Effect of Treatment on Body Fluid in Patients with Unilateral Aldosterone Producing Adenoma: Adrenalectomy versus Spironolactone

Che-Hsiung Wu, Ya-Wen Yang, Szu-Chun Hung, Yao-Chou Tsai, Ya-Hui Hu, Yen-Hung Lin, Tzong-Shinn Chu, Kwan-Dun Wu, Vin-Cent Wu, Che-Hsiung Wu, Ya-Wen Yang, Szu-Chun Hung, Yao-Chou Tsai, Ya-Hui Hu, Yen-Hung Lin, Tzong-Shinn Chu, Kwan-Dun Wu, Vin-Cent Wu

Abstract

Aldosterone affects fluid retention in the body by affecting how much salt and water that the kidney retains or excretes. There is limited information about the effect of prolonged aldosterone excess and treatment on body fluid in primary aldosteronism (PA) patients. In this study, body composition changes of 41 PA patients with unilateral aldosterone producing adenoma (APA) were assessed by a bio-impedance spectroscopy device. Patients with APA receiving adrenalectomy, as compared with those treated with spironolactone, had significantly lower relative overhydration (OH) and urine albumin excretion, and significantly higher urine sodium excretion four weeks after treatment. These differences dissipated 12 weeks after the initial treatment. Independent factors to predict decreased relative OH four weeks after treatment were male patients and patients who experienced adrenalectomy. Patients who underwent adrenaelctomy had significantly decreased TNF-α and increased serum potassium level when compared to patients treated with spironolactone 4 and 12 weeks after treatment. In this pilot study, we found that adrenalectomy leads to an earlier increase in renal sodium excretion and decreases in body fluid content, TNF-α, and urine albumin excretion. Adrenalectomy yields a therapeutic effect more rapidly, which has been shown to ameliorate overhydration in PA patients.

Trial registration: ClinicalTrials.gov NCT00746070.

Figures

Figure 1. Trial profile.
Figure 1. Trial profile.
*Abbreviations: APA, aldosterone producing adenoma.
Figure 2. Factors associated with relative overhydration…
Figure 2. Factors associated with relative overhydration (OH) at baseline.
Univariate analysis of correlations of baseline relative OH with the (a) cystatin C, (b) ln urine albumin-to-creatinine ratio (ACR)(a) cystatin C vs. relative OH at baseline r = 0.456, p = 0.005. (b) ln urine albumin-to–creatinine ratio (ACR) vs. relative OH at baseline r = 0.336, p = 0.042.
Figure 3. Generalized estimating equations to examine…
Figure 3. Generalized estimating equations to examine the effect of different treatment strategies on various time-sequential variables.
Panels a-c: BCM parameters; Panels d-g: hormones and biomarkers; and Panels h-n: renal parameters. (a) The Relative overhydration (Rel. OH) between group, p = 0.062. Changes in time period contributed to changes in Rel. OH after 4 weeks (p = 0.011). Rel. OH was significantly different at 12 weeks (p = 0.008). (b) The Relative fat (Rel. Fat) between group, p = 0.034. Changes in time period contributed to changes in Rel. Fat after 4 weeks (p = 0.0105). (c) The Relative lean tissue mass (Rel. LTM) between group, p = 0.73. (d) The plasma aldosterone concentration (PAC) between group, p = 0.1942. PAC was significantly different at 4 weeks (p = 0.0034) and 12 weeks (p = 0.001). (e) The N-terminal pro-brain natriuretic peptide (NT-proBNP) between group, p = 0.448. (f) The C-reactive protein (CRP) between groups, p = 0.89. (g) The Tumor necrosis factor-alpha (TNF-α) between groups, p < 0.001. Changes in time period contributed to changes in TNF-α after 4 weeks (p < 0.001). TNF-α was significantly different at 12 weeks (p < 0.001). Changes in time period contributed to changes in TNF-α after 12 weeks (p < 0.001). (h) The serum creatinine (Cr) between groups, p = 0.46. (i)The cystatin C between groups, p = 0.570. (j) The urine albumin-to-creatinine ratio (ACR) between groups, p = 0.607. Changes in time period contributed to changes in ACR after 4 weeks (p = 0.003). (k) The serum sodium (Na) between groups, p = 0.49. (l) The serum potassium (K) between groups, p < 0.001. Changes in time period contributed to changes in K after 4 weeks (p < 0.001). Changes in time period contributed to changes in K after 12 weeks (p < 0.001). (m) The urine sodium (UNa) between groups, p = 0.26674. Changes in time period contributed to changes in UNa after 4 weeks (p < 0.001). (n) The mean arterial blood pressure (MAP) between groups, p = 0.7761. MAP was significantly different at 4 weeks (p = 0.003) and 12 weeks (p < 0.001).

References

    1. Young W. F. Jr. Minireview: primary aldosteronism–changing concepts in diagnosis and treatment. Endocrinology 144, 2208–2213 (2003).
    1. Nomura K. et al. Plasma aldosterone response to upright posture and angiotensin II infusion in aldosterone-producing adenoma. J Clin Endocrinol Metab 75, 323–327 (1992).
    1. Milliez P. et al. Evidence for an increased rate of cardiovascular events in patients with primary aldosteronism. J Am Coll Cardiol 45, 1243–1248 (2005).
    1. Group T. S. et al. Association of kidney function with residual hypertension after treatment of aldosterone-producing adenoma. Am J Kidney Dis 54, 665–673 (2009).
    1. Fardella C. E., Mosso L. M. & Carvajal C. A. [Primary aldosteronism]. Rev Med Chil 136, 905–914 (2008).
    1. Ichikawa S. et al. Effect of spironolactone on fluid volumes and adrenal steroids in primary aldosteronism. Jpn Circ J 48, 1184–1196 (1984).
    1. Agarwal R., Andersen M. J. & Pratt J. H. On the importance of pedal edema in hemodialysis patients. Clin J Am Soc Nephrol 3, 153–158 (2008).
    1. Matthie J. R. Bioimpedance measurements of human body composition: critical analysis and outlook. Expert Rev Med Devices 5, 239–261 (2008).
    1. Jaffrin M. Y. & Morel H. Body fluid volumes measurements by impedance: A review of bioimpedance spectroscopy (BIS) and bioimpedance analysis (BIA) methods. Med Eng Phys