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PubMed1992

Fresh and frozen articular cartilage allografts.

Fresh and frozen cartilage allografts both function well to relieve joint pain due to cartilage injury. Fresh cartilage allografts appear to remain alive for many months and are most applicable to small injuries such as osteochondritis dissecans, traumatic defects, and osteonecrosis. Frozen cartilage allografts have been used mostly for treatment of bone tumors which most often involve the subchondral and the metaphyseal areas of the long bones, particularly around the knee and hip. Frozen cartilage allografts appear to survive well and maintain joint space for several years. Deterioration of either type of graft does not appear to result in joint pain, making these grafts useful for long periods of time.

Adaptation, Physiological↗

PubMed1995

Ex vivo coating of islet cell allografts with murine CTLA4/Fc promotes graft tolerance.

To test the hypothesis that blockade of B7-triggered costimulation by donor cells could preclude allograft rejection, we coated crude islet allograft preparations in vitro for 1 h with a murine CTLA4/Fc fusion protein. Murine CTLA4/Fc blocks the proliferative response in primary mixed lymphocyte cultures (MLC) and Con A-stimulated murine spleen cell cultures by 85 to 95%. Responder cells from a primary MLC containing mCTLA4/Fc were hyporesponsive upon restimulation to the same stimulator cells in a secondary MLC lacking mCTLA4/Fc. Because of mutations in the Fc gamma RI and C'1q binding sites of the Fc portion of the murine CTLA4/Fc fusion protein, the molecule binds to, but does not target, cells for Ab-dependent cellular cytotoxicity or complement-directed cytolysis. Although systemic immunosuppression was not applied, 42% (10 of 24) of B6AF1 recipients of islet allografts pretreated with CTLA4/Fc were permanently engrafted. Further, 50% of hosts bearing functioning islet allografts more than 150 days post-transplant were formally proved to be tolerant to donor tissues. A persistent CD4+ and CD8+ T cell infiltrate surrounding, but not invading, islet grafts in tolerant hosts was discerned. In control experiments, 89% (8 of 9) of islet allografts coated with mIgG3, and 100% (n = 10) pretreated with media alone were rejected. Thus, we conclude that 1) B7-triggered costimulation by donor APCs is an important element of rejection, and 2) blockade of the B7 pathway by in vitro allograft manipulation is able to induce tolerance.

Abatacept↗

PubMed1993

Airway obstruction and bronchiolitis obliterans after lung transplantation.

Bronchiolitis obliterans, defined histologically or clinically, is the most significant long-term cause of morbidity and mortality after lung transplantation. It shares many pathogenetic features with chronic allograft dysfunction that can occur in bone marrow, liver, heart, and kidney recipients. Lessons learned in the prevention and management of this disorder in lung recipients therefore should have application to the analogous process that develops in other organ allograft recipients. Because the lung is exposed to the external environment, it can be sampled repeatedly by techniques like bronchoalveolar lavage and transbronchial lung biopsy with little or no long-term adverse consequence to the allograft. Excellent pulmonary function tests also are available with which to assess the functional capacity of the allograft and to correlate with the results from immunologic testing. For these reasons, this disorder in lung recipients could serve as a model to determine the pathogenesis and treatment of the analogous disorder that may develop in other major organ recipients. Because this disorder most likely is immunologic in origin, advances in transplant immunology that create tolerance between the donor and recipient as well as efforts to prevent CMV infection and airway ischemic injury likely will be effective preventive measures. Although augmented immunosuppression appears to be of some benefit in treating bronchiolitis obliterans, it is far from optimal and new or better use of current immunosuppressive medications is warranted. Because the number of recipients at any one center is too few to critically assess the efficacy and safety of different immunosuppressive regimens, it is likely that collaboration between transplant centers will be necessary for success to be achieved.

Adrenal Cortex Hormones↗

PubMed1998

Characteristics of long-term renal transplant survivors.

