Kidney transplantation in blacks at the University of Wisconsin.
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Biomedical subjects
Publications and source records attributed to M Kalayoglu.
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The effect of donor pretreatment with Dibenzyline (phenoxybenzamine) on hepatic arterial vasospasm was studied in a porcine asphyxia model. Nine pigs underwent hepatectomy without pretreatment, while six were given 2 milligrams per kilogram of Dibenzyline prior to hepatic dissection. Hepatic arterial blood flow was monitored with an electromagnetic flow probe, and after cardiac arrest, arteriograms of the hepatic circulation were obtained. Hepatic arterial vasospasm occurred in seven of the pigs in group 1 and in only one of group 2 (p less than 0.05). Agonal hepatic arterial blood flow remained constant (415 +/- 30 milliliters per minute) in pretreated pigs during asphyxia, but was markedly reduced (98.6 +/- 63.3 milliliters per minute) in nonpretreated pigs (p less than 0.05). Results of this study demonstrate the agonal occurrence of hepatic arterial vasospasm and its prevention with Dibenzyline. Donor pretreatment with alpha-adrenergic antagonists may be indicated in clinical organ procurement to prevent agonal arterial vasospasm and its potentially adverse effect on early hepatic allograft function.
Graft availability remains the major limitation to organ transplantation. Belzer-UW solution has been used for multiple organ procurement in 20 consecutive donors. Belzer-UW solution was used for both aortic in situ flush and ex vivo cold storage. From 20 donors, a total of 20 pancreatic grafts, 20 livers, 39 kidneys, and 10 hearts were procured. Mean preservation time was 14.2 hours for the pancreas, 16 hours for the kidney transplanted with the pancreas, 13.8 hours for the liver, and 29.9 hours for the isolated kidneys, which were machine perfused. Graft survival of the organs transplanted at the University of Wisconsin was 100% for kidney and pancreas, 93.3% for the isolated kidney, and 78.5% for the liver. When the organs referred to other centers were included, 84 of 89 procured organs were functioning at 1 month. It is concluded that multiorgan procurement with Belzer-UW solution yields excellent graft function for all abdominal organs.
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.
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)
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.
Since February 1986, 23 patients have received Orthoclone OKT3 treatment at our transplant center for renal allograft rejection resistant to steroids and antilymphocyte globulin (ALG). They have been followed for at least 4 months as of this study time (range: 4-15 months). We report here our experience with OKT3, including five late responders--as late as 116 days after OKT3 treatment. Overall rejection was reversed in 19/23 (83%). Rejection was controlled in 95% of primary and 50% of nonprimary transplants; 89% of the male and 80% of the female patients were treated successfully; 94% of the cadaver-donor and 80% of the living-donor transplants responded successfully. The one-year rerejection rate after OKT3 was 50%, and 38% of rerejection episodes were treated successfully. Time (days) required to reverse the episodes of acute graft rejection after the start of OKT3 is plotted, and it shows a distinctive bimodal distribution: first, early responders with a mean +/- SD of 12 +/- 5 days (range: 4-20 days) and second, late responders with a mean +/- SD of 58 +/- 31 days (range: 30-116 days). We conclude that OKT3 is very effective in treating steroid- and ALG-resistant acute rejection episodes, and also that it is important to be aware of the potential late response to OKT3 antirejection therapy and recommend delaying transplant nephrectomy or immunosuppressive withdrawal for as long as possible (probably up to 4 months) for patients who have received OKT3 treatment.
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 total of 205 patients who underwent donor-specific transfusions with azathioprine (DST+AZA) treatment from 1982 to 1987 included 25 patients (12%) who developed antibodies cytotoxic to donor T cells (+T warm crossmatch). When we examined a series of 14 variables in relation to the risk of sensitization using a univariate analysis, panel-reactive antibody (PRA) pre-DST of greater than 40%, pregnancy, female sex, male-to-female DST, and HLA antigen match all were significant (P less than .05) risk factors. Of these variables, only PRA pre-DST greater than 40% proved to be statistically significant (P less than .002) in a multivariate logistic regression model (overall P less than .001). Of those patients who went on to transplant with the donor-specific kidney, 41/170 (24%) developed early on or before day 5 posttransplant) rejection episodes. Univariate analysis of 17 variables in relation to early (less than 5 days) rejection episodes indicated no significant variables. Nonetheless using a multivariate logistic regression model (overall P = .09), HLA match (P less than .004), perioperative transfusions (P less than .05), and azathioprine withdrawal for greater than 1 week during DST (P less than .05) all correlated with the incidence of early rejection episodes. In a smaller multivariate model involving 47 patients for whom MLC/blocking factor data were available, the presence of plasma blocking factor at the time of transplant was associated with a decreased incidence of early rejection (P = .07). We conclude that the factors that influence the rate of T+ sensitization are distinct from those that influence the rate of early rejection episodes in a DST+AZA protocol.
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