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Forty allograft nephrectomies (28 males and 12 females, mean age of 33.2 years), performed between 1986 and 1999, were selected. Twenty patients had been grafted from cadaveric donors; of the remaining cases, 15 had received a kidney from a living related donor. Except for six patients who received steroid-azathioprine immunosuppression, all recipients were treated with cyclosporine A and low doses of steroids. None had primary or acquired hyperoxaluria as the cause of original end-stage renal disease, and none had a history of kidney stones or urinary infection. Kidney failure occurred after a time period ranging from 2 days to 11 years posttransplant and was secondary to acute rejection in 17 cases, chronic rejection in 15, ischemic necrosis in five, acute or chronic pielonephritis in two, and allergic microangiopathy in one. No blood chemistry evaluations for oxalemia were performed. Clinical data are summarized in Table 1. Multiple sections cut from formalin-fixed, paraffin-embedded blocks and stained with haematoxylin-eosin (H&E) were examined using partially crossed polarizing screens. The presence of calcium oxalate crystals in different segments of the nephron or in the interstitium was recorded. Birefringent deposits with characteristic green iridescence, presenting as large plate-like or diamondshaped crystals, or any shape, provided that the crystals displaced tissue structures, were studied. Confirmation of the crystal nature was obtained using Yasue’s method, a histochemical stain considered to be specific for calcium oxalate, while usual stains for calcium (alizarin red and von Kossa’s method) were negative. Silver nitrate–rubeanic acid with 5% acetic acid pretreatment (Yasue’s method) stains only calcium oxalate, since calcium phosphate and calcium carbonate are dissolved with the acetic acid. A thyroid with multiple deposits of calcium oxalate and hydroxyapatite crystals was used as a positive control for the histochemical stains.

Recent evidence indicates that indirect allorecognition plays a key role in initiating and sustaining graft rejection. This self-restricted T cell response is generally limited to a restricted set of dominant immunogenic peptides derived from allogeneic HLA molecules. Here, we have examined whether peptide analogues of the dominant determinant of HLA-DRbeta1*0101 molecule (peptide DR1/22-35), recognized in the context of HLA-DRbeta1*1101 protein, are able to modulate the T cell response against the wild-type peptide Ag. The peptide analogues were generated by introducing single amino acid substitutions at putative MHC and TCR contact positions. Two analogues, 25R/A and 28E/Q, which bound to soluble DR11 protein, but did not stimulate an anti-DR1-specific T cell clone, inhibited the response of the clone to the wild-type peptide by TCR antagonism. Analogs 25R/A and 28E/Q were also able to inhibit the differentiation of Th precursors specific for peptide DR1/22-35. Two other peptides, 26L/I and 27L/V, acted as powerful TCR agonists, inducing a higher proliferative response of the DR1-specific T cell clone, compared with the wild-type peptide. At high concentrations, these peptides induced hyporesponsiveness of TCC-ZL36 in a manner similar to the wild-type peptide. Taken together, the results of this study indicate that specific suppression of indirect allorecognition can be achieved by using structural variants of the dominant allodeterminant.

As reported in the literature, the mortality rates for patients with Acute Hepatic Failure (AHF) approaches 80% in cases in which liver transplantation is not possible. Post-transplant mortality mostly depends on the severity of the neurological condition at the time of the operation (20% in I-II degree coma patients and 44% in III degree coma patients). The primary indications for liver transplantation in AHF are Fulminant Hepatitis (FH)(93%), Subfulminant Hepatitis (5%) and other indications (2%). Other causes of AHF are Primary Non-Function (PNF) and Delayed Function (DF), which occur in 7-10%. Therefore it becomes necessary to monitor the patients with a Liver Support Device to be able to improve the clinical condition of the patients before liver transplantation (LT). In our experience we used the Molecular Adsorbent Recirculating System (MARS) (MARS Monitor; Teraklin AG, Rostock Germany), which enables the selective removal of albumin-bound substances accumulating in liver failure by the use of albumin-enriched dialysate. The system is used as a bridging device to orthotopic liver transplantation (OLT) of patients with FHF. We studied 34 patients, including 16 males and 18 females: 9 were affected by Primary-Non-Function (PNF), nine by Fulminant Hepatitis (FH), six by Delayed-Non-Function (DNF), and ten by Acute on Chronic Hepatic Failure (AOCHF). The average age of the patients was 41.8 years and the average number of applications was 6.4; the median length of application was about eight hours. The parameters that we monitored, before and after each treatment, were neurological status (EEG, cerebral CT, Glasgow Coma Score), haemodynamic parameters, acid base equilibrium, and blood gas analysis. We also monitored hepatic and renal function. In addition, the clinical conditions of the patients were monitored using kidney and liver ultrasound/ultrasonography (US). Inclusion criteria were bilirubin15 mg/dL, ammonia160 micro g/dL and a Glasgow Coma Score between 6 and 11. The reduction of bilirubin and ammonia were very significant (P0.01), whereas the changes of International Normalized Ratio (INR) were not significant. Also the modifications of albumin, total protein, sodium, potassium and calcium were not significant. In conclusion, four out of nine patients with PNF are alive without a second transplantation and were discharged after about 48 days; four out of nine underwent OLT, while one out of nine died; five out of six patients with DF are alive without a second transplantation, and they were discharged after an average time of 55.5 days, one out of six died; six out of nine patients with fulminant hepatitis underwent OLT and four of these are alive, while two died due to sepsis; three patients are alive without OLT. Four patients with AOCHF underwent OLT and are alive, three patients are alive and on a waiting list, two died while on a waiting list and one patient who experienced reactivation of HBV infection during chemotherapy for non-Hodgkin's lymphoma is alive. In spite of the limited number of cases of our study, we believe that MARS can be applied with high tolerance for a very long period of time. In addition, its repeatability allows it to be used in patients with DNF and FH as a bridge to transplant. In patients with DNF, it is used while waiting for complete recovery of the transplanted organ.