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Nephrol Dial Transplant (2004) 19: 1332
Nephrol Dial Transplant Vol. 19 No. 5 © ERA-EDTA 2004; all rights reserved
Reply
Sir,I am grateful to the authors of the letter for their praise and laudatory comments regarding my comprehensive review on aldosterone and progressive renal disease.
The authors raise two interesting questions, which are worthy of consideration—i.e. (i) the complexity of the determinants of aldosterone secretion and (ii) whether circulating aldosterone levels constitute an appropriate marker for cardiovascular and renal risk. (i) In 1978 we conducted a study assessing the role of volume per se as the determinant of plasma aldosterone in anephric man [1]. The rationale was that this would provide a ‘unique window’ for assessing the effects of volume, independent of the confounding effects of the renin angiotensin system. This study emphasized the critical importance of avoiding changes in volume during the interdialytic intervals in order to assess the role of volume on aldosterone. Implicit in this is the notion that any determinations of aldosterone in ESRD patients without rigorous maintenance of the constancy of volume during the interdialytic period usually confounds the observed results. (ii) Recent additional considerations regarding our unique new understanding of aldosterone indicates that any simplistic correlation of serum aldosterone levels with target organ dysfunction is overly simplistic. In a recent review [2], I have delineated why circulating aldosterone levels fail to predict either CV and renal risk or the therapeutic benefit of aldosterone receptor blockade. In brief, recent studies indicate that synthesis of aldosterone occurs at extra-adrenal sites, including the endothelium and vascular smooth muscle cells (VSMC), showing direct evidence that vascular cells per se are aldosteronogenic. Duprez et al. [3] proposed that locally produced aldosterone in the vascular endothelial cell may act on the VSMC through binding to the receptor, thereby acting in a paracrine manner. Secondly, the ostensible dissociation cited by the authors of the letter is consistent with the formulation that the determinants of aldosterone effects include both ambient aldosterone levels and aldosterone responsiveness per se. Observations by Horiuchi et al. [4] and Takeda et al. [5] are consistent with an increase in aldosterone responsiveness. Clearly aldosterone response can be readily dissociated from circulating aldosterone levels. Consequently, only utilization of aldosterone receptor antagonists as a pharmacological probe can rigorously unmask the pathogenetic role of aldosterone.
Conflict of interest statement. None declared.
Nephrology Section University of Miami School of Medicine 8 VA Medical Center Miami USA Email: murraye{at}gate.net
References
- Epstein M, Sancho J, Perez G, Haber E, Re R, Loutzenhiser R. Volume as a determinant of plasma aldosterone in anephric man. J Clin Endocrinol Metab 1978; 46: 309–316[Abstract]
- Epstein M. Aldosterone and the hypertensive kidney: its emerging role as a mediator of progressive renal dysfunction: a paradigm shift. J Hypertens 2001; 19: 829–842[CrossRef][ISI][Medline]
- Duprez D, De Buyzere M, Rietzchel ER, Clement DL. Aldosterone and vascular damage. Curr Hypertens Rep 2000; 2: 327–334[Medline]
- Horiuchi M, Nishiyama H, Hama J et al. Characterization of renal aldosterone receptors in genetically hypertensive rats. Am J Physiol 1993; 264: F286–F291
- Takeda Y, Yoneda T, Demura M. Miyamori I, Mabuchi H. Cardiac aldosterone production in genetically hypertensive rats. Hypertension 2000; 36: 495–500
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