Eva Jancova

Long-Term Outcome of Patients with Antineutrophil Cytoplasmic Autoantibody-Associated Vasculitis with Renal Involvement

Background: Despite treatment, renal involvement in antineutrophil cytoplasmic autoantibody (ANCA)-positive vasculitis is still associated with significant long-term mortality and remains an important cause of end-stage renal failure. Methods: We retrospectively analyzed a series of 61 consecutive patients with newly diagnosed ANCA-associated renal vasculitis (54.1% Wegener’s granulomatosis, 23% renal-limited vasculitis, 16.4% microscopic polyangiitis, 4.9% Churg-Strauss syndrome) diagnosed between 1986 and 1997. Results: The median creatinine level at diagnosis was 221.5 (63–762) µmol/l, i.e. 2.5 (0.7–8.6) mg/dl, 32.8% were dialysis-dependent. All patients were treated with cyclophosphamide. Remission was achieved in 87% of patients. Relapses occurred in 44.7%. The median renal disease-free interval was 62.5 (0–138) months. The estimated patient survival at 5 and 10 years was 78.3 and 62.2%, respectively. Mortality was associated with age (p = 0.04 when age limit 50 years) and advanced renal failure (p = 0.038 when compared dialysis-dependent and independent patients). Estimated renal survival time at 5 and 10 years was 69.2 and 55.8%, respectively. At the end of follow-up, 50.8% of patients were in complete remission, 31% had died. The median serum creatinine level was 137.5 (77–469) µmol/l, i.e. 1.56 (0.87–5.3) mg/dl, 24.6% of patients were on regular dialysis treatment. Conclusion: Patient survival, relapse rate and mortality were comparable to similar reports. In view of the severity of the renal disease and the length of follow-up, renal survival was very good. Despite effective treatment, the long-term outcome of patients with ANCA-associated renal vasculitis remains unsatisfactory.

Silica and Asbestos Exposure in ANCA-Associated Vasculitis with Pulmonary Involvement

Silica and asbestos exposure are thought to belong to the triggering factors of antineutrophil cytoplasm antibodies (ANCA)-associated vasculitis. We carried out a study to find out whether patients with pulmonary involvement attributable to ANCA-associated vasculitis (AAV) have been exposed to silicon-containing materials. Thirty-one patients (12 women, 19 men, median age 51 years) were interviewed using a structured questionnaire. Occupational exposure to silicon-containing chemicals was reported by 22.6% of the patients (12.9% to SiO2, 9.7% to asbestos), compared with 0% of control subjects (p < 0.05). Our findings support the pathophysiologic role of silica in AAV.

Treatment of lupus nephritis with cyclosporine - an outcome analysis.

Background: The optimal therapy for lupus nephritis (LN), including the role of cyclosporine (CsA), still lacks scientifically valid clinical experience. We evaluated the efficacy of CsA in the induction and maintenance treatment of patients with biopsy-proven LN. Patients and Methods: A total of 31 patients (25 women, 6 men, mean age 29.5 years) were enrolled in the study. The majority had proliferative LN. The mean follow-up was 85.6 ± 24.7 months. Results: CsA was used as first-line treatment in 38.7% of patients and as second-line treatment in 61.3% of patients. Complete remission was achieved in 93.5% of patients. The relapse rate was 45.2%. The mean disease-free interval was 33 months. At the end of follow-up, a total of 67.9% of the patients were in remission. The treatment led to significant improvement in proteinuria (p = 0.001) and stabilization of renal function. Conclusion: CsA might be an appropriate and a less toxic alternative drug for LN both as a first-choice and rescue therapy.

Secondary membranous nephropathy--one center experience.

Introduction. Secondary membranous nephropathy (MN) is most commonly seen in the setting of autoimmune disease, infection, and neoplasia, and with certain therapeutic agents. The aim of our study was to analyze the presenting features and outcome of the patients with secondary MN. Patients and Methods. We retrospectively studied patients with secondary MN diagnosed between the years 1991–2002. In this period, we performed a total of 1874 renal biopsies. MN was diagnosed in 129 cases. Results. In 40 patients (31%), an underlying primary cause was verified (70% women, 30% men, median age 49.5 years). In 18 patients (45%), the disease was drug induced, 11 patients (27.5%) had autoimmune disease, seven patients (17.5%) solid tumors, three patients (7.5%) hepatitis B, and one patient was diagnosed with both hepatitis B and prostate carcinoma. At presentation, median proteinuria was 4.09 g/24 h; 60% were nephrotic. Most of the patients had normal renal function with a median serum creatinine 79 µmol/L and a median GFR 1.285 ml/s. The patients were treated according to the underlying disease. At the end of the follow-up, the patients with drug-induced MN were in complete remission after the discontinuation of the drug. The patients with autoimmune disease were treated with immunosuppression, most of them with very good results. The outcome of the patients with neoplasia was much worse. Conclusion. A thorough and repeated exclusion of secondary forms of MN has significant prognostic and therapeutic implications, especially in drug-induced and autoimmune MN.

