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PubMed1986

Renal allografts: evaluation by MR imaging.

The value of magnetic resonance (MR) imaging in assessing renal transplants was prospectively studied in 45 patients with 46 allografts. Four allografts were imaged at two different times, and separate diagnoses were given for both examinations. Therefore, this study was based on 50 proved diagnoses: nine normally functioning allografts, four allografts with acute tubular necrosis (ATN), 29 with acute rejection, one with chronic rejection, five with cyclosporin nephrotoxicity, and two with local inflammation secondary to adjacent abscess. Twenty-seven of the allografts had concomitant fluid collections. Normal renal structures with preservation of corticomedullary contrast (CMC) on T1-weighted images were demonstrated in all the normally functioning allografts. Decreased or absent CMC on T1-weighted images, reflecting a long T1 relaxation time for cortex, was found to be the most consistent sign of acute renal allograft rejection (27/29). No abnormalities on on MR images were observed in allografts compromised by cyclosporin nephrotoxicity. Hydronephrosis of the renal allograft was easily diagnosed with MR. Perirenal abscess (three cases) and perirenal hematomas (five cases), because of their higher MR signal intensity on T1-weighted images (TR = 0.5 sec, TE = 28 msec), could be differentiated from clinically insignificant postoperative fluid seromas (seven cases), lymphoceles (11 cases), and urinoma (one case).

Adult↗

PubMed2006

Impact of donor and recipient factors on allograft survival in lung transplantation: A single-center analysis.

BACKGROUND: It remains unclear which donor and recipient factors influence long-term allograft function in lung transplantation (LTx). METHODS: From October 1988 to February 2005, a total of 280 recipients underwent LTx at our center. Donor data and cause of death (CoD) were analyzed. The CoD was categorized according to rate of increase in intracranial pressure at the time of death. Each donor and recipient factor was correlated with long-term graft function. Recipient details, type of transplant, indication for transplant, and time on waiting list were analyzed. Recipients were stratified based on allograft ischemia time (AIT): 0 to 6, 6 to 8, 8 to 10, and >10 hours. RESULTS: Mean donor age was 30.9 years (36.7% male); 49.8% were cytomegalovirus (CMV) positive. Donor CoD was characterized by a slow rise in intracranial pressure (ICP) in 34.4%, rapid ICP in 18.7%, an intermediate ICP in 44.3%, and with no rise in 2.6%. A graft survival benefit was seen with female donors (P = .048); 34.4% of recipients ultimately developed graft failure at long term follow-up. Mean recipient age was 48 years; 63% were male and mean body-mass index (BMI) was 23.6; 60.2% had single lung transplantation, and mean wait list time was 323 days. Mean AIT totaled 421 minutes. Graft survival was longer with AIT of 8 to 10 hours compared to 6 to 8 hours (P = .03). CONCLUSIONS: Donor factor analysis implied only female donor status conferred a long-term graft survival advantage. Intracranial pressure rise differences appear clinically unimportant. Prolonged cold ischemic time (>10 hours) or low recipient BMI did not adversely affect allograft function in our review.

Adult↗

PubMed2000

Immunosuppressive activity of the Chinese medicinal plant Tripterygium wilfordii. I. Prolongation of rat cardiac and renal allograft survival by the PG27 extract and immunosuppressive synergy in combination therapy with cyclosporine.

BACKGROUND: PG27 is an immunosuppressive fraction purified from an extract of a Chinese medicinal plant, Tripterygium wilfordii. We tested PG27 in rat cardiac and renal allotransplantation, and we examined the immunosuppressive interaction with cyclosporine (CsA). METHODS: Brown Norway (BN) rat heart or kidney allografts were transplanted into the abdomen of Lewis rats, which were treated by the intraperitoneal or oral route with PG27, CsA, or both. RESULTS: PG27 administered intraperitoneally to Lewis recipients for 16 days at 10-30 mg/kg/day significantly increased the median survival time of BN heart allografts from 7 to 18-22 days. Oral administration was effective, with cardiac allograft survival prolonged to > 100 days with 52 days of treatment. PG27 at 20-30 mg/kg/day significantly extended the median survival time of BN kidney allograft recipients from 9 to 36.5-77 days, and 30 mg/kg/day for 52 days extended survival beyond 200 days. PG27 combined with CsA significantly enhanced heart and kidney allograft survival, even at doses of CsA ineffective when administered alone. The addition of 5 or 10 mg/kg/day PG27 reduced by 50-75% the CsA dose needed for 100% kidney allograft survival. The combination index was less than 1.0, indicating synergy of PG27 with CsA in prolonging cardiac and renal allograft survival. Furthermore, the PG27/CsA combination exerted a positive influence on renal allograft function. PG490 (triptolide, a constituent of PG27) and PG490-88 (a semisynthetic derivative of PG490) suppressed rejection of cardiac and renal allografts. CONCLUSIONS: The PG27 herbal extract demonstrated immunosuppressive activity by prolonging heart and kidney allograft survival, displaying synergy in the immunosuppressive interaction with CsA, and improving renal allograft function in combination with CsA. PG490 and PG490-88 compounds were also effective.

