Renal transplantation.
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Biomedical subjects
Publications and source records attributed to A J Matas.
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OBJECTIVE: The authors determined whether the use of kidney allografts with multiple renal arteries adversely effects post-transplant graft and patient outcome or increases the incidence of vascular and urologic complications. BACKGROUND: Kidney grafts with multiple renal arteries have been associated with an increased incidence of early vascular and urologic complications. Kidney transplants with single versus multiple renal arteries have not been compared in regard to long-term graft and patient outcome or post-transplant incidence of hypertension, acute tubular necrosis, rejection, and late vascular and urologic complications. METHODS: We analyzed 998 adult kidney transplants done from December 1, 1985 through June 30, 1993, in which only the recipient's external or internal iliac artery was used for anastomosis. We divided the study population into 3 groups: Group A-1 renal artery, 1 arterial anastomosis (n = 835), Group B-->1 renal artery, 1 arterial anastomosis (n = 112), Group C-->1 renal artery, > 1 arterial anastomosis (n = 51). We compared the incidence of post-transplant hypertension, acute tubular necrosis, acute rejection, and vascular and urologic complications; mean creatinine levels at 1, 3, and 5 years post-transplant; and patient and graft survival. Univariate and multivariate analyses were done to identify risk factors for vascular complications. RESULTS: We found no significant differences among the three groups for the following variables: post-transplant hypertension, acute tubular necrosis, acute rejection, creatinine levels, early vascular and urologic complications, and graft and patient survival. In kidneys with single arteries, the presence (vs. absence) of an aortic patch and the type of the arterial anastomosis (end-to-end to the hypogastric vs. end-to-side to the external iliac artery) did not have an impact on the incidence of early or late vascular complications. In kidneys with multiple arteries, only the rate of late renal artery stenosis was higher, the rate of early vascular and urologic complications was not different. Our multivariate analysis identified acute tubular necrosis as a risk factor for renal artery and vein thrombosis; graft placement on the left side for arterial thrombosis; and preservation time > or = 24 hours and multiple renal arteries for renal artery stenosis. CONCLUSIONS: Results of kidney transplants using allografts with multiple versus single arteries are similar.
Acute renal insufficiency in the setting of hemolysis and thrombocytopenia, a triad that constitutes adult or pediatric hemolytic uremic syndrome, can be associated with or triggered by diverse conditions such as verocytotoxin-producing Escherichia coli, viral infections, pregnancy, malignant hypertension, scleroderma, renal radiation, allograft rejection, lupus erythematosus, and assorted medications such as mitomycin C, cyclosporine, and oral contraceptives. Recurrent and de novo hemolytic uremic syndrome occur after renal transplantation. Relapses are also common and probably reflect incomplete resolution of the initial episode. The major differential diagnoses of hemolytic uremic syndrome in the renal allograft include acute vascular rejection, cyclosporine, FK506 or antilymphocyte antibody nephrotoxicity, and malignant hypertension, all of which may display overlapping clinical and histologic features with primary hemolytic uremic syndrome; in such instances, the exact diagnosis may be quite difficult. It is possible that the risk of recurrence may be reduced by proper timing of transplantation and suitable choice of immunosuppressive agents. Intensive plasmapheresis in conjunction with fresh frozen plasma and supportive management of renal failure may lessen mortality and morbidity even in recurrent hemolytic uremic syndrome after transplantation.
