Aldosterone breakthrough during therapy with angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers in proteinuric patients with immunoglobulin A nephropathy

Published on Oct 1, 2006in Nephrology2.506
· DOI :10.1111/J.1440-1797.2006.00665.X
Yoshio Horita12
Estimated H-index: 12
,
Kouichi Taura6
Estimated H-index: 6
+ 2 AuthorsShigeru Kohno86
Estimated H-index: 86
(Nagasaki University)
Sources
Abstract
SUMMARY: 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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References24
Newest
The renin-angiotensin-aldosterone system (RAAS) blockade is currently the best-documented treatment strategy to delay the progression of chronic nephropathies. Angiotensin-converting enzyme inhibitors (CEIs) or angiotensin II type 1 receptor antagonists (ARBs) should be used in every normotensive and hypertensive patient with chronic proteinuric nephropathy of both diabetic and non-diabetic origin. The therapy should be initiated as early as possible, bearing in mind that the renoprotection is m...
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#1Atsuhisa SatoH-Index: 18
#2Koichi Hayashi (Keio: Keio University)H-Index: 45
Last. Takao Saruta (Keio: Keio University)H-Index: 83
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We have recently shown that mineralocorticoid receptor blockade may represent optimal therapy for patients with early diabetic nephropathy who show aldosterone breakthrough during angiotensin-converting enzyme (ACE) inhibitor treatment, and who no longer show the maximal antiproteinuric effects of ACE inhibition. In this study, we explored the effects of the mineralocorticoid receptor antagonist spironolactone on urinary protein excretion in patients with chronic renal disease with proteinuria p...
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#1Yoshio HoritaH-Index: 12
#2Masato TadokoroH-Index: 8
Last. Shigeru Kohno (Nagasaki University)H-Index: 86
view all 7 authors...
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) ...
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#1K. J. Schjoedt (Steno Diabetes Center)H-Index: 13
#2Steen Andersen (Steno Diabetes Center)H-Index: 21
Last. H. H. Parving (AU: Aarhus University)H-Index: 17
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Aims/hypothesis It has been suggested that aldosterone plays a role in the initiation and progression of renal disease independently of arterial blood pressure and plasma angiotensin II levels. We evaluated the influence of plasma aldosterone levels on progression of diabetic nephropathy during long-term blockade of the renin–angiotensin–aldosterone system.
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#1Dierk EndemannH-Index: 19
#2Konrad WolfH-Index: 21
Last. Bernhard K. KrämerH-Index: 66
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Background: Aldosterone seems to play a role in the development of chronic renal failure and proteinuria. We investigated the adrenal aldosterone production and the adrenal renin-an
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#1Atsuhisa SatoH-Index: 18
#2Koichi HayashiH-Index: 45
Last. Takao SarutaH-Index: 83
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It has been reported that continuous ACE inhibitor therapy does not necessarily produce a maintained decrease in plasma aldosterone levels, which may remain high or increase eventually during long-term use (aldosterone escape). We have examined the role of aldosterone escape in 45 patients with type 2 diabetes and early nephropathy treated with an ACE inhibitor for 40 weeks. With treatment, there was a 40% reduction in average urinary albumin excretion, although urinary albumin excretion in pati...
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#1Mitsuhide NaruseH-Index: 53
#2Akiyo TanabeH-Index: 25
Last. Kazue TakanoH-Index: 38
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Aldosterone breakthrough during ACE inhibitor therapy has been reported. This study investigates changes in plasma aldosterone concentration (PAC) and its mechanism and effects on target organ damage during long-term angiotensin II type 1 (AT1) receptor antagonist (AT1A) therapy in hypertensive rats. An AT1A (candesartan, 1 mg/kg per day PO) was administered in stroke-prone spontaneously hypertensive rats from 4 weeks of age for 34 weeks. PAC was significantly decreased during the first 4 weeks ...