Animals↗

PubMed2004

Histologic findings of antibody-mediated rejection in ABO blood-group-incompatible living-donor kidney transplantation.

The purpose of this study was to characterize the histology of antibody-mediated rejection (AMR) in ABO blood-group-incompatible (ABOI) kidney transplants as well as on protocol biopsies performed at the time of stable allograft function. Between 5/99 and 1/02, we performed 32 ABOI kidney transplants (13 A2, 19 non-A2 blood-group living donors). Nineteen biopsies were performed for allograft dysfunction, and 127 protocol biopsies were performed 0, 3, 7, 14, 28 days and 3 and 12 months post transplant. Twenty-five of 32 patients have functioning allografts (mean 585 days post transplant). Nine of 32 (28%) developed clinical AMR. Biopsy revealed glomerular thrombi (78%), mesangiolysis (78%), peritubular capillary C4d staining (56%) and neutrophil infiltration (67%), interstitial hemorrhage and necrosis (56%) and arteriolar thrombi (33%). Subclinical AMR was diagnosed by protocol biopsies in four patients. Findings consisted of glomerular thrombi (100%), mesangiolysis (25%), and C4d staining (100%). In late protocol biopsies performed 214-420 days post transplant, mild mesangiolysis was seen in 2/17 (11.7%), and C4d immunostaining was detected in 3/12 (25%). AMR is characterized by glomerular thrombi, mesangiolysis, peritubular capillary neutrophil infiltration interstitial hemorrhage, necrosis, and C4d deposition. Glomerular thrombi appear early in AMR and may appear prior to graft dysfunction.

ABO Blood-Group System↗

PubMed1987

Possible causes and consequences of hypertension in stable renal transplant patients.

Previous epidemiologic studies of hypertension in renal transplant patients have produced contradictory results. Therefore, the incidence and clinical setting of chronic hypertension were examined in 201 stable renal transplant patients using a multivariate approach. Hypertension was present in 52.7% of patients at one year, and in 46.3% at the time of last follow-up, 5.0 +/- 1.9 years (mean +/- SD) after transplantation. Among possible causative factors, discriminant analysis demonstrated that body weight, the presence of native kidneys, and variables linked to allograft function were most closely associated with hypertension at both one year and last follow-up. One year after transplantation, age, sex, pretransplant hypertensive nephrosclerosis, and diabetes were also independently associated with hypertension. However, renal function declined to a greater degree in hypertensive patients, and only body weight, the presence of native kidneys, and variables linked to allograft function were associated with hypertension at last follow-up. Results also demonstrated that hypertension was associated with elevated serum lipid levels and an increased likelihood of dying or returning to dialysis. Thus, these results suggested several important risk factors for hypertension and its consequences in renal transplant patients.

Adult↗

PubMed2004

BK virus in kidney transplantation: a case study.

Prevention as well as treatment of viral infections in transplant recipients relies on minimal immunosuppressive therapy consistent with graft survival and the use of antiviral therapies in proportion to perceived risk. BK virus creates an even greater challenge in posttransplant management and graft survival because of difficulty in diagnosing and treatment. BK nephropathy develops in 1% to 5% of transplant recipients, with loss of allograft function occurring in 50% of the cases. We present a case of a 67-year-old man who developed BK virus allograft nephropathy 9.5 months after transplantation. His allograft function was extended through rigorous treatment with an antiviral agent, reduction of immunosuppressant, and monitoring in an outpatient setting.

Aged↗

PubMed2000

Recipient FK506 pretreatment regimens in rat small bowel transplantation: allograft survival, function, and systemic infection.

