Primary Cause Of Graft Failure Research Articles

Outcomes for pediatric liver retransplantation from living donors.

The only therapeutic option for patients with a failing allograft is retransplantation. Living donor liver transplantation (LDLT) is a well-accepted therapeutic option for end-stage liver disease, but retransplantation from a living donor (Re-LDLT) has not previously been discussed. A total of 547 LDLTs were performed in 519 children (<18 years old) at Kyoto University Hospital from June 1990 to October 2002. During the same study period, a total of 28 Re-LDLTs were performed in 27 recipients (Re-LDLT performed twice in 1 patient). Patient survival was analyzed with respect to various preoperative factors, such as functional status, pretransplantation apheresis, cause of primary graft failure, interval from primary to subsequent transplants, and laboratory values of total bilirubin and creatinine. Kaplan-Meier survival rate from the date of Re-LDLT to 1 year was 47.6%. Functional status, pretransplantation apheresis, interval to Re-LDLT, and bilirubin and creatinine levels all exerted an adverse impact on survival after Re-LDLT. Pathologically proven major causes of primary graft failure were chronic rejection (n=10, 35.7%), chronic cholangitis (n=6, 21.4%), and vascular complications (n=7, 25.0%). Among these causes, vascular complications displayed the strongest adverse impact on survival, compared with chronic cholangitis and chronic rejection (1-year survival was 35.7% in vascular complications; 66.7% in chronic cholangitis; and 60.0% in chronic rejection). Re-LDLT can save patients with a failing allograft. To achieve better results after Re-LDLT, further investigations are necessary to understand the factors leading to poor outcome after Re-LDLT.

Maintenance triple immunosuppression with cyclosporin A, mycophenolate sodium and steroids allows prolonged survival of primate recipients of hDAF porcine renal xenografts.

To date, the best results in life-supporting pig-to-primate renal xenotransplantation have been obtained in recipients exposed to long-term immunosuppression with cyclophosphamide. As this agent is frequently associated with side-effects, we have explored the potential of a mycophenolate sodium-based maintenance immunosuppression in this model. Human decay-accelerating factor (hDAF) transgenic kidneys were transplanted into splenectomized and bilaterally nephrectomized cynomolgus monkeys immunosuppressed with mycophenolate sodium, cyclosporin A and steroids, and exposed to a brief induction course with cyclophosphamide (up to four doses). After transplantation, the primates were monitored daily for biochemical and haematological evaluations and for the measurements of haemolytic anti-pig antibodies (APA). A detailed histological analysis of each explanted graft was also performed. All the animals showed very poor initial graft function but survived for up to 51 days. In contrast to our previous studies in xenograft recipients on long-term immunosuppression with cyclophosphamide, minimal or no circulating xeno-directed antibodies, as measured by the evaluation of APA titres, were detected in this series although some degree of acute humoral rejection was observed in all the explanted grafts and was the primary cause of graft failure. Furthermore, in addition to areas of humorally mediated graft damage, we have observed for the first time areas with exclusive and prominent infiltration by CD2+ and CD8+ mononuclear cells presenting patterns compatible with tubulitis, glomerulitis and arteritis, which we have called acute cellular xenograft rejection (ACXR). In addition, CD68+ infiltrating macrophages and CD20+ B-cells were also present. This study demonstrates that a triple maintenance immunosuppression with mycophenolate sodium, cyclosporin A and steroids is a viable alternative to a cyclophosphamide-based immunosuppression to obtain prolonged survival of porcine organs transplanted into primates. However, a more stringent control of antibody forming cells remains essential to further extend the survival of xenografts in this model. In addition, the use of the immunosuppressive regimen reported here in the primate is associated with the occurrence of a new category of cell-mediated xenograft injury (ACXR) whose significance has yet to be clarified.

Liver transplantation for fulminant hepatic failure: experience with more than 200 patients over a 17-year period.

