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Analysis of the immune status in the recipients with long-term well-functioning kidneys allografts.

The immune status of thirteen living and related kidney transplant recipients with stable allografts were examined. The immunological assays consisted of a mixed lymphocyte reaction (MLR), cell-mediated lympholysis (CML) assay, interleukin-2 (IL-2) production in mixed lymphocytes culture (MLC) and IL-2 receptor (IL-2 R) expression on MLC cells. The suppression rates of the monoclonal antibodies (mAbs) against IL-2 R were tested on MLRs. The stimulation indices (SI) of the MLR against both donor and third-party cells increased compared with those of pretransplantation. The MLC responder cells stimulated by donor cells produced detectable amounts of IL-2, these amounts were lower than those by third-party cells. The MLC cells against donor cells expressed IL-2 R alpha and beta chains to the same degree as those against third-party cells. Anti-IL-2 R mAbs equally inhibited the MLRs between recipient and donor or third-party cells. Cytotoxic T lymphocytes (CTL) against donor cells were not generated, even with the addition of recombinant IL-2 in any of recipients except one, while anti-donor CTL had been detected prior to transplantation and the CTL against third-party cells were induced in posttranspalnt CML assays. These results indicate that the clonal anergy phenomenon might mediate the specific CTL unresponsiveness observed in kidney transplant recipients and the anergy phenomenon might serve in the long-term acceptance of allograft.

Adult↗

[Embolization of non-functioning renal allograft: efficacy and control of systemic inflammation].

BACKGROUND: The graft intolerance syndrome (fever, pain, haematuria) may lead to a chronic inflammatory disease, with cardiovascular repercussion. Nephrectomy is considered the classical treatment of these cases but nowadays renal vascular embolization has been suggested as a possible alternative treatment. The present study concerns seven cases trated with renal vascular embolization in our hospital summarizing data of graft intolerance syndrome and the chronic inflammatory disease. MATERIAL AND METHODS: Between january 2000 and december 2003 seven renal vascular embolization were performed in nonfunctioning renal allograft. The procedure was made with calibrated particles of 300-500micron. Data about complications related to the technique the same as analitic inflammatory parameters before and after treatment (CRP, ferritin, serum albumin, hemoglobin, erythropoietin) were registered. RESULTS: The patients were two men and five women, with median age of 39,7 +/- 8,8 years. The period beween the dialysis and the embolization was of 10,0 +/-8,2 months. Comparing the perion of admission in the hospital due to nephrectomy which was of 17,86+/-4,41 days, the period because of embolization was shorter, being 8,14 +/- 4,53 days. All analitic parameters studied, clearly improved after embolization with decrease of ferritin and CRP, increase of albumin and better hemoglobin level with lower erythropoietin dose. In five of the seven patients there was no renal captation with CT or gammagraphy. Four patients presented a postembolization syndrome, but no other important complication was registered. Neither reembolization nor renal nephrectomy was neccesary in any of the seven cases. CONCLUSION: Percutaneous renal embolization is a simple, easy, safety and effective technique that must be considered as an alternative treatment to nephrectomy, resolving the chronic inflammatory disease secondary to the graft intolerance syndrome.

Adult↗

Pancreas transplantation in streptozotocin-diabetic juvenile pigs. Evaluation of function among duct-ligated, duct-occluded, and nonligated allografts.

This study examined pancreatic allograft function in transplanted diabetic juvenile pigs. The grafts were transplanted with ligated, occluded (Ethibloc) or open ducts. No immunosuppression was used. Irreversible and permanent diabetes was induced by streptozotocin. Graft function was assessed by measuring glucose tolerance and insulin production during an i.v. glucose tolerance test. The fractional growth rate of the transplanted host was used to evaluate the long-term consequence of transplantation. Normal glucose tolerance was achieved in 50%, and a slight impairment in 10% of the animals. In 35%, no detectable graft function was observed. Duct-ligated and Ethibloc-occluded grafts had a significantly lower function rate within the first week compared with grafts with open ducts. The fractional growth rate was significantly decreased in animals receiving grafts with occluded ducts. This was probably not due to different insulin production. No graft failures were observed within the first week in open-duct graft transplantations. Graft failures were associated with elevated serum alpha-amylase and were probably due to vascular impairment. Normal glucose tolerance in transplanted pigs was associated with elevated levels of normal insulin and C-peptide in peripheral blood, concomitant with low levels of proinsulin. Our results show that a pancreatic graft should be transplanted with open ducts. Obstructed ducts lead to an increased frequency of graft failure, while the transplanted hosts with such functioning grafts show retarded growth due to unidentified factors.

Animals↗

Sequential antilymphoblast globulin and cyclosporine for renal transplantation.

The nephrotoxic effects of cyclosporine (CsA) seem to be augmented by co-existing renal injury. A high rate of prolonged delayed function (acute tubular necrosis [ATN]) and non-function (NF) has been associated with the use of CsA prior to and following renal transplantation. Cyclosporine has also been associated with a slower recovery of allograft function and poor baseline renal function even in allografts that function immediately compared with conventionally treated recipients. In 1983 we hypothesized that the rate of ATN and NF following renal transplantation could be decreased and more normal kidney function achieved if renal injury was resolved before adding the nephrotoxic effects of CsA. A group of 300 nonsplenectomized, uremic recipients have received 304 renal transplants and have been initially immunosuppressed with azathioprine, prednisone, and Minnesota antilymphoblast globulin (ALG) prior to starting maintenance CsA and prednisone. The incidence of NF has been 1.9% and the development of ATN has been 7.6% following transplantation with sequential use of ALG and CsA. Other benefits to the renal recipient have also occurred with use of this immunotherapy protocol. Renal allograft survival for recipients of first, second, and third renal allografts has been higher than that generally reported with cyclosporine and prednisone alone. Rejection episodes have been infrequent during the first six months posttransplant, as 75% and 62% of first and second renal allograft recipients have remained rejection-free. Clinically significant infectious complications were infrequent. No cadaver recipient has developed a lymphoma. Moreover, the initial hospitalization following transplantation with sequential ALG/CsA has been short and generally uncomplicated. We conclude that sequential ALG/CsA following renal transplantation provides excellent early posttransplant immunosuppression while avoiding the nephrotoxic effects of CsA and also provides the steroid and infection-sparing benefits derived from maintenance CsA therapy.

