Results of pancreas-transplant registry.

From December 1966 to March 1988, 1394 pancreas transplants were reported to the International Pancreas Transplant Registry. For the 1129 cases since 1982, the overall 1-yr graft and recipient survival rates were 46 and 82%, respectively. When analyzed according to the three most common duct-management techniques, polymer injection (n = 324), intestinal drainage (n = 282), and bladder drainage (n = 462), the 1-yr function rates were 47, 45, and 54%, respectively. The graft survival rates were also similar, whether whole (n = 492) or segmental (n = 634) grafts were transplanted (47 vs. 46% at 1 yr). Graft survival rates according to preservation times were 49, 42, and 43% at 1 yr for those stored less than 6 h (n = 694), 6-12 h (n = 237), and greater than 12 h (n = 89), respectively. Immunosuppressive regimens that included both cyclosporin and azathioprine were associated with significantly (P less than .03) higher graft survival rates than those that included only one of the drugs, with 1-yr graft survival rates for technically successful grafts of 67, 54, and 39% for patients treated with azathioprine plus cyclosporin (n = 602), cyclosporin without azathioprine (n = 201), and azathioprine without cyclosporin (n = 44). Pancreas-graft survival rates differed according to whether a kidney was or was not transplanted and according to the timing of the transplant: 53, 40, and 32%, respectively, at 1 yr for cases in which a simultaneous kidney was transplanted (n = 685), a kidney had previously been transplanted (n = 201), or a kidney had never been transplanted (n = 202).(ABSTRACT TRUNCATED AT 250 WORDS)

Dialysis symptoms and stabilization in long-term dialysis. Practical application of the CUSUM plot.

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 1 1/2 months of dialysis. Even then, symptoms will be found during each dialysis.

Cytomegalovirus disease in renal allograft recipients: a prospective study of the clinical features, risk factors and impact on renal transplantation.

Fifty-nine renal transplant recipients with overt CMV disease were treated at the University of Minnesota Health Sciences Center between October 1, 1977 and November 15, 1978. In a group of 141 consecutive transplant patients, the incidence of overt CMV disease was 31%. Fifty-three patients (90%) developed clinical manifestations of CMV disease within 4 months of transplantation, and it was during this time period that overt CMV disease was associated with a significantly increased incidence of transplant nephrectomy and death. Fever was the most common presenting symptom (95% of patients), and overt CMV disease was found to be the single most common cause of fever in all hospitalized transplant recipients. Prolonged fever, diffuse pulmonary infiltrates, gastrointestinal bleeding, pancreatitis, transplant nephrectomy and development of other systemic infections were clinical features used to categorize patients according to disease severity. A number of these features were found to be significantly associated with the diagnosis of overt CMV disease. Twelve patients (20%) developed lethal CMV disease characterized by the presence of most of these features, 6 (10%) had severe disease, 9 (15%) had disease of moderate severity and 32 patients (54%) had mild CMV disease with fever being essentially their only clinical finding. Development of secondary systemic infection was most ominous, and occurred before death in 10 of the 12 patients with lethal CMV disease. The only patients to die with serious bacterial, fungal or protozoan infection during the period of this study had concomitant overt CMV disease. Abnormal liver function tests and leukopenia were common, and the degree of abnormality correlated with the severity of CMV disease. Of the multiple factors analyzed for their influence on the risk of developing overt CMV disease, several factors related to the kidney donor (the relationship of the donor to the recipient, HLA matching and CMV serology) appeared to be most important.

Fever in renal transplant recipients: causes, prognostic significance and changing patterns at the University of Minnesota Hospital.

During a three year period in which 433 renal transplants were performed, 194 episodes of fever were documented in allograft recipients hospitalized at the University of Minnesota. Viral infections were responsible for over half of the febrile episodes, and 98 (51 percent) of the fevers were associated with cytomegalovirus (CMV), either occurring alone or in conjunction with allograft rejection or another systemic infection. Bacterial infections, fungal infections and rejection were other important causes of fever, accounting for 14 percent, 5 percent and 13 percent of the febrile episodes, respectively. Most fevers occurred in the first four months after transplantation; although about two thirds of these fevers were due to CMV, only 17 percent of fevers that occurred more than one year after the renal transplant were due to CMV. Bacterial and fungal infections and malignancy were important causes of these fevers. Of the febrile illnesses associated with transplant nephrectomy or death, a majority occurred in patients with CMV disease. Secondary bacterial and/or fungal infections were observed in a large majority of patients with lethal CMV disease. During the third year of this study there was a significant decrease in the proportion of febrile episodes due to CMV.

