NDT Advance Access originally published online on April 3, 2007
Nephrology Dialysis Transplantation 2007 22(6):1787-1788; doi:10.1093/ndt/gfm123
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Association of low-grade urinary albumin excretion with left ventricular hypertrophy in the general population: a reply
Email: abomback{at}unch.unc.eduSir,
In their study of the relationship between urine albumin-to-creatinine ratio (UACR) and left ventricular hypertrophy (LVH) in the general population, Dr Lieb and colleagues [1] showed that the prevalence of LVH rose significantly with levels of urinary albumin excretion. While an observational study can only show association and not causation, the authors suggested that elevations in blood pressure may be the pathophysiological link between UACR and LVH.
We believe that the interaction of aldosterone and salt is another, equally plausible, ‘missing link’ in the physiology connecting albuminuria and LVH. Aldosterone plays an essential role in salt and water balance, by acting on epithelial mineralocorticoid receptors. Yet, aldosterone's effects via mineralocorticoid receptors in non-epithelial tissues may play a more important role in the pathogenesis of chronic heart and kidney disease than its classical, epithelial effects. In animal models, administration of aldosterone with excess salt produces cardiac fibrosis and hypertrophy, independent of blood pressure, reflecting a direct effect of aldosterone on the heart [2,3]. Similarly, unopposed aldosterone in the presence of high salt intake causes increased glomerulosclerosis and severe proteinuria via non-epithelial, pro-fibrotic effects on the kidney [4–6].
These fibrotic effects of aldosterone physiologically explain recent clinical trials in which mineralocorticoid receptor blockers, such as eplerenone and spironolactone, have emerged as effective therapy for chronic heart and kidney disease [7–11]. These effects also may explain the important results of Dr Lieb and colleagues’ study, if albuminuria and LVH are truly linked by a common intermediary mechanism: mineralocorticoid receptor activation in the presence of high sodium cofactor.
Conflicts of interest statement. None declared.
Department of Medicine,
Division of Nephrology
and Hypertension,
University of North Carolina
School of Medicine, Chapel Hill, NC
References
- Lieb W, Mayer B, Stritzke J, et al. Association of low-grade urinary albumin excretion with left ventricular hypertrophy in the general population: the MONICA/KORA Augsburg Echocardiographic Substudy. Nephrol Dial Transplant (2006) 21:2780–7.
[Abstract/Free Full Text] - Fullerton MJ, Funder JW. Aldosterone and cardiac fibrosis: in vitro studies. Cardiovasc Res (1994) 28:1863–1867.
[Abstract/Free Full Text] - Rocha R, Stier CT Jr, Kifor I, et al. Aldosterone: a mediator of myocardial necrosis and renal arteriopathy. Endocrinology (2000) 141:3871–3878.
[Abstract/Free Full Text] - Greene EL, Kren S, Hostetter TH. Role of aldosterone in the remnant kidney model in the rat. J Clin Invest (1996) 98:1063–1068.[Web of Science][Medline]
- Rocha R, Chander PN, Zuckerman A, Stier CT Jr. Role of aldosterone in renal vascular injury in stroke-prone hypertensive rats. Hypertension (1999) 33:232–237.
[Abstract/Free Full Text] - Hollenberg NK. Aldosterone in the development and progression of renal injury. Kidney Int (2004) 66:1–9.[CrossRef][Web of Science][Medline]
- Pitt B, Zannad F, Remme WJ, et al. The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators. N Engl J Med (1999) 341:709–717.
[Abstract/Free Full Text] - Pitt B, Remme W, Zannad F, et al. Eplerenone, a selective aldosterone blocker, in patients with left ventricular dysfunction after myocardial infarction. N Engl J Med (2003) 348:1309–1321.
[Abstract/Free Full Text] - Epstein M, Williams GH, Weinberger M, et al. Selective aldosterone blockade with eplerenone reduces proteinuria in patients with type 2 diabetes. Clin J Am Soc Nephrol (2006) 1:940–951.[CrossRef][Medline]
- Chrysostomou A, Pedagogos E, MacGregor A, Becker GJ. Double-blind, placebo-controlled study on the effect of aldosterone receptor antagonist spironolactone in patients who have persistent proteinuria and are on long-term angiotensin-converting enzyme inhibitor therapy, with or without an angiotensin II receptor blocker. Clin J Am Soc Nephrol (2006) 1:256–262.[CrossRef][Medline]
- Schjoedt KJ, Rossing K, Juhl TR, et al. Beneficial impact of spironolactone on nephrotic range albuminuria in diabetic nephropathy. Kidney Int (2006) 70:536–542.[Web of Science][Medline]
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