Acute Kidney Injury↗

Cold-reactive alloantibodies and allograft malfunction occurring immediately posttransplant.

Certain kidney allografts function promptly, whereas others subjected to similarly optimal procurement and preservation methods do not. Previous reports have indicated that such unexplained allograft malfunction (AM) could be due to the presence of cold-reactive IgM alloantibodies (i.e., lymphocytotoxins and agglutinins) present in renal transplant recipients. These investigations were undertaken to determine whether the presence of such alloantibodies was associated with any histological abnormalities. Pretransplant and 1-hr posttransplant biopsies were analyzed from 49 cadaveric renal allografts that came from ideal donors and were subjected to "optimal" preservation. First, no correlation could be made between AM and the severity of renal tubular cell disruption. However, glomerular lesions in the posttransplant biopsy correlated significantly with the development of AM. Segmental glomerular intracapillary red blood cell aggregates and fibrin deposition were present in 71% of biopsies in the 21 allografts with AM, whereas such lesions were present in 29% of biopsies in the 28 allografts with immediate function (P less than 0.005). Development of glomerular lesions correlated significantly with the presence of cold-reactive lymphocytotoxins (CRL) in the recipient (60% vs. 9%). Sera containing CRL were found to also have IgM antiendothelial cell antibody. These observations suggest that another possible mechanism for lack of prompt allograft function is a self-limiting vascular injury, that occurs in the cold and is immune-mediated.

Antilymphocyte Serum↗

Prospective randomized trial of azathioprine in cryopreserved valved allografts in children.

BACKGROUND: The purpose of this study was to prospectively assess the effects of azathioprine on the humoral immune response to HLA alloantigens and allograft function in children receiving cryopreserved valved allografts. METHODS: We randomized 13 children to receive azathioprine or not to receive azathioprine (controls) after receiving a cryopreserved valved allograft. Azathioprine patients received intraoperatively 4 mg/kg of azathioprine and 2.0 +/- 0.5 mg/kg once daily for 3 months after operation. Panel reactive antibodies against HLA class I and class II alloantigens were measured before, 1 month, and 3 months after operation. RESULTS: Panel reactive antibodies were not significantly different between the azathioprine and control groups before (0.0% +/- 0% versus 1.6% +/- 1%), 1 month (59% +/- 17% versus 71% +/- 12%), or 3 months (84% +/- 15% versus 96% +/- 1.3%) after operation. There were no differences in degree of allograft valve stenosis between azathioprine (31.5 +/- 26 mm Hg, 13.4 +/- 7 months postoperatively) and control groups (25.4 +/- 11 mm Hg, 17.2 +/- 10 months postoperatively) or allograft valve insufficiency. CONCLUSIONS: Azathioprine does not significantly decrease the immune response to HLA alloantigens or affect the function of cryopreserved valved allografts used in children to repair congenital heart defects.

Adolescent↗

Limb-sparing treatment for osteosarcoma in dogs.

Twenty dogs with spontaneously developing osteosarcoma of the extremities were treated with 1 of 3 multimodality limb-sparing procedures. Excision of the tumor was preceded by intra-arterial (IA) administration of cisplatin (cis-diamminedichloroplatinum) alone directed to the affected extremity, irradiation plus IA administration of cisplatin, or irradiation plus IV administration of cisplatin. All dogs were free of apparent metastatic disease at the time of initial treatment. After diagnosis, dogs administered cisplatin IA had selective angiography performed on arteries supplying the tumor, and 70 mg of cisplatin/m2 of body surface was administered over 2 hours. This protocol was repeated 3 weeks later. Dogs that were irradiated received 25 or 40 Gy in 10 fractions over a 22-day period. The first and last radiation doses were immediately preceded by IA administration of cisplatin. Dogs given IV treatment received 10 mg of cisplatin/m2 2 hours before each radiation fraction was administered. Three weeks after the last treatment, tumors were excised and the limb underwent orthopedic reconstruction, generally using cortical allografting and bone plating. Limb function, allograft healing, local tumor control, and metastatic dissemination were monitored. Limb function was good to excellent in 69% (11/16) of dogs evaluated. Forelimb-sparing procedures were generally associated with better function than were limb-sparing procedures performed on hind limbs. Local tumor control was obtained in 79% (11/14) of dogs thoroughly evaluated, with local recurrences in 3 dogs at 3, 4, and 7 months after treatment. Fifteen dogs developed metastatic disease at a median time of 8 months from the time of diagnosis. Mean and median survival times for all dogs, regardless of cause of death, were 11.7 and 8 months, respectively. Tumor necrosis greater than 80% was statistically associated with lack of recurrence. Of 16 dogs, 5 (31%) developed infections at the surgical site. Multimodality limb-sparing treatment is believed to be a viable alternative for appropriately selected dogs with osteosarcoma. The optimal method of treatment prior to or after tumor excision has not yet been established.

Angiography↗