Anatomical variations of the hepatic artery: a closer view of rare unclassified variants.

BACKGROUND: Defining the hepatic artery anatomy is of great importance for both surgeons and radiologists. Michel classification was designed to classify hepatic artery variations. Nevertheless, there are variations that do not fit into this classification. In this study, we aim to define the incidence of all variations in a healthy liver donor by reviewing their computed tomography (CT) scan with special emphasis on variations that do not fit in any of the Michel classes. MATERIALS AND METHODS: A retrospective analysis of CT scan of donors and potential liver donors who were evaluated by triphasic CT scan. The CT scans were reviewed independently by a radiologist and two transplant surgeons. Cases that did not fit in any of the Michel classes were classified as class 0. RESULTS: Out of 241 donors, 210 were classified within the Michel classification, of which 60.9% were class I and 9.1% class II. Thirty-one (12.9%) donors classified as class 0. Of which, nine, three, two and three had replaced right hepatic artery from pancreaticoduodenal artery, gastroduodenal artery, aorta and coeliac artery, respectively. Two and six donors had accessory right hepatic artery from pancreaticoduodenal artery and gastroduodenal artery, respectively. Segment 4 artery originated from left and right hepatic artery in 56.8% and 31.9%, respectively. CONCLUSIONS: A great caution should be taken when evaluating the hepatic artery anatomy, clinicians should anticipate and be familiar with the rare unclassified variations of the hepatic artery.

Three Consequent Pediatric Liver Transplant Deaths in the COVID-19 Era.

The effect of COVID-19 on the transplant recipients is not well-established. Many reports underestimate the effect of COVID-19 on the immunosuppressed population. Herein, we report on 3 pediatric liver transplant recipients who were transplanted at our center between February 11 and March 10, 2020-during the COVID-19 pandemic era. The 3 patients aged between 5 and 10 months, had a rapid and aggressive respiratory deterioration that necessitated mechanical ventilation and extracorporeal life support; and eventually died. The clinical and pathological pictures likely represent COVID-19 pneumonia. Chest x-rays showed progressive infiltrates. Lung autopsies showed diffuse alveolar damage in two cases. We concluded that COVID-19 is very likely to have catastrophic effects on transplant recipients.

Cadaveric liver transplantation in biliary atresia splenic malformation syndrome with the absence of retrohepatic inferior vena cava, preduodenal portal vein, and intestinal malrotation: a case report.

A 9-month-old female infant with biliary atresia underwent cadaveric liver transplantation due to progressive cholestatic hepatitis following a Kasai operation. She had biliary atresia splenic malformation syndrome (BASM) composed of an absent retrohepatic inferior vena cava with an azygous connection, preduodenal portal vein, polysplenia, and intestinal malrotation. A portal vein thrombosis developed on the 4th postoperative day requiring immediate treatment by thrombectomy. The patient is well with normal liver function at 3 months follow-up. Although BASM may render the transplantation more difficult, the presence of BASM is no longer a contraindication to liver transplantation.

The impact of donor variables on the outcome of orthotopic liver transplantation for hepatitis C.

Morphologic characteristics of the graft have been proposed as a major contributor to the long-term outcomes in orthotopic liver transplantation (OLT). Our objective was to determine the impact of donor variables, including donor age, donor-recipient HLA match, and type of donation (DCD vs donation after brain death [DBD]), on the outcome of OLT in 192 patients with hepatitis C virus (HCV). Fourteen patients underwent OLT from donation after cardiac death (DCD) donors and 188 from DBD donors. Mean donor age, warm ischemia time at recovery, and cold ischemia time were similar between the groups. Overall graft survival rate at 1 year (55% DCD vs 85% DBD) and 5 years (46% DCD vs 78% DBD) was significantly lower in the DCD group (P = .0003). Similarly, patient survival rate at 1 year (62% DCD vs 93% DBD) and 5 years (62% DCD vs 82% DBD) was significantly lower in the DCD group (P = .0295). Incidences of hepatic artery thrombosis, portal vein thrombosis, and primary nonfunction were similar between the DCD and DBD groups. The incidence of liver abscess with ischemic-type biliary stricture was higher in recipients from DCD as compared with DBD (42% vs 2%). A trend toward lower graft survival was noted in recipients from donors older than 60 years of age in the HCV population (P = .07), with statistically lower patient survival (P = .02). Donor- recipient HLA matching did not appear to correlate with OLT outcome in patients with HCV. DCD donors and donors older than 60 years of age significantly impact patient and graft survival. Lower graft and patient survival in recipients from DCD donors does not appear to be related to early disease recurrence.

