Changes in liver graft rejections over time.

Incidence and possible risk factors of acute rejection, time to acute rejection, graft rejection within 3 months, multiple rejections within 1 year, steroid-resistant rejection, and graft lost to chronic rejection or to chronic dysfunction were evaluated in 388 liver transplantations. HLA matches, anti-HLA class I antibodies, positive crossmatch test, or positive cytomegalovirus serology did not have an effect on the occurrence of acute or chronic rejection. Increased total bleeding diminished occurrence of acute rejection, lengthened the time to acute rejection, and reduced the risk of steroid-resistant rejection. Immunological pretransplant factors did not have a major effect on the occurrence of rejection after liver transplantation. Different types of rejections diminished over time and the time period to the first acute rejection increased, although the basic immunosuppression stayed mainly the same over 20 years in our center.

Risk factors predicting survival of liver transplantation.

Prognostic models were developed for analyzing graft survival in a single-center study consisting of all 388 adult liver transplantations performed during 20 years. Proportional hazard models and generalized linear models were used to assess which risk factors, related to donor and recipient characteristics as well as graft preservation and operation, had an effect on graft survival. The prognostic modeling evidenced favorable trends in graft survival time during the successive quinquennials 1982-1987, 1988-1992, and 1993-1997, in comparison to the referent time period 1998-2002. Significant predictors of graft survival time were donor's age, recipient-donor gender compatibility, recipient's blood group, intraoperative blood transfusion, size of the transplanted organ, and indication for transplantation. Conventional histocompatibility matching did not correlate with graft outcome.

Histological alterations in implant and one-year protocol biopsy specimens of renal allografts.

BACKGROUND: The natural course of histological changes and their correlations with clinical parameters have not been studied in large numbers in renal allograft specimens. The aim of this study was to determine whether any histological alterations developed during the first posttransplantation year. Immunological and nonimmunological factors possibly associated with subsequent histopathological changes and development of chronic rejection were also assessed. METHODS: We studied 102 cadaveric kidney allografts for which both implant and 1-year protocol biopsy specimens were available. The chronic allograft damage index (CADI) was used to quantify the extent of histological changes that developed during the first year. RESULTS: Overall, an increase in histological alterations were seen during the first posttransplantation year, and the CADI increased significantly. The mean CADI was 0.7 in relation to implant biopsy samples and 2.9 in relation to 1-year biopsy samples (P<0.05). Although the degree of changes increased during the first posttransplantation year, they were seldom severe. Significant increases in incidences of interstitial inflammation and fibrosis, tubular atrophy, and basement-membrane thickening were seen. Vascular intimal proliferation and glomerular mesangial matrix increase and glomerular sclerosis were also noted. In contrast, anisometric vacuolization in the tubular epithelium decreased significantly in incidence during the first year. CADI values 1 year after transplantation were significantly affected by donor age, occurrence of acute rejection episodes, and prevalence of HLA-DR mismatches. CADIs were also significantly higher in grafts with decreased function. CONCLUSIONS: Histopathological alterations increased in almost every graft, even well-functioning grafts, during the first year. The CADIs relating to alterations seen in cases of chronic rejection increased significantly and were strongly affected by both immunological and nonimmunological factors.

Long-term results of 1047 cadaveric kidney transplantations with special emphasis on initial graft function and rejection.

We studied the effect of initial graft function and acute rejection on graft survival in 1047 cadaveric renal transplantations during 1991-1997 with a constant policy of donor selection, graft allocation, and immunosuppression. The overall 1- and 5-year patient survival rates were 96 % and 88 %, and the 1- and 5-year graft survival (GS) rates were 92 % and 78 %. Delayed graft function (DGF) occurred in 31 % and there were 1.2 % never-functioning grafts. One-year GS in transplantations with early graft function (EGF) was 95 % compared to 87 % in DGF (P < 0.001). Donor age and cause of death, type of graft perfusion and cold ischemia time, and type and length of dialysis treatment were significant factors in determining the onset of graft function. These factors did not have a significant direct effect on GS. Early ( < 100 days) acute rejection occurred in 25 %. In transplantations without rejection, the 1 and 5-year GS was 93.3 % and 80.8 %. In acute rejection responding to steroids, the GS was equal to that up to 3 years, but after that a significantly worse survival rate was observed (1- and 5-year GS: 93.6 % and 73.4 %). DGF was detrimental to GS both in transplantations without rejection and in all rejection types.

