Changing mizoribine administration from three divided doses to one single dose induced remission of relapsed membranous nephropathy.
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Biomedical subjects
Publications and source records attributed to Yoshio Horita.
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BACKGROUND: Reports indicate that acetazolamide (ACZ) induces the vasodilation of all vessels in animal models, as well as in small and medium kidney vessels in animal models. However, the effect of ACZ on the renal circulation of patients with essential hypertension remains unknown. In this study we examined the effects of a carbonic anhydrase inhibitor, acetazolamide (ACZ), on the renal circulation of patients with essential hypertension. METHODS: We directly infused 1000 mg of ACZ into the main renal arteries of 10 patients with essential hypertension who had undergone cardiac catheterization. We then evaluated the effects of ACZ upon heart rate, renal artery blood pressure (BP), renal artery cross-sectional area, renal Doppler blood flow velocity, renal blood flow (RBF), and renal vascular resistance (RVR). RESULTS: The infusion of ACZ was not associated with any significant changes in heart rate or in systolic or diastolic BP. However, the velocity-time integral was increased by 11.1% +/- 7.2%, from 17.6 +/- 1.8 to 20.0 +/- 3.7 cm (P = .009); RBF was increased by 39% +/- 21%, from 300 +/- 43 to 422 +/- 96 mL/min/m(2) (P = .002); and RVR was reduced by 38% +/- 20% from 24,351 +/- 2,291 to 17,651 +/- 2,731 dynes.sec.cm(-5) (P < .01). In contrast the cross-sectional area of the renal artery did not change. CONCLUSIONS: The results of the present study demonstrated that ACZ has a potent vasodilatory effect on the renal circulation of patients with essential hypertension, leading to an obvious decrease in RVR and an increase in RBF.
BACKGROUND: We are investigating whether aldosterone breakthrough negatively impacts on the antiproteinuric effects of angiotensin-converting enzyme (ACE) inhibitors and/or angiotensin II receptor blockers (ARB). METHODS: We examine the role of aldosterone breakthrough in 43 normotensive, proteinuric (0.7 +/- 0.3 g/day) outpatients (aged 41.5 +/- 10.9 years) with immunoglobulin A nephropathy (IgAN) accompanied by stable renal function (creatinine clearance >50 mL/min). The patients were treated with temocapril (1 mg; n = 14), losartan (12.5 mg; n = 16), or a combination therapy (n = 13) for 12 months. We prospectively evaluated blood pressure (BP), urinary protein excretion (UPE), biochemical parameters and the renin-angiotensin-aldosterone system before and after 12 months of treatment. RESULTS: Although the overall plasma aldosterone concentrations values did not change after any of the treatments administered for 12 months, they eventually increased in 23 (temocapril, seven patients; losartan, eight patients; combination, seven patients) of the 43 patients (53.4%; aldosterone breakthrough), and fell in the remainder (46.6%). Blood pressure and renal function did not differ among the three groups at 12 months. In contrast, UPE was significantly higher in patients with, than without aldosterone breakthrough during temocapril and losartan administration. However, combination therapy induced a more remarkable reduction in UPE regardless of aldosterone breakthrough. CONCLUSIONS: A combination of ACE inhibitors and ARB in normotensive patients with IgAN produces a more profound decrease in proteinuria than either monotherapy. This additive antiproteinuric effect is not dependent on aldosterone breakthrough. Additional larger, prospective, randomized studies will be needed for general acceptance of this strategy.
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We describe a 39-year-old Japanese man with post-streptococcal acute glomerulonephritis (PSAGN) super-imposed on long-term immunoglobulin A nephropathy (IgA-N). The histological findings of the first renal biopsy, done at 21 years of age, revealed mild mesangial proliferative glomerulonephritis with mesangial IgA deposition. Nineteen years later, acute nephritic syndrome with hypocomplementemia and an increasing anti-streptolysin O (ASO) titer developed 2 weeks after the onset of an upper respiratory infection. A second renal biopsy revealed severe segmental endocapillary proliferative and exudative glomerulonephritis, with fibrocellular crescents in about 40% of the glomeruli. Immunofluorescence showed that more C3 than IgA was deposited in the mesangium and that the IgA deposits had decreased. Electron microscopy revealed "hump" electron-dense deposits on the epithelial side of the glomerular basement membrane. These features were consistent with PSAGN superimposed on IgA-N. After 2 weeks of observation, blood pressure, C3 level, and ASO titer had returned to normal, although the persisting nephritic syndrome necessitated steroid therapy. Six months after the onset of the acute nephritic syndrome, the patient remained asymptomatic, except for microhematuria.