Despite the high rates of rejection, allograft failure, and patient death in the early years of renal transplantation, some patients have done remarkably well. Forty-three (17 living related donor and 26 cadaver donor recipients) such patients with an allograft that functioned for 19 years or more (range, 19 to 29 years) were followed up at this center. The patients included 24 men and 19 women, with a mean age at transplantation of 29 years, of whom 39 were white and four were black. At most recent follow-up, the mean daily dose of azathioprine was 104 mg (range, 50 to 175 mg) and that of prednisone was 10 mg (range, 5 to 20 mg). Mean serum creatinine level was 1.6 mg/dL (range, 0.7 to 5.4 mg/dL). Acute rejection occurred in 14 (33%) patients. Nine patients had one episode and five patients had two episodes of acute rejection. Long-term risks to the recipients appeared in the form of coronary artery disease in 10 (23%) patients; malignancy in 13 (30%) patients, which included nine patients with skin malignancy; and chronic hepatitis C virus (HCV) infection in four patients, two of whom died of complications of liver failure. Other complications included avascular bone necrosis in five patients, which required total hip replacement in two patients; hyperlipidemia requiring treatment in 16 (37%) patients; posttransplantation diabetes mellitus in 10 (23%) patients after a median of 17.5 years (range, 1 to 23 years); and hypertension in 23 (53%) patients. There were seven deaths (three of coronary artery disease, two of liver failure, one each of sepsis and malignancy) and eight graft losses (five to death with function, two to chronic rejection, and one to focal and segmental glomerulosclerosis). Although long-term allograft success results in patients receiving minimal amounts of immunosuppression and having good renal function, long-term renal transplant survivors are at risk for significant morbidity even in the third decade posttransplantation.

Adolescent↗

PubMed1997

Open heart operations after renal transplantation.

BACKGROUND: Because of the increasing number of renal transplantations performed, secondary cardiac operations in these patients are discussed concerning their impact on patient and graft survival. METHODS: We reviewed our experience in 45 patients (33 male and 12 female) who underwent open heart operations after previous renal transplantation. Thirty-one patients (group I) received coronary artery bypass grafting and 14 (group II) underwent valve replacement. Mean age at the time of operation was 55 +/- 9 years. The interval between renal transplantation and cardiac operation was 57 +/- 39 months (range, 5 days to 174 months). All patients had functioning renal allografts with preoperative serum creatinine levels ranging from 100 to 338 mol/mL (mean +/- standard deviation, 195 +/- 86). RESULTS: Overall early operative mortality (30 days) was 8.8% (group I, 1 patient; group II, 3 patients). Underlying causes of death were septic endocarditis (n = 2, group II), necrotizing enterocolitis (n = 1, group I), and myocardial infarction (n = 1, group II). One further patient in group II also died of septic endocarditis after 69 days (in-hospital death). The mean follow-up of the 40 surviving patients was 44 +/- 31 months. There was another late death (24 months postoperatively) caused by coagulopathy. Four patients had returned to hemodialysis at intervals of 27 to 83 months (mean, 51 months) because of renal transplant failure. In all patients, the function of the renal allograft was not impaired by open heart operation. CONCLUSIONS: Open heart operations in renal transplant recipients have acceptable mortality and morbidity rates. In almost all patients, function of the transplanted organ can be maintained at the preoperative level.

Coronary Artery Bypass↗

PubMed1998

Transitional cell carcinoma in a renal allograft.

A large urothelial tumor was detected by ultrasonography in the dilated collecting system of a well-functioning renal allograft 15 years after transplantation. The tumor was confirmed at computed tomography. Nephrectomy showed a transitional cell carcinoma. The occurrence of malignant tumors in renal allografts is a well known but rare complication.

Carcinoma, Transitional Cell↗

PubMed1975

Glomerular lesions after renal transplantation.

Significant changes in glomeruli on light microscopy has been observed in 27 of 109 cadaveric renal allografts which functioned beyond 6 months. Tissue was available for study from all but two allografts. The histologic lesions were classified as follows: recurrent glomeruloneophritis, 9 cases (3 focal scierosis, 2 mesangial immunoglobulin A[IgA] disease, 2 mesangiocapillary glomerulonephritis, 1 dense deposit disease, 1 familial nephritis); de novo glomerulonephritis, 1 case (diffuse proliferative glomerulonephritis with crescents); and glomerular change of uncertain etiology, 17 cases (10 mesangiocapillary, 5 focal scierosis, 1 focal proliferative and 1 mesangial proliferative). These lesions were not distinguishable on light, fluorescent and electron microscopy from those in patients with spontaneous renal disease. All patients with glomerular lesions had proteinuria, and all but 3 had microscopic hematuria. Glomerular lesions were not significantly associated with early clinical rejection episodes or HLA compatibility. Presensitization of HLA antigens was significantly related to the occurence of a nonrecurrent glomerular lesion. Vescoureteral reflux was significantly more frequent in those with glomerular change (14 of 24) than in those without (13 of 48). Glomerular lesions were associated with a higher rate of graft loss due to renal transplant failure; renal function in survivors was significantly worse than in those without glomerular lesions.

Adolescent↗

PubMed2002

Mortality risk assessment after renal transplantation.

