Persistent microalbuminuria after treatment with renin-angiotensin axis blockers: causes and results of treatment intensification

Robles, Nicolás Roberto; Velasco, José Antonio Velarde Ruiz; Espinosa, J.; Mena, Candido; Angulo, E.

doi:10.1177/1470320310374215

Cited by 7 publications

(7 citation statements)

References 39 publications

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“…Indeed, ACE inhibitors or ARBs are often the first drugs used for renal protection in chronic kidney disease, but even when these RA system-inhibiting drugs are used, there may be no reduction in albuminuria, or albuminuria may develop during the course of treatment. [26][27][28] It is well known that the renal protective effect of RA system inhibitors is not sustained over the course of chronic treatment.…”

Section: Discussionmentioning

confidence: 99%

Effect of aldosterone breakthrough on albuminuria during treatment with a direct renin inhibitor and combined effect with a mineralocorticoid receptor antagonist

Sato

Fukuda

2013

Hypertens Res

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We have reported observing aldosterone breakthrough in the course of relatively long-term treatment with renin-angiotensin (RA) system inhibitors, where the plasma aldosterone concentration (PAC) increased following an initial decrease. Aldosterone breakthrough has the potential to eliminate the organ-protective effects of RA system inhibitors. We therefore conducted a study in essential hypertensive patients to determine whether aldosterone breakthrough occurred during treatment with the direct renin inhibitor (DRI) aliskiren and to ascertain its clinical significance. The study included 40 essential hypertensive patients (18 men and 22 women) who had been treated for 12 months with aliskiren. Aliskiren significantly decreased blood pressure and plasma renin activity (PRA). The PAC was also decreased significantly at 3 and 6 months; however, the significant difference disappeared after 12 months. Aldosterone breakthrough was observed in 22 of the subjects (55%). Urinary albumin excretion differed depending on whether breakthrough occurred. For the subjects in whom aldosterone breakthrough was observed, eplerenone was added. A significant decrease in urinary albumin excretion was observed after 1 month, independent of changes in blood pressure. In conclusion, this study demonstrated that aldosterone breakthrough occurs in some patients undergoing DRI therapy. Aldosterone breakthrough affects the drug's ability to improve urinary albumin excretion, and combining a mineralocorticoid receptor antagonist with the DRI may be useful for decreasing urinary albumin excretion. When the objective is organ protection in hypertensive patients, a two-pronged approach using combination therapy to inhibit both the RA system and aldosterone may be highly effective.

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Section: Discussionmentioning

confidence: 99%

Effect of aldosterone breakthrough on albuminuria during treatment with a direct renin inhibitor and combined effect with a mineralocorticoid receptor antagonist

Sato

Fukuda

2013

Hypertens Res

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“…Criteria for diagnosis have been published elsewhere [16]. An initial measurement of albumin excretion ratio by stick (MICROALBUSTIX©, Bayer AG, Leverkusen, Germany) was performed and, when it rendered positive, the measurements of UAE was reassured in 24-h urine collections.…”

Section: Methodsmentioning

confidence: 99%

“…In a previous report we have described the possible causes of resistant microalbuminuria and the results of intensive treatment [16]. This report describes the characteristics of patients who became normoalbuminuric compared to those who remained microalbuminuric after modifying treatment.…”

Section: Introductionmentioning

confidence: 98%

Intensive treatment of persistent microalbuminuria: determinants of treatment resistance

Robles

Velasco²,

Mena³

et al. 2013

Open Medicine

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“…[5][6][7] However, even with the administration of RAS inhibitors, failure to achieve adequate anti-albuminuric effects, renoprotective effects and a reduction in cardiovascular events has also been reported. [8][9][10][11][12] To achieve more complete RAS inhibition in patients with type 2 diabetes, concomitant treatment with different types of RAS inhibitors has been promising. However, some clinical studies, including those in Japanese patients, have shown that concomitant treatment with an ACEI and ARB, or also including a direct renin inhibitor, may not provide a clinical synergistic effect in reducing cardiovascular events or preventing a decline in renal function, but conversely, may cause an increase in the incidence of adverse reactions such as hyperkalemia and acute renal insufficiency.…”

Section: Introductionmentioning

confidence: 99%

The necessity and effectiveness of mineralocorticoid receptor antagonist in the treatment of diabetic nephropathy

Sato

2015

Hypertens Res

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Diabetes mellitus is a major cause of chronic kidney disease (CKD), and diabetic nephropathy is the most common primary disease necessitating dialysis treatment in the world including Japan. Major guidelines for treatment of hypertension in Japan, the United States and Europe recommend the use of angiotensin-converting enzyme inhibitors and angiotensin-receptor blockers, which suppress the renin-angiotensin system (RAS), as the antihypertensive drugs of first choice in patients with coexisting diabetes. However, even with the administration of RAS inhibitors, failure to achieve adequate anti-albuminuric, renoprotective effects and a reduction in cardiovascular events has also been reported. Inadequate blockade of aldosterone may be one of the reasons why long-term administration of RAS inhibitors may not be sufficiently effective in patients with diabetic nephropathy. This review focuses on treatment in diabetic nephropathy and discusses the significance of aldosterone blockade. In pre-nephropathy without overt nephropathy, a mineralocorticoid receptor antagonist can be used to enhance the blood pressure-lowering effects of RAS inhibitors, improve insulin resistance and prevent clinical progression of nephropathy. In CKD categories A2 and A3, the addition of a mineralocorticoid receptor antagonist to an RAS inhibitor can help to maintain 'long-term' antiproteinuric and anti-albuminuric effects. However, in category G3a and higher, sufficient attention must be paid to hyperkalemia. Mineralocorticoid receptor antagonists are not currently recommended as standard treatment in diabetic nephropathy. However, many studies have shown promise of better renoprotective effects if mineralocorticoid receptor antagonists are appropriately used.

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Persistent microalbuminuria after treatment with renin-angiotensin axis blockers: causes and results of treatment intensification

Cited by 7 publications

References 39 publications

Effect of aldosterone breakthrough on albuminuria during treatment with a direct renin inhibitor and combined effect with a mineralocorticoid receptor antagonist

Effect of aldosterone breakthrough on albuminuria during treatment with a direct renin inhibitor and combined effect with a mineralocorticoid receptor antagonist

Intensive treatment of persistent microalbuminuria: determinants of treatment resistance

The necessity and effectiveness of mineralocorticoid receptor antagonist in the treatment of diabetic nephropathy

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