To analyze outcomes after liver transplantation (LT) in patients with fulminant hepatic failure (FHF) with emphasis on pretransplant variables that can potentially help predict posttransplant outcome. FHF is a formidable clinical problem associated with a high mortality rate. While LT is the treatment of choice for irreversible FHF, few investigations have examined pretransplant variables that can potentially predict outcome after LT. A retrospective review was undertaken of all patients undergoing LT for FHF at a single transplant center. The median follow-up was 41 months. Thirty-five variables were analyzed by univariate and multivariate analysis to determine their impact on patient and graft survival. Two hundred four patients (60% female, median age 20.2 years) required urgent LT for FHF. Before LT, the majority of patients were comatose (76%), on hemodialysis (16%), and ICU-bound. The 1- and 5-year survival rates were 73% and 67% (patient) and 63% and 57% (graft). The primary cause of patient death was sepsis, and the primary cause of graft failure was primary graft nonfunction. Univariate analysis of pre-LT variables revealed that 19 variables predicted survival. From these results, multivariate analysis determined that the serum creatinine was the single most important prognosticator of patient survival. This study, representing one of the largest published series on LT for FHF, demonstrates a long-term survival of nearly 70% and develops a clinically applicable and readily measurable set of pretransplant factors that determine posttransplant outcome.

Revision anterior cruciate ligament reconstruction: a midterm patient assessment

Twenty patients who underwent revision anterior cruciate reconstruction were retrospectively reviewed. Before revision surgery all patients reported functional instability with daily and or sporting activities. The causes of primary graft failure have been identified. Four different types of graft were used for the revision reconstruction. A comprehensive knee analysis was used to assess the graft performance both subjectively and objectively at an arranged follow-up visit. In general our study shows that although there is residual antero-posterior laxity on clinical assessment and KT-1000 instrumentation after revision surgery, the majority of patients thought the results were subjectively good or excellent. The study highlights the well-recognised technical failures of primary anterior cruciate ligament reconstruction and confirms good subjective results. The poor correlation between the physical examination (objective) and the patient's perception (subjective) of the revision surgery is discussed.

OUTCOME OF MECHANICAL ASSISTANCE AFTER PRIMARY GRAFT FAILURE FOLLOWING ORTHOTOPIC HEART TRANSPLANTATION

PURPOSE: Primary graft failure (PGF) is a catastrophic event often leading to death. We sought to determine the incidence and early outcome of PGF following orthotopic heart transplantation. METHODS: In retrospect, 799 consecutive orthotopic heart transplants were performed at UCLA between January 1992 and January 2001. During this time frame, we expanded our donor pool by recruiting older and marginal donor organs and initiated an alternate recipient list. Myocardial protection during orthotopic implantation is accomplished with a continuous drip of topical endocardial cold plasmalyte solution and reperfusion with leukocyte-depleted, aspartate-glutamate-enriched warm blood cardio-plegia for 4 min followed by leukocyte-depleted warm blood prior to releasing the aortic cross-clamp. Early primary graft failure was defined as cardiac dysfunction immediately post implantation requiring mechanical assistance (e.g. IABP, ECMO, LVAD, RVAD and/or BiVAD). RESULTS: The recipients had a mean age of 46.6 yr (range, 0.13–72.5) and 43% were UNOS status 1 at engraftment. The myopathic diagnoses were ischemic 43%, idiopathic 31%, valvular 7%, transplant coronary artery disease 6%, congenital heart disease 3%, postpartum 2%, adriamycin toxicity 1%, and other 7%. Mean donor ischemia time was 174 min (range, 60–930). Thirty-four out of 799 (4.3%) experienced early primary graft failure. The causes of primary graft failure included cellular and humoral rejection, suboptimal donor organ or poor preservation, sepsis and multiple organ failure and major cerebrovascular accidents. Seven out of 34 patients (21%) with failing grafts recovered with mechanical support. There were 68 out of 799 (8.5%) and 127 out of 732 (17%) early and late deaths during this eight-year period. Four out of 68 (6%) of the early mortality group had PRA > 10% versus 5 out of 127 (3.9%) for the late mortality group. The mean follow-up period was 45.6 mos (range, 0–116). CONCLUSIONS: Despite tailored matching of donor to recipient, improved myocardial preservation techniques and aggressive immunologic surveillance and treatment, primary graft failure remains a devastating complication occurring in 4% of our transplant patients. The high mortality rate in this subgroup is potentially reversible with expeditious mechanical support, prompt diagnosis and treatment.