PURPOSE: Successful small bowel transplantation requires effective immunosuppression that preserves intestinal function but avoids opportunistic infection. This study aims to evaluate FK506 as a single immunosuppressant in different pretreatment regimens in a rat high responder strain combination. METHODS: Lewis --> DA rat heterotopic small bowel transplantation was performed. Studied groups were (1) untreated control, n = 12; (2) FK-1, n = 8; (3) FK-3, n = 8. FK506 (2 mg/kg/d, intramuscularly) was given to the recipients for 1 day (FK-1) and 3 days (FK-3) before small bowel transplantation, followed by 2 weeks of subtherapeutic treatment (0.3 mg/kg/d, intramuscularly) after small bowel transplantation. Syngeneic small bowel transplantation also was performed (n = 8). FK blood levels, maltose absorption test, histology, and bacteriology were performed at different postoperative days. RESULTS: Allograft survival was prolonged significantly with FK pretreatment, being more so in FK-3 group (FK-1, 22.2 +/- 1.5 d; FK-3, 40.7 +/- 14.1 d; control, 6.6 +/- 0.8 d; P< .01). In the first postoperative week, FK blood level was significantly higher in FK-3 group (19.8 +/- 1.5 ng/mL) than in FK-1 group (5.0 +/- 0.4 ng/mL; P < .05). There was no evidence of systemic infection in either FK-treated group. For maltose absorption, control allograft was abnormal on day 7 correlating to severely damaged intestinal architecture. In contrast, FK-treated allografts showed well-protected intestinal structure and normal absorption on days 7 and 21. CONCLUSION: High FK506 blood levels in the first postoperative week, achieved with FK pretreatment, prolonged intestinal allograft survival and preserved intestinal structure and function without allowing systemic infection.

Animals↗

PubMed1995

Donor-gifted allograft lithiasis: extracorporeal shockwave lithotripsy with over table module using the Lithostar Plus.

Allograft lithiasis is usually secondary. Donor-graft lithiasis is a rare cause and only 5 cases have been reported. We report 2 such cases which are the first in the live-related transplantation programme. The pressing need to increase the donor pool in developing countries, safety of therapy in graft lithiasis coupled with minimal estimated risk of lithiasis recurrence in the donor are the main justifications for accepting calculi bearing kidney for transplantation. The 2 cases underwent extracorporeal shockwave lithotripsy using the overhead table module of the Lithostar Plus. The technical ease of lithotripsy using an on-line ultrasound module in these 'ectopically' placed kidneys is discussed. The effect of shockwaves on allograft function was studied by a pre- and post-renal scan (99Tc-DTPA) and serum creatinine. No adverse effect of shockwave on allograft function was noted both on short- and long-term follow-up.

Adult↗

PubMed2005

[The living kidney donor: laparoscopy versus open surgery].

INTRODUCTION: Living renal donors are an important source of transplanted kidneys due to the number of patients on waiting list is progressively increasing. On the other side, they allow the pre-emptive kidney transplantation. With the aim of reducing donor obstacles such as pain, hospital stay or cosmetic results and in creasing the number of living donors, in 1995 Ratner performed the first laparoscopic nephrectomy (LLDN). By now, LLDN is a routine procedure in more than 200 centres worldwide. METHODS: Literature databases are searched. We have reviewed the data from our experience after performing 50 laparoscopic nephrectomies. RESULTS: Preoperative living donor assessment and contraindications to LLDN do not differ from the open approach. Results are very influenced by the surgeon's situation in the learnig curve. Operating times use to be longer in laparoscopic procedures. The overall complication rate and mortality of LLDN are the same for both of the approaches. Conversion to open-donor nephrectomy has been reported in 0-13% of cases (8% in our data). Postoperative pain and donor estimated blood loss are lower for LLDN, as well as the convalescence period. To avoid the possible negative effects of the laparoscopic technique on kidney graft function a lot of method's variations have been proposed for gaining access and harvesting the kidney, including the hand-assistance techniques, with the aim of minimizing operative time, pneumoperitoneus negative effect on graft function and warm ischemia time (WIT). The higher WIT is not related to delayed graft function or acute rejections when it is less than ten minutes. Delayed graft function does not differ in both approaches and creatinine values from the first month until the third year after transplantation show no differences in randomized studies. CONCLUSIONS: The laparoscopic approach to harvest the allograft from the living donor is a save and effective technique and has the advantage of being less invasive and allowing the donor a shorter convalescence. It has no negative effects on allograft function in the short term follow-up. Further studies are required to evaluate long term donor complications and allograft function and survival.

Age Factors↗

PubMed1988

Hyperuricemia after renal transplantation.

