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The critical shortage of cadaver donor organs for renal transplantation has resulted in the increased use of living donors. We reviewed the outcomes of the assessments of potential living kidney donors. One hundred seventeen potential donors evaluated over a 39-month period were included in the study. The work-up of the potential donors consisted of a step-wise progression of clinical, blood, and radiological tests. Of the 117 potential donors, only 20 were ultimately used. Five percent of the donors were found to be unsuitable because of medical problems at the initial visit. A further 25% were blood group incompatible, 13% were excluded following the investigations, 9% had psychosocial problems, and in 4% there were recipient problems. Twenty-two percent of suitable donors were not used either because another live donor was used or because a cadaver donor kidney was available. In conclusion, although the assessment of potential donors requires much time and effort, only a small minority of donors assessed are ultimately used.

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OBJECTIVES: The costs of immunosuppressive drugs in renal transplant recipients remains prohibitively high. Ketoconazole (KZ) has, in limited studies, been shown to significantly reduce the dose of cyclosporin (CyA) after renal transplantation. We report our long-term experience with the use of KZ in a large group of renal transplant recipients. Although this study was not a formal health economic assessment, we undertook a cost-saving analysis of the CyA-KZ combination usage. METHODS: The 170 patients (174 transplants) undergoing renal transplantation between 1991 and 1997 included in the study received CyA (10 mg/kg/day), prednisone (30 mg/day) and azathioprine (100 mg/day) in the immediate perioperative period. At 1 month post-transplantation, KZ (100 mg twice daily) was added and the CyA dose reduced to 25% and the prednisone dose to 50%. The CyA dose was adjusted to maintain trough levels of 150-200 ng/ml. RESULTS: There was an 85% reduction in the dose of CyA. The average costs were 10.61 pounds sterling for CyA alone compared with pound 2.26 (pounds sterling) for the CyA-KZ combination, which represents an average savings of 8.35 pounds sterling (79%) per patient per day. The estimated savings during the study period was 999,930 pounds sterling. The patient and graft survival for patients receiving KZ was similar to patients on the South African Dialysis and Transplant Registry. Graft survival was significantly worse in black patients. CONCLUSION: The use of KZ with CyA in renal transplant recipients with stable allograft function results in a significant reduction in the dose of CyA and a significant cost savings, without compromising patient or graft survival. The regimen may be useful in countries with limited resources.

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Microsporidia are intracellular protozoa that are emerging as significant opportunistic infections in AIDS patients. Although there are numerous published reports of intestinal and disseminated infections in patients with AIDS, there have been only two previous reports in transplantation medicine, both on intestinal microsporidiosis. We report here the first documented case of extra-intestinal microsporidiosis in a transplant recipient. A 39-year-old renal transplant recipient presented with a pyrexia and deteriorating graft function. Light microscopic examination of a renal allograft biopsy revealed numerous microsporidian spores within the renal tubular epithelium. Transmission electron microscopy confirmed the presence of an Encephalitozoon infection and was highly suggestive of Encephalitozoon intestinalis. Therapy with albendazole was extremely effective and resulted in recovery of renal function. Although a rare cause of renal allograft dysfunction, microsporidiosis is curable. It may be underdiagnosed, and should be considered in the differential diagnosis of transplant recipients presenting with opportunistic infections.

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Fine needle aspiration biopsy with cytology provides a useful and easily repeated method of obtaining cell samples from a grafted kidney, enabling a more accurate diagnosis of rejection. The technique is simple to perform and is minimally invasive. It is easily repeated, daily if necessary, to evaluate events within the graft and the response to therapy. In addition to the findings of rejection (high total corrected incremental score and activated lymphocytes), both cyclosporin toxicity and acute tubular necrosis can be diagnosed. In the patient with a non-functioning graft with acute tubular necrosis, repeated fine needle aspiration biopsy may reveal early rejection. In rare cases, unusual graft infections have also been diagnosed by means of fine needle aspiration biopsy.

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In this study, patients with acute tubular necrosis (ATN) after renal transplantation were prospectively randomized to either conventional immunosuppression or withdrawal of cyclosporine and replacement with anti-thymocyte globulin (ATG). The patients treated with cyclosporine withdrawal and ATG had a significantly shorter duration of ATN (8.9 +/- 1.5 vs 10.8 +/- 1.4 days; P < 0.05) and better renal function (mean serum creatinine on day 5 postoperatively: 740 +/- 49 vs 918 +/- 73 micromol/l; P < 0.05). The incidence of acute rejection was lower in the patients with cyclosporine withdrawal and ATG. In conclusion, cyclosporine is toxic to the renal allograft with ATN, and withdrawal of cyclosporine shortens the duration of ATN and improves renal function.