Beliefs of Living Donors About Recipients' End-Stage Liver Failure and Surgery for Organ Donation.

BACKGROUND: The concept of beliefs could provide a basis for how donors may perceive recipients' end-stage liver failure (ESLF) and surgery for organ donation. However, there is no such quantitative study. Therefore, the objective of this study was to explore beliefs of living donors about recipients' ESLF and surgery for organ donation. METHODS: The sample comprised 16 living donors who donated a part of their liver to a patient who had ESLF. The data were analyzed by following established procedures for inductive qualitative analysis. RESULTS: Analysis showed that donors' beliefs can be viewed in a number of groups. Beliefs about recipients' ESLF included diverse explanations for ESLF (blaming oneself and physicians) and physical symptoms (developmental slowing down). Beliefs about being a donor included reasons for being a donor (performing a good deed, being healed), barriers to being a donor (other people being ignorant and selfish), ways to manage these barriers (following one's gut feeling), and factors facilitating being a donor (the feeling that one does not have many people to leave behind). Beliefs about surgery for organ donation included physical effects (pain, feeling stiff). Beliefs about organ donation included views that general organ donation should be encouraged and that people's awareness should be raised. CONCLUSIONS: Existing psychological perspectives could help to interpret some beliefs. Nevertheless, other beliefs, not previously reported, could be considered as targets for individual consultations/psycho-educational programs for fostering emotional well-being.

Liver Transplantation: Recipients' Evaluation of Life From the Perspective of Living Donors.

AIM: Liver transplantation affects not only recipients and living donors' lives, but also the nature and quality of their relationship. Moreover, the ways in which recipients of liver transplant experience life and views of living donors on how recipients experience life may differ. These differences may account for relational changes. It is also important to understand how recipients and their living donors' views differ if the aim is to devise psychoeducational programs for recipients and living donors. Therefore, the present study examined the recipients' experience of life after a diagnosis of end-stage liver failure (ESLF) and transplantation surgery from donors' perspective. METHODS: The sample consisted of 16 living donors who donated a part of their liver to a patient with ESLF. Thematic analysis was undertaken in parallel with interviews during which an interview guide was followed. FINDINGS: Donors felt that recipients evaluated life after the diagnosis of ESLF and transplantation surgery in terms of limitations, mixed relationships, emotional changes, and improvement in life. CONCLUSION: Experience of social limitations, negative emotions, and the feeling that one is supported by others could be interpreted in terms of existing psychological theory. Some ways of adjusting that have not been reported before within the context of ESLF extended the literature. These included others being frightened of being infected by ESLF and being insensitive, experience of positive emotions, and ways of improving. Overall, compared with findings of previous qualitative work among recipients, our findings suggest that donors' evaluation of recipients' lives converge with that of recipients.

OKT3 rescue therapy in pancreas-allograft rejection.

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.

Early detection of rejection in pancreas transplantation.