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#1W. H. Wilson Tang (Stanford University)H-Index: 3
#2Randall H. Vagelos (Stanford University)H-Index: 24
Last. Michael B. Fowler (Stanford University)H-Index: 59
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Abstract Objectives We sought to compare the neurohormonal responses and clinical effects of long-term, high-dose versus low-dose enalapril in patients with chronic heart failure (CHF). Background Examination of neurohormonal and clinical responses in patients receiving different doses of angiotensin-converting enzyme (ACE) inhibitors may provide insight into the potential for additional suppression with angiotensin II (AT-II) or aldosterone antagonists. Methods Seventy-five patients with CHF we...
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The prevalence of end-stage renal disease is increasing at an alarming rate. In 2000, chronic kidney failure developed in over 90,000 people in the United States; the current population of patients on dialysis numbers about 300,000, and 80,000 patients are living with transplanted kidneys. Both the prevalence and the incidence of end-stage renal disease are approximately twice what they were 10 years ago.1 Indeed, in 2000, the number of patients with newly diagnosed renal failure exceeded the nu...
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#1Edmond J Lewis (Rush University Medical Center)H-Index: 1
Last. Itamar RazH-Index: 69
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Background It is unknown whether either the angiotensin-II–receptor blocker irbesartan or the calcium-channel blocker amlodipine slows the progression of nephropathy in patients with type 2 diabetes independently of its capacity to lower the systemic blood pressure. Methods We randomly assigned 1715 hypertensive patients with nephropathy due to type 2 diabetes to treatment with irbesartan (300 mg daily), amlodipine (10 mg daily), or placebo. The target blood pressure was 135/85 mm Hg or less in ...
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Cited By61
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#1Zhihao Huo (Southern Medical University)H-Index: 1
#2Huizhen Ye (SYSU: Sun Yat-sen University)H-Index: 2
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Background IgA nephropathy (IgAN) is still one of the most prevalent forms of primary glomerulonephritis globally. However, no guidelines have clearly indicated which kinds of renin angiotensin system blockade therapies (ACEIs or ARBs or their combination) in patients with IgAN result in a greater reduction in proteinuria and a better preservation of kidney function. Thus, we conducted a Bayesian network analysis to evaluate the relative effects of these three therapy regimens in patients with I...
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#1Srinivas Shenoy (Manipal University)H-Index: 2
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The therapeutic options for preventing or slowing the progression of chronic kidney disease (CKD) have been thus far limited. While angiotensin converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARBs) are, without a doubt, safe and effective drugs, a significant proportion of patients with CKD still progress to end-stage kidney disease. After decades of negative trials, nephrologists have finally found cause for optimism with the introduction of sodium-glucose cotransporter-2...
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#8Yu Zhang (Peking Union Medical College)H-Index: 5
Background: The purpose of this meta-analysis was to evaluate the controversy of angiotensin-converting enzyme inhibitor (ACEI) in combination with angiotensin-receptor blocker (ARB) in the treatment of chronic kidney disease (CKD) based on dose. Methods: PubMed, EMBASE, and Cochrane Library were searched to identify randomized controlled trials (RCTs) from inception to March 2020. The random effects model was used to calculate the effect sizes. Potential sources of heterogeneity were detected u...
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#2Heng Fan (UNNC: The University of Nottingham Ningbo China)H-Index: 6
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Background: Angiotensin converting enzyme inhibitor (ACEI) and angiotensin receptor blocker (ARB) as the commonly used renin-angiotensin aldosterone system inhibitor are widely used in patients with IgA nephropathy (IgAN), but the effect is controversy. In this study, we used a meta-analysis to evaluate the efficacy and safety of ACEI and/or ARB for the patients with IgAN.
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Resistant hypertension is associated with a poor prognosis due to organ damage caused by prolonged suboptimal blood pressure control. The concomitant use of mineralocorticoid receptor (MR) antagonists with other antihypertensives has been shown to improve blood pressure control in some patients with resistant hypertension, and such patients are considered to have MR-associated hypertension. MR-associated hypertension is classified into two subtypes: one with a high plasma aldosterone level, whic...
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#1Marisa K. Ames (CSU: Colorado State University)H-Index: 9
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