Histopathological findings in renal allografts at time of transplantation and correlation with onset of graft function.

Histopathological changes quantified using the chronic allograft damage index (CADI) have been shown to predict subsequent graft outcome and developing chronic rejection. The aim of the study reported here was to investigate the extent to which cadaveric renal allografts exhibit histopathological changes at time of transplantation, focusing on changes covered by the CADI. We also analysed whether any histopathological change predicts delayed graft function. One hundred and twenty-eight cadaveric kidney allografts with adequate protocol biopsy were studied. Tubular epithelial anisometric vacuolization was the commonest change, found in 62% of grafts and scored moderate or severe in 28% of these cases. Other prevalent changes were interstitial fibrosis, vascular hyalinosis, glomerular sclerosis and tubular basement-membrane thickening in 40%, 37%, 28% and 22% of biopsies, respectively. Intensities were, however, scored as mild in over 95% of specimens. The mean CADI for all grafts was 0.74. A significant difference in CADIs was seen between grafts from donors under and over 40 years of age. Grafts with early, delayed and no function had a similar incidence of histopathological changes. Histopathological changes in renal allografts were mostly uncommon and mild at time of transplantation, but some grafts exhibited changes which were quantified using the CADI. Though histopathological changes quantified with the CADI are predictive of subsequent graft function, they did not affect onset of graft function.

Long-term graft outcome is not necessarily affected by delayed onset of graft function and early acute rejection.

BACKGROUND: Both acute rejection episodes and delayed graft function (DGF) have been shown to be associated with decreased 1-year renal allograft survival. In our center, the incidence and the intensity of acute rejection episodes have been reduced by cyclosporine-based triple-drug therapy. We have also shown that DGF alone is not a risk factor for long-term graft survival. METHODS: We have now investigated whether an acute rejection episode together with DGF significantly effects long-term graft outcome. This study involved 862 first cadaveric renal allografts and 182 regrafts. RESULTS: The incidence of DGF was 33% after first transplants and 44% after retransplants. The overall incidence of acute rejection episodes was 23% in first grafts and 28% in regrafts. After first grafts, there were no statistically significant differences in graft survival rates and half-lives between the early graft function (EGF) and DGF groups with or without acute rejection. In regrafts, graft survival was significantly higher in the EGF group without acute rejection than in the DGF group with acute rejection. However, if all other causes except chronic rejection were censored, the half-life in the EGF group without acute rejection was 17.3 years in first grafts, and in the DGF group with acute rejection, that number was 11.5 years in first grafts; for regrafts, the half-life was 12.3 years and 6.1 years, respectively. CONCLUSIONS: Acute rejection together with DGF could contribute to initial damage to the graft, and this might lead to later chronic allograft failure. In our study, this effect was evident only in the case of retransplants.

Spontaneous recovery of post partus liver necrosis in a patient listed for transplantation.

The patient was a young previously healthy woman, who after a normal grosses, during delivery got severe abdominal pain. The liver function tests were highly pathological and the patient became anuric and developed first grade of encephalopathy. In computer tomography, 90% of the liver parenchyma was damaged and liver biopsy showed necrosis. The patient had fulminant hepatic failure including hepatorenal syndrome and was put on the Scandiatransplant high urgent waiting list for a liver transplant. No suitable liver was found. After eight days, the general situation of the patient was better and the liver function tests started to improve. She was taken off the waiting list. Twenty-seven days after delivery the patient was discharged in good condition. At check up six months later the patient was feeling well and the clinical tests were normal.

Long-term consequences of different immunosuppressive regimens for renal allografts.

