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PubMed2004

Update in renal transplantation.

Renal transplantation is the treatment of choice for most patients with end-stage renal disease. The shortage of donor organs, however, remains a major obstacle to successful, early transplantation. This shortage has actually worsened despite an increase in living family-related and unrelated donors. On the other hand, over the last 10 years, allograft and recipient survival have significantly improved. This encouraging outcome reflects many factors, particularly a favorable shift in the balance between the efficacy and toxicity of immunosuppressive regimens. As acute rejection and early graft loss have become less common, the focus is increasingly directed toward the prevention and treatment of the long-term complications of renal transplantation. These include suboptimal allograft function, premature death, cardiovascular disease, and bone disease. Thus, a multidisciplinary approach--rather than management of immunological issues alone--is now required to optimize long-term outcomes of renal transplant recipients.

Antibody Formation↗

PubMed1984

Growth in children with various therapies for end-stage renal disease.

The growth of children undergoing continuous ambulatory peritoneal dialysis (CAPD) therapy for end-stage renal disease (ESRD) was compared with the growth of children undergoing hemodialysis and that of children after successful kidney transplantation. The bone ages of the children were used to predict expected growth velocities. The actual growth velocities observed were then expressed as percentages of the predicted rates. Children receiving CAPD therapy grew better than those treated by hemodialysis and as well as the children who received a kidney transplant. There was some correlation between growth and allograft function in the transplant recipients. Children receiving CAPD were less acidotic and were more likely to exhibit improvement in renal osteodystrophy than children treated by ongoing hemodialysis. There were no significant differences in reported caloric intake between the two groups.

Adolescent↗

PubMed1987

Vesicoureteral reflux and urinary tract infections in renal transplant recipients.

Fifty-six children who received kidney transplants were evaluated for postoperative vesicoureteral reflux and frequency of urinary tract infection. Two methods of ureteral implantation were compared: a nonantireflux extravesicular ureteroneocystostomy and an antireflux intravesicular ureteroneocystostomy. Reflux was found in 79% of children who had the nonantireflux procedure vs 19% of children who had the antireflux procedure. This disparity was present regardless of sex and age. Infections occurred at a rate of one per 11 patient-months after the nonantireflux procedure vs one per 40 patient-months after the antireflux procedure. Regardless of surgical technique, the incidence of infection was higher in children with reflux. The potentially harmful effect of infection with reflux warrants concern. Because of the need to maximize allograft function for a longer time period, an antireflux procedure is recommended in all pediatric kidney transplants.

Adolescent↗

PubMed1994

Second renal transplantations. Ethical issues clarified by outcome; outcome enhanced by a reliable crossmatch.

OBJECTIVE: To determine whether the appropriate use of scarce donor resources has been accomplished by renal retransplantation by reviewing the initial and long-term outcomes of second-renal transplant recipients at the Massachusetts General Hospital, Boston. PATIENTS AND RESULTS: With a mean follow-up of nearly 5 years following transplantation, 54 (68%) of 80 second-transplant recipients had functioning allografts (allograft failure was defined by patient death or a return to dialysis). Rejection was the most common cause of failure (14 [54%] of 26 patients). The 1-, 3-, and 5-year actuarial allograft survival rates were 86%, 78%, and 69%, respectively, which were not significantly different from the survival rates of primary allografts at this center. These results support the continued approach of providing both cadaver-donor and living-donor renal allografts for recipients whose primary renal allograft has failed. The antiglobulin crossmatch may have contributed to the successful outcome by accurately determining compatibility and by averting early rejection failures. CONCLUSIONS: Health care policy reviewers should clearly distinguish the prospects for successful second renal transplants from the outcomes of extrarenal retransplantation. Moreover, because excellent second-renal allograft survival is attainable and comparable to primary-renal allograft survival and because the costs are comparable, restricting suitable patients to subsequent lifelong dialysis becomes unethical.

Adult↗

PubMed2005

Mini-BEAM and autologous hematopoietic stem-cell transplant for treatment of post-transplant lymphoproliferative disorders.

