patients received cadaver donor grafts while the remaining donations were living-related (12) or living-unrelated (2). A sequential antilymphocyte globulin/cyclosporine protocol was employed, with cyclosporine therapy delayed until adequate renal function occurred. Overall patient and graft survival is 92.1% and 60.5%, respectively, after a mean follow-up of 20.0 months. The mean serum creatinine is 1.64 mg/dl in the 46 functioning allografts. Graft survival is 63.6% for secondary grafts, 28.6% for tertiary grafts, and 66.7% for fourth kidney transplants. In second transplants, recipients of cadaver donor kidneys have a graft survival of 58.5%, while living-related donor graft survival is 84.6% (P = 0.07). In the cadaver retransplant population, duration of previous transplant function greater than one year and HLA-DR matching were associated with increased graft survival, while age over 39 and presence of diabetes mellitus with reduced graft survival. However, these trends were not significant. Peak PRA above 50% did demonstrate a significant negative impact on graft survival both in the univariate and multivariate analyses of risk factors. Acute rejection occurred in 50 patients (65.8%), and was successfully reversed 50% of the time. Of the 30 grafts lost, 25 (83.3%) occurred within four months of retransplantation. Transplant nephrectomy was performed in 20 patients. Cyclosporine was not administered in 21 (70%) of these early graft failures, negating any potential beneficial effect. Retransplantation can be performed safely, with living-donor graft survival superior to cadaver retransplant rates. Rejection and early graft loss are common, especially in the highly sensitized patient. The impact of cyclosporine immunosuppression in renal retransplantation is much less dramatic than in primary transplantation in a protocol that delays cyclosporine therapy until allograft function is demonstrated.

Forty-three whole-pancreas transplantations with pancreaticocystostomy were performed. Eighteen patients received pancreas transplants after previously receiving living-related kidney transplants, 18 patients received simultaneous kidney and pancreas transplants, and seven patients received pancreas transplants after previously receiving cadaver kidney transplants. All patients were immunosuppressed with quadruple immunosuppression including antilymphocyte globulin, prednisone, cyclosporine, and azathioprine. Overall graft survival for pancreas transplants is 73.1%. In the group with pancreas after living-related kidney, 1-year graft survival was 50% for the pancreas and 95.4% for the kidney. In the pancreas after cadaver kidney group, pancreas and kidney survival rates were 100% at 1 year, and in the simultaneous pancreas and kidney group, pancreas 1-year graft survival was 87.5% and kidney transplant survival was 93.8%. Overall patient survival at 1-year is 95.6%. Technical complications occurred in 21 patients. These included wound infections, intra-abdominal abscess formation, bleeding, and disruption of the pancreaticocystostomy. We believe that pancreas transplantation can now be performed with acceptable graft and patient survival.

The complications of long-term steroid immunosuppression are well known. During a 12-month period, 52 living-donor renal transplant recipients were entered into a protocol of intentional early steroid withdrawal. Selection criteria were primary living-related renal transplants in HLA-identical (12) or one-haplotype match (40) patients. The study population consisted of 25 diabetics (48.1%) with a mean age of 32.4 years. All patients received preoperative blood transfusions (3 donor-specific in haplotype-matched, 3 random in HLA-identical recipients). Immunosuppression consisted of cyclosporine, azathioprine, and corticosteroids, with deliberate steroid withdrawal after two weeks. Forty-six patients (88.5%) were successfully tapered off steroids, while the six protocol failures (11.5%) were due to early rejection or leukopenia that prevented steroid withdrawal. Twenty-three patients (50%) subsequently were returned to steroid therapy for rejection (21) or leukopenia (2). Inadequate immunosuppression precipitated six rejection episodes and were preventable, while the remaining 15 were true breakthrough crises. The overall rejection rate was 50%, with 92.3% of initial rejection episodes occurring within five weeks of steroid withdrawal. Rejection episodes were responsive to steroid therapy alone in 73.2% of cases. No graft loss from rejection has occurred after a mean follow-up interval of 8.5 months. At present, 33 patients (63.5%) are off steroids. In HLA-identical recipients, all but one successfully completed the protocol and 75% are currently steroid-free. In haplotype-matched patients, 87.5% completed the protocol and 60% are steroid-independent. Comparison with well-matched control groups on steroids failed to reveal any difference in graft or patient survival, rejection, infection, or mean serum creatinine level. No discriminating risk factors could be identified that were predictive of steroid withdrawal success or failure. In select patients, early steroid withdrawal can be accomplished without jeopardizing graft function. Long-term follow-up is required to assess the risk-benefit ratio of steroid withdrawal upon immunosuppressive morbidity.

