Background: We previously reported that idiopathic membranous nephropathy (IMN) strongly correlated with HLA-DRB1*1501-DRB5*0101-DQAI*0102-DQB1* 0602, a specific haplotype of human major histocompatibility complex (MHC), in Japanese patients. To investigate the role of MHC in the development of rat Heymann nephritis (HN), an animal model of membranous nephropathy, a monoclonal antibody (mAb) specific to rat MHC class II antigen (RT1B) was administered, and its effectiveness in inhibiting HN was assessed. Methods: Active HN was induced in HN-sensitive Lewis rats by administering brush border proteins of rat proximal uriniferous tubules (FX1A). Rats were divided into four groups: rats treated with 1,000 µg anti-rat MHC class II mAb, rats treated with 100 µg anti-rat MHC class II mAb, rats treated with murine myeloma IgG, and rats that did not receive either FX1A or any other mAb. We examined the differences in 24-hour urinary protein excretion and serum alloantibody titers against FX1A between groups at different time intervals, and the histologic features of kidneys at the end of the study. Results: HN was induced in Lewis rats by inoculation with FX1A antigen. Administration of anti-MHC class II mAb successfully lowered urinary proteins, production of anti-FX1A alloantibodies, and the development of glomerular lesions in a dose-dependent manner. Conclusion: The present results demonstrated that the MHC class II molecule itself is directly involved in the pathogenesis of HN, and suggest that this therapy would be any better (or less toxic) than nonselective immunosuppressants in the treatment of IMN.
BackgroundIt is controversial whether a single-pill fixed-dose combination of angiotensin II type 1 receptor blocker and calcium channel blocker (CCB) is effective for all types of hypertension.MethodsThirty-five patients with uncontrolled blood pressure (BP) under treatment with valsartan 80 mg/day or amlodipine 5 mg/day were enrolled. They were randomly divided into two treatment groups: a single-pill fixed-dose combination of valsartan 80 mg/day and amlodipine 5 mg/day in the morning (VA group), or valsartan 80 mg/day in the morning and nifedipine CR 20 mg/day at night (VN group), and treated for 16 weeks. If the patient did not reach the target office BP at 8 weeks, they received double doses of CCBs.ResultsIn the VN group, morning diastolic BP was significantly lower than the respective values in the VA group at 8 weeks. The percentage of patients who required a double dose of CCB in the VN group was significantly lower than that in the VA group. At 16 weeks, the BP levels in both groups were significantly reduced. Urinary albumin/creatinine at 16 weeks was significantly less than that at 0 weeks in the VN group.ConclusionCombination therapy with valsartan and nifedipine CR may help to control morning BP and protect the kidneys.
Background: Cardiovascular morphological changes are often conspicuous in autopsy examination of chronic hemodialysis (HD) patients. On the other hand, the fluctuation pattern in blood pressure (BP) during HD treatment varies from one patient to another. Cardiovascular changes may correlate with clinical findings including BP fluctuation patterns during HD, although no autopsy studies have previously examined this issue. Methods: In this study, 53 autopsies of patients who had been on chronic HD were reviewed. We determined the relationship between BP fluctuation during HD treatment along with stable and cardiovascular morphology, including heart weight, ventricular wall thickness, circumferences of the valves and the severity of aortic arteriosclerosis and coronary stenosis. Patients were divided into 4 groups according to the pattern of BP fluctuation during HD treatment at about 6 months before death: group 1 (n = 13), symptomatic hypotension and/or decline pattern during HD; group 2 (n = 11), continuously high BP during HD treatment; group 3 (n = 17), continuous normal BP during HD treatment, and group 4 (n = 12), continuously low BP without symptomatic hypotension during HD treatment. Results: Heart weight and ventricular wall thickness were greatest in group 2. The scores for aortic arteriosclerosis in groups 1 and 2 were higher than in groups 3 and 4. The coronary stenosis index was significantly higher in group 1 than in the other groups, and that in group 2 was higher than in group 4. Multiple regression analysis showed that age, HD duration and pulse pressure were independent variables for the score of arteriosclerosis, and the decline pattern of BP fluctuation during HD and pulse pressure were independent variables for coronary stenosis index. Conclusions: Our results suggest that certain clinical parameters including BP during HD may reflect cardiovascular morphological changes in stable HD patients, although further examination, such as 24-hour blood pressure measurement is recommended to elucidate the pathophysiology of cardiovascular diseases in HD patients.
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