115 patients with first cadaver kidney transplants followed two to seven and a half years. A multifactorial analysis.

One hundred fifteen consecutive patients received first transplants from cadaver donors at the University of Minnesota between January 1, 1968, and May 31, 1973. All patients have been followed for at least two years. The two-year survival rate is 70 per cent and the two-year transplant function rate is 58 per cent. Considerable improvement in both patient survival and transplant function has been noted since 1971. The success of transplantation appears to depend to a large degree on the age of the transplant recipient, the number of HLA antigens matched between donor and recipient, and the dose of antilymphoblast globulin (ALG) administered to the recipient during the first two weeks after transplantation. Each of these factors appears to be important even when the other factors are controlled, and when patients with diabetes, suffering technical failure or hyperacute rejection, are excluded. The results utilizing well-matched cadaver kidneys plus large doses of ALG appear to be equivalent to those obtained with the use of mismatched kidneys from relatives, but further analysis will be required to draw a definite conclusion. Patients receiving poorly-matched cadaver kidneys do far less well than patients receiving mismatched related grafts, however, even when ALG is utilized.

Patient and graft survival in amputated versus nonamputated diabetic primary renal allograft recipients.

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%. Diabetic renal allograft recipients living long enough to require amputation have more severe manifestations of vascular disease. These amputees display both an 11% lower patient and graft survival after the first year following transplantation, as well as an accelerated rate of graft loss following amputation. Those diabetics requiring an amputation do significantly more poorly than nonamputees of the corresponding demographic category if diabetes onset occurred at age 10 to 20 years, diabetes duration prior to transplant was less than 20 years, age at transplant was less than 30 years, dialysis duration was less than 4 months, and donor type was HLA-nonidentical related. Nevertheless, more than 50% of the diabetics undergoing amputation will be alive with functioning allografts 4 years after amputation. On the other hand, diabetics not requiring amputation do particularly well if they survive 1 year, with more than 80% chance that they will be alive with a functioning graft 4 years after transplantation.

Renal transplantation between living-related sibling pairs matched for zero-HLA haplotypes.

The functional survival rates of kidney grafts from zero-HLA haplotype-matched sibling pairs are similar to one-haplotype-matched pairs and superior to cadaver grafts. From January 1980 to March 1988, 318 primary renal transplants from sibling donors (151 matched for two, 130 for one, and 37 for zero HLA haplotypes), and 352 cadaver graft transplants were performed at the University of Minnesota. The renal graft survival rates at two years were 94%, 91%, and 94% for the 2, 1, and 0-haplotype pairs versus 75% for cadaver graft recipients (P less than 0.04). When analyzed across the different immunosuppression protocols the same trends held up, similar graft functional survivals for 1- and 0-haplotype-matched pairs both being superior to cadaver graft recipients. The graft functional survival rates at two years of recipients of 0-haplotype-matched sibling donor grafts (n = 37) was 94% versus 80% for recipients of cadaver donor grafts matched for greater than or equal to 4 HLA antigens. In addition, for recipients of 0-haplotype-matched grafts, hospital stay was shorter, fewer patients required dialysis posttransplant, and, despite a slightly higher incidence of rejection episodes (51% versus 40%, P = ns), the creatinine values one year posttransplant were significantly lower (1.5 mg/dl versus 1.9 mg/dl, P less than 0.02) than those of recipients of cadaver grafts matched for greater than or equal to 4 HLA antigens. These data support the use of cadaver grafts for patients not having a willing sibling donor, and the use of all willing sibling donors, whether or not they are a zero-haplotype match, for patients fortunate to have that family commitment.

