Improved clinical outcome of lupus nephritis during the past decade: importance of early diagnosis and treatment.

OBJECTIVE: To evaluate the differences in the outcome of lupus nephritis diagnosed either in the 1980s or the 1990s in Heidelberg, Germany. METHODS: Fifteen patients with biopsy confirmed lupus nephritis (LN) were followed up between 1980 and 1989 and 41 patients were followed up between 1990 and 2000. Their status at diagnosis and their treatment schedules and outcome were analysed. 68% had WHO IV nephritis. RESULTS: In the decade from 1990 to 2000 there was significantly less proteinuria (46 v 17 g/l, p=0.008), significantly lower rates of renal failure (40% v 17%, p=0.02), and fewer histological signs of chronicity (33% v 10%, p=0.01) at the time of diagnosis of LN than in the decade from 1980 to 1989. The mean (SD) time from the first appearance of proteinuria until kidney biopsy was significantly shorter in the later decade (15.4 (15.6) v 3.9 (4.7) months). Although treatment schedules were not significantly different, the outcome of the disease was significantly better in the patients who were diagnosed with LN between 1990 and 2000 (p=0.045). Whereas 6/15 (40%) patients between 1980 and 1989 had terminal renal failure after a mean time of 94 months, in the group of 1990-2000 no patient developed terminal renal failure (median observation time 24 months). In both groups one patient died from infection. A high chronicity index in histology and the presence of arterial hypertension or renal failure, or both, at the time of diagnosis were significant risk factors for the development of terminal renal failure in the course of the disease. CONCLUSIONS: The outcome of patients with newly diagnosed LN was significantly better between 1990 and 2000 than between 1980 and 1989. Kidney damage and chronic histological changes at time of diagnosis were significantly less common between 1990 and 2000, which is attributable to earlier diagnosis and treatment in the later decade.

Loss of CD95 expression is linked to most but not all p53 mutants in European hepatocellular carcinoma.

Experimental data have shown p53-dependent CD95 induction to be associated with increased levels of apoptosis after cytostatic treatment in hepatoma cells. A study of Japanese hepatocellular carcinoma (HCC) has reported an inverse correlation between CD95 and p53 expression. To examine the interaction of p53 and CD95 in tumors we investigated which alterations in p53 can be linked to loss of CD95 expression in European HCC. In 39 tumors we analyzed CD95 by immunohistochemistry and assessed the correlation between the findings of the p53 status as determined by immunohistochemistry and single-strand conformation polymorphism with polymerase chain reaction sequencing. In 10 of 14 tumors with evidence of p53 aberration there was also loss of CD95 expression, compared to 6 of 25 samples with apparent wild-type p53 (P<0.01). Three tumors with p53 mutations but sustained CD95 expression showed single base substitutions mapping to a narrow region of 20 codons in p53. A significant correlation with differentiation status of the tumor was found for the p53 aberration but not for CD95 expression. This is the first study to link loss of CD95 expression to specific p53 alterations in HCC. Functional p53 appears to be a major factor for CD95 expression in hepatocytes, the loss of which could contribute to chemoresistance and possibly immune evasion in hepatocellular carcinoma. Sustained CD95 expression in tumors with certain p53 aberrations may indicate functional heterogeneity of p53 mutants.