Hyperuricemia is common in cyclosporine-treated renal allograft recipients. An increased incidence of gout in patients receiving both diuretics and cyclosporine has been reported, but the effect of hyperuricemia on renal allograft function has not been studied. In a prospective, randomized trial of cyclosporine and prednisone versus azathioprine, prednisone, and antilymphocyte globulin for immunosuppression in renal allograft recipients, 105 of 131 cyclosporine and prednisone-treated patients (80 percent) experienced hyperuricemia (serum uric acid level above 8 mg/dl) and 13 of 131 (10 percent) were severely hyperuricemic (serum uric acid level above 14 mg/dl). In contrast, hyperuricemia developed in 63 of 115 patients (55 percent) treated with azathioprine, prednisone, and antilymphocyte globulin (p less than 0.002). Despite the frequent occurrence of hyperuricemia, gout was rare. Clinical gout developed in six patients in the cyclosporine and prednisone group and in 0 patients in the azathioprine, prednisone, and antilymphocyte globulin group between 1 and 43 months (median 22.5 months) after transplantation. Neither severe hyperuricemia nor diuretic therapy were associated with a significantly increased incidence of gout. The mean serum creatinine concentration of severely hyperuricemic patients (all on cyclosporine and prednisone) was similar to that of normouricemic cyclosporine and prednisone patients (1.8 mg/dl versus 1.6 mg/dl, p greater than 0.2), and the severely hyperuricemic patients had a 4-year graft survival rate of 90 percent. Asymptomatic hyperuricemia after renal transplantation does not adversely affect allograft function, requires no specific therapy, and is not a contraindication to use of diuretics.

Antilymphocyte Serum↗

PubMed2005

Increasing incidence of post-kidney transplant anemia in children.

Anemia status at 1-year post-kidney transplant was documented retrospectively in 231 pediatric recipients (mean age: 12.6 +/- 5.0, range: 1.9-20.7 years) at Cincinnati Children's Hospital Medical Center between 1978 and 2003. Anemia was present in 59 (25.5%) patients. The prevalence of anemia has increased in the more recent eras (1978-1985: 7.8%, 1986-1997: 29%; 1998-2003: 32%, p < 0.01). Logistic regression analysis determined that the use of calcineurin inhibitors or impaired allograft function predicted anemia at 1-year post-transplant. Kaplan-Meier analysis showed that children with anemia at 1-year post-transplant had a significantly worse overall allograft survival than children without anemia (p = 0.02). However, when data were analyzed using a Cox proportional hazards model, only lower allograft function at 1-year post-transplant, black race and older era, but not anemia, independently predicted worse graft survival in children. This study suggests that the recent increase in the incidence of anemia post-kidney transplant is related to modern immunosuppressive therapy and that post-transplant anemia is more likely a marker of allograft dysfunction in children rather than its cause.

Adolescent↗

PubMed2004

Hemoadsorption to improve organ recovery from brain-dead organ donors: a novel therapy for a novel indication?

While brain-dead organ donors represent the majority of the organ donor pool, it appears that graft survival is adversely affected by brain death itself. Brain death has been shown to cause severe disturbances in the hormonal, hemodynamic and immunological homeostasis, which could in part be responsible for the inferior outcome of organs originating from brain-dead donors compared to living donors. Hemodynamic effects of brain death lead to a wide fluctuation in mean perfusion pressures, blood flow to the organs and systemic oxygen consumption, altering regional perfusion. In addition, a wide array of immunological changes has been shown to occur after brain death contributing to organ injury and hemodynamic instability. Recent studies have shown that brain death upregulates multiple lymphocyte- and macrophage-derived cytokines and the injured brain itself may be the source of proinflammatory factors such as S100B. This increased inflammatory response seen during and immediately after brain death has also been associated with poor allograft function. Furthermore, there is evidence to suggest that the massive inflammatory response seen in brain-dead donors could also lead to increased immunogenicity and accelerated allograft rejection after transplantation. Hence, we hypothesize that nonspecific downregulation of this inflammatory response by hemoadsorption could potentially lead to improved donor organ and allograft function. As a 'proof of concept' we tested the ability of a novel hemoadsorbent to remove S100B in vitro using two human glioblastoma cell lines. Our results indicate a >80% reduction in S100B after 2 h of circulation with the sorbent.

Brain↗

PubMedDate not supplied

Angiography in non-functioning renal allografts receiving cyclosporin A.

