The Incremental Cost of Incompatible Living Donor Kidney Transplantation: A National Cohort Analysis.

Incompatible living donor kidney transplantation (ILDKT) has been established as an effective option for end-stage renal disease patients with willing but HLA-incompatible living donors, reducing mortality and improving quality of life. Depending on antibody titer, ILDKT can require highly resource-intensive procedures, including intravenous immunoglobulin, plasma exchange, and/or cell-depleting antibody treatment, as well as protocol biopsies and donor-specific antibody testing. This study sought to compare the cost and Medicare reimbursement, exclusive of organ acquisition payment, for ILDKT (n = 926) with varying antibody titers to matched compatible transplants (n = 2762) performed between 2002 and 2011. Data were assembled from a national cohort study of ILDKT and a unique data set linking hospital cost accounting data and Medicare claims. ILDKT was more expensive than matched compatible transplantation, ranging from 20% higher adjusted costs for positive on Luminex assay but negative flow cytometric crossmatch, 26% higher for positive flow cytometric crossmatch but negative cytotoxic crossmatch, and 39% higher for positive cytotoxic crossmatch (p < 0.0001 for all). ILDKT was associated with longer median length of stay (12.9 vs. 7.8 days), higher Medicare payments ($91 330 vs. $63 782 p < 0.0001), and greater outlier payments. In conclusion, ILDKT increases the cost of and payments for kidney transplantation.

Safe Conversion From Tacrolimus to Belatacept in High Immunologic Risk Kidney Transplant Recipients With Allograft Dysfunction.

There is no literature on the use of belatacept for sensitized patients or regrafts in kidney transplantation. We present our initial experience in high immunologic risk kidney transplant recipients who were converted from tacrolimus to belatacept for presumed acute calcineurin inhibitor (CNI) toxicity and/or interstitial fibrosis/tubular atrophy. Six (mean age = 40 years) patients were switched from tacrolimus to belatacept at a median of 4 months posttransplant. Renal function improved significantly from a peak mean estimated glomerular filtration rate (eGFR) of 23.8 ± 12.9 mL/min/1.73 m(2) prior to the switch to an eGFR of 42 ± 12.5 mL/min/1.73 m(2) (p = 0.03) at a mean follow-up of 16.5 months postconversion. No new rejection episodes were diagnosed despite a prior history of rejection in 2/6 (33%) patients. Surveillance biopsies performed in 5/6 patients did not show subclinical rejection. No development of donor-specific antibodies (DSA) was noted. In this preliminary investigation, we report improved kidney function without a concurrent increase in risk of rejection and DSA in six sensitized patients converted from tacrolimus to belatacept. Improvement in renal function was noted even in patients with chronic allograft fibrosis without evidence of acute CNI toxicity. Further studies with protocol biopsies are needed to ensure safety and wider applicability of this approach.

Quantifying the risk of incompatible kidney transplantation: a multicenter study.

Incompatible live donor kidney transplantation (ILDKT) offers a survival advantage over dialysis to patients with anti-HLA donor-specific antibody (DSA). Program-specific reports (PSRs) fail to account for ILDKT, placing this practice at regulatory risk. We collected DSA data, categorized as positive Luminex, negative flow crossmatch (PLNF) (n = 185), positive flow, negative cytotoxic crossmatch (PFNC) (n = 536) or positive cytotoxic crossmatch (PCC) (n = 304), from 22 centers. We tested associations between DSA, graft loss and mortality after adjusting for PSR model factors, using 9669 compatible patients as a comparison. PLNF patients had similar graft loss; however, PFNC (adjusted hazard ratio [aHR] = 1.64, 95% confidence interval [CI]: 1.15-2.23, p = 0.007) and PCC (aHR = 5.01, 95% CI: 3.71-6.77, p < 0.001) were associated with increased graft loss in the first year. PLNF patients had similar mortality; however, PFNC (aHR = 2.04; 95% CI: 1.28-3.26; p = 0.003) and PCC (aHR = 4.59; 95% CI: 2.98-7.07; p < 0.001) were associated with increased mortality. We simulated Centers for Medicare & Medicaid Services flagging to examine ILDKT's effect on the risk of being flagged. Compared to equal-quality centers performing no ILDKT, centers performing 5%, 10% or 20% PFNC had a 1.19-, 1.33- and 1.73-fold higher odds of being flagged. Centers performing 5%, 10% or 20% PCC had a 2.22-, 4.09- and 10.72-fold higher odds. Failure to account for ILDKT's increased risk places centers providing this life-saving treatment in jeopardy of regulatory intervention.