Mortality after renal allograft loss is significantly increased as compared to patients with a well-functioning graft. This further emphasizes the beneficial effects of renal transplantation in prolonging life in patients with end-stage renal disease. Factors that impact DWFG also are associated with the risk of cause-specific mortality after graft loss. Factors that were associated with an increased risk of DAGL included prolonged waiting time on dialysis, poor renal function at one year, diabetes mellitus and acute rejection, but not longer time with a functioning transplant. It is possible that by modifying some of these variables, overall mortality might be influenced in a positive way. Just as important, the increased mortality after graft loss further emphasizes the importance of maintaining a well-functioning renal allograft.

Cause of Death↗

PubMed1995

The effect of ureteric stenting on the function and morphology of long-term rat renal allografts.

In the development of a reliable model for chronic rejection in rat renal allografts, the effect of modifying the ureteric anastomosis was tested. Rats, tolerized by pretreatment with two donor blood transfusions under Cyclosporin A, received renal allografts with either sewn or stented ureter. Control groups received isografts or underwent uninephrectomy with insertion of ureteric stents. For the first 6 days after transplantation, serum creatinine and urea values were lower in allograft recipients with stented ureters than in the group with sewn ureters. The method of ureteric anastomosis did not affect the long-term incidence of abnormal function. Allograft morphology was extremely variable from minor to extensive tubular atrophy, interstitial fibrosis, glomerular hypertrophy, focal and segmental glomerulosclerosis as well as vascular changes. Glomerulosclerosis was absent in controls and increased with time in the allografts. Two hundred days after transplantation all allograft recipients with sewn ureters exhibited some glomerulosclerosis, in half of these kidneys more than 25% of glomeruli were affected. Only 33% recipients of allografts with stented ureters exhibited some glomerulosclerosis and less than 20% of glomeruli were affected. The stented ureteric anastomosis provides a reliable method, a reduction of the technical failure rate, a reduction of the incidence of hydronephrosis, allows more accurate assessment of early renal function and may be of importance in reducing the occurrence and prevalence of glomerulosclerosis in the long-term allografts.

Animals↗

PubMed2000

CT findings in ten patients with failed renal allografts: comparison with findings in functional grafts.

Our aim is to report the computed tomography (CT) features of the long-term failed renal allograft. Ten patients with failed renal transplants in whom the graft was left in situ underwent CT for various unrelated indications. The majority of the failed grafts showed marked shrinkage and coarse punctate diffuse parenchymal calcifications. Small cysts were seen in four grafts. A long-term failed renal transplant appeared on CT as a small rounded soft tissue mass. The graft was almost always heavily calcified. Lack of awareness of the nature of such a mass may mislead the radiologist in interpreting it as a space-occupying lesion.

Adult↗

PubMed1997

Emphysematous pyelonephritis in a nonfunctioning renal allograft of a patient undergoing hemodialysis.

A hemodialysis patient with insulin-dependent diabetes mellitus and a non-functioning renal allograft in whom fever, low blood pressure, and confusion developed is reported. She underwent extensive evaluation and allograft nephrectomy for emphysematous pyelonephritis that was diagnosed by the presence of air in the collecting system of the transplanted kidney during computerized tomography of the abdomen. In nine patients with emphysematous pyelonephritis in renal allografts reported previously, this is the first instance of emphysematous pyelonephritis in a renal allograft with coagulase-negative staphylococcus.

Coagulase↗

PubMed1970

Male fertility in uremia: restoration by renal allografts.

Spermatogenesis has been studied in eight chronic uremic patients on hemodialysis and in 11 recipients of well-functioning renal allografts. Sexual activity, semen analysis and testicular biopsy are abnormal in chronic uremic patients. Spermatogenesis remains "arrested" even when uremia is well controlled by intermittent hemodialysis. Marked improvement occurs in sexual performance, semen analysis and testicular biopsy after successful kidney transplantation. Immunosuppressive treatment, at dosages used six months after allografting, does not appear to affect male fertility adversely.

Adolescent↗

PubMed1977

Possible persistent endocrine function of a rejected renal allograft.

The case is described of a patient on intermittent hemodialysis who had had a bilateral nephrectomy but had hypertension and a surprisingly mild degree of anemia. Repeated determinations showed high plasma renin activity and plasma erythropoietin activity within the detectable range. These results were thought to be related to a completely calcified renal allograft which had been inserted 8 years before and which had been rejected four years later, but left in situ. The patient had become anuric. It is suggested that chronically rejected renal allografts, even calcified, may maintain some endocrine activity in the absence of any excretory function.

Adult↗

PubMedDate not supplied

Avascular necrosis of the bone in 99 renal allograft recipients.