During a two-year period angiography was performed in 10 out of 40 initially perfused kidney allografts within the first 3 postoperative weeks. Immunosuppression was in all cases performed with cyclosporin A. The indication for angiography was mainly deterioration in the graft function as judged from the renograms or inadequate demonstration of the graft during intravenous radionuclide angiography. At angiography, neither arterial nor venous occlusion was found, and it was normal in 5 patients. It is concluded that during cyclosporin A treatment angiography cannot be recommended on the above mentioned indications in the early postoperative period. A graft biopsy seems sufficient.

Cyclosporins↗

PubMed1994

Renal function in patients receiving long-term cyclosporine therapy.

The site at which the vasomotor effects of cyclosporine are associated with acute nephrotoxicity appears to be the afferent arteriole. Proposed mechanisms mediating these effects include sympathetic nerve stimulation, disruption of the balance between vasodilating and vasoconstricting prostaglandins, hypersensitivity to vasoactive peptides, and endothelin release. These mechanisms mediate cyclosporine-associated intrarenal vasoconstriction, yet the causal relationship between these changes and the obliterative vasculopathy seen in association with chronic progressive renal allograft dysfunction is uncertain. Histologic findings seen in chronic progressive renal dysfunction are nonspecific and cannot be correlated solely with cyclosporine use. Retrospective studies analyzing both aggregate serial serum creatinine and reciprocal creatinine determinations did not report a pattern of progressive attrition consequent to toxic nephropathy. Prospective studies with serial GFR determinations with various reference substances found no progressive deterioration in allograft function. Both the retrospective and prospective studies indicate that the attrition of renal allograft function associated with cyclosporine use reflect the chronic effects of immunologic injury. Renal function in extrarenal transplant recipients immunosuppressed with cyclosporine can be characterized by an initial decline in native renal function followed by subsequent stabilization beyond the first 6 months. There does not appear to be an inordinate rate of progression to ESRD.

Creatinine↗

PubMed1981

Kidney allograft survival in dogs treated with total lymphoid irradiation.

Total lymphoid irradiation (TLI) is immunosuppressive and, in rodent, can induce a state where transplantation of allogeneic bone marrow results in chimerism and permanent acceptance of organ allografts from the donor strain. We attempted to apply this treatment to a large animal model. Twelve splenectomized dogs were treated with TLI (150 rads per fraction, total dose 1950-3000 rads) before bilateral nephrectomy and renal allotransplantation. Eight dogs received bone marrow from the kidney donor. In 13 untreated control dogs renal allografts functioned (serum creatinine level less than 2.0 mg/dl) for a mean +/- (SE) of 4.7 +/- 0.3 days. In the four TLI treated dogs who did not receive bone marrow the renal allografts functioned for 15-76 days (two dogs died with functioning grafts). In the eight TLI treated dogs who received donor bone marrow, two died immediately after transplantation, two rejected at 3 and 13 days, one died at 13 days with a functioning graft, and two have had the grafts function for longer than 500 days. Chimerism was not detected in the one dog tested. The response of peripheral blood lymphocytes to stimulation with phytohemagglutinin and in mixed lymphocyte culture was suppressed for at least on month after TLI. The results confirm the immunosuppressive effect of TLI. The absence of kidney rejection in two recipients of donor bone marrow show the potential of this approach to induce long-term immunologic unresponsiveness as to an organ allograft, but the outcome is unpredictable and further experiments are needed to define the optimal conditions for administration of TLI and bone marrow to the recipients.

Animals↗

PubMed2000

Roux-en-Y venting jejunostomy in pancreatic transplantation: a novel approach to monitor rejection and prevent anastomotic leak.