Multimodality therapy and liver transplantation in patients with cirrhosis and hepatocellular carcinoma: 6 years, single-center experience.

The treatment of patients with cirrhosis and hepatocellular carcinoma (HCC) has improved dramatically over the past 10 years. We conducted a 6-year prospective study, using multimodality ablation therapy (MMT) combined with liver transplantation (LTx) for patients with cirrhosis and unresectable HCC. Subjects were classified as: group 1 (n = 35), intention to treat with MMT + LTx; group 2 (n = 16), contemporaneous LTx with "incidental" HCC on explants; group 3 (n = 94), MMT alone; and group 4 (n = 19), palliative care alone. MMT included trans-arterial chemo-embolization (54.4%), trans-arterial chemo-infusion (28.6%), and radio frequency ablation (17%). Group 1, with a mean wait time of 11.6 months pre-MELD era and 5.4 months post-MELD era, had a mean of 2.4 +/- 1.2 MMTs and achieved 1- 3-, and 5-year patient survivals of 100, 100, and 76%, respectively, which was not different from group 2 (incidental HCC), namely 93, 93, and 93%, respectively; or to a contemporaneous non-HCC LTx group: namely 84.3, 78.7, and 73.9%, respectively. Despite careful pretransplant HCC staging, 22.8% (8 of 35) group 1 subjects were understaged. Those subjects in group 1 with true T1-2 stage HCC achieved 100% cancer-free survival at 5 years. Only three cases of HCC recurrence occurred in our series, all of whom were understaged. Our data suggest that pretransplant MMT followed by timely LTx provides excellent disease-free survival at 5 years for patients with true T1-2 stage HCC and cirrhosis. Pretransplant HCC understaging contributes to posttransplant HCC recurrence after LTx.

Molecular markers in stored kidneys using perfluorocarbon-based preservation solution: preliminary results.

BACKGROUND: Delayed graft function (DGF) is a problem in kidney transplantation and cold ischemia has been identified as a risk factor. Perfluorocarbons (PFC) have an enhanced ability to dissolve and release oxygen. We evaluated histologically and a number of molecular changes induced by ischemia in stored kidneys with University of Wisconsin (UW) and PFC-based preservation solutions (PFC-UW). MATERIALS AND METHODS: ACI rats were used as kidney donors. UW (control group) or PFC-UW (study group) preservation solutions were used for kidney perfusion. All kidneys were stored at 4 degrees C for 12, 24, and 36 hours. After this time, intragraft histologic evaluation as well as mRNA HO-1 and iNOS levels were also analyzed. RESULTS: In the kidneys stored at 24 hours, mRNA HO-1 levels were elevated in the study group when compared with the control and mRNA iNOS was decreased. CONCLUSION: We observed overexpression of HO-1 and underexpression of iNOS in the kidney tissue stored with PFC-UW solution at 24 hours. These preliminary data suggest that increasing oxygen delivery by PFC added to the perfusion solution triggers cytoprotective mechanism in kidney transplantation.

Massive hepatic artery atherosclerosis of an otherwise suitable donor liver: a case report.

Most of the few reports about hepatic artery disease found in the literature describe hepatic artery aneurysms or hepatic artery calcifications. Atherosclerosis of the hepatic artery is not commonly evaluated during deceased donor liver procurement. Herein we present a case of a stable 47-year-old Caucasian female donor whose liver function tests were within normal limits and a liver biopsy showed less than 5% steatosis. The liver when received at our center appeared grossly unremarkable. Back-table evaluation showed a complete occlusion of the trunk of the proper hepatic artery. The pathology report revealed hepatic occlusion due to arterial atherosclerosis. Transplantation was canceled, and the liver was used for isolated hepatocyte perfusion, revealing < 25% hepatocyte viability. Hepatic artery atherosclerosis and patency need to be evaluated at the time of procurement to prevent recipient morbidity due to anesthetic induction, or initiation of a recipient abdominal incision prior to declining the liver graft for this rare finding.