Post-transplant lymphoproliferative disorder (PTLD) represents a spectrum of lymphoid proliferative diseases seen as result of immunosuppression in recipients of solid organ or hematopoietic stem-cell transplantation. Options of treatment include reduction or discontinuation of immunosuppressive agents, antiviral drugs, rituximab, chemotherapy, and radiation. We report two unique cases of PTLD (CNS and plasmacytoma-like) treated successfully with salvage chemotherapy, mini-BEAM chemotherapy, and autologous stem-cell transplant. In both cases, patients were also treated with sirolimus and prednisone as immunosuppression, and neither patient rejected their solid organ transplants. With over 30 months of follow-up, both patients remain in complete remission with excellent allograft function.

Adult↗

PubMed1982

Experiences with cadaver renal allograft contamination before transplantation.

Microbial contamination occurred in 23 (13 per cent) of 177 cadaver donor kidneys prior to renal transplantation. In 16 cases there were no complications directly attributable to the organisms recovered from the preservation media. Three patients developed perinephric infections associated with renal artery anastomotic disruption and required emergency transplant nephrectomy. A fourth patient developed renal artery stenosis and a hypogastric artery aneurysm that required correction 6 months later with preservation of renal allograft function. In 3 cases no follow-up information was available. None of the 154 uncontaminated kidneys developed arterial disruption or aneurysm. Candida albicans and Pseudomonas aeruginosa infections were responsible for the nearly disastrous arterial disruptions and possibly the hypogastric arterial aneurysm. These findings demonstrate the importance of bacteriological surveillance of perfusion media to detect nosocomial infection, to guide antibiotic chemotherapy and to direct surgical management of septic complications. In our experience contamination was not necessarily incompatible with long term satisfactory results; however, when complications did occur they were serious. It is likely that the size of the microbial inoculum, the patient's immune competence and the protective effect of antibiotic therapy administered to the donor and recipient affected the eventual outcome.

Adult↗

PubMed1986

Aspirate cellularity as a rapid indicator of renal allograft rejection.

No rapid and unequivocal test exists to diagnose renal allograft rejection. Despite advances in immunosuppression over the last 20 years, rejection is still the major problem in clinical organ transplantation. Most transplant centres report a renal graft survival rate of about 60 per cent at 5 years and the majority of graft losses are due to rejection. An influx into the graft of various cell types has been implicated in the diagnosis of rejection but it takes up to 24 h to obtain such information histologically. We have carried out fine needle aspiration biopsy of the allografts and estimated the number of white cells in the aspirate using a fluorescence activated cell sorter. Studies were performed in 34 cases of normal allograft function, 8 of rejection, 8 of acute tubular necrosis and 8 of cyclosporin nephrotoxicity. There was a statistically significantly higher cell number in the group undergoing rejection (P less than 0.01; Wilcoxon unpaired test) when compared to each of the other three groups. We believe that this technique, which takes only a few minutes to perform, could yield much valuable information. It deserves further study.

Biopsy, Needle↗

PubMed1994

Aplastic anemia after liver transplantation for fulminant liver failure.

We determined the incidence and outcome of aplastic anemia among 56 patients who underwent liver transplantation for fulminant liver failure at the University of Nebraska Medical Center between July 1985 and December 1993. Aplastic anemia developed in 6 of 18 (33%) children and 1 of 19 (5%) adults who had fulminant non-A, non-B hepatitis; no cases of aplastic anemia occurred among patients with other causes of fulminant liver failure. None of these patients had evidence of a preexisting hematological disorder or infection with hepatitis C virus (as determined with a second-generation ELISA). Aplastic anemia was diagnosed at a median of 4 wk after the onset of hepatitis, with five cases seen before transplantation. Six patients received antithymocyte globulin to promote remission of aplastic anemia. Three children died (fungal infection in two, intracranial hemorrhage in one)--one at 43, one at 108 and one at 119 days after transplantation--without remission of aplastic anemia. Among the four surviving patients, with median follow-up of 25 mo, complete and partial remission of aplastic anemia have occurred in three and one, respectively. Liver allograft function is stable in all surviving patients. The data demonstrate that aplastic anemia is a common complication among children who undergo liver transplantation for fulminant non-A, non-B hepatitis. It is associated with a high rate of mortality, although most survivors appear to have full hematological recovery.

Adolescent↗

PubMed1997

Aplastic anemia complicating orthotopic liver transplantation.

