[Kidney replacement therapy].
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Biomedical subjects
Publications and source records attributed to M Mebel.
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The aim of the present study was to evaluate the influence of a pretreatment of the heart and kidney donor with the photosensitizer 8-methoxypsoralen plus ex vivo longwave ultraviolet irradiation of the graft (PUVA) on survival time and immunogenicity of rat heart and kidney allografts. PUVA pretreatment significantly prolonged the survival of these transplants in allogenic recipients. Furthermore, a synergistic effect with conventional immunosuppression (azathioprine, cyclosporine) was demonstrated. Immunohistological studies using monoclonal antibodies showed a significant reduction of MHC class II antigen expression in heart cryostat sections after PUVA treatment. In clinical kidney transplantation the number of rejection episodes was significantly lower in the first 3 months in the PUVA-treated patient group.
Extended experimental experience with the efficacy of pretreating the kidney donor and the allograft by means of photochemotherapy (photosensitizer + UVA irradiation = PUVA) was adopted in clinical kidney transplantation. In a preliminary unrandomized study similar patient populations were treated by generally uniform methods. Thirty-three PUVA-pretreated kidneys (group A) were compared with the experience regarding 26 non-pretreated kidney allografts (group B). The number of rejection episodes was significantly lower in the first 3 months in group A (p less than 0.05 vs group B) and fewer grafts failed because of irreversible rejection (2 vs 5). Furthermore, in group A the rate of infectious complications was lower (18% vs 34%). The cumulative allograft survival at 3 months was improved from 65% in group B to 81% in group A and at 12 months from 65% 76%, respectively. These differences were not significant. Therefore, our preliminary clinical experience with a photochemical donor pretreatment is encouraging and further use in a randomized study seems to be necessary.
In a retrospective study of 303 patients with renal cell carcinomas the prognostic influence of the percutaneous transvasal embolization of the renal artery was demonstrated. In form of the life-table-method we compared statistically the survival rates of preoperatively or palliatively embolized patients with such ones who were only nephrectomized or treated only symptomatically. In the tumour stages T2 and T3 the preoperative percutaneous transvasal embolization leads to a clearly higher survival rate; in stage T2 statistically significant. After palliative embolization the improvement of the prognosis is evident compared with the inoperable patients who were treated only symptomatically. The prognosis after palliative preoperative percutaneous transvasal embolization and retarded nephrectomy is not worse than after preoperative percutaneous transvasal embolization and immediate nephrectomy. The effect of the preoperative and palliative embolization improving the prognosis should incite all partners who up to now objected to this therapeutic method to reconsider their therapy concept.
Pretreatment of the kidney donor with 8-methoxy-psoralen (8-MOP) and direct longwave ultraviolet (UVA) irradiation of the kidney graft (PUVA therapy) significantly prolonged survival in allogeneic recipients. 40% of the recipients survived more than 100 days with normal transplant function. The addition of standard clinical immunosuppressive agents azathioprine and prednisolone (both at dosages of 15 mg/kg body weight/day for 21 days) to the PUVA therapy further improved graft survival rate, with a recipient survival rate of 62.5%. The two drugs alone were less effective in prolonging graft survival rate (28.5%). A synergistic effect of PUVA therapy and standard immunosuppressive treatment with azathioprine and prednisolone was demonstrated. This suggested a possible clinical application of this type of immunosuppression and immunoregulation.
Pretreatment of the kidney donor with 8-methoxypsoralen (8-MOP) and ex vivo longwave ultraviolet irradiation (UVA) of the kidney prolonged the subsequent survival on allogeneic recipients. The efficacy of this treatment seems to be dependent on the time and dose of UVA irradiation rather than on the dose of 8-MOP. In conclusion, PUVA treatment is effective in reducing the immunogenicity of the rat kidney allograft, although the mechanism remains unclear. These experimental findings are new and preliminary results in clinical human kidney transplantation are favourable.
To prevent the complications of ureteral and parenchymal ischemia it is important to revascularize all accessory and main branches of the renal arteries in kidney transplantation. 11 allografts underwent ex vivo microsurgical repair of injured polar arteries prior to allotransplantation, and 1 patient had an in situ repair. Three extracorporeal reconstructive techniques are used that are applicable to most of the vascular injuries presented by multiple renal arteries. These are simple and effective methods that avoid subjecting the allograft to prolonged warm ischemia. There were no operative complications, and only one late arterial stenosis occurred; five transplants currently are functioning. The 1-year graft survival in this group, which is 50%, does not differ significantly from those of all transplants (58%). As a result of our policy, 10.5% more allografts were utilized.
It is reported on early and late complications on the efferent urinary system by 667 transplantations of allogenic kidneys of corpses. The complication rate runs to 6.3%. Indication and performance of reconstructive surgical interventions are descended to in detail.