Selection and outcome of living donors for adult to adult right lobe transplantation.

BACKGROUND: The shortage of cadaveric livers has sparked an interest in adult-to-adult living donor transplantation. Right lobe donor hepatectomy is frequently required to obtain a graft of adequate size for adult recipients. Careful donor selection is necessary to minimize complications and assure a functional graft. METHODS: A four-step evaluation protocol was used for donor selection and satisfactory results of all tests in each step were required before proceeding to the next. Donors were selected based on a battery of laboratory studies chosen to exclude unrecognized infection, liver disease, metabolic disorders, and conditions representing undue surgical risk. Imaging studies included ultrasonography, angiography, magnetic resonance imaging, and intraoperative cholangiography and ultrasonography. The information obtained from liver biopsy was used to correct the estimated graft mass for the degree of steatosis. RESULTS: From March 1998 to August 1999, 126 candidates were evaluated for living donation. A total of 35 underwent donor right lobectomy with no significant complications. Forty percent of all donors that came to surgery were genetically unrelated to the recipient. A total of 69% of those evaluated were excluded. ABO incompatibility was the primary reason for exclusion after the first step (71%) and the presence of steatosis yielding an inadequate estimated graft mass after the second step (20%). CONCLUSIONS: Donor selection limits the application of living donor liver transplantation in the adult population. Unrelated individuals increase the size of the donor pool. Right lobe hepatectomy can be performed safely in healthy adult liver donors. Preoperative liver biopsy is an essential part of the evaluation protocol, particularly when the estimated graft mass is marginal.

Emergency adult to adult living donor liver transplantation for fulminant hepatic failure.

BACKGROUND: The high mortality rate associated with fulminant hepatic failure combined with the limited availability of cadaveric organs requires consideration of alternatives to conventional cadaveric transplantation. Use of the donor right lobe in adult-to-adult living donor transplantation holds promise in a variety of circumstances, including high-acuity situations. METHODS: A 28-year-old male with fulminant hepatic failure secondary to hepatitis B was referred to our institution. He rapidly progressed to grade IV encephalopathy, and laboratory values were indicative of a poor prognosis without transplantation. He was listed for transplantation as UNOS status I. Three siblings were simultaneously evaluated for living liver donation. Following established protocols, we completed donor evaluation in less than 24 hr, and donor right lobectomy and living donor transplantation were performed within 36 hr of the recipient's admission to our center. RESULTS: The donor surgery was uncomplicated, and the patient was discharged on postoperative day 4. The recipient experienced full recovery and was discharged home on postoperative day 14. Of note, the first offer for a cadaveric liver came more than 60 hr after living donor transplantation. CONCLUSIONS: Thorough donor workup can be completed in less than 24 hr without inappropriate abbreviation of the evaluation. Simultaneous workup of willing individuals prevents unnecessary delay. Living donor transplantation should be considered for patients with fulminant hepatic failure who are appropriate transplant candidates.

Emergency portacaval shunt for control of hemorrhage from a parenchymal fracture after adult-to-adult living donor liver transplantation.

As more adults undergo transplantation with partial liver grafts, the unique features of these segments and their clinical significance will become apparent. A patient presented with life-threatening hemorrhage from an iatrogenic laceration to a right lobe graft 11 days after transplantation. The creation of a portacaval shunt effectively controlled the bleeding, allowing more elective replacement of the organ with another right lobe graft. The regeneration process combined with increased portal blood flow and relative outflow limitation may have set the stage for this complication. Any disruption of the liver parenchyma during transplantation should be securely repaired and followed cautiously. Portacaval shunting is an option for controlling hemorrhage from the liver in transplant recipients. The timely availability of a second organ was likely the ultimate determinant of survival for this patient.

Liver regeneration and function in donor and recipient after right lobe adult to adult living donor liver transplantation.

