Withdrawal of methylprednisolone at the sixth month in renal transplant recipients treated with cyclosporine.
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Biomedical subjects
Publications and source records attributed to S Sandrini.
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The presence and titres of specific serum IgG and IgM antibodies to cytomegalovirus, herpes simplex virus and varicella-zoster virus were evaluated in 50 haemodialysis patients by complement fixation, immunofluorescence and Elisa tests. A second serum sample was tested in 24 patients after four weeks. Specific serum IgG antibodies to Epstein-Barr virus were also measured by immunofluorescence in 26 patients. By immunofluorescence and Elisa tests, the prevalence of cytomegalovirus, herpes simplex virus and Epstein-Barr virus infection is approximately 100 per cent, and varicella-zoster virus 60 per cent. High titres of IgG specific antibodies found by Elisa tests, detection of IgM antibodies in 16-18 per cent of patients and sero-conversion in 25 per cent of patients, suggests continuous antigenic stimulation.
Total body water (TBW), extracellular water (ECW), exchangeable potassium pool (EKP), and alkali-soluble nitrogen in skeletal muscle tissue (N) were determined in 9 CAPD patients on treatment from 5 to 14 months (mean 8.6 months). The parameters were reevaluated in 6 of these patients 5 to 13 months later (mean 8.6 months). The mean value of TBW was normal and directly correlated to body weight (BW), but TBW was abnormally distributed between extracellular and intracellular space. ECW volume was significantly lower than the predicted value (12.1 +/- 1.4 versus 16.8 +/- 1.9 l) and out of proportion to TBW (34.8 +/- 3.9% versus 47.8 +/- 1.5%). The calculated intracellular water, therefore, appeared clearly hyperexpanded. The mean value of EKP was slightly reduced, but in three patients there was a 25% reduction. N content was low in 5 out of 9 patients. When the parameters were re-evaluated BW and TBW were unchanged in two subjects. A third patient showed a simultaneous increase in both BW (12.7%) and TBW (19%). TBW variations (+19%, -23%, -24%) without changes in BW were seen in three patients. The mean value of EKP was unchanged, but there was a 25% reduction in one patient. N content improved in two and worsened in one of the three patients in whom it was determined. The data suggest that cell overhydration was the distinctive feature in our CAPD patients, and that the evolution of the nutritional status was variable, since the patients could remain stable, gain or loose body fat, and probably change their lean body mass.
Total body water (TBW) and extracellular water (ECW) were determined in 9 CAPD patients on treatment from 5 to 14 months (mean 8.6 months). The mean value of TBW was normal and directly correlated to body weight, but TBW was abnormally distributed between extracellular and intracellular space. ECW volume was significantly lower than the predicted value (12.1 +/- 1.4 l versus 16.8 +/- 1.9 l) and out of proportion to TBW (34.8 +/- 3.9% versus 47.8 +/- 1.5%). The calculated ICW, therefore, appeared clearly hyperexpanded. The data suggest that cell overhydration was the distinctive feature in our CAPD patients.
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In an investigation of the reliability of the measurement of HbA1 by microcolumn chromatography for monitoring glucose metabolism in chronic renal failure, measurements were made in 96 uremic patients. Thirty-one patients were undialyzed, 42 patients including 10 with primary diabetes mellitus were on hemodialysis, and 23 patients were on continuous ambulatory peritoneal dialysis (6 with primary diabetes mellitus). Significantly raised HbA1 values were observed in all groups, whether their glucose tolerance was normal or decreased. Azotemia was not statistically correlated either with HbA1 values, or with glucose tolerance. Dialyzed primary diabetic patients showed HbA1 levels which were significantly higher than those in non-diabetics, but some overlap was evident. The results suggest that the increased values of HbA1 in uremic patients depend on the plasma concentration of either glucose which leads to the formation of glycosylated Hb or of urea which leads to the formation of carbamylated Hb. These are indistinguishable by microcolumn chromatography. Therefore this method cannot be recommended for evaluation of glucose metabolism in uremic patients.
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Histopathological features of transplanted kidneys which gradually lose graft function have been traditionally reported with the term of chronic rejection (CR). In 1997 Banff's classification indicated the adoption of a new term for all these histological features, namely Chronic allograft nephropathy (CAN), recommending that the presence of morphological aspects suggestive of chronic rejection, such as chronic transplant glomerulopathy (CTG) and proliferative endoarteritis (PE), has to be specified. On the basis of these criteria we reviewed the renal biopsies of 92 patients who underwent kidney transplantation from 1999 to 2002. In all cases the biopsy had been performed 6 months after organ transplantation. In 30 of the 92 patients CTG and/or PE was evident supporting a diagnosis of CR; on the contrary, in 11 of the 92 patients the final diagnosis based on histological evidence was that of CAN. Clinical and laboratory tests revealed that the presence of proteinuria in patients with CR at the time of diagnosis was the single statistically significant difference between these two groups. In 7 of the 32 patients where the diagnosis of CR was based on the presence of early features of CTG, the treatment with ACE-I induced complete remission of the proteinuria. Cyclosporine-induced arteriolopathy (CSA) represents an additional histological finding which has been associated with graft loss in the transplanted kidney. The observation of arteriolopathy, similar to CSA in patients who did not receive calcineurine inhibitors, suggests some caution in the use of this diagnostic criteria.