The clinical characteristics and outcome of posttransplantation aplastic anemia (AA) were determined in 12 of 1,736 patients (0.007%) undergoing orthotopic liver transplantation (OLT) that were afflicted with AA. None of the affected patients had a history of hematologic disease. Median patient age was 53 years (range, 2-61 years); 10 of the affected patients were men, and 2 were women. The etiologies of AA included non-A, non-B, non-C fulminant hepatic failure (FHF) (3 patients), graft-versus-host disease (4 patients), Parvovirus-induced (1 patient), and idiopathic (4 patients). The median duration between OLT and the onset of AA was 12 days (range, 11-14 days) in the 3 patients undergoing OLT for FHF; in contrast, AA developed in the other 9 patients at 37 days (range, 27-51 days) after OLT. Eleven patients were treated with reduction of their cyclosporine or tacrolimus dosage, granulocyte colony-stimulating factor, anti-thymocyte globulin, and Solumedrol. Two of the 3 patients developing AA following OLT for FHF achieved hematologic recovery 21 and 92 days after diagnosis. In contrast, all 9 non-FHF patients developing AA after OLT died, 5 due to infectious complications and 4 following intracranial bleeding. AA is an unusual complication of OLT. In the setting of FHF, it affects young males in the early posttransplantation period, and, when infectious complications can be avoided, remission and stable allograft function can be anticipated. However, in the non-FHF patient, AA occurs in older individuals later in the posttransplantation period and has a uniformly poor outcome.

Adult↗

PubMed1990

Assay methods for cyclosporine monitoring following liver transplantation.

This article reviews therapeutic drug monitoring for cyclosporine in liver transplantation. Brief descriptions of various immunoassay methods include sample matrix selection, assay reagents, and metabolite cross-reactivity information. Multiple comparisons of the various methods are outlined. Examples of the method-dependent relationship between clinical events and changes in cyclosporine concentration are presented. Other potential predictors of liver allograft function are listed.

Chromatography, High Pressure Liquid↗

PubMed1992

Doppler and color Doppler ultrasonography in renal transplants: chronic rejection.

Although Doppler and color Doppler ultrasonography has been used extensively to examine acute changes in renal allograft function, there have been few reports on the role of Doppler ultrasonography in the assessment of chronic rejection. In those studies that have addressed chronic rejection, there is agreement that changes in renal function are not accompanied by consistent changes in flow wave-form shape. The pathology of chronic rejection may be very different from the changes seen in acute rejection and its onset is usually gradual. Some authors have suggested that the decline in function is accompanied by lower Doppler frequency shifts (corresponding to lower velocities) in intra-renal arteries. In a preliminary study comparing grafts with normal renal function and with biopsy-proven chronic rejection, it has been shown that for grafts with chronic rejection, observed intra-renal velocities are lower, especially at segmental and interlobar levels. This may be a more reliable reflection of reduced renal blood flow in chronic rejection than conventional Doppler ultrasound analysis of flow waveform shape. However, the diagnostic use of changes to intra-renal flow velocities in chronic rejection is currently very limited.

Graft Rejection↗

PubMed1993

Management of advanced ovarian epithelial cancer in the renal transplant patient.

Stage IIIC, grade 1 papillary serous adenocarcinoma of the ovary was diagnosed in a 28-year-old renal transplant recipient. She had been treated with the immunosuppressive agents azathioprine and methylprednisolone for 7 years prior to the discovery of the ovarian cancer. Surgical excision of the tumor was suboptimal due to involvement of the allograft; however, the patient achieved a complete clinical response after eight courses of cisplatin and cyclophosphamide. Since multiagent immunosuppressant therapy may have contributed to the development of the ovarian carcinoma, the intensity of immunosuppression was decreased by discontinuing the azathioprine as soon as the diagnosis of ovarian cancer was made. The methylprednisolone, however, was continued to decrease the possibility of organ rejection. After completion of chemotherapy, the patient was started on a daily regimen of low-dose oral cyclophosphamide as an immunosuppressant. Four months following the completion of cytotoxic therapy, she developed clinically evident disease in the pelvis. Subsequent salvage therapy with carboplatin failed. The patient died from progressive disease 26 months after initial diagnosis. She never developed evidence of renal rejection. Combined modality cancer therapy, preservation of allograft function, and modification of immunosuppressant therapy are important goals in the renal transplant patient with advanced ovarian carcinoma.