INTRODUCTION: Pancreatic transplantation (PTx) with portal venous delivery of insulin and enteric drainage of the exocrine secretion is more physiologic than bladder-systemic (BS) drainage. With portal-enteric (PE) PTx, the diagnosis of acute rejection (AR) requires a percutaneous biopsy. The roux-en-y (RNY) venting jejunostomy in patients with PEPTx offers a novel approach to monitor rejection and prevent anastomatic leaks. METHODS: From January 1996 to December 1998, we performed 17 simultaneous kidney/pancreas transplants (SKPTx). The initial 4 patients underwent BS drainage and the subsequent 13 patients underwent RNY venting jejunostomy with PE drainage. All patients were treated with quadruple therapy. There were 9 males, 14 patients were Caucasian with a mean age of 32 yr (range 30-54 yr), and a mean pre-transplantation duration of diabetes of 25 yr. Six patients underwent endoscopic donor duodenal biopsy through the jejunostomy to rule out clinically suspected AR. Gastrograffin was inserted into the jejunostomy to examine the integrity of anastamosis when indicated. In 9 out of 13 patients, the venting jejunostomy was taken down 9-12 months post-transplantation after allograft function was stable. RESULTS: Actual patient, kidney, and pancreas graft survival rates were 100, 100 and 94%, respectively, after a mean follow-up of 16 months. Renal allografts functioned immediately in 89% of patients. The mean length of hospital stay was 19 d. Four (23%) patients (2 with BS drainage and 2 with PE drainage) suffered an AR episode in the first month, and 4 (23%) patients had five AR from 3-36 months post-transplantation. Other complications were post-operative bleeding in 3 patients, wound infection in 2 patients and a proximal duodenal stump leak in 1 patient. In patients with clinical rejection, endoscopy through the venting jejunostomy showed inflamed, friable doudenal mucosa and doudenal biopsy findings were compatible with AR. CONCLUSION: These preliminary results suggest that RNY venting jejunostomy with PE drainage can be used safely to diagnose and monitor pancreas AR and to diagnose and prevent anastamotic leaks. This technique will be even more useful to visualize transplanted duodenal mucosa, collect pancreatic secretions (amylase) for analysis and perform endoscopic retrograde cholangiopancreatography if needed to obtain pancreatic biopsies.

Adult↗

PubMed2002

Usefulness of B-type natriuretic peptide levels in predicting hemodynamic perturbations after heart transplantation despite preserved left ventricular systolic function.

The aim of this prospective study was to evaluate the association of peripheral B-type natriuretic peptide (BNP) levels with clinical symptoms and central hemodynamic and echocardiographic measures in cardiac transplantation. BNP reflects ventricular wall stress and correlates with severity of heart failure. No previous investigation has comprehensively assessed the rapid bedside BNP assay for predicting hemodynamic measures of cardiac allograft function in heart transplantation. We evaluated BNP levels using a rapid point-of-care assay in 87 stable cardiac transplant recipients who had 237 consecutive measurements along with endomyocardial biopsy, right-sided cardiac catheterization, and echocardiography. Using median tendencies, 2 groups were identified: the low BNP group (n = 116, BNP <150 pg/ml) and the high BNP group (n = 121, BNP >/=150 pg/ml). The high BNP group had increased right atrial pressures, higher pulmonary artery systolic pressures, pulmonary capillary wedge pressures, and lower cardiac index. Besides hemodynamic variables, the presence of right ventricular dysfunction (p = 0.05) and significant tricuspid regurgitation (p = 0.003) were associated with higher BNP levels. Independent predictors of BNP levels on multivariate analysis included elevated pulmonary capillary wedge pressure, lower cardiac index, and symptoms of dyspnea and fatigue. This initial investigation establishes the accuracy of a point-of-care BNP assay in predicting cardiopulmonary hemodynamic aberrations despite preserved left ventricular systolic function in heart transplant recipients. Rapid bedside BNP analysis may provide a noninvasive surrogate method for the comprehensive assessment of cardiac allograft function and hemodynamics in heart transplantation.

Adult↗

PubMed2006

Prolonged survival of allogeneic islets in cynomolgus monkeys after short-term anti-CD154-based therapy: nonimmunologic graft failure?

Conventional drug therapy and several anti-CD154 mAb-based regimens were tested in the nonhuman primate (NHP) islet allograft model and found to be inadequate because islets were lost to rejection. Short-term therapy with an optimized donor-specific transfusion (DST) + rapamycin (RPM) + anti-CD154 mAb regimen enables immunosuppression drug-free islet allograft function for months following cessation of therapy in the NHP islet allograft model. After a substantial period of drug-free graft function, these allografts slowly and progressively lost function. Pathologic studies failed to identify islet allograft rejection as a destructive islet invasive lymphocytic infiltration of the allograft was not detected. To evaluate the mechanism, immunologic versus nonimmunologic, of the late islet allograft loss in hosts receiving the optimized therapeutic regimen, we performed experiments with islet autografts and studied islet function in NHPs with partial pancreatectomy. The results in both experiments utilizing autologous islet allografts and partially pancreatectomized hosts reinforce the view that the presence of a marginal islet mass leads to slowly progressive nonimmunological islet loss. Long-term clinically successful islet cell transplantation cannot be realized in the absence of parallel improvements in tolerizing regimens and in the preparation of adequate numbers of islets.

Animals↗