Intracellular cytokine production in ANCA-associated vasculitis: low levels of interleukin-10 in remission are associated with a higher relapse rate in the long-term follow-up.

BACKGROUND AND AIMS Dysregulation of cell-mediated immune response likely plays a role in the pathogenesis of anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (AAV), but it has not yet been fully established. The aim of this study was to assess the intracellular cytokine production in patients with AAV at different stages of the disease, in particular, in relation to the long-term prognosis. METHODS We included 69 patients with AAV and 24 healthy controls. Using flow cytometry, the following intracellular cytokines (IC) were measured in all patients: interferon-gamma (IFN-gamma), tumor necrosis factor alpha (TNF-alpha), interleukin-2 and interleukin-4 in CD3+T cells and interleukin-10 (IL-10) and interleukin 12 (IL-12) in monocytes. Patients were then prospectively followed for a median of 43 months and cytokine production was related to the long-term prognosis. RESULTS When compared to healthy controls, increased IL-12 production was observed in AAV patients, both active (p<0.01) and in remission (p<0.05). In remission, increased IFN-gamma production was also found (p<0.01). IL-10 production was higher in active patients than in patients in remission (p<0.05) but did not differ from controls. Patients in remission who developed a relapse during follow-up had significantly lower IL-10 production than those without relapse (p<0.01). Results of this prospective study of IC production in AAV confirm findings of previous studies measuring circulating cytokine levels. CONCLUSIONS Activation of the immune system in AAV patients is noticeable even in remission. Patients with AAV display increased IL-12 production, which seems to be counterbalanced by IL-10. Low IL-10 levels in remission are associated with a higher relapse rate in the long-term follow-up.

Prevalence and Risk of Hypertension in Renal Disease – Data from the Czech Registry of Renal Biopsies

Background/Aims: We intended to compare the risk and prevalence of hypertension in patients undergoing renal biopsy with those of the general population and to investigate the possible effects of various independent factors (age, sex and degree of renal insufficiency) on the prevalence of hypertension. Methods: Data obtained within the Czech Registry of Renal Biopsies over an 8-year period (1995–2002) were statistically evaluated and compared with those of the general population obtained within the Post-MONICA Study conducted in 2000/2001. Results:Hypertension was present in 1,839 out of a total of 3,601 renal patients (51.1%). The risk of hypertension in the patients with renal disease was increased in all age groups compared with the general population (OR = 1.3–5.3). The prevalence of hypertension increased significantly with age, serum creatinine and proteinuria (p < 0.001). Male sex was identified as an independent risk factor for the presence of hypertension (p < 0.01). Sex, age and glomerular filtration rate were shown to be more important determinants of the risk of hypertension than the underlying biopsy-proven diagnosis itself. Conclusion: Hypertension occurs as a common complication of renal disease, even in its early stages, and irrespective of the histological finding.

IgA Nephropathy in Czech Patients - Are We Able Reliably Predict the Outcome?

Background/Aims: The aim of our study was to retrospectively analyse data of 520 Czech patients with IgA nephropathy (IgAN) and to specify the risk factors affecting renal survival of IgAN patients. Methods: Cox proportional hazards regression model was used to evaluate the effects of different variables on renal survival during a median follow up of six years. McNemar´s test was used to analyse the progression of renal function according to Bartosik´s formula. Results: In our retrospective analysis of 520 Czech IgAN patients Cox proportional hazards regression model with five variables [hypertension, sex, GFR, proteinuria, age] was used. Significant regression coefficient was found for GFR, hypertension and proteinuria. Using stepwise algorithm GFR (OR = 3.09), hypertension (OR = 2.09) and proteinuria (OR = 1.97) were found as the most important factors for renal survival in our group of IgAN patients. Among patients with CKD 3 we found significantly better renal survival in patients with proteinuria < 1g/day compared to patients with higher proteinuria. We did not find the significant difference between predicted progression of renal function due to Bartosik´s formula and real progression of renal parametres assessed by GFR at the end of the follow up in our group of IgAN patients. Conclusion: Our retrospective study of 520 Czech IgAN patients confirmed GFR, hypertension and proteinuria as the most important factors affecting the prognosis of IgAN patients. We validated Toronto Bartosik´s formula to predict prognosis of IgAN patients.