By own experiences on 336 children, 212 of whom were operated on, and a critical review of the relevant literature, the indication to the antireflux plastic in childhood is derived. It is tried to establish certain principles which shall facilitate the treatment. It is referred to the extraordinarily complex character of the diagnosis and the individual techniques are valuated.
50 patients were serially monitored for C-reactive protein (CRP) in serum after kidney transplantation. Compared with a control group the post-operative peak at days 1 and 3 was strongly depressed in the immunosuppressive-treated transplant group (p less than 0.01). In 29 out of 30 patients CRP concentration showed an average rise from 9.4 to 30.0 micrograms/ml between the 5th and 2nd day before onset of the rejection episodes (p less than 0.01). The dynamics of CRP concentration before, during and after prednisolone anti-rejection bolus therapy was considered in 22 cases. The first bolus led to a greater or smaller decrease in CRP concentration in almost all patients. After the second bolus treatment CRP dropped to zero already in more than half of the patients with reversible rejection episodes (p less than 0.01). In case of irreversible rejection crises CRP never reached zero.
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The long-term course before, during and after successful pregnancy in six women 3 to 6 years after receiving CD-kidney transplants from dead donors is described. Multiple risk factors such as hypertension, considerable proteinuria, preceding rejection crises etc. have been taken into account. The analysis includes the observation of a pregnancy which began already in the 1st month after transplantation. With the exception of a patient with hydronephrosis, whose functional data remained normal, the transplants of all patients showed better functional data after delivery than before pregnancy (maximum period of observation: 5 years 3 months post delivery). The patients mainly received alternating prednisolone therapy. Immunosuppression was generally reduced in the second trimester and was temporarily increased above the maintenance dosage after delivery. All children were eutrophic at birth and developed normally without complications. Important factors leading to the good overall clinical result were intensive out-patient care and the cooperation between nephrologists, urologists, gynecologists and neonatalogists. Despite our very good experience with 6 pregnancies successfully carried to full term by women with kidney transplants, the risk for mother and child should only cautiously be estimated, taking into account the results of future larger studies.
In a retrospective analysis of survival after 587 kidney transplants from dead donors performed in one centre, the influence of incompatibilities in the HLA-A-B system and the influence of the sex of the donor were analysed. The survival curves for 0, 1, 2, 3 and 4 incompatible antigens of the A and B loci showed no significant differences from the 1st to the 4th years after transplantation. The best survival rate was found among 212 men with kidneys from male donors, despite other disadvantageous factors in this group, whereas 155 women with kidneys from male donors (with a histoincompatibility of the H-Y antigen) had statistically significant low survival rates between 10.1 and 21% (p less than 0.001 - less than 0.003). The survival rates of kidneys from female donors showed no significant differences between men and women (p less than 0.05). The findings indicate that the incompatibility of the histoincompatibility antigen Y can be important for the results of clinical kidney transplantation.
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Osteonecrosis is a frequently disabling complication of renal transplantation. Thirty-one of 244 patients (12.7%), who received cadaver renal transplants from 1968 to 1978 developed an osteonecrosis. An analysis of 14 possible risk factors suggested that only the following were significantly more frequent in the osteonecrosis group: greater than 3 pulse doses of 1.2 g prednisolone, serum creatinine greater than 133 mumol/L, steroid-induced diabetes mellitus and second and subsequent transplantation. An important decline in the incidence of osteonecrosis (26.7 per cent to 6.5 per cent) was seen with prophylactic vitamin D2 treatment and the onset of osteonecrosis was on average one year later. Dangerous side effects of the large doses of vitamin D2 were minimal. Hypercalcaemia due to overdosage with vitamin D2 during simultaneous prednisolone therapy was usually mild and returned to normal in a few days by dose reduction.
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Following a firm diagnostic and therapeutic schedule for patients with prostatic carcinoma. 89Strontium therapy was introduced for multiple metastases. Positive skeletal scintigraphy with 99mTc-EHDP induced check for affinity to Sr using 85Sr scintigraphy. Of 80 patients, multiple metastases were found in 26. Therapy with 1 mCi of 89Sr-chloride was started in 20 cases. In 8 patients, relief from severe pain appeared shortly afterward, and a further 8 it was possible to prevent the development of pain. Moderate success in 3 cases and a failure to provide relief in 1 were observed.
The effect of prednisone therapy on renal hemodynamics was studied in normal, autotransplanted as well as homotransplanted dog kidneys. After intravenous administration of prednisone (8 and 16 mg/kg/min) the total blood flow decreased and vascular resistance increased significantly. This effect was more pronounced if the drug was directly injected into the arteria renalis. The same changes were observed in autotransplanted and homotransplanted kidneys and in kidneys in rejection. Our results suggest that high dosage of prednisone decreases the renal blood flow and this adverse effect has to be considered in the therapy. The administration of the drug directly into the arteria renalis may have to be avoided.