A major dilemma in pancreas transplantation is the lack of reliable methods for the early detection of allograft rejection. Over a 26-mo period, 70 rejection episodes occurred in 36 patients (13 isolated-pancreas, 23 simultaneous pancreas-kidney recipients) with pancreaticoduodenocystostomy. A total of 300 radionuclide pancreas examinations were performed (mean 8.3/patient) utilizing 99mTc-labeled DTPA. Computer analysis generated a quantitative measure of blood flow to the allograft (technetium index, TI). Rejection episodes were defined as isolated pancreas, isolated kidney, or combined pancreas-kidney. Mean urinary amylase (UA) levels and TI during normal allograft function were 30,256 U/L and 0.57%, respectively, whereas levels heralding rejection were 6873 U/L and 0.39% (P less than .05). The treatment of rejection based on kidney dysfunction or combined pancreas-kidney dysfunction resulted in significantly higher graft salvage and a lower incidence of hyperglycemia compared with isolated-pancreas-allograft rejection. After therapy, a TI greater than 0.3% was associated with 95.9% graft survival, whereas levels less than 0.3% resulted in a 72.7% rate of graft loss (P less than .001). Similarly, pancreas allografts with a UA greater than 10,000 U/L had 92.2% functional survival, whereas levels less than 10,000 U/L resulted in a 53.3% rate of graft loss (P less than 0.001). Overall, reversal of rejection occurred in 80% of cases, with 10 pancreas and 2 kidney allografts lost due to rejection. Monitoring pancreas-allograft function by UA, TI, and renal function in simultaneous transplants allows for the timely diagnosis and successful treatment of pancreas-allograft rejection.

Use of UW solution in pancreas transplantation.

We have recently reported successful 72-h preservation of the canine pancreas with a new cold-storage solution developed at the University of Wisconsin (UW solution). Over 10 mo, we performed 11 combined pancreas-kidney and 4 isolated-pancreas transplants with this solution. In situ cooling of the donor pancreas was performed with 1000 ml of UW solution followed by ex vivo perfusion with an additional 250-500 ml. Graft preservation times ranged from 3 to 19 h (mean 10.2 h). Pancreas transplants were vascularized whole-organ grafts with pancreaticoduodenocystostomy. Early graft function was excellent as assessed by immediate insulin independence, high urinary amylase and low serum amylase levels, and a technetium perfusion index indicating good pancreatic blood flow. There were no episodes of primary nonfunction, graft pancreatitis, or vascular thrombosis. Actuarial patient and graft survival at 1 mo was 92.9%. We conclude that UW solution provides excellent early graft function for up to 19 h of cold storage. Based on previously reported data on its efficacy in liver and kidney preservation, UW solution seems ideally suited as a universal intra-aortic flush and cold-storage solution.

Conversion of stable liver transplant recipients from a twice-daily Prograf-based regimen to a once-daily modified release tacrolimus-based regimen.

INTRODUCTION: Modified release (MR) tacrolimus is an extended release formulation administered once daily. The purpose of this pharmacokinetic (PK) study was to evaluate tacrolimus exposure in stable liver transplant recipients converted from Prograf twice a day to MR tacrolimus once daily. METHODS: This was an open-label, multicenter study with a single sequence, four-period crossover design. Eligible patients were 18 to 65 years of age, >6 months posttransplant with stable renal and hepatic function and receiving stable doses of Prograf twice a day for >2 weeks prior to enrollment. Patients received Prograf twice a day on days 1 to 14 and 29 to 42. Patients were converted to the same milligram-for-milligram daily dose of MR once daily on days 15 to 28 and 43 to 56. Twenty-four-hour PK profiles were obtained on days 14, 28, 42, and 56. Laboratory and safety parameters were also evaluated. RESULTS: Of 70 patients, 62 completed all four PK profiles. The AUC0-24 of tacrolimus was comparable for Prograf twice a day (days 14 and 42) and MR tacrolimus once daily (days 28 and 56). The 90% confidence intervals for MR tacrolimus versus Prograf at steady state (days 28 and 56 vs days 14 and 42) was 0.85 to 0.92 for AUC0-24. MR tacrolimus was well tolerated with a safety profile comparable to that of Prograf. AUC0-24 was highly correlated to Cmin for Prograf (day 14, r = .93; Day 42, r = .89) and for MR tacrolimus (day 28, r = .93; day 56, r = .92). Renal and liver function remained stable. One patient experienced acute rejection. CONCLUSION: The steady-state tacrolimus exposure of MR tacrolimus once daily is equivalent to Prograf twice a day after a milligram-for-milligram conversion in stable liver transplant recipients.