A major problem in vascularized pancreas transplantation is the lack of reliable methods for the early diagnosis and effective treatment of allograft rejection. Over a 2-year period, 54 rejection episodes occurred in 31 patients (13 isolated pancreas, 18 simultaneous pancreas-kidney recipients) with pancreaticoduodenocystostomy. A total of 253 radionuclide pancreas examinations were performed (mean 8.4 per patient) utilizing 99mtechnetium-DTPA. Computer analysis generated a quantitative measure of blood flow to the allograft caused the technetium index (TI). Rejection episodes were characterized as isolated pancreas (22), combined pancreas-kidney (16), or isolated renal (16) allograft rejection in combined engraftments. The majority of rejection episodes occurred early (within 3 months of transplant, N = 47) and were more responsive than late rejection to anti-rejection therapy (89.4% vs 42.9%, P = 0.01). Mean urinary amylase (UA) levels and TI during normal allograft function were 29,398 U/l and 0.55%, while levels heralding rejection were 6,528 U/l and 0.40%, respectively (P less than 0.05). The treatment of rejection based upon renal dysfunction or combined renal and pancreas dysfunction resulted in significantly higher graft salvage with a lower incidence of hyperglycemia when compared to isolated pancreas allograft rejection. Of the 11 patients who developed hyperglycemia, 8 (72.7%) ultimately lost their pancreas grafts (P less than 0.001). Following therapy, a TI above 0.3% was associated with 97.4% graft survival, while levels below 0.3% resulted in a 70% rate of graft loss (P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

In 4 patients with a small contracted bladder and end stage renal failure ileocecocystoplasty bladder augmentation was done in conjunction with renal transplantation. All 4 patients have stable renal and bladder function 13 to 46 months after transplantation. In carefully selected patients bladder augmentation may be an alternative to urinary diversion.

There is growing evidence for the existence of an idiotypic network in the mammalian response to alloantigens, in particular to MHC antigens. The direct evidence for induction of Ab-2 to particular donor HLA-specificities by DST is strong; in addition, there is recent evidence for Ab-2 to Ab-1 specific for constant regions of HLA-ABC antigens in the sera of multiply-transfused patients. On the other hand, evidence for induction of anti-TCR antibodies by DST is based primarily on functional specificity rather than biochemical evidence; the evidence available suggests that MLC BF induced by DST may be directed against V beta family or public idiotypes on recipient T cells, since the amount of inhibition obtained is weak and no evidence of "clonotypic" antibodies has been found in studies of T cell lines or lymphoblasts. Better molecular probes, including human monoclonal antibodies, T cell clones, and purified TCR are needed to screen for specific anti-idiotypes in transfused patients.

Two technical modifications have been suggested for whole-pancreas transplantation with bladder drainage. The duodenal button technique (DB [Madison]) and the duodenal segment technique (DS [Iowa]) are the most commonly performed procedures (1,2). From December 1985 until May 1988 we performed 32 combined pancreas-kidney transplants using DB and DS techniques in 17 and 15 patients, respectively. Bladder leaks, pancreatitis, bleeding episodes, and surgically related infections were all decreased with the duodenal segment technique. Metabolic acidosis was more common with DS but was easily managed with oral sodium bicarbonate. The one-year actuarial graft survival with DB is less when compared with DS (76.1% vs. 87.5%). Three technical graft losses occurred with DB vs. none with DS. One graft was lost in each group to rejection. Our results indicate that the duodenal segment technique of bladder implantation adds safety to whole-pancreas transplantation and must now be considered the procedure of choice.

We have tested the predictive model for risk of sensitization by donor-specific transfusions developed at the University of California, San Francisco for its applicability to the DST experience at UW/Madison. Patient sample sizes between the two groups were similar (n = 249 for UW/Madison, n = 261 for UCSF) and the two groups of patients had similar compositions in terms of mean age, ABO type, baseline panel-reactive antibody, and pregnancy rate. The two groups differed in that the UW/Madison group had a higher percentage of males, diabetic patients, previously transplanted patients, and 0 haplotype-matched (2 HLA-mismatched related and unrelated) recipients. In addition, all the UW/Madison patients received azathioprine (AZA) whereas only half the UCSF group was given AZA. Despite these differences, application of the UCSF model for prediction of sensitization by DST gave remarkably similar results in our patient population, with pregnancy, prior transplant, baseline PRA, and HLA antigen sharing giving similar odds ratios and P values. However, when female sex was included in the model along with the other variables, the significance of pregnancy risk disappeared. We have developed an alternative multivariate model using stepwise logistic regression that identifies baseline PRA greater than 40%, female sex, and prior transplant as significant risk factors for sensitization, while number of HLA (A, B, DR) antigens shared and increasing recipient age significantly decreased risk of sensitization by DST.