Cytomegalovirus as a risk factor in renal transplantation.

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). Several risk factors have been considered as possible indicators of CMV disease. These include age, sex, diabetic status, time of onset of CMV, donor and recipient CMV complement-fixing (CF) and indirect fluorescence (IF) titers. The same variables were analyzed to determine whether they might also predict the severity of the disease. Donor CF is the single most important risk factor. Recipient serology alone was not found to be a significant risk factor but 15 of 27 (56%) persons who had a negative titer and received a kidney from a donor with a positive CF titer contracted overt CMV. Nine of those 15 (60%) had moderate, severe, or lethal illness.

Improved patient and primary renal allograft survival in uremic diabetic recipients.

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 greater than or equal to 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.

The effect of mismatching for HLA-DR in recipients of renal allografts sharing one HLA-ABC haplotype with related donors.

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 donor-recipient 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 HLA-ABC haplotype with the recipient. There were 156 primary grafts and 16 retransplants; 147 donor-recipient 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 less than or equal to 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 donor-recipient pairs in whom DR typing was satisfactory, 33% were mismatched for 0, 64% for 1, and 3% for 2 DR antigens. The one-year absolute graft survival rates in recipients of kidneys from donors with 0 mismatches for DR was 92% (n = 49); in those with one mismatch for DR it was 82% (n = 94); and from those with two mismatches it was 50% (n = 4). The one-year graft survival rate in 25 donor-recipient 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 DR-mismatched groups were not statistically significant.(ABSTRACT TRUNCATED AT 400 WORDS)

The impact of cyclosporine and combination immunosuppression on the incidence of posttransplant diabetes in renal allograft recipients.

The incidence of posttransplant diabetes mellitus (PTDM) was compared in three groups of renal transplant recipients: nondiabetic patients who had been randomized between 1980 and 1983 to receive antilymphoblast globulin (ALG), azathioprine (AZA), and prednisone (P) (group 1) or cyclosporine (CsA) plus prednisone (group 2). Group 3 consisted of a more recent (1984-85) cohort who were given a combination of azathioprine, cyclosporine, and prednisone (+/- ALG). PTDM developed in 20 of 173 previously nondiabetic 18-55-year-old patients. Three of 47 patients (6.4%) in group 1, 4 of 58 patients (6.9%) in group 2, and 13 of 68 patients in group 3 (19.1%) developed PTDM. Thus in the two groups composing the concurrent prospective randomized trial (groups 1 and 2) the incidence of PTDM did not differ. The subsequent patients who were given a combination of ALG, azathioprine, cyclosporine, and prednisone developed a significantly greater incidence of PTDM even though the total dose of cyclosporine and prednisone were lower than in groups 1 and 2. PTDM usually occurred within two months of transplantation, and 11 of 17 patients who initially required insulin are still dependent upon exogenous insulin. The incidence of PTDM was not significantly affected by sex of the recipient, HLA-type, primary renal disease, rejection episodes, primary vs. secondary transplant, or prior splenectomy. The incidence of PTDM is greater in patients older than 45 (34.2% vs. 5.2%), and heavier than 70 kg (21.1% vs. 5.1%); in recipients of cadaveric allografts (15.7% vs. 4.6%); and in patients who were hospitalized for infections (22.4% vs. 4.7%). CsA levels tended to be higher in the group 2 and 3 patients who developed PTDM than in those who remained nondiabetic. One-year actuarial patient survival in those with PTDM was 83.3% vs. 98% (P less than .01) in the nondiabetic and graft survival was 77.1% vs. 87.1% (NS). The combination of Minnesota ALG, azathioprine, cyclosporine, and prednisone appears to predispose older, heavier recipients of cadaver allografts to the development of PTDM. The risk of PTDM must be weighed against the more usual results of improved patient and graft survival using this combination of immunosuppression.

Thromboembolic complications in renal allograft recipients. A report from the prospective randomized study of cyclosporine versus azathioprine-antilymphocyte globulin.

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 single-center experience of renal transplantation in thirteen Jehovah's Witnesses.

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.

Allograft renal vascular thrombosis--lack of increase with cyclosporine immunosuppression.