BACKGROUND: Regeneration of the liver to a predetermined size after resection or transplantation is a well described phenomenon, but the time course over which these events occur has not been well defined. It is not clear how initial liver mass, reperfusion, immunosuppression, or steatosis influence this process. METHODS: Liver regeneration was assessed prospectively by volumetric magnetic resonance imaging (MRI) in living right lobe liver donors and the recipients of these grafts. Imaging was performed at regular intervals through 60 days after resection/transplantation, and liver mass was determined. Liver function tests and synthetic function were monitored throughout the study period in donors and recipients of these grafts as well as recipients of cadaveric grafts. RESULTS: MRI consistently overestimated liver mass by a mean of 45 g (+/-65) (range 10-123). Donor liver mass increased by 101%, 110%, 115%, and 144% at 7, 14, 30, and 60 days after resection, respectively. Recipient liver mass increased by 87,101, 119, and 99% at 7, 14, 30, and 60 days after transplantation, respectively. Steatosis did not influence the degree of regeneration or graft function, nor was there a functional difference between grafts of >1% graft to recipient body weight ratio or <1%. CONCLUSIONS: MRI accurately determines right lobe mass. Most liver regeneration occurs in the 1st week after resection or transplantation, and the time course does not differ significantly in donors or recipients. The mass of the graft or remnant segment affects the duration of the regeneration process, with a smaller initial liver mass prolonging the course. Steatosis of <30% had no bearing on liver function or regeneration and, therefore, should not be an absolute criterion for exclusion of donors. A calculated graft to recipient body weight ratio of 0.8% is adequate for right lobe living donor liver transplantation.

Single-center analysis of the first 40 adult-to-adult living donor liver transplants using the right lobe.

The first adult-to-adult living donor liver transplant using the right hepatic lobe in the United States was performed only 2 years ago. Although initial reports were encouraging, continuous review of the results and appropriate modifications in patient management will be necessary to minimize donor risk and optimize recipient outcome. The results of 40 such transplantations were analyzed and are summarized. Recipients were listed for transplantation according to the usual criteria. Living donors were not considered for United Network for Organ Sharing status IIA patients after the initial 22 patients. Donor evaluation followed a rigid protocol. A graft-to-recipient body weight ratio of at least 0.8% was the minimum required throughout most of the study. The surgical procedures were similar, except the plane of transection was modified to better accommodate donor biliary anatomy, and uniform stenting of bile ducts was practiced after the first 10 transplants. Immunosuppression consisted of tacrolimus, mycophenolate mofetil, and a prednisone taper. The target tacrolimus level was decreased and mycophenolate was withdrawn more rapidly in the second half of the study because of the absence of acute cellular rejection. Donor morbidity has been limited to minor complications, and transplant recipient biliary complications decreased from 35% to 0%. Acute cellular rejection has not been observed despite less aggressive immunosuppression, and septic complications decreased dramatically. There have been no recipient deaths since these changes were instituted. Right lobectomy can be performed safely in the donor population. Recipient biliary complications can be minimized with stenting. Less aggressive immunosuppression is well tolerated and minimizes septic complications and attributable mortality.

Surgical management of anatomical variations of the right lobe in living donor liver transplantation.

OBJECTIVE: To review the anatomical variations of the right lobe encountered in 40 living liver donors, describe the surgical management of these variations, and summarize the results of these procedures. SUMMARY BACKGROUND DATA: Anatomical variability is the rule rather than the exception in liver and biliary surgery. To make effective use of liver segments from living donors for transplantation, surgical techniques must be adapted to the anomalies. METHODS: Donor evaluation included celiac and mesenteric angiography with portal phase, magnetic resonance angiography, and intraoperative ultrasonography and cholangiography. Arterial anastomoses were generally between the donor right hepatic artery and the recipient main hepatic artery. Jump-grafts were constructed for recipients with hepatic artery thrombosis, and double donor arteries were joined to the bifurcation of the recipient hepatic artery. The branches of a trifurcated donor portal vein were isolated during the parenchymal transection, joined in a common cuff, and anastomosed to the recipient main portal vein. Significant accessory hepatic veins were preserved, brought together in a common cuff if multiple, and anastomosed to the recipient cava. The bile ducts were individually drained through a Roux-en-Y limb, and stents were placed in most patients. RESULTS: Forty right lobe liver transplants were performed between adults. No donor was excluded because of prohibitive anatomy. Seven recipients had a prior transplant and five had a transjugular intrahepatic portosystemic shunt (TIPS). Arterial anomalies were noted in six donors and portal anomalies in four. Arterial jump-grafts were required in three. Sixteen had at least one significant accessory hepatic vein, and one had a double right hepatic vein. There were no vascular complications. Multiple bile ducts were found in 27 donors. Biliary complications occurred in 33% of patients without stents and 4% with stents. CONCLUSIONS: Anatomical variations of the right lobe can be accommodated without donor complications or complex reconstruction. Previous transplantation and TIPS do not significantly complicate right lobe transplantation. Microvascular arterial anastomosis is not necessary, and vascular complications should be infrequent. Biliary complications can be minimized with stenting.