According to an analysis of 100 consecutive kidney transplants from live donors performed at our center over a 25-month period beginning in June 1980, only two patients have died, and five other patients had graft loss from acute or chronic rejection; this resulted in an overall actuarial 2-year patient survival rate of 98% and a graft survival rate of 90%. Eighty-five of the 93 patients with functioning grafts have excellent renal function, with serum creatinine levels less than or equal to 2 mg/dl. Complications occurred in 24 patients but rarely jeopardized the patients' lives or grafts or resulted in permanent disability. The functional capacity of most of the patients was improved by transplantation or was excellent both before and after transplantation. Forty-three transplants were possible through the use of the original or Imuran-modified donor-specific transfusion protocol, so that the lack of compatible donors rarely limited the availability of this therapy. New therapies that might improve graft or patient survival rate cannot reasonably be evaluated in recipients of live donor kidney transplants, because these results are already good. We have estimated that as much as $3.6 million in health care funds could be saved every 2 years at our center if we offered kidney transplants from healthy willing donors to all recipients before instituting dialysis. From our study we conclude that live donor kidney transplantation is an available, highly effective, and cost-efficient form of therapy for patients with end-stage renal disease.

The activity of systemic lupus erythematosus (SLE) was investigated in 18 recipients of 20 renal transplants by retrospective analysis of their medical records and by screening the ten patients with more than one year follow-up. Eight grafts were lost, all because of rejection occurring within the first year. From the 12 patients with functioning transplants, one was lost to follow-up at seven years and another had not completed one year. The remaining ten patients were studied, and no evidence of lupus nephritis was found despite serologically active SLE in four cases. Their follow-up was 4.5 +/- 1.3 years. Our study provides the relatively scarce literature on renal transplantation in patients with SLE with a series of 18 recipients of 20 allografts, confirms that the recurrence of lupus nephritis in the allografts is very rare, as previously suggested, and discloses that graft and patient survivals are comparable with those of the general nondiabetic transplant population.

We compared the infections encountered in 23 renal transplant patients given the monoclonal anti-T-cell antibody, Orthoclone OKT3 (OKT3), for treatment of steroid-resistant rejection in 1986 and in 23 control patients from 1984 to 1985 with resistant rejection matched demographically, for severity of rejection and for risk factors predisposing to infection, who did not receive OKT3; recipients of OKT3 received substantially less prednisone, cyclosporine, and antilymphocyte globulin (ALG) than control patients for treatment of the rejection episode. Fourteen (61%) patients given OKT3 developed one or more infections in the 3-month period following treatment as compared with 9 control patients (39%) given conventional antirejection therapy with high-dose steroids and, usually, ALG. Patients given OKT3 were significantly more likely to develop serious infections (pneumonia, bacteremia, meningitis, or severe viral infection; 16 episodes vs. 4, P = .02). Six recipients of OKT3 (26%) acquired infections typically encountered in states associated with depressed cell-mediated immunity (CMI)--Listeria sepsis (2), disseminated nocardiosis and Mycobacterium tuberculosis infection (1), cytomegalovirus (CMV) pneumonia (1), Yersinia infection with severe dermatophytosis (1), and Epstein-Barr virus-associated lymphoproliferative syndrome (1)--as compared with 1 case of mild CMV infection in the control group (P = .08). Trimethoprim-sulfamethoxazole (TMP-SMZ) was given to 19 patients in each group; all 4 recipients of OKT3 who did not receive TMP-SMZ prophylaxis developed life-threatening infection, 3, bacteremia (2 with Listeria) and 1, disseminated nocardiosis and M tuberculosis infection. These data suggest that OKT3 given for treatment of resistant rejection in renal transplantation predisposes the patient to serious infection, particularly with opportunistic pathogens characteristically associated with depressed cell-mediated immunity. Prophylaxis with TMP-SMZ, which is safe, well tolerated, and effective for reducing the incidence of infection in renal transplantation, may be especially important during OKT3 therapy.

We have followed a group of 18 uremic patients through living-related donor renal transplantation (RTX) using pattern-reversal VEPs. Recordings were made prior to and 10 weeks after surgery at high, medium and low spatial frequencies. Prior to RTX, mean latency of the P100 component of the VEP was 107 msec. Individual values did not correlate with blood urea nitrogen or creatinine. Patients requiring hemodialysis did not differ from non-dialyzed patients. Ten weeks after RTX P100 latencies were significantly shortened while N75 latencies were unchanged. Several diabetic patients exhibited the appearance of previously unrecorded wave forms. P100 latency increased significantly with increasing spatial frequency before and after transplantation. Diabetic patients demonstrated a consistent increase in P100 amplitude while non-diabetic patients demonstrated a consistent decrease in P100 amplitude after RTX. The data indicate that renal transplantation has beneficial effects on the central nervous system of uremic patients not seen with chronic hemodialysis and that these effects may be quantitatively measured using the VEP. The data further suggest that electrophysiological effects of uremia and diabetes may be additive, but reversible after RTX. Alterations in the uremic and diabetic VEP may be related to retinal or more proximal central nervous system structures.