Avascular necrosis of bone is a serious complication associated with steroid therapy in high dose. Ninetynine patients with functioning renal allografts transplanted 1964-1973 and subjected to steroid therapy were examined with regard to this complication. Osteonecrosis developed in 8 patients afflicting 13 joints. The process was localized to the femoral head, the condyles of the femur, tibia and the head of the humerus. The symptoms became manifest 7-33 months after the first transplantation. The severity of the disorder in 3 patients did not allow rehabilitation by conservative means. The roentgenographic, scintigraphic and clinical findings are described and the orthopaedic treatment discussed.

Bone Diseases↗

PubMed1997

[Experience of the Valdivia Hospital in renal transplant: an analysis of our first 100 cases].

From September 1980 until October 1995 we have performed 100 renal transplant on 95 patients. Up to May of 1996 the medium follow-up was of 69.7 months (in a range of: 15 to 196 months). Seventy-nine kidney implants were performed from related living donors and 21 from dead donors. The average age of recipients was 35.8 years (SD: +/- 12.5 years). Chronic renal insufficiency of recipients is reviewed as well as their accompanying pathology. We found that in a 20% of the cases the donor's kidney had multiple renal arteries. In most of the ureteral vesical implantations were performed with Salvatierra's technique. Preservation cold time for the cadaveric donor kidneys was over 24 hours. In only a 33% of the cases Cyclosporine was used as the immunosuppression therapy. The 9% of ureteral complications are outlined. TBC is an important cause of complications and death of patients. To date there are 76 functioning kidney allografts and 14 lost graft kidneys. Ten patients have died, 3 of them with functional graft kidney. Actuarial graft survival rate for 1, 5 and 10 years are 92.7%, 78.7% and 59.3% respectively.

Adult↗

PubMed1994

Alloantigen-independent factors lead to signs of chronic rejection in long-term kidney isografts.

Chronic rejection is the most important cause of graft failure after the first year of transplantation. In addition to the effects of host immunological injury, antigen-independent factors may gain in importance over the long term. We therefore assessed the influence of such factors on rat kidney isografts functioning for prolonged periods and compared our findings with those observed in naive control rats and in allograft recipients. Functional, morphological, and immunohistological changes in the isografts became obvious 32 weeks after engraftment, and by 52 weeks the findings mimicked those of chronic allograft rejection. As allografted kidneys sustained these changes earlier on and more intensely, both alloantigen-independent and -dependent factors are thought to be implicated in this process.

Animals↗

PubMed1974

Clinical evaluation of equine antithymocyte globulin in recipients of renal allografts: Analysis of survival, renal function, rejection, histocompatibility, and complications.

Equine antithymocyte globulin combined with azathioprine and prednisone as immunosuppressive therapy in 50 transplant recipients prolonged allograft survival and seemed to modify the severity of rejection episodes. Although nine patients died from a variety of causes, only three kidneys were lost to rejection, one of which was hyperacute. There were no serious untoward hematologic or systemic effects caused by the ATG, and all patients completed the course of therapy. Infection, a serious and frequent complication of transplant patients, was encountered no more often than in other transplant series not using ALG. The data pertaining to the clinical value of ATG, although suggestive in terms of its immunosuppressive effects, is still not conclusive; and a definitive answer to this question awaits further evaluation in a series of cadaveric recipients in a randomized-double-blind study.

Adolescent↗

PubMed2002

Microgravity culture condition reduces immunogenicity and improves function of pancreatic islets1.

BACKGROUND: The failure of pancreatic islet allotransplants observed in almost all clinical attempts is related to poor initial islet function and allograft rejection. To remedy these problems we cultured islets in microgravity conditions to improve their function and to reduce their immunogenicity. METHODS: Fresh mouse islets or mouse islets cultured in stationary dishes or microgravity bioreactors were transplanted to streptozotocin-induced diabetic mouse recipients. RESULTS: Both allogeneic dish- or bioreactor-cultured islets survived more than 100 days compared with fresh allogeneic islets, which were rejected in less than 15 days. Islet titration studies revealed that 250 fresh or dish-cultured, but only 30 to 120 bioreactor-cultured, islets were necessary to produce euglycemia. Furthermore, glucose tolerance tests showed that bioreactor-cultured islets functioned better compared with fresh and dish-cultured islets on day 30 postgrafting. Immunostaining and transmission electron microscopy (TEM) analyses showed the gradual disappearance of dendritic cells in cultured islets compared with fresh islets. TEM revealed that the ultrastructure of islets from bioreactor, but not dish, appeared healthy and closely resembled fresh islets. Interestingly, TEM and scanning electron microscopy showed that only bioreactor-cultured islets developed unique and multiple nutritional channels between arrays of islet cells. TEM with colloidal lanthanum tracer revealed that only bioreactor islet cell cultures were devoid of tight junctional complexes, which may facilitate channel formation. CONCLUSION: Microgravity condition decreases immunogenicity and significantly improves the function of secretory cells.

Animals↗