Adult↗

PubMed1998

Hepatic uptake of amino acids immediately after liver transplantation is well preserved despite altered plasma profiles.

BACKGROUND: The liver is one of the principal organs responsible for the uptake and release of amino acids in the body. The ability of the transplanted liver to clear plasma amino acids is associated with a functioning allograft. However, clinical assessment is limited by the inability to access the portal vein postoperatively. Therefore, using a porcine liver transplant model, we examined (1) the plasma levels of amino acids presented to the new hepatic allograft and (2) the capacity of the new allograft to clear these amino acids from the circulation. MATERIALS AND METHODS: Two groups of commercially bred pigs were studied: a control group (n = 8) underwent laparotomy and a transplanted group (n = 6) underwent orthotopic liver transplantation (LT) using veno-venous bypass. All pigs had catheters placed in the carotid artery and portal and hepatic veins and ultrasonic transit time flow probes placed around the hepatic artery and portal vein. Plasma profiles of 23 amino acids were analyzed by high-pressure liquid chromatography. Hepatic balances of amino acids, using arteriovenous difference techniques coupled with hepatic blood flows, were also analyzed on postoperative day 1. RESULTS: Neither portal vein blood flow (703 +/- 74 ml/min vs 666 +/- 82 ml/min) nor hepatic artery blood flow (322 +/- 43 ml/min vs 209 +/- 59 ml/min) was significantly different between the control and the transplanted groups, respectively. The transplanted group had significantly increased plasma levels of alanine (135 +/- 13 mumol/l vs 382 +/- 72 mumol/l), hydroxyproline (30 +/- 5 mumol/l vs 60 +/- 9 mumol/l), methionine (25 +/- 2 mumol/l vs 55 +/- 10 mumol/l), ornithine (36 +/- 5 mumol/l vs 141 +/- 33 mumol/l), phenylalanine (84 +/- 5 mumol/l vs 120 +/- 12 mumol/l), threonine (75 +/- 9 mumol/l vs 159 +/- 27 mumol/l), and tryptophan (17 +/- 2 mumol/l vs 31 +/- 4 mumol/l). The transplanted group also had significantly decreased plasma levels of isoleucine (122 +/- 12 mumol/l vs 85 +/- 8 mumol/l) and taurine (71 +/- 7 mumol/l vs 35 +/- 7 mumol/l). These individual amino acid changes were not accompanied by impairment in the net hepatic amino acid balance or the hepatic fractional extraction of amino acids between the two groups. CONCLUSION: These results suggest that the circumstances associated with liver transplantation alter the fasting amino acid profile immediately postoperatively. However, liver transplantation does not impair the normal hepatic allograft uptake of most plasma amino acids. Thus, the changes observed in the circulating levels of amino acids may represent alterations in nonhepatic production and/or utilization. Furthermore, altered plasma amino acid profiles following liver transplantation are not necessarily indicative of impaired hepatic allograft amino acid metabolism.

Amino Acids↗

PubMed1998

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.

Animals↗

PubMed1992

Protective effect of vasodilators in donors requiring pressor support.

Renal dose dopamine given to organ donors improves renal blood flow and therefore should theoretically improve the quality of the renal grafts and increase the incidence of immediate graft function (IGF). Allografts which function immediately have a better long-term survival. Dopamine, in doses of less than 4 microg/kg per min, acts directly on receptors in blood vessel walls in the splanchnic bed causing vasodilation. In contrast, dopamine given at doses of greater than 4 microg/kg per min to hypotensive donors to elevate the systemic blood pressure has a direct adrenergic effect and causes vasoconstriction. This vasoconstriction when combined with the reperfusion injury which occurs after transplantation may jeopardize the chance of the graft functioning immediately. We studied 31 consecutive donors to see if those donors requiring pressor support (dopamine) to maintain systemic blood pressure had a lower incidence of IGF and whether this could be modified by giving the donor vasodilator drugs during procurement of the organs.

Blood Pressure↗

PubMed1995

Opportunistic upper gastrointestinal infection in transplant recipients.

