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Mineralocorticoid Receptor Blockers and Chronic Kidney Disease

Gaurav Jain, Ruth C. Campbell and David G. Warnock
CJASN October 2009, 4 (10) 1685-1691; DOI: https://doi.org/10.2215/CJN.01340209
Gaurav Jain
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Ruth C. Campbell
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David G. Warnock
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    Figure 1.

    Molecular mechanisms that may link angiotensin receptors, and EGF receptors with mineralocorticoid receptors in renal epithelial cells. Dietary salt excess may also increase of intrarenal angiotensin II and reactive oxygen species (27). Aldo, aldosterone; Ang II, angiotensin II; EGFR, EGF receptor; MMP, matrix metalloproteinase; MR, mineralocorticoid receptor; ROS, reactive oxygen species. (Adapted, with permission from references (17,18)).

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    Table 1.

    Rationales for combined therapy with MRBs and other RAAS inhibitors

    Use of MRBs with ACEIs or ARBS
    1.Aldosterone “escape” or “breakthrough” (6, 8, 46)
    2.Beneficial effects of MRBs can be demonstrated even in the absence of elevated systemic circulating aldosterone levels (42)
    3.Upregulation or activation of mineralocorticoid receptors at the target organ level implies that tissue damage can occur even with normal systemic levels of aldosterone (19, 25, 47)
    4.MRBs, ACEIs, and ARBs reduce oxidative stress and generation of reactive oxygen species (20, 21, 33, 34, 49, 50)
    Use of MRBs with ARBs Rather than ACEIs
    5.The specificity of ARBs may be permissive of beneficial effects of angiotensin II mediated through non-AT-1 receptor pathways; ACEIs reduce angiotensin II generation and would not necessarily favor non-AT-1 receptor effects (48)
    6.There may be beneficial effects of individual ARBs that are not explained by class effects or inhibition of AT-1 receptors (49, 50)
    7.Current cost differential between ARBs and ACEIs does not favor using ARBs alone as a first-line therapy in CKD (51)
    • ACEI, angiotensin-converting enzyme inhibitor; ARBs, angiotensin receptor blockers; AT-1, angiotensin II type-1 receptor; CKD, chronic kidney disease; MRBs, mineralocorticoid receptor blockers; RAAS, renin-angiotensin-aldosterone system.

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    Table 2.

    Suggestions for minimizing and managing serious adverse events in CKD patients treated with MRBs

    1. Unless there is a compelling indication, avoid using MRBs in patients with eGFR <60 ml/min/1.73 m2.

    2. Avoid starting MRB therapy in any patient with baseline serum K+ in excess of 5.0 mEq/L.

    3. MRBs can be used as adjuncts to ACE inhibitors or ARBs in CKD patients with overt proteinuria (>300 mg/d) in whom maximal doses of ACE inhibitors or ARBs have not achieved the target for proteinuria reduction.

    4. MRBs should be started at low doses. Serum K+ should be checked 1 wk after starting or changing the MRB dose, and regularly thereafter.

    5. Dietary prudence with respect to K+ intake and regular bowel habits will help minimize elevations of serum K+. Avoid oral K+ supplements and salt substitutes.

    6. Be cautious using MRBs with more than 1 other inhibitor of the RAAS, with K+-sparing diuretics or with any other agent that suppresses renin secretion or activation (calcineurin inhibitors, non-steroidal anti-inflammatory agents, β-blockers, aliskiren, Vitamin D receptor agonists).

    7. Concomitant use of thiazides or furosemide may help control serum K+ in CKD patients with serum K+ > 4.5 mEq/L.

    8. If serum K+ rises above 5.0 mEq/L, decrease the dose of MRB or ACEI or ARB, modify the dietary K+ intake and check for constipation.

    9. If serum K+ is >5.5 mEq/L, stop the administration of MRBs, ACEIs, and ARBs, and modify dietary K+ intake. Check 24-h urine for K+ and Na+ excretion to confirm dietary patterns and interventions.

    • ACEI, angiotensin-converting enzyme inhibitor; ARB, angiotensin receptor blockers; CKD, chronic kidney disease; eGFR, estimated glomerular filtration rate; MRBs, mineralocorticoid receptor blockers; RAAS, renin-angiotensin-aldosterone system.

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Clinical Journal of the American Society of Nephrology
Vol. 4, Issue 10
1 Oct 2009
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Mineralocorticoid Receptor Blockers and Chronic Kidney Disease
Gaurav Jain, Ruth C. Campbell, David G. Warnock
CJASN Oct 2009, 4 (10) 1685-1691; DOI: 10.2215/CJN.01340209

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Mineralocorticoid Receptor Blockers and Chronic Kidney Disease
Gaurav Jain, Ruth C. Campbell, David G. Warnock
CJASN Oct 2009, 4 (10) 1685-1691; DOI: 10.2215/CJN.01340209
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