The interrelationship between portal and arterial blood flow after adult to adult living donor liver transplantation.

BACKGROUND: When adults are transplanted with segmental grafts, disparity between the size of the graft and the native organ is almost universal. These grafts presumably still receive all of the native portal inflow despite a reduced vascular bed and dramatically elevated blood flow may result. The hemodynamic changes after segmental transplantation in adults have not yet been studied and their clinical significance is unknown. METHODS: Portal venous and hepatic arterial blood flow were measured intraoperatively in right lobe liver donors and recipients with electromagnetic flow probes. Postoperative evolution was monitored in recipients with ultrasonography. RESULTS: Portal flow to the right lobe ranged from 601 to 1,102 ml/min before resection and from 1,257 to 2,362 ml/min after transplantation. There was a statistically significant linear correlation between the change in portal flow and graft to recipient body weight ratio. Arterial blood flow ranged from 213 to 460 ml/min before resection and from 60 to 300 ml/min after transplantation. Preoperative portal peak systolic velocity was uniformly around 10 cm/sec. Values on postoperative day 1 were increased to 30 cm/sec in recipients of cadaveric organs, to 50 cm/sec in recipients of organs with graft to recipient body weight ratios of more than 1.2%, and to 115 cm/sec in recipients of organs with ratios less than 0.9%. A decreasing tendency was universally observed. Arterial systolic velocity was inversely related to portal systolic velocity. Neither graft dysfunction nor vascular complications occurred. CONCLUSIONS: The hemodynamic pattern after right lobe transplantation is predictable and intraoperative measurements and ultrasonography are useful for monitoring. The size of the graft influences the magnitude of the hemodynamic changes.

Right lobe living donor liver transplantation.

BACKGROUND: The shortage of livers for transplantation has prompted transplant centers to seek alternatives to conventional cadaveric liver transplantation. Left lateral segmentectomy from living donors has proven to be a safe operation for the donor with excellent results in the pediatric population. Left lobectomy, conceived to supply more tissue, still provides insufficient liver mass for an average size adult patient. Right lobectomy could supply a graft of adequate size. METHODS: Donors were considered only after recipients were listed according to United Network for Organ Sharing (UNOS) criteria. Donor evaluation included liver biopsy, magnetic resonance imaging, and celiac and mesenteric angiography. The donor operation consisted of a right lobectomy uniformly performed throughout the series as described herein. RESULTS: Twenty-five right lobe living donor liver transplants were performed between adults, with no significant complications in donors. Recipient and graft survival was 88%, with three recipient deaths secondary to uncontrolled sepsis in patients at high risk for liver transplant; all three had functioning grafts. CONCLUSIONS: Right lobe living donor liver transplantation poses challenges that require a meticulous surgical technique to minimize morbidity in the recipient. Right lobectomies for living donation can be performed safely with minimal risk to both donor and recipient although providing adequate liver mass for an average size adult patient.

Intragraft cytokine expression in tolerant rat renal allografts with rapamycin and cyclosporin immunosuppression.