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In this study, we compared the patient and graft survival after renal transplantation in patients followed up in rural centers against those in a major transplant center. There was a greater proportion of patients having a living related donor transplant and having prolonged cold ischemic times in the group followed up in a rural centre. The patient and graft survival at 1, 3 and 5 years were similar for local and rural patients. We conclude that a centralized transplant unit with follow-up of patients in rural centers optimizes the use of highly skilled personnel.

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BACKGROUND: Two major routes by which cytotoxic T lymphocytes induce apoptosis in target cells are the perforin-granzyme and the Fas ligand/Fas pathways. Intragraft expression of message for these immune activation genes has been shown to correlate very closely with clinical rejection. We have immunolabeled fine-needle aspiration biopsy samples using a panel of cytotoxic T-cell activation markers to evaluate the immunocytochemical identification of the protein products of these genes in the verification of human renal allograft rejection. METHODS: In this retrospective pilot study, 140 fine-needle aspiration biopsy samples from 50 human renal allografts were labeled using alkaline phosphatase/ anti-alkaline phosphatase immunocytochemistry incorporating monoclonal antibodies to perforin, granzyme B, and Fas ligand. Levels of positive labeling for these markers were compared with the original clinical diagnosis of rejection. RESULTS: An excellent correlation with clinical rejection was obtained when all three antibodies were positive. The false positive rate for each antibody was sufficient to make any one alone or in combination with one other unreliable for diagnosing rejection. When all three antibodies gave positive labeling, agreement with clinical rejection status was superior to using conventional morphological cytology. CONCLUSIONS: In addition to providing valuable morphological information regarding the composition of inflammatory leukocyte populations and the preservation status of renal parenchymal cells, fine-needle aspiration biopsy samples may be labeled using combined perforin, granzyme B, and Fas ligand immunocytochemistry to offer a safe and reliable method for diagnosing rejection with an excellent level of accuracy.

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This paper compares early graft function (EGF) of the first transplanted kidney (group 1) with the kidney transplanted second (group 2) in kidney pairs from the same cadaver donor. Thirty-one pairs of kidneys were harvested from cadaver donors between January 1997 and October 1998. Each pair was transplanted using a standard technique by the same team of surgeons, one after the other, as a result of limitations in theatre time and staff availability. Incidence of acute rejection (AR), acute tubular necrosis (ATN) and need for post-transplant dialysis was recorded for both groups, and was compared using the relevant statistical methods. Patients in both groups were well matched for age, gender and mode of dialysis pre-transplant. Human leucocyte antigen (HLA) matching and panel reactive antibody (PRA) status were similar in the two groups (p > 0.05). Cold ischaemia time (CIT) in the two groups was 14.1 +/- 5.7 and 19.2 +/- 6.9 h, respectively, the difference being statistically significant (p < 0.05). The incidence of AR was similar in the two groups. However, ATN (on renogram) was significantly more common in group 2 (p < 0.05; 12 patients versus 5 patients in group 1). All patients with ATN required post-transplant dialysis. Hospital stay was significantly prolonged in group 2 patients (p < 05; 20 +/- 10.6 versus 16.3 + 6.2 d for group 1). Even a relatively short increase in CIT can cause the second transplanted kidney of a pair to have a significantly higher incidence of ATN, resulting in need for dialysis and prolongation of hospital stay. Simultaneous transplantation, in areas lacking organ sharing networks, would not only improve EGF, but also improve long term graft survival. In addition, the reduced requirement for post-transplant dialysis and a shorter hospital stay would balance any increased demand on resources.

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Immunosuppressed patients after renal transplantation are at increased risk of developing infective complications, including tuberculosis. We describe four renal transplant patients who presented with tuberculosis isolated to the renal allograft. The three patients with adequate follow-up presented with a febrile illness 12-26 months after the transplant. The mycobacterial infection was found in the graft nephrectomy specimen in three patients. One patient with renal allograft dysfunction had a percutaneous biopsy that showed tuberculosis. The latter patient recovered renal allograft function after anti-tuberculous therapy. None of the patients had evidence of tuberculosis elsewhere. We conclude that tuberculosis isolated to the renal allograft, especially in an endemic area, may be the cause of renal dysfunction, and appropriate therapy could lead to salvage of the graft.

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Mixed lymphocyte reaction (MLR) assays were performed serially over 24 months in 19 first cadaver renal transplant recipients. Immunosuppression consisted of cyclosporine, methylprednisolone and azathioprine. Cyclosporine was withdrawn at 6 months postoperatively. The MLR reactivity gradually decreased over the first 3 months following transplantation. However, there was a significant increase in MLR reactivity at 12 months postoperatively after the cyclosporine withdrawal. This rebound effect in MLR reactivity following cyclosporine withdrawal could account for the increased incidence of acute rejection episodes.

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