BACKGROUND: Ulcers of the upper gastrointestinal tract after renal transplantation have been reported as a frequent and often lethal complication. Considering the continuous expansion of renal recipient criteria, we reviewed our experience with post-transplant ulcers after 1,034 renal transplants performed during the cyclosporine era. STUDY DESIGN: Our retrospective study analyzed only endoscopy-proven ulcers of the esophagus, stomach, and duodenum in 439 (42 percent) living related adult recipients and 595 (58 percent) cadaver or living unrelated adult recipients. For ulcer prophylaxis, only oral antacids were routinely given post-transplant. RESULTS: There were 41 ulcers in 33 patients (esophageal: n = 5, 12 percent; gastric: n = 17, 42 percent; duodenal: n = 19, 46 percent). Significant complications (n = 16) included 15 bleeding episodes and one perforation. The pathogenesis was viral in seven cases (gastric: n = 6, 15 percent; duodenal: n = 1, 2 percent). The ulcers occurred significantly earlier post-transplant in cadaver or living unrelated compared with living related recipients (median, 53 compared with 508 days, p = 0.02). Nonoperative treatment was successful for 96 percent of all ulcers. We found no ulcer-related mortality or graft loss. For living related recipients, the actuarial graft survival rate at three years was 69 percent for patients with ulcers compared with 86 percent for those without ulcers (p = 0.02); for cadaver or living unrelated recipients, it was 48 percent for patients with ulcers compared with 77 percent for those without ulcers (p = 0.9). For living related recipients, the actuarial patient survival rate at three years was 92 percent for patients with ulcers compared with 93 percent for those without ulcers (p = 0.8); for cadaver or living unrelated recipients, it was 59 percent for patients with ulcers compared with 88 percent for those without ulcers (p = 0.002). CONCLUSIONS: With more specific immunosuppression and more effective antiviral therapy, the incidence of post-transplant ulcers is low. Considering the excellent results of nonoperative ulcer therapy and a zero percent ulcer-related mortality rate, renal transplantation is safe for patients with specific (e.g., ulcer history) as well as nonspecific (e.g., chronic obstructive pulmonary disease) ulcer risk factors.
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The identification of peripheral donor cells in solid organ transplant recipients has led to speculation as to the tolerogenic role of circulating donor cells. Also being debated is the possible significance of persistent donor alloantigen-presenting cells in inducing and maintaining an alloantigen-specific unresponsive state. Previously, we showed that donor antigen-specific hyporeactivity is a useful marker for identifying kidney, lung, or heart recipients at low risk for immunologic complications; we found donor antigen-specific hyporeactivity in 25% of kidney, 35% of lung, and 22% of heart recipients. All 3 hyporeactive subgroups experienced fewer late (> 3 months) rejection episodes and a lower incidence of chronic rejection. The purpose of the current study was to determine whether peripheral blood microchimerism correlates with the development of donor antigen-specific hyporeactivity and affects clinical outcome. We correlated the detection of microchimerism with in vitro proliferative response to donor antigen in 19 lung recipients who were > or = 12 months posttransplant. Allogeneic peripheral blood microchimerism was studied with a PCR-based limiting detection assay using HLA-DR sequence-specific primers. We detected microchimerism in 47% (9 of 19) of the lung recipients tested. All recipients who were donor antigen-specific hyporesponsive had microchimerism, and all recipients without detectable microchimerism were responsive to donor antigen. However, not all recipients with microchimerism developed donor antigen-specific hyporeactivity. Further, none of the hyporesponsive recipients has been diagnosed with obliterative bronchiolitis (OB). In contrast, 2 of the 4 with microchimerism who were responsive to donor antigen have been diagnosed with OB, as have 5 of the 10 who were negative for both hyporeactivity and microchimerism. Thus, long-term graft outcome may correlate more closely with donor antigen-specific hyporeactivity than with microchimerism.
Nephrotoxicity remains a concern for patients on long-term cyclosporine. We have previously reported on renal function in a cohort of kidney transplant recipients followed up to 10 years posttransplant. The current study extends the analysis to 12 years. We find no evidence of cyclosporine-induced renal failure.