The Th-1/Th-2 paradigm proposes clonal expansion of Th-2 lymphocytes as the basis of tolerance towards allografts. Intragraft cytokine expression was evaluated in a highly stringent model of renal transplantation. ACI and Lewis rats were used as donors and recipients, respectively, for heterotopic renal transplantation. Group A (n = 8) received a single dose of rapamycin and cyclosporin 12 h prior to engraftment, followed by 7 d of cyclosporin post-operatively. Isografts (Group B, n = 5) and control allografts (Group C, n = 4) received no immunosuppression. Sacrifice was performed after 120 d. Intragraft expression of IL-10, IL-4, and IFN-gamma was determined using qualitative reverse transcriptase-polymerase chain reaction (RT-PCR). All groups had functionally normal grafts at sacrifice, with 50% histological tolerance among Group A animals. No isografts showed evidence of cellular infiltrate, and all control allografts showed severe rejection. IL-10 was only detected in the tolerant animals (p < 0.001). Similarly, IL-4 was detected predominantly in the tolerant allografts (p < 0.05). IFN-gamma was only isolated in rejected allografts, whether treated or untreated (p < 0.001). We conclude that the expansion of Th-2 cells is associated with tolerance, while the expansion of Th-1 cell is associated with acute cellular rejection.

Intragraft cytokine expression and tolerance induction in rat renal allografts.

BACKGROUND: Intragraft cytokine expression was evaluated in a model of renal transplantation. ACI and Lewis rats were used as donors and recipients, respectively, for heterotopic renal transplantation. METHODS: Treated allograft rats (n=10) received a preoperative dose of rapamycin and cyclosporine, followed by 7 days of cyclosporine postoperatively. Isograft rats (n=5) and control allograft rats (n=4) received no immunosuppression. Sacrifice was performed after 120 days. Expression of interleukin (IL)-4, IL-10, and interferon-gamma (IFN-gamma) transcripts was determined with semiquantitative reverse transcriptase-polymerase chain reaction. RESULTS: All treated allograft rats had normal function with 50% histologic rejection. All isografts had normal function. IL-4 and IL-10 were in greater density in allografts with normal histology, whereas IFN-gamma was only seen in allografts with cellular rejection. No IL-10 was seen in isografts, but IL-4 was detected in 3/5 isografts. CONCLUSIONS: We conclude that the lymphocyte population's elaboration of IL-4 and IL-10 is associated with tolerance, whereas the production of IFN-gamma and absence of IL-4 is associated with histology suggestive of acute cellular rejection.

Adenosine rinse in human orthotopic liver transplantation: results of a randomized, double-blind trial.

OBJECTIVE: The study was aimed at determining whether the vasodilator, adenosine, shown to produce dramatic improvement in liver graft and animal acute and long-term survival, would be beneficial in human liver transplantation. METHODS: A prospective, randomized, double-blind trial of an adenosine rinse preservation solution in human orthotopic liver transplantation (OLTX) was conducted in 43 consecutive transplants. Intraoperative and postoperative care was performed by a single transplant team utilizing a quadruple drug immunosuppressive protocol, with complete 5-year patient follow-up. At implantation all allografts were flushed with a 4 degrees C (pH 7.4) Normosol solution, with 0.12 mM adenosine or without adenosine. RESULTS: Recipient characteristics were similar in the treated and control groups including age, pre-OLTX diagnosis, and United Network for Organ Sharing (UNOS) status. Donor variables were equivalent in the two groups including age, weight, prothrombin time, and serum chemistries. Operative variables showed no differences except a significant (p = 0.006) reduction of veno-venous bypass time in the adenosine treated group. Liver allograft function improved in the adenosine rinse groups as measured by both postoperative bile production (218 +/- 156cc/24h adenosine vs. 116 +/- 78 cc/24 h without adenosine, p = 0.03) and Factor 7 production at day 3 (64 +/- 26% adenosine vs. 51 +/- 20% without adenosine, p = 0.08). The adenosine treated group had an insignificant 10% patient and graft improvement in survival at 6 months to 60 months compared to the control group. CONCLUSIONS: These results suggest that adenosine added to the intraoperative flush solution during human liver transplantation is safe, does not reduce cardiac stability at reperfusion, improves early liver allograft function, but has an insignificant short- and long-term affect on allograft survival.

Flow cytometric analysis of chimerism in the rat tolerant to a renal allograft.

