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Background: Tacrolimus has been shown to have a less adverse effect on the lipid profiles of transplant patients when the drug is started as induction therapy. In order to determine the effect tacrolimus has on lipid profiles in stable cyclosporine-treated renal transplant patients with established hyperlipidemia, a randomized prospective study was undertaken by the Southeastern Organ Procurement Foundation., Methods: Patients of the 13 transplant centers, with cholesterol of 240 mg/dl or greater, who were at least 1 year posttransplant with stable renal function, were randomly assigned to remain on cyclosporine (control) or converted to tacrolimus. Patients converted to tacrolimus were maintained at a level of 5-15 ng/ml, and control patients remained at their previous levels of cyclosporine. Concurrent immunosuppressants were not changed. Levels of total cholesterol, triglycerides, total high-density lipoprotein, low-density lipoprotein (LDL), very-low-density lipoprotein, and apoproteins A and B were monitored before conversion and at months 1, 3, and 6. Renal function and glucose control were evaluated at the beginning and end of the study (month 6)., Results: A total of 65 patients were enrolled; 12 patients failed to complete the study. None were removed as a result of acute rejection or graft failure. Fifty-three patients were available for analysis (27 in the tacrolimus group and 26 controls). Demographics were not different between groups. In patients converted to tacrolimus treatment, there was a -55 mg/dl (-16%) (P=0.0031) change in cholesterol, a -48 mg/dl (-25%) (P=0.0014) change in LDL cholesterol, and a -36 mg/dl (-23%) (P=0.034) change in apolipoprotein B. There was no change in renal function, glycemic control, or incidence of new onset diabetes mellitus in the tacrolimus group., Conclusion: Conversion from cyclosporine to tacrolimus can be safely done after successful transplantation. Introduction of tacrolimus to a stable renal patient does not effect renal function or glycemic control. Tacrolimus can lower cholesterol, LDL, and apolipoprotein B. Conversion to tacrolimus from cyclosporine should be considered in the treatment of posttransplant hyperlipidemia.

Objective: This study determined whether renal allograft recipients with antibodies to hepatitis C virus (HCV) at the time of transplantation experienced increased morbidity or mortality from hepatitis, liver disease, or hepatocellular carcinoma compared with patients without anti-HCV., Summary Background Data: Chronic liver disease is a cause of significant morbidity and mortality after kidney transplantation and the contribution of HCV to this problem has not been determined. The recent characterization of the HCV genome has resulted in the development of screening tests for antibody to HCV, allowing the identification of end-stage renal disease patients with anti-HCV who are candidates for transplantation. The risk to these patients for the development of hepatic complications after subsequent transplantation is unknown., Methods: Archived sera obtained from 163 kidney transplant recipients at the time of transplantation were tested for anti-HCV using the Abbott HCV 2.0 second-generation test system. Sera containing anti-HCV were further analyzed for reactivity against specific HCV recombinant proteins, including core, NS3 (c33c), and NS4 (c100-3), to determine whether a pattern could be identified in patients with hepatic complications. The follow-up of all patients was current (mean length of follow-up was 33 months) to identify patients with hepatic complications. All patients had previously been tested for HBSAg., Results: Twenty-nine patients (18%) had anti-HCV and three (1.8%) had HBSAg. Forty-five patients (28% of total) had transient elevations of AST or ALT without subsequent evidence of liver disease. Three patients had a syndrome of acute hepatitis. Chronic liver disease developed in only six patients (3.6%) after transplantation. Four had anti-HCV only, one had HBSAg only, and one was positive for both. However, of the 29 patients with anti-HCV, chronic liver disease developed in 5 (17%), including 1 patient who was positive for HBSAg. No patient had hepatocellular carcinoma., Conclusions: Perturbations of liver function were common in the kidney transplant recipients studied, most were self-limited, and few were associated with evidence of viral hepatitis. The risk of developing

Data were collected prospectively on 8581 cadaveric renal transplants performed by institutions of the South-Eastern Organ Procurement Foundation (SEOPF) during the period November 1, 1983 through December 31, 1987. Cyclosporine was the initial then always used immunosuppressant for 5742 of these patients while 1050 never received cyclosporine. The drug was started late in the course of 481 transplants and stopped early in 378 cases. This allowed for 7651 transplants to be analyzed regarding these four categories of cyclosporine use or non-use. Actuarial graft survival for the cyclosporine "ALWAYS" group was 75% at one year, 68% at two years, 62% at three years, and 59% at four years compared with 55%, 49%, 45%, and 43%, respectively for the cyclosporine "NEVER" group (P less than 0.0001). Inclusion of the 930 cases that could not be categorized regarding cyclosporine use or for which actuarial data was not complete allowed all 8581 transplants to be analyzed by multivariate methods. This analysis disclosed significant effects on graft survival due to delayed graft function, prior transplant, recipient race, HLA match, level of PRA, and cyclosporine use. Organ sharing had no effect on graft outcome. While cyclosporine improves outcome in renal transplantation, the importance of other biologic factors affecting graft survival is not diminished by its use.