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This study investigates the ability of low doses of angiotensin-converting-enzyme inhibitors, in combination with angiotensin II receptor blockers, to exert antiproteinuric effects in normotensive and proteinuric outpatients with immunoglobulin A (IgA) nephropathy confirmed by biopsy. We performed a prospective, randomized, 6-month study of the effects of temocapril 1 mg (n=10), losartan 12.5 mg (n=10), and both (n=11) on mild-to-moderate proteinuria 0.76+/-0.35 g/day (range, 0.4 to 1.6 g/day) and renal function. The study subjects comprised 31 normotensive and proteinuric outpatients with IgA nephropathy accompanied by normal, or mild-to-moderately reduced but stable renal function (glomerular filtration rate>50 ml/min) without steroid or immunosuppressive therapy. We prospectively evaluated blood pressure, proteinuria, renal function and biochemical parameters before and after 6 months of therapy. The combination therapy significantly reduced proteinuria (63.2%) compared with either temocapril or losartan alone (41.3% and 36.6%, respectively, p=0.04 and 0.01, respectively). Blood pressure was most decreased in the group that received combination therapy. The reduced proteinuria did not correlate with reduced systolic or diastolic blood pressure or mean arterial pressure in any of the groups. The glomerular filtration rate fell during the first 3 months of combined therapy, but became reversible after a further 3 months of therapy. The combination significantly decreased angiotensin II (p <0.01), and this decrease was greater than that by either drug alone. In conclusion, the effectiveness of the combined therapy may have been at least partly due to the greater inhibition of the action of angiotensin II in patients with IgA nephropathy. This strategy apparently reduced mild-to-moderate proteinuria in patients with normotensive IgA nephropathy.
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OBJECTIVE: The present study examines whether or not baseline and acetazolamide (ACZ) Tc-99m MAG3 renography can assess renal blood flow reserve. METHODS: Renography proceeded for 50 min after sequential injections of 370 MBq Tc-99m MAG3 for baseline renography and 10 min after a 1,000 mg injection of ACZ for ACZ renography. Effective renal plasma flow of renal cortex (cERPF) in each kidney and the percentage change in cERPF of those parameters (deltaERPF) were obtained before and after the administration of ACZ in 10 subjects without hypertension or diabetes (normal group), in 10 with essential hypertension (hypertensive group) and in 10 who had Type 2 diabetes with hypertension (diabetic group). A placebo test was performed in the 10 without hypertension or diabetes using distilled water instead of ACZ (placebo group). RESULTS: The placebo test performed in the 10 without hypertension or diabetes using distilled water instead of ACZ indicated that the parameter variance between the two types of renogram was below 3.2%. The cERPF of baseline and ACZ Tc-99m MAG3 renography and deltaERPF in the normal, hypertensive and diabetic groups were 89 +/- 10 and 110 +/- 10 ml/min, 89 +/- 14 and 117 +/- 22 ml/min, 100 +/- 23 and 112 +/- 23 ml/min, respectively, and 24.5 +/- 13.5%, 26.0 +/- 9.7% and 12.3 +/- 11.1%, respectively. The difference in the cERPF value was significant in the normal and hypertensive groups whereas this did not change in the diabetic group before or after ACZ administration. CONCLUSIONS: We suggested that the deltaERPF determined by baseline and ACZ Tc-99m MAG3 renography is a useful parameter for assessing renal blood flow reserve.
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AIM: To assess the relation between intima-media thickness (IMT) of the common carotid artery and atherosclerotic renal artery stenosis (ARAS) > or =50% (one or both renal arteries) in type 2 diabetic patients with hypertension. METHODS: We performed a retrospective study of type 2 diabetic patients with hypertension who underwent magnetic resonance angiography or digital subtraction angiography for renal artery stenosis at the National Cardiovascular Center or at the Nagasaki Municipal Medical Center between May 1999 and May 2001. Renal artery stenosis was defined as a narrowing of the artery to at least 50% of normal. Thirty type 2 diabetic patients with hypertension (17 men and 13 women, mean age 65.4 +/- 7.6 years) were identified and divided into two groups: those with ARAS in one or both renal arteries (n = 15) and those without ARAS (n = 15). We used high-resolution B-mode ultrasonography to measure the IMT of the common carotid artery. RESULTS: With and without ARAS were 9 men and 6 women (mean age 65.0 +/- 7.6 years) and 8 men and 7 women (mean age 65.7 +/- 6.8 years), respectively. The IMT of the carotid artery was significantly greater in patients with ARAS than in patients without ARAS (1.07 +/- 0.10 vs. 0.84 +/- 0.12 mm, p < 0.01). However, the only clinical findings that statistically significantly differed were systolic blood pressure and plasma renin activity. CONCLUSION: Our findings suggest that the measurement of the IMT of the carotid artery may be useful as a noninvasive screening method for the defection of ARAS even in asymptomatic type 2 diabetic patients.