Several recent reports have demonstrated an increased incidence of allograft renal vascular thrombosis in patients receiving cyclosporine alone or as part of multiple drug regimens when compared with patients receiving azathioprine (AZA) and prednisone (P). To determine whether CsA therapy is indeed a risk factor for renal artery or vein thrombosis, we examined the incidence of these complications in 224 adult renal allograft recipients who were prospectively randomized and stratified by risk to treatment with either CsA-P (n = 117) or AZA-P-antilymphocyte globulin (n = 107) between September 1980 and October 1983, and in 452 adult and 87 pediatric patients on triple (AZA-P-CsA) or quadruple (AZA-P-CsA-ALG) therapy protocols between July 1984 and November 1987. In the randomized trial, one of 107 AZA-P-ALG patients (0.9%) and two of 117 CsA-P patients (1.7%) developed renal vein thrombosis (P = 0.94), and there were no cases of arterial thrombosis. Though CsA levels were elevated in one of the two CsA-treated patients at the time of their events, and both these patients demonstrated other predisposing factors for thrombosis. In the triple/quadruple therapy era, there were no cases of renal vein thrombosis, and the only case of renal artery thrombosis occurred in a pediatric recipient who was not receiving CsA at the time. These data, when taken together with a critical review of the conflicting literature, strongly suggest that factors other than immunosuppression with CsA, including surgical technique, allograft rejection, use of multiple artery and/or pediatric donor kidneys, and postoperative hypotension, are important in the pathogenesis of allograft renal vascular thrombosis. It seems possible, however, that high initial dosing of CsA might trigger this complication in the early posttransplant period when other predisposing factors are present.

Long-term effect of splenectomy versus no splenectomy in renal transplant patients. Reanalysis of a randomized prospective study.

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 less than .05) better (10% overall, 12% for cadaver, 14% for nonidentical-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 nonsplenectomized 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 nonsplenectomized 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 nonsplenectomized 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 pretransplant 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. (ABSTRACT TRUNCATED AT 400 WORDS)

Similar renal allograft functional survival rates for kidneys from sibling donors matched for zero-versus-one haplotype with the recipient.

From January 1968 to December 1983, 536 primary renal transplants from siblings donors were performed at a single institution; of the donor-recipient pairs, 246 were matched for two, 205 for one, and 43 for zero HLA haplotypes. Renal allograft functional survival rates at two years were 93%, 75%, and 83% for the 2, 1, and 0-haplotype matched pairs. Corresponding patient survival rates were 95%, 85%, and 93%. The functional survival rate of grafts from the HLA-identical sibling donors was significantly better than the rates in both mismatched donor groups (P = .004), but the difference between the one-haplotype and the zero-haplotype matched pairs was not significant. Most transplant units do not perform transplants between siblings mismatched for both haplotypes because it is assumed that the graft survival rates will be inferior to what can be achieved with a one-haplotype match, and that the outcome will be no better than with cadaveric transplantation. Our results do not support that presumption. Although HLA-identical siblings are the best donors, a sibling should not be excluded as a donor simply because he or she is a complete mismatch. The graft survival rate (83%) is still superior to that achieved with cadaveric transplants (64% at two years, n = 618), and is at least as good as that achieved with transplants from siblings matched for one HLA haplotype. The advent of donor-specific blood transfusion has resulted in liberalization of criteria for acceptance of related donors, but the results of our analysis suggest that a liberal policy, at least in regard to haplotype matching, has always been justified--and certainly at this time the recipient with a willing living donor, regardless of match, should not be relegated to receive a cadaver graft (a scarce resource) that could otherwise be transplanted to someone else who does not have a related donor.

The effects of delayed function on recipients of cadaver renal allografts. A study of 158 patients randomized to cyclosporine or ALG-azathioprine.