Living donor liver transplantation: a life-saving option in emergency situations for diffuse hepatic neuroendocrine tumor metastasis.

Liver metastasis is the main cause of death in patients with gastroenteropancreatic neuroendocrine tumors (GEP-NETs), but only 10%-20% of metastasis in these cases is resectable at the time of diagnosis. In some cases, medical and interventional radiological treatments may not be effective. Liver transplantation, although controversial, may be an option. Worldwide organ-sharing systems do not provide exception points, but give recommendations for liver transplantation in cases of hepatic metastasis from GEP-NETs due to the issue of fair access to donor organs. Living donor liver transplantation is an option in select cases. Presented here are 2 cases in which living donor liver transplantation was performed in emergency situations as a life-saving procedure, with acceptable survival and without donor complications.

Acquired factor XI deficiency: a rare complication after liver transplantation.

BACKGROUND: A majority of coagulation factors are synthesized in the liver. Factor XI (FXI) deficiency (Rosenthal syndrome) is one of the rare inherited coagulation disorders with an extremely low risk of transmission by liver transplantation (LT). CASE REPORT: We report here the case of a 50-year-old man who unknowingly acquired FXI deficiency by LT. During 1 year of post-transplant follow-up, his activated partial thromboplastin time (aPTT) remained prolonged, but he did not develop bleeding complications. The patient required retransplantation due to chronic rejection and is currently doing well 4 years after his first liver transplantation. CONCLUSIONS: The presence of a prolonged aPTT in a deceased donor should raise suspicion for the presence of rare coagulation factor deficiencies. During urgent, lifesaving procedures such as LT, it may be impossible to avoid transmission. Awareness of this possibility will allow early detection and management.

Chlamydia pneumoniae-infected monocytes exhibit increased adherence to human aortic endothelial cells.

Interactions between monocytes and endothelial cells play an important role in the pathogenesis of atherosclerosis, and monocyte adhesion to arterial endothelium is one of the earliest events in atherogenesis. Work presented in this study examined human monocyte adherence to primary human aortic endothelial cells following monocyte infection with Chlamydia pneumoniae, an intracellular pathogen associated with atherosclerosis by a variety of sero-epidemiological, pathological and functional studies. Infected monocytes exhibited enhanced adhesion to aortic endothelial cells in a time- and dose-dependent manner. Pre-treatment of C. pneumoniae with heat did not effect the organism's capacity to enhance monocyte adhesion, suggesting that heat-stable chlamydial antigens such as chlamydial lipopolysaccharide (cLPS) mediated monocyte adherence. Indeed, treatment of monocytes with cLPS was sufficient to increase monocyte adherence to endothelial cells, and increased adherence of infected or cLPS-treated monocytes could be inhibited by the LPS antagonist lipid X. Moreover, C. pneumoniae-induced adherence could be inhibited by incubating monocytes with a mAb specific to the human beta 2-integrin chain, suggesting that enhanced adherence resulted from increased expression of these adhesion molecules. These data show that C. pneumoniae can enhance the capacity of monocytes to adhere to primary human aortic endothelial cells. The enhanced adherence exhibited by infected monocytes may increase monocyte residence time in vascular sites with reduced wall shear stress and promote entry of infected cells into lesion-prone locations.

Characterization of low-density lipoprotein uptake by murine macrophages exposed to Chlamydia pneumoniae.