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Xenoreactive antibodies are an integral part of the natural immune barrier to successful xenotransplantation between phylogenetically disparate species. Studies in primates suggest that the critical targets involved in hyperacute rejection of pig organs are glycoproteins expressed on endothelial cells and platelets. However, there is little information regarding the targets of xenoreactive antibodies and their cellular distribution in other experimental models of hyperacute xenograft rejection, including the commonly used guinea pig-to-rat model. The aim of this study was to characterize the target antigens on guinea pig platelets and endothelial cells that are recognized by rat anti-guinea pig antibodies. Using guinea pig platelet membrane proteins or intact guinea pig endothelial cells as antigens in an ELISA, we demonstrated that rat serum contains IgG* and IgM anti-guinea pig antibodies; levels of antiplatelet antibodies correlated with those against endothelial cells. Serum from naive or complement-depleted rats transplanted with a guinea pig heart was investigated by immunoblotting against membrane proteins extracted from guinea pig platelets and endothelial cells. Normal rat serum revealed numerous bands on either platelet or endothelial cell immunoblots, without obvious similarities in banding pattern under reduced or nonreduced conditions. Absorption of rat serum with intact guinea pig endothelial cells reduced reactivity against numerous bands on endothelial cell membrane blots, but only partially reduced reactivity with three platelet bands (141, 155, and 210 kDa). Absorption of rat serum with intact guinea pig platelets resulted in reduction in reactivity against both platelet and endothelial cell immunoblots. Antibodies eluted from those intact guinea pig endothelial cells and platelets used to absorb rat sera were found to yield patterns of membrane blot reactivity similar to those with unabsorbed sera, suggesting that the proteins recognized are expressed on the cell surface. Lectin affinity blotting demonstrated many of the guinea pig endothelial cell and platelet membrane proteins to be glycosylated. However, digestion of endothelial cell and platelet immunoblots with a mixture of glycosidases failed to change the xenoreactivity with naive rat serum. Immunoblot analysis of serum samples taken daily from complement-depleted rats carrying a functioning guinea pig heart for 3-4 days showed an increase in intensity for specific protein bands on platelets (38, 48, 56, 141, and 155 kDa) and endothelial cells (30, 210, and 270 kDa); no new protein bands were observed. Increased reactivity at several bands correlated with highly elevated rat serum anti-guinea pig antibody titers, as determined by ELISA.(ABSTRACT TRUNCATED AT 400 WORDS)
Recipient selection criteria for pancreas (Px) transplantation differ among centers, based on perceived recipient risk factors, and their validity has not been determined. At the University of Minnesota we have been very liberal in accepting patients for Tx, some of whom have risk factors cited as exclusion criteria by other centers, giving us the opportunity to determine, retrospectively, the impact of their presence on outcome. Between July 1986 and March 1993, we performed 319 bladder-drained cadaver Px Txs at the University of Minnesota, 166 simultaneous with a kidney (SPK), 68 after a kidney (PAK), and 85 alone (PTA). To determine which putative "risk factors" influence patient and graft survival, we used uni- and multivariate (Cox regression) analyses to assess the impact of recipient category, duration of diabetes, and age at onset and at Tx; presence of pre-Tx cardiac (CD) disease (myocardial infarction, bypass, angioplasty), peripheral vascular disease (PVD) (stroke, bypass, angioplasty, amputation); blindness, hypertension, and excess weight; and of Px re-Txs. The incidences of all risk factors except re-Tx were significantly higher in SPK than PTA recipients. Px re-Txs comprised 40% of PAK, 26% of PTA, and 10% of SPK cases (P < 0.0001). Duration of diabetes correlated (P < or = 0.01) with all risk factors but one (hypertension). Recipient age correlated (P < or = 0.01) with CD, blindness, duration of diabetes, and age at onset of diabetes; CD risk factors correlated (P < 0.015) with hypertension and PVD. Recipient age (> or = 45) influenced the technical failure rate only in SPK recipients, with a relative risk (RR) of 2.13 (P = 0.08). Recipient age influenced Px graft and patient survival rates in both SPK and PAK recipients; for those > or = 45, the RR of graft loss was 1.73 and 1.76, respectively (P < or = 0.25), and the RR for ultimately dying was 3.07 in PAK (P = 0.02) and 5.86 in SPK (P = 0.17) recipients. SPK recipients with CD factors were at higher risk to ultimately die (RR = 3.78, P = 0.009), independent of age. Px re-Txs were not at higher risk to fail in PTA, but were in PAK recipients (RR = 1.86, P = 0.09); the risk for technical failure was higher for re-Txs only in SPK recipients (RR = 2.11, P = 0.24). Blindness, hypertension, PVD, and duration of diabetes did not negatively influence patient and graft outcome in any recipient category.(ABSTRACT TRUNCATED AT 400 WORDS)
Living unrelated donor (LURD) transplants have immunologic barriers similar to cadaver transplants, yet the outcome is better (1-year graft survival = 96%). One advantage of LURD transplants is that, with the extremely short preservation time, the kidney functions immediately. We studied whether the quality of initial renal function affects the outcome of primary cadaver transplants. We divided 301 non-6-antigen-matched recipients transplanted between 1/1/86 and 8/1/92--who had no graft loss due to hyperacute rejection, primary nonfunction, or technical reasons--into 5 groups based on the quality of initial renal function (serum creatinine level in the first week). We determined patient and graft survival rates for each group. We found that the quality of initial function had a significant effect on patient and graft survival rates. Recipients whose serum creatinine level was < 3 mg/dl on posttransplant day 5 (groups 1 and 2) had better patient and graft survival than either those whose serum creatinine level was > 3 mg/dl on day 7 (group 4) or those who required dialysis (group 5). Because some early dysfunction may be immunologic, we reanalyzed the data excluding patients with percent reactive antibody > or = 15; the quality of initial function in this group had a significant impact on outcome. Similarly, when patients with graft loss due to "death with function" were excluded, the quality of initial function had a significant impact on survival rates. We conclude that the quality of early posttransplant function is an important predictor of long-term outcome. Cadaver recipients with immediate good function have outcomes similar to living donor recipients. Our data suggest that increased effort should be made to improve immediate posttransplant function.