We randomized 158 recipients of cadaver renal allografts to cyclosporine-prednisone (83) or antilymphocyte globulin-azathioprine-prednisone (75) to evaluate: the effects of immunosuppression and pretransplant risk factors on the incidence of delayed graft function, the effects of immunosuppression on the resolution of delayed graft function, and the effects of delayed graft function and pretransplanted risk factors on patient and graft survival. Cyclosporine did not increase the incidence of delayed graft function, compared with ALG-azathioprine-treated patients (33% versus 27%, P = 0.550) but doubled the mean (+/- SD) duration of oliguria (11.8 +/- 11.0 versus 5.9 +/- 3.2 days, P = 0.002) and the number of required dialyses (6.6 +/- 7.6 versus 3.2 +/- 1.3, P = 0.031). Retransplanted patients had a higher incidence of delayed graft function that recipients of primary grafts in both the cyclosporine (82% versus 25%, P = 0.001) and ALG-azathioprine (55% versus 22%, P = 0.025) treatment groups. The presence of delayed function reduced one-year graft survival from 89% in all patients without delayed function to 72% (P = 0.011) in all patients with delayed function. Cyclosporine-treated patients had a slightly, but not significantly better one-year graft survival rate than ALG-azathioprine treated patients both with (73% versus 68%, P = 0.750) and without (92% versus 82%, P = 0.069) delayed graft function. A preservation time longer than 24 hr did not increase the incidence of delayed graft function in cyclosporine-treated patients (34% versus 32%, P = 0.811) or ALG-azathioprine-treated patients (27% versus 27%, P = 0.902). Cyclosporine-treated patients given kidneys with greater than 24 hr of preservation time had reduced graft survival only when delayed graft function occurred (67% versus 92%, P = 0.009). In conclusion, (1) cyclosporine did not increase the incidence of delayed graft function over ALG-azathioprine treatment; (2) cyclosporine did significantly slow recovery of kidneys with delayed function; (3) delayed graft function correlated with poorer graft survival rate in both treatment groups; but (4) prolonged preservation time did not increase the incidence of delayed graft function or reduce graft survival.

Transplant renal artery stenosis.

A group of 31 patients with transplant renal artery stenoses was identified among 2002 patients undergoing renal transplantation at the University of Minnesota; 29 of the stenoses were at the anastomosis. A total of 43 procedures were performed to correct the stenosis. Angioplasty was performed 25 times, with 3 patients cured and 2 patients improved; 20 procedures resulted in a poor result (3) or a failure (17). The failures were usually due to recurrent stenosis (7 patients) or to arterial injury that resulted in graft loss (4 patients) or successful emergency surgery to save the transplant (3 cases). Surgical repair of the stenosis was performed 18 times. No grafts were lost and 13 patients were cured or improved. These data suggest that angioplasty for anastomotic stenosis yields poor results and that a surgical repair is probably warranted. All 7 patients who had a poor results or failed a technically successful intervention did not have a rise in creatinine secondary to captopril or had a systolic pressure gradient of less than 60 mmHg across the anastomosis. These data also suggest that patients without physiological evidence of renal artery stenosis may not have improvement in their hypertension following repair.

Local immunosuppression with reduced systemic toxicity in a canine renal allograft model.

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 untreated (P = 0.007) 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 greater than 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 less than 0.0005 and P = 0.01, respectively) but not when renal function became severely impaired (P = 0.34). 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.

Single-center 1-15-year results of renal transplantation in patients with systemic lupus erythematosus.

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. Thirty-two SLE patients receiving 33 transplants between December 1969 and December 1987 were studied retrospectively and compared with controls matched for age, sex, donor source, HLA match, date of transplant, and diabetic status. A total of 69% (22/32) of patients underwent less than 1 year of dialysis prior to transplantation, and 50% (16/32) experienced biopsy-proved acute rejection, which was reversible in 67% (11/16). Actuarial graft function and patient survival rate in SLE patients were not significantly different from those in the matched control group. Duration of prior dialysis did not affect outcome. Surviving grafts have excellent function as measured by serum creatinine (1.3 +/- 0.4 mg/dl, means +/- SD). Causes of death were sepsis (5) and myocardial infarction (1). One patient lost the graft from rejection after withdrawal of immunosuppression because of a malignancy one month posttransplant. Three patients lost graft function due to chronic rejection. To date no patients have had evidence of recurrent SLE nephritis.