Opportunistic infection of the upper gastrointestinal tract by cytomegalovirus (CMV) or invasive fungal infection was studied in 219 consecutive kidney and kidney/pancreas transplant recipients with regard to incidence, presentation, and clinical outcome. Prompt upper endoscopy was done in all patients with these symptoms: dyspepsia, dysphagia, or bleeding. Multiple biopsies were obtained for fungal culture, CMV culture, CMV assay, and histologic examination for fungal invasion. Between April 1991 and July 1993, 57/219 (26%) transplant patients developed upper gastrointestinal symptoms. At endoscopy, gross mucosal abnormality was evident in 48/57 (84%). Opportunistic infection was found in 21/48 (44%); however, CMV infection was also detected in 2/9 (22%) who had a normal study. Overall, CMV was present in 15/57 (26%) and invasive fungal infection in 8/57 (14%). All 23 infections were successfully eradicated. Opportunistic infection occurred in 12/31 (39%) with dyspepsia, 9/14 (64%) with dysphagia, and 2/12 (17%) with bleeding. Graft loss occurred in 5/23 (22%) with opportunistic infection vs 23/196 (12%) other recipients. Upper gastrointestinal symptoms are indicative of serious opportunistic infection in a significant number of transplant recipients. As opportunistic infection may jeopardize allograft function, all patients with upper gastrointestinal tract symptoms require prompt endoscopy and biopsy to effect appropriate therapy. Random biopsy is also recommended in the face of a normal endoscopic examination.

Adult↗

PubMed1993

Renal allograft artery stenosis: results of medical treatment and intervention. A retrospective analysis.

In a retrospective analysis of 1165 renal transplantations in our center, 65 cases of renal allograft artery stenosis were diagnosed angiographically (prevalence 5.5%). Hypertension was present in all cases; a bruit over the allograft and an increase in serum creatinine level were additional reasons for angiography. Shortly after diagnosis of the stenosis, two patients died and two others lost their grafts due to thrombosis. In 24 patients the decision was made not to correct the stenosis. One of these grafts was lost because the stenosis could not be corrected. Medical management of hypertension in these patients resulted in a decrease in diastolic blood pressure from 109 +/- 22 to 96 +/- 12 mm Hg (P < 0.01) 3 months after diagnosis with the use of almost twice as many antihypertensive drugs as at the time of diagnosis (P < 0.01). The stenosis was corrected if the angiography showed it to be so severe that it jeopardized renal allograft function or caused uncontrollable hypertension. Only three of nine percutaneous transluminal angioplasty (PTA) procedures resulted in a definitive correction of the stenosis. Surgical intervention was performed in 30 patients, including two patients whose PTAs had proved unsuccessful. Surgery led to graft loss due to thrombosis in 6 of 30 operations (20%), whereas restenosis occurred twice (7%). In three other cases (10%), the correction was not successful due to local anatomical variations or concomitant rejection.(ABSTRACT TRUNCATED AT 250 WORDS)

Angioplasty, Balloon↗

PubMed1992

Pretransplant assessment of human liver grafts by plasma lecithin: cholesterol acyltransferase (LCAT) activity in multiple organ donors.

In spite of the improved outcome of orthotopic liver transplantation (OLTx), primary graft nonfunction remains one of the life-threatening problems following OLTx. The purpose of this study was to evaluate plasma lecithin: cholesterol acyltransferase (LCAT) activity in multiple organ donors as a predictor of liver allograft viability prior to OLTx. Thirty-nine donors were studied during a 5-month period between April and August 1988. Allograft hepatectomy was performed using a rapid technique or its minor modification with hilar dissections, and the allografts were stored cold (4 degrees C) in University of Wisconsin (UW) solution. Early post-transplant allograft function was classified as good, fair, or poor, according to the highest SGOT, SGPT, and prothrombin time within 5 days following OLTx. Procurement records were reviewed to identify donor data, which included conventional liver function tests, duration of hospital stay, history of cardiac arrest, and graft ischemic time. Blood samples from the donors were drawn immediately prior to aortic crossclamp, and from these plasma LCAT activity was determined. Plasma LCAT activity of all donors was significantly lower than that of healthy controls (12.4 +/- 8.0 vs 39.2 +/- 13.3 micrograms/ml per hour, P less than 0.01). LCAT activity (16.4 +/- 8.3 micrograms/ml per hour) in donors of grafts with good function was significantly higher than that in those with fair (8.6 +/- 4.5 micrograms/ml per hour, P less than 0.01) or poor (7.3 +/- 2.4 micrograms/ml per hour, P less than 0.01) function.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