The long-term effects of four different immunosuppressive regimens on renal allografts have been investigated up to four years. A total of 128 recipients of first cadaveric renal allograft were randomized, after an initial induction period, to receive either triple drug therapy--i.e., (low-dose) cyclosporine, azathioprine, and methylprednisolone, or any possible combination of two drugs--i.e., Aza plus CsA, Aza plus MP, and CsA plus MP. The actual four-year graft survival rates for the triple therapy, Aza plus CsA, Aza plus MP, and CsA plus MP groups were 72%, 69%, 75%, and 59%, and patient survival rates were 78%, 81%, 81%, and 84%, respectively, with no significant differences. The cumulative number of chronic rejections up to 4 years was 0.09, 0.29, 0.25, and 0.34 per patient per group (P = ns), respectively. At 2, 3, and 4 years posttransplantation, the graft function was significantly worse in the Aza plus MP group compared with the triple therapy group (P < .05). Of the 98 patients who did not have type I or II diabetes at the time of transplantation, 17 developed posttransplantation diabetes mellitus or an abnormal glucose tolerance test within 2 years posttransplantation. All these patients had received steroids and none of the patients without steroids had these abnormalities. At two years the mean cholesterol level was highest in the Aza plus MP group, 6.8 mmol/L and lowest in the group receiving triple therapy, 5.8 mmol/L (P = ns). The use of (low-dose) CsA was not associated with lipid abnormalities or with disturbances in glucose metabolism. A protocol graft biopsy was performed at two years on all functioning kidneys, and the histological changes were scored blindly. No CsA-specific changes, except isometric vacuolation in tubuli, were found. Histological alterations characteristic of chronic rejection were expressed as "chronic allograft damage index." Chronic allograft damage index was lowest in the triple therapy group, 1.5, compared with the other groups, 3.2-4.3 (P = .01), indicating the least histopathological change in the triple therapy group. In conclusion, this long-term study did not show any serious cyclosporine-related side-effects when used in low dose in combination with two other drugs. Some side-effects, such as posttransplant diabetes mellitus and probably some lipid abnormalities, could rather be traced to a higher dose of steroids. Moreover, the triple drug therapy was more efficacious than any double drug regimen in the prevention of chronic histological changes in renal allografts.

Acute vascular rejection in renal transplantation--diagnosis and outcome.

Thirty episodes of histologically verified acute vascular rejection in kidney transplant recipients were studied. In 11 grafts the rejection was mainly vascular, whereas in 19 grafts a concomitant cellular rejection was seen. Histological features prognostic for bad outcome were glomerular necrosis and thrombi in the arteries and arterioles. Characteristic findings in transplant cytology, i.e., high number of monocytes and low number of lymphocytes and blast cells were noted prior to the onset of clinical signs of rejection, and this finding was also persisting throughout the rejection episode. The numbers of lymphocytes and blast cells were significantly lower in grafts with a pure vascular rejection than in grafts with a concomitant cellular rejection. Vascular rejection was reversible in 15 cases. As rescue therapy plasmapheresis and added immunosuppression were often successful.

Histopathological findings in well-functioning, long-term renal allografts.

One hundred and twenty-eight patients with a first cadaveric kidney allograft participated in a prospective, randomized, clinical trial comparing triple treatment, consisting of initial low-dose cyclosporine (CsA), azathioprine (Aza) and methylprednisolone (MP), with all possible combinations of two immunosuppressive drugs. A protocol core biopsy was performed on all patients with a functioning graft two years after transplantation. The histological findings were evaluated blindly and correlated to possible risk factors for renal allograft damage. The most common histological features were diffuse fibrosis in 62% of biopsies, tubular atrophy in 64% and diffuse inflammation in 30%. Two other important findings were glomerulosclerosis (43%) and vascular intimal proliferation (36%). The histological findings were scored mostly mild. A total of 77% (69 of 89) of patients had normal or only slightly increased serum creatinine. Decreased graft function was related to increased interstitial fibrosis, inflammation, glomerulosclerosis, mesangial matrix increase of glomeruli, intimal proliferation of vessels and tubular atrophy. These findings are characteristic, but not pathognomonic, of chronic renal allograft rejection both in experimental models and in humans. Possible risk factors were correlated to graft histology. Donor age correlated strongly with mesangial matrix increase, intimal proliferation, and tubular atrophy; there was no correlation with interstitial changes. The number of acute rejections and cold ischaemia time did not correlate with any one of the histological findings at two years following transplantation. Cyclosporine dose and concentration had a negative correlation to interstitial inflammation. A "chronic allograft damage index" was eventually created for the comparison of the four different treatment groups.(ABSTRACT TRUNCATED AT 250 WORDS)