Cellular changes in transplanted human corneas.

To measure endothelial cell and keratocyte densities in transplanted corneas and the changes in these densities with time. The endothelia of 500 consecutive penetrating corneal transplants were studied longitudinally by specular microscopy for 10 to 20 years. The keratocytes of 36 corneal transplants that varied in postoperative times from 1 month to 20 years were studied cross-sectionally by clinical confocal microscopy. The keratocytes of five transplanted corneas were studied longitudinally by confocal microscopy at 1 day, 1 week, and 1 month postkeratoplasty. Endothelial cell density decreased progressively at an accelerated rate for 20 years after transplantation, with concurrent increases in the coefficient of variation of cell area and corneal thickness and decreases in the percentage of hexagonal cells. Grafts with insufficient endothelial cells developed late endothelial failure, which was the primary cause of graft failure after the first 5 postoperative years. The grafts with late endothelial failure did not lose endothelial cells faster than grafts that did not fail, but instead had fewer cells immediately after transplantation, diminishing to a critically low cell density earlier. The keratocyte density was also decreased in transplanted corneas. Keratocytes became "activated" during the first week after keratoplasty and in grafts with late endothelial failure. It should be possible to prevent or delay late endothelial failure, the primary cause of graft failure, by increasing the number of endothelial cells on transplanted corneas. The status of the keratocytes appears to affect corneal transparency and, thus, visual quality in the grafted eye.

Primary Graft Failure Caused by Herpes Simplex Virus Type 1

To present a cluster of four patients with primary graft failure (PGF) who consecutively underwent a penetrating keratoplasty (PKP) during a period of 17 days in one institution. PKP was performed for reasons unrelated to herpes simplex infection. Herpes simplex virus type 1 (HSV-1) is presented as the possible cause of these PGFs. Viral culture of conjunctival swabs and of a bandage contact lens was performed on VERO, MRC-5, and Hep-2 cells. The four patients underwent subsequent regrafting. Polymerase chain reaction (PCR) for HSV-1 was carried out on aqueous humor and on a sample of iris and cornea with primers. Aqueous humor specimens were pretreated by boiling, and a qiagen extraction was performed according to the instructions of the manufacturer on biopsies of iris and cornea. Immunohistopathology was performed with polyclonal antibodies directed against HSV-1 and -2. Culture of a conjunctival swab in three patients and culture of a bandage contact lens in the fourth patient were positive for HSV-1. In three of the four patients, PCR was positive for HSV-1 on aqueous humor and corneal graft tissue. PCR on iris tissue was positive in all patients. In three patients, culture for HSV-1 of aqueous humor and of iris tissue could not be carried out because of insufficient sample. Viral culture of the iris tissue in one patient and of the corneal graft in the four patients were negative. Immunohistopathologic examination was positive for HSV-1 in three cases. These case reports strongly support the hypothesis that HSV-1 can be the cause of PGF.

This month in J Lab Clin Med: Issue highlights for December 2000

This month in J Lab Clin Med: Issue highlights for December 2000

Treatment of primary graft dysfunction after kidney transplantation by renal artery stent