In our experience, cancer is the second cause of death after renal transplantation. In fact, 27% of the deaths we observed at 15-year follow-up were due to neoplasm and 30% to cardiovascular disease. Cancer is a late complication that becomes more common after the fifth year of transplantation. The probability of suffering from cancer is 8.2% and 29.2% at 5 and 15 year, respectively. More specifically, after a 15-year follow-up, the probability rate for skin cancer is 16.4%, solid cancer 12.8%, lymphoproliferative disease (PTLD) 3% and Kaposi's sarcoma 2.2%, respectively. PTLD has the highest mortality rate (44% after 12 months from diagnosis), followed by solid cancer (24%) and Kaposi's sarcoma (8%). According to the literature, patient-age is the main risk factor for neoplasm; double therapy (Cyclosporine + Azathioprine) can increase both the skin cancer and PTLD risk but not the risk of solid cancer. No difference between Cyclosporine and Tacrolimus has been observed in the incidence of neoplasm. Both in vitro and in vivo studies have documented the ability of Rapamycin to inhibit primary and metastatic tumour growth. If these results are also obtained on patients, Rapamycin will be of considerable interest for the future of immunosuppression. In cancer patients, immunosuppression must always be reduced, especially when dealing with PTLD. After standard chemotherapy, patient mortality rate due to infectious complications is very high. Therefore, chemotherapy should be a second-choice therapy and administered in reduced doses. Many studies have documented that lymphocytes B-cells CD20 positive PTLD can be efficiently treated with Retuximab.
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Renal transplantation is an effective therapeutic tool for patients with end-stage renal diseases (ESRDs). Data reported in this article summarize the results obtained from 30 years' activity in the North Italy Transplant program (NITp), the first transplant organization in Italy that implemented a donor procurement and organ transplantation network. In the NITp kidney allocation is governed by a computerized algorithm, NITK3, put in place in 1997, aimed at ensuring equity, transparency and traceability during the stages of the allocation decision-making process. The NITp working group has recognized the NITK3 criteria and they are periodically reviewed following the results of the analysis of patients' transplantation odds. The results obtained with the use of the NITK3 algorithm have been very satisfactory: after 6 yrs, a significantly higher percentage of patients at immunological risk (sensitized or waiting for re-transplant), of patients waiting for >3 yrs and of patients with 0-1 HLA A,B,DR mismatches have been transplanted. Moreover, a higher percentage of kidneys were used locally (in a hospital within the procurement area), and this is known to stimulate donor procurement. Finally, we performed a preliminary statistical analysis of transplants carried out from 1998-2002 in 5/16 centers of the NITp area, demonstrating the quality of the NITp program in terms of patient and graft survival, and that donor and recipient age are the variables significantly impacting on transplant results.
BACKGROUND: It is well known that the human herpes virus 8 (HHV8) is linked to several malignancies such as Kaposi's sarcoma (KS). Moreover, pancytopenia due to hemophagocytic syndrome could be associated with HHV8 infection. In renal transplant recipients affected by KS, the tapering of immunosuppression often leads to KS remission, but also results in graft loss in >50% of cases. Chemotherapy and antiviral therapy have also been used, mainly in the presence of visceral involvement. CASE REPORT: We describe a transplant recipient with widespread cutaneous and visceral KS HHV8 associated, complicated by hemophagocytic syndrome. At transplantation the patient's serology for HHV8 was negative, but thereafter it became positive. The first step in treatment (cyclosporine dose reduction until suspension) failed to improve the clinical course. Therefore, therapy combining liposomal doxorubicin and foscarnet was started. Clearance of HHV8 in the blood and complete resolution of the KS lesions were achieved. Immunosuppression with cyclosporine was resumed. No KS relapse has occurred, blood tests for HHV8 are negative, and graft function is good after a 5-yr follow-up. CONCLUSIONS: Therapy combining liposomal doxorubicin and foscarnet was effective in this renal transplant recipient with KS and HHV8 infection and enabled us to resume immunosuppressive therapy; therefore, reducing the risk of acute/chronic rejection.
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Artery stenosis in the transplanted kidney is the most frequent vascular complication; hypertension onset or worsening may be associated and, at an end stage, also renal insufficiency. The diagnosis must be early and accurate and provide guidelines for medical, interventional or surgical therapy. To assess the diagnostic reliability or MRA, 27 patients were examined. On the basis of clinical, biochemical, pharmacological (Captopril test) and instrumental (color-Doppler US) examinations, the artery of the transplanted kidney was considered normal in 6 patients and stenotic in 21. In the control group, MRA results were in agreement with color-Doppler findings. On the contrary, in 8 of 21 abnormal conditions, the two techniques were in disagreement. Digital angiography, considered as the gold standard, was performed in any questionable case, confirming a slight overestimation of the stenoses by MRA (3 cases) and 2 false positives by color-Doppler US. The authors believe color-Doppler US to be a reliable technique for screening stenosed arteries in the transplanted kidney. MRA is proposed as a complementary investigation useful to define stenosis type and to provide guidelines for treatment.