An acute renal transplant rejection episode has been shown to be associated with decreased 1-year graft survival. The impact on long-term outcome is undefined. We studied the impact of an acute rejection episode on t1/2, the time it takes for 1/2 of the grafts functioning at 1 year to fail. Use of t1/2 avoids inclusion of early graft loss to acute rejection or complications of treatment. Since 1/1/86, a total of 653 patients have received a primary kidney transplant and had at least 1 year of function. Recipients were divided by the incidence and timing of rejection: no rejection; 1 rejection within the first year; > 1 rejection, the first episode in the first year; and > or = 1 rejection, the first episode after the first year. A single rejection episode in the first year reduced t1/2 (45 +/- 11 years in those with no rejection vs. 25 +/- 8 years in those with 1 in the first year). Multiple rejections (t1/2 = 5 +/- 11 years) and a first rejection after the first year (t1/2 = 3 +/- 1 years) have a significant effect (P < .05). Both living and cadaver donor recipients with rejection had shortened t1/2. For those with > 1 rejection, the first episode in the first year, and those with > or = 1 rejection, the first episode after the first year, chronic rejection was the predominant cause of graft loss; noncompliance also played a role. We conclude that a single rejection episode shortens t1/2. Those with > 1 rejection, the first episode within the first year, and those with > or = 1 rejection, the first episode after the first year, are at high risk for late graft loss.
Cytomegalovirus disease occurs frequently after solid organ transplantation and has been associated with decreased patient and allograft survival. We hypothesized that CMV transmission or reactivation begins immediately or soon after transplantation, and that a short-duration ganciclovir (GCV)-based regimen would obviate the need for long-term antiviral agent administration, perhaps serving to interdict CMV infection and disease as well as, or perhaps even more effectively than, a more prolonged, oral acyclovir (ACV)-based form of prophylaxis. A total of 311 patients were stratified according to allograft type, age, and presence or absence or diabetes mellitus, and were then randomized to receive either long-duration ACV prophylaxis (800 mg orally or 400 mg i.v. q.i.d. for 12 weeks after transplantation or 6 weeks after any antirejection therapy) versus short-duration GCV (5 mg/kg/12 hr i.v. for 7 days after transplant or after any antirejection therapy) plus human immune globulin (HIg; Sandoglobulin or Minnesota CMV immune globulin) 100 mg/kg i.v. administered on days 1, 4, and 7 after transplant or after any antirejection therapy. A total of 266 patients (ACV, n = 133; GCV+HIg, n = 133) completed the protocol and were available for follow-up. CMV disease occurred in fewer patients (n = 28, 21.0%) in the ACV group, while significantly more patients (n = 42, 31.6%) in the GCV + HIg group developed group developed CMV disease slightly later (2.83 +/- 0.70 months) than those who received GCV/HIg (2.15 +/- 0.21 months, P > 0.01). Multivariate analysis demonstrated (2.15 +/- 0.21 months, P > 0.1). Multivariate analysis demonstrated that receiving antirejection therapy, a liver transplant, or a donor organ from a CMV-seropositive individual if the recipient was CMV seronegative were major risk factors for the development of CMV disease (P < 0.001), while the difference between ACV versus GCV + HIg prophylaxis was also significant (P = 0.054). No differences in actuarial patient or allograft survival, however, were noted between the 2 prophylaxis groups. Overall, ACV prophylaxis appeared to be more effective in reducing the incidence of posttransplant CMV disease, although this effect was diminished in high-risk groups of patients. Our findings indicate that CMV transmission or reactivation may best be prevented by long-term antiviral agent administration, and that the primary morbidity of CMV disease is the need for rehospitalization when either prolonged ACV or short-duration GCV + HIg prophylaxis is used in this patient population.
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