Reported are 204 primary external ureteroneocystostomies and 16 primary ureteroureterostomies in a series of 220 consecutive renal transplants. A total of 12 (5%) complications occurred; however, only seven (3%) required major operative repair, whereas five (2%) were minor and were repaired by cystoscopic or transvesical procedures. There was no mortality and no allograft loss from these complications, which tend to occur late and be amenable to prompt repair. Since the complications of external ureteroneocystostomy differ from those of the internal ureteroneocystostomy, a discussion of their treatment is provided. A review of literature shows that the external repair is growing in popularity because of its good results. The good results are attributable to the use of a short length of ureter, to the use of a continuous monofilament suture that produces an anastomosis less likely to leak, and to the need of a very small cystostomy.

Antibodies that react with heterophile transplantation antigen (HTA) have been shown previously not to react with HLA-A, B, or C antigens. This paper presents evidence that anti-HTA does react with a subpopulation of human lymphocytes which is comprised primarily of B cells. Anti-HTA reactivity was removed from sera by absorption with each of three different human B lymphocyte cell lines, but it was unaffected by absorption with platelets or thymocytes. Selected high titer anti-HTA sera absorbed with human platelets, human blood group type AB erythrocytes, and sheep erythrocytes caused lysis of a lymphocyte subpopulation principally composed of B lymphocytes. Absorption of these sera with rat erythrocytes removed both lymphocytic activity and anti-HTA activity. Antibody recovered by affinity purification with rat erythrocyte membrane preparations contained both lymphocytic and anti-HTA reactivity. These data, considered with previous studies, seem to establish that B cell sensitization may be acquired by a substantial segment of the population by natural immunization from enteric flora and/or by infections with enteric bacteria.

The morphological distribution of heterophile transplant antigen (HTA) was determined in rat tissues using an indirect immunofluorescence technique. Human anti-HTA sera were used to localize HTA in rat kidney, liver, heart, skeletal muscle, spleen, and stomach. HTA was found in basement membrane and supporting stromal elements of all tissues studied. In the kidney, HTA was demonstrated in tubular basement membrane but not glomerular basement membrane. No evidence for cell surface antigen distribution could be ascertained except for erythrocyte membranes. HTA was not found on endothelium of rat blood vessels. We know of no antigens previously implicated in histocompatibility that are stromal in location.

Ten autotransplants are presented. Renal autografts were performed in the correction of renal artery stenosis, renal artery aneurysm, and intrarenal arteriovenous fistula. All were successful. Jejunal autografts were used to replace the cervical esophagus twice and the entire esophagus once. All grafts were successful, although one patient with advanced cancer died. Pancreatic segmental autografts were used to prevent diabetes following three subtotal pancreatectomies for chronic pancreatitis and one total pancreatectomy for carcinoma. Two patients have functioning grafts, require no insulin, and are free of disease at present. One patient is free of pancreatitis but is diabetic, and one patient died of probable pulmonary embolus. These experiences suggest that organ autografts can be used with greater frequency in clinical surgery and may alter standard therapy for several problems.

The light and electron microscopic morphology of 57 cadaver renal allografts was assessed at the time of procurement and again after revascularization. Twenty-two kidneys (39%) did not function immediately after transplantation and 19 of these (86%) contained morphologic evidence of acute tubular necrosis (ATN) in the procurement biopsy. The morphology of the post-transplant biopsy was abnormal in all 22 kidneys with delayed function. There was a wide spectrum of morphologic change between the time of procurement and revascularization in all kidneys with normal function. These changes were mild in nature, were usually confined to proximal tubules, and were of unknown clinical significance. The morphology of kidneys that were damaged by the time of procurement was surprisingly different after storage with simple hypothermia (ice) than after storage with hypothermic pulsatile perfusion. The changes attributed to ice storage included endothelial swelling and vacuolation with obliteration and collapse of capillary lumens, fracture and splitting of peritubular basement membrane, and hyalinization of the renal interstitium. It was unknown whether these morphologic abnormalities were associated with delayed recovery of function of the injured kidneys.

The presence or absence of the heterophile transplantation antigen was sought in renal tissue from stillborn infants, primary cell cultures, and several organs from adult human cadavers. The heterophile transplantation antigen was found in renal tissue at birth, was retained in human renal cell culture, and was present in human organs other than kidney. The most likely explanation for these results is that the heterophile transplantation antigen is an intrinsic component of many human tissues.

"External" ureteroneocystostomy is a method of reconstructing the urinary tract for renal transplantation. As performed by us, it is a modification of the technique of Witzel, Sampson, and Lich. It has the advantages of requiring a very short length of ureter, avoiding a separate and large cystotomy, and retaining the antireflux mechanism. This technique is described in detail. Ureteroureterostomy has been used as the preferred procedure when the bladder wall is very thin or when the vascular attachments are such that a ureteral length of greater than 6-7 cm would be required for bladder implantation. Since using these techniques we have reduced the early complication rate of ureteral implantation from 11.9% in a consecutive series of 126 transplants to 0% in the last 88 consecutive transplants. A review of the literature which led to the adoption of these techniques is also presented.

Antibodies to heterophile transplant antigen (HTA) were tested for reactivity with antigens on human umbilical cord antigenic specificities on isolated endothelial cells. Furthermore, there are antigens on endothelial cells that are distinct from HLA-A,B, C, and from HTA. It is concluded that the HTA and the VEC antigens are different.