BACKGROUND: Chimerism, produced by the two-way migration of cells between graft and host, is a proposed mechanism by which tolerance occurs. The appearance of donor/recipient chimeras in tolerant ACI to Lewis rat heterotopic renal transplants was assessed in peripheral blood leukocytes using flow cytometry after staining with monoclonal antibodies. MATERIALS AND METHODS: ACI and Lewis rats were used as donor and recipient, respectively, after Rapamycin and Cyclosporin immunosuppression with or without donor blood or bone marrow transfusion. ACI and Lewis animals were also used for isograft and single-kidney controls. Animals were sacrificed at various time points after initial operation. Flow cytometry was performed on isolated peripheral blood leukocytes at sacrifice. Histologic and functional data were also obtained. The monoclonal antibody panel included RT1(a) (ACI, MHC I) combined with CD2, CD4, CD8, CD16, and CD25 or RT1(a,c) (bone marrow chimeras). RESULTS: RT1(a)+, CD8+ cells were transiently present in the peripheral blood leukocytes of Lewis recipients with the exception of allogeneic bone marrow recipients. No significant number of RT1(a)+, CD16+ ("dendritic" cell-line) chimeras was seen. Veto cells (RT1(a,c)+) were transiently present in the bone marrow recipients, but they did not lead to improved outcome. Furthermore, no correlation was made between histologic tolerance and any of these donor-derived cells. CONCLUSION: Donor/recipient chimerism, and the veto cell phenomenon are not operational tolerance mechanisms in this stringent model of ACI to Lewis rat renal transplantation.

The immunologic role of IFN-gamma in ACI to Lewis kidney transplantation.

BACKGROUND: One of the proposed mechanisms of tolerance induction is the Th-1/Th-2 paradigm. The Th-1 cell is proinflammatory, secreting IFN-gamma and IL-2. Conversely, the Th-2 cell is anti-inflammatory, secreting IL-4 and IL-10. In our earlier studies a shift toward Th-2 dominance was required for tolerance induction in this model. MATERIALS AND METHODS: ACI and Lewis rats were used as donors and recipients, respectively. Twelve hours prior to engraftment, rapamycin 1.5 mg/kg po and cyclosporin 10 mg/kg sc were given, followed by 5 mg/kg sc postop (days 1-7). Lewis rats were used as isografts. Functional allograft tolerance was induced consistently in 100% of the recipients with 50% of the allografts exhibiting normal histology beyond 120 days. Qualitative RT-PCR was performed on the grafts to determine IFN-gamma expression with beta-actin housekeeping gene as control. RESULTS: IFN-gamma was expressed in all untreated allografts (5/5) and all treated, yet rejecting, allografts (4/4). None of the isografts (0/5) or histologically tolerant allografts (0/4) expressed IFN-gamma. This distribution was statistically significant (P < 0.001, Fischer's exact test). CONCLUSION: Our findings support a shift from Th-2 to Th-1 predominance as the corollary mechanism responsible for preventing histologic tolerance.

Should vein be saved for future operations? A 15-year review of infrainguinal bypasses and the subsequent need for autogenous vein.

The decision to use prosthetic or autogenous vein as the initial conduit for first-time vascular bypass of the lower extremity depends in part on the likelihood of subsequent need for autogenous conduit for another leg or heart bypass. The true frequency of these later events is not known. To answer this question, we analyzed a database of infrainguinal and coronary artery bypasses (CABG) performed at one institution between January 1980 and July 1995, to determine how many patients required subsequent infrainguinal bypass or CABG after their initial leg bypass. Five hundred and seventy-two infrainguinal bypasses were performed on 440 patients (mean age 63.9); average follow-up was 5.6 years. The clinical philosophy favored autogenous vein for first bypass, which was used in 84% of first operations performed during the study period while prosthetic material was used in 16%. For patients in which vein was used for the first operation, and who went on to have a second operation, the use of prosthetic conduit rose from 16% of operations to 27% (p < 0.05). The rate of subsequent CABG after leg bypass was very low, 2% at 5 years, 3% at 10 years. The cumulative probability of requiring a subsequent infrainguinal bypass was 27% at 5 years, 32% at 10 years. Of these, 46% were ipsilateral and 54% were contralateral. Considering only subsequent tibial bypasses (where vein might be considered obligatory), the cumulative 5-year rate of subsequent leg bypass was only 13%. Another bypass was most likely to occur within the first 3 years, rarely thereafter. In summary, after primary infrainguinal bypass, additional procedures using vein may arise in 1/4 to 1/3 of patients, mostly in the first 3 years. However, only 13% will definitely need vein for tibial bypass in 5 years, and subsequent CABG is uncommon.