Exposure to Chlamydia pneumoniae is correlated with atherosclerosis in a variety of clinical and epidemiological studies, but how the organism may initiate and promote the disease is poorly understood. One pathogenic mechanism could involve modulation of macrophage function by C. pneumoniae. We recently demonstrated that C. pneumoniae induces macrophages to accumulate excess cholesterol and develop into foam cells, the hallmark of early atherosclerotic lesions. To determine if C. pneumoniae-induced foam cell formation involved increased uptake of low-density lipoprotein (LDL), the current study examined macrophage association of a fluorescent carbocyanine (DiI)-labeled LDL following infection. C. pneumoniae enhanced the association of DiI-LDL with macrophages in a dose-dependent manner with respect to both C. pneumoniae and DiI-LDL. Interestingly, increased association was inhibited by native LDL and occurred in the absence of oxidation byproducts and in the presence of antioxidants. However, enhanced DiI-LDL association occurred without the participation of the classical Apo B/E native LDL receptor, since C. pneumoniae increased DiI-LDL association and induced foam cell formation in macrophages isolated from LDL-receptor-deficient mice. Surprisingly, DiI-LDL association was inhibited not only by unlabeled native LDL but also by high-density lipoprotein, very low density lipoprotein, and oxidized LDL. These data indicate that exposure of macrophages to C. pneumoniae increases the uptake of LDL and foam cell formation by an LDL-receptor-independent mechanism.

Delayed response to orthoclone OKT3 treatment for renal allograft rejection resistant to steroid and antilymphocyte globulin.

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.

Successful extrarenal transplantation from non-heart-beating donors.

The current organ shortage has made utilization of organs from less-than-ideal donors more common. Although several transplant centers use kidneys from non-heart-beating donors (NHBDs), there has been reluctance to extend the use of these donors to extrarenal organs. Of the 130 donors referred to our organ procurement organization between January 1993 and May 1994, 16 (12.3%) were NHBDs. Organ retrieval from 10 of these resulted in extrarenal donation, 5 resulted in renal donation only, and 1 resulted in no retrieval as a result of prolonged warm ischemia (> 2 hr). A total of 39 organs were transplanted from these NHBDs. A rapid en bloc retrieval technique was used for extrarenal NHBDs. The mean warm ischemic time was 15.4 min; preservation times were similar for both NHBDs and heart-beating donors. After liver transplantation (n = 5), one episode of primary nonfunction that was technical in origin required retransplantation. Following simultaneous pancreas-kidney transplantation (n = 6), all patients were insulin independent and free of graft pancreatitis; one patient required hemodialysis (16.7%). After isolated renal transplantation (n = 21), 3 patients (14.3%) required hemodialysis. Three of 4 liver recipients are alive after a mean follow-up period of 12.7 months; all simultaneous pancreas-kidney and renal transplant recipients are alive after a mean follow-up period of 8.4 and 8.3 months, respectively. Three liver allografts, 5 pancreas and kidney allografts, and 19 renal allografts are functioning. The lung allograft was lost to rejection 81 days after transplantation; however, the recipient is alive 3 months after retransplantation. Our results demonstrate that in controlled situations, extrarenal organs can be utilized from NHBDs and can be expected to function similarly to organs retrieved from heart-beating donors. We increased the number of transplanted organs by 8.6% using NHBDs for both renal and extrarenal donation. Continued application of these techniques will likely further increase the number of organs retrieved for transplantation.

Determinants of graft survival after renal transplantation.

We studied multiple determinants of graft survival at a single center and the effects of nonimmunologic graft loss on transplant survival. This retrospective study examined the results of 589 cadaver donor transplants performed between 1986 and 1992. Graft survival rates were calculated using Kaplan-Meier estimates for both overall graft survival (all causes of graft loss) and immunologic graft survival (function lost due to acute or chronic rejection and noncompliance). Cadaver graft survival was significantly poorer with an increasing degree of DR mismatch (P=0.02). An analysis of pretransplant variables showed graft loss risk was highest with greater DR mismatches, two B-antigen mismatch, higher donor serum creatinine, and younger recipient age. After transplantation, acute rejection was the most significant factor associated with long-term graft survival. Our data demonstrate a significant advantage for zero DR and one DR mismatch cadaver donor transplants, with excellent immunologic graft survival. This study suggests that a combination of immediate graft function, prevention of acute rejection by appropriate early immunosuppressive therapy, and acceptable DR match enhances cadaveric graft survival.

Kidney retransplantation in the cyclosporine era.

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.

Withdrawal of steroid immunosuppression in renal transplant recipients.

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.

Multivariate analysis of risk factors for sensitization and early rejection episodes in a donor-specific transfusion plus azathioprine protocol.

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.