To assess the antihypertensive and antiproteinuric efficacy and safety of the angiotensin II type 1 receptor blocker telmisartan in patients with hypertension and chronic kidney disease.
A ...multicenter, prospective trial was performed in adults with hypertension systolic blood pressure (SBP)/diastolic blood pressure (DBP) >130/85 mmHg), chronic renal insufficiency (serum creatinine <4.0 mg/dl), and proteinuria (>1 g/24 h). In addition to existing antihypertensive therapy, the nature and doses of which remained unchanged throughout the study, patients received once-daily telmisartan 40 mg for the first 3 months followed by forced titration to telmisartan 80 mg for the subsequent 3 months to achieve a target SBP/DBP of <130/85 mmHg. The rationale for using telmisartan was its long half-life efficacy, greater antihypertensive effect compared with valsartan or losartan, and newly discovered potential antidiabetic effect.
The study was conducted in 92 patients (45 men, 47 women), of whom 60 had diabetes mellitus (54 patients with type 2 disease). Five patients discontinued prematurely: two because of hyperkalemia, two because of protocol violation, and one because of lack of efficacy. After 6 months' telmisartan treatment, office trough seated SBP was reduced by 19.6 mmHg (P<0.001) from 154.9+/-14.6 mmHg and DBP by 11.8 mmHg (P<0.001) from 91.7+/-8.1 mmHg. Seated trough SBP/DBP of <130/85 mmHg was achieved at 6 months in 34.8% of patients. Ambulatory blood pressure monitoring also demonstrated significant reductions in mean daytime SBP of 10.9 mmHg (P=0.01), night-time SBP of 12.1 mmHg (P=0.05), daytime DBP of 3.1 mmHg (P=0.05), and night-time DBP of 6.5 mmHg (P=0.05). Proteinuria decreased significantly from 3.6+/-3.4 to 2.8+/-2.8 g/24 h (P=0.01). A decrease in proteinuria depended significantly on a decrease in SBP at the end of the study (P=0.044). Each decrease in SBP of about 10 mmHg led to a decrease in proteinuria of about 0.79 g/24 h (95% CI 0.02-1.56 g/24 h). Serum creatinine increased from 1.96+/-0.79 to 2.08+/-0.89 mg/dl (P=0.01), whereas creatinine clearance did not change significantly.
Telmisartan effectively and safely reduced blood pressure and brought about regression of proteinuria in diabetic and nondiabetic, hypertensive, proteinuric patients with chronic kidney disease, even in those with mild-to-moderate chronic renal failure.
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-γ (IFN-γ), tumor necrosis factor alpha (TNF-α), 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-γ 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.
The aim of the study was to assess the contribution of carbonyl and oxidative stresses to the development of amyloidosis in patients suffering from chronic rheumatic diseases, and the potential ...influence of renal function to their concentrations was considered.
We investigated 17 patients with chronic rheumatological diseases and histologically proven diagnosis of AA amyloidosis (group AA-RA), 26 patients suffering from rheumatoid arthritis without any signs of AA amyloidosis (group nonAA-RA) and 20 healthy volunteers (Co). In all patients, advanced glycation end products (AGEs), advanced oxidation protein products (AOPP), pregnancy-associated plasma protein A (PAPP-A) and other selected proinflammatory markers were measured.
An increase in serum levels of AOPP and AGEs was found in the AA-RA group in comparison with nonAA-RA patients and also with Co (p < 0.001 for all comparisons). AGEs positively correlated with serum creatinine (r = 0.67, p = 0.004) and negatively with glomerular filtration rate (r = -0.54, p = 0.027). We did not find a correlation between AOPP and any other assessed parameters including proteins and renal parameters. PAPP-A levels were not significantly increased in any group of patients (AA-RA, nonAA-RA) in comparison with Co.
Increased plasma levels of AGEs and AOPP in the group of patients with AA-RA may have been partly explained by the diminished renal clearance. However, the increase in AOPP levels was higher than what is expected in this degree of renal failure (glomerular filtration rate in the AA-RA group corresponding to chronic kidney disease stage III).
Background Clinical experience with mycophenolate mofetil (MMF) in glomerulonephritis still remains limited. Methods In order to assess the experience of one center with the efficacy and tolerability ...of MMF in patients with glomerulonephritis, we performed a retrospective 6-year analysis of 68 patients treated by MMF for glomerular disease, mainly anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV: n = 34) and systemic lupus erythematosus and lupus nephritis (SLE: n = 24). Indications were maintenance treatment in 40% of patients, induction treatment in patients not tolerating cyclophosphamide in 27%, and disease relapse in 33%. Mean treatment duration was 11.5 months. Results Efficacy endpoints were serum creatinine, urinary protein excretion, and steroid dose. In AAV patients, MMF was associated with significant improvement in 18%, partial improvement in 26%, stabilization in 29%, and disease progression in 12%; adverse event dropouts totalled 15%. In SLE, the respective figures were 30, 22, 9, and 22%, with 17% adverse event dropouts. The most frequent side effects were gastrointestinal events ( n = 7) and infections ( n = 3). None was life-threatening and there were no deaths. Conclusions MMF, in the relatively low doses used, was safe and effective, stabilizing or improving AAV in 73% of patients and SLE in 61%. Further prospective randomized controlled trials with MMF in renal vasculitis and lupus nephritis are clearly warranted.
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.
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.
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.
CsA might be an appropriate and a less toxic alternative drug for LN both as a first-choice and rescue therapy.
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.
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.
The median creatinine level at diagnosis was 221.5 (63-762) micromol/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) micromol/l, i.e. 1.56 (0.87-5.3) mg/dl, 24.6% of patients were on regular dialysis treatment.
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.
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.
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