Renal artery stenosis is a rare cause of primary graft failure after kidney transplantation [1]. Percutaneous transluminal angioplasty (PTA) is the treatment of choice, however, this technique has its limitations in elastic stenoses that are resistant to dilatation [2,3]. The procedure is of high risk, especially in the early phase after transplantation. If renal artery stenosis is refractory to PTA, the placement of an endovascular prosthesis (Palmaz stent) may be necessary. To our knowledge there are no reports in the literature regarding transplant renal artery stenting in the early period after transplantation. artery (Figure la). Renal biopsy ruled out rejection and other parenchymal disorders. Arterial angiography confirmed the CDS diagnosis and angioplasty was performed using a 5-mm dilation balloon (Figure 2a). However, due to elastic recoil, there was not much improvement angiographically and kidney function and blood pressure did not substantially improve. To overcome the remaining high-grade stenosis, an intravascular endoprosthesis (Palmaz stent, 10 mm in length, dilated up to 5 mm) was successfully implanted into the stenotic region (Figure 2b). Immediately thereafter, diuresis increased (3000 ml/day), serum creatinine level dropped to 141.4 umol/1, and blood pressure improved. Control CDS confirmed that the endoprosthesis was correctly placed with just a slight narrowing at the suture, but no turbulences were detected (Figure lb). Three months postoperatively, the patient had stable renal function with a serum creatinine of 123.7 umol/1.

Causes of primary graft failure after in situ saphenous vein bypass grafting

In situ saphenous vein bypass grafts originating in the groin were performed in 455 consecutive patients. Primary failure occurred in 92 grafts during follow-up, including 22 (4.8%) with nonocclusive stenosis and 70 (15.4%) with occlusion. The cause for failure could not be determined in seven grafts; 104 contributory causes were identified in the remaining 85 grafts. Among the 104 likely causes, 66 (63%) were intrinsic to the graft itself and contributed to failure of 55 (12.1%) of 455 grafts. These causes included perianastomotic stenosis (48), vein stricture (14), focal vein stenosis (10), valvulotome injury (9), kink (6), retained valve leaflet (4), intimal flap (3), and residual arteriovenous fistula (2). Among these intrinsic causes, 20 were directly related to the in situ technique, contributing to failure of 15 (3.3%) of 455 grafts. Thirty-eight (37%) of the 104 causes were extrinsic to the graft, including compromised inflow (2) or outflow (19), hypercoagulability (9), systemic hypotension (6), and graft sepsis (2). Hypothetically, improvements in technique, patient selection, and perioperative management might have eliminated 46 (44%) of 104 causes of primary graft failure. Delayed graft and anastomotic stenosis and late progression of outflow disease remain resistant to modern therapy. (J Vasc Surg 1992;15:113–20).

Causes of primary graft failure after in situ saphenous vein bypass grafting

In situ saphenous vein bypass grafts originating in the groin were performed in 455 consecutive patients. Primary failure occurred in 92 grafts during follow-up, including 22 (4.8%) with nonocclusive stenosis and 70 (15.4%) with occlusion. The cause for failure could not be determined in seven grafts; 104 contributory causes were identified in the remaining 85 grafts. Among the 104 likely causes, 66 (63%) were intrinsic to the graft itself and contributed to failure of 55 (12.1%) of 455 grafts. These causes included perianastomotic stenosis (48), vein stricture (14), focal vein stenosis (10), valvulotome injury (9), kink (6), retained valve leaflet (4), intimal flap (3), and residual arteriovenous fistula (2). Among these intrinsic causes, 20 were directly related to the in situ technique, contributing to failure of 15 (3.3%) of 455 grafts. Thirty-eight (37%) of the 104 causes were extrinsic to the graft, including compromised inflow (2) or outflow (19), hypercoagulability (9), systemic hypotension (6), and graft sepsis (2). Hypothetically, improvements in technique, patient selection, and perioperative management might have eliminated 46 (44%) of 104 causes of primary graft failure. Delayed graft and anastomotic stenosis and late progression of outflow disease remain resistant to modern therapy.

Development and Structure of Unusual Xylem Elements During Graft Union Formation in Picea sitchensis L.

Electron microscope studies of Sitka spruce have been undertaken to observe the sequence of cellular development following grafting. Observations at the graft interface reveal a recovery and regeneration sequence associated with union formation. Xylem elements differentiated directly from the vascular cambia of the rootstock and scion are different from elements arising from parenchymatous callus derived from ray parenchyma, which may be produced in an attempt to establish a connecting water conducting system as rapidly as possible. Failure to form such a system may be a primary cause of graft failure.

Effect of external pressure on axillofemoral bypass grafts.

External compression of axillofemoral grafts has been suggested many times as a cause for graft thrombosis. Thrombosis during sleep is the most common presentation of axillofemoral graft failure. Therefore, external compression of the graft by the body weight has been implicated in graft thrombosis. Six consecutive patients with axillofemoral bypass grafts for aortoiliac disease were studied on routine clinic visits. Pulsatile flow characteristics were studied by pulse volume recordings (PVR) and segmental Doppler pressure measurements in calf and ankle, prior to and during attempted graft compression, by having the patient lay on the graft. External compression by body weight did not alter the PVR and segmental Doppler pressure (P = NS) in the distal circulation. Therefore, these data suggest that external compression by the body weight may not be the primary cause of graft failure.

Pathology of liver transplantation.

Experience with renal transplantation indicates failure of the graft is usually due to immunological rejection. In a previous study of human liver transplantation, rejection was the major cause of transplant failure in 4 of 17 patients )24%); in this review of 76 liver transplantations, 64 of which survived the first postoperative week, rejection was the primary cause of graft failure in only 4 of these 64 cases (6%). The two most common causes of transplant failure were technical difficulties with the operative procedure and sepsis; these accounted for 47 (62%) graft failures of the total of 76 transplants. Biliary obstruction and sepsis are more common causes of liver failure than rejection, and patients with recurrent jaundice are now studied intensively for evidence of obstruction. Only after obstruction is excluded, is immunosuppression intensified. These results are a basis for optimism concerning the future of liver transplantation in management of potentially fatal liver disease.

Human renal allografts: Analysis of lesions in long-term survivors

Two hundred thrity-five renal allografts were transplanted into 211 drug-modified recipients at the Peter Bent Brigham Hospital during the period 1959 to 1970. Of these, 74 grafts have survived beyond 650 days. Biopsy specimens were taken from 18 kidney transplants in this long-surviving group. They were obtained for specific clinical indications at times beyond 650 days, and their study is the basis for this report. All 18 grafts showed intimal fibro-obliterative arterial lesions, and in seven these lesions were sufficiently severe to be a major cause of graft failure. In four of the latter the initimal lesion progressed rapidly following cessation of immunosuppressive therapy, and extensive deposits of IgM, β 1c, and fibrin were demonstrable by immunofluorescence. Fibrinoid necrosis of arteries with medial IgG deposits and neutrophilic infiltrates and acute cellular rejection were also present at such times. All grafts showed glomerular alterations of varying degrees consisting of devascularization, folding of glomerular basement membranes, focal hypercellularity, pedicel fusion, increased basement membrane thickening with subendothelial changes, altered mesangial substance, and focal-linear deposits of IgG, IgM, β 1c, or Fib, irrespective of the recipients' original disease. These changes were considered to be due to combinations of ischemia and rejection. Distinctive subepithelial deposits were noted in one kidney and may represent either recurrent or de novo glomerulonephritis. Spherular basement membrane inclusions suggestive of Herpesvirus capsid were noted in five grafts. Glomerular injury did not appear to be a primary cause of graft failure in any of these 18 recipients. Acute cellular rejection was seen as early as two days and as late as five years after transplantation. Immunofluorescent deposits of globulins were demonstrable in the tubular basement membranes in 12 grafts. At times these were associated with albumin deposits, possibly representing tubular dysfunction. IgA was identified in cytoplasmic granules of infiltrating eosinophils in grafts that showed chronic rejection. The lesions in arteries, glomeruli, and peritubular capillaries are probably due to rejection and may result from endothelial injury with subsequent thrombosis. Recipients of grafts with deteriorating function that show accumulations of microthrombi and lipophages in arteries on early biopsies, or that demonstrate intimal fibroproliferative lesions, glomerular basement membrane thickening, and deposits of fibrin in the vasculature in later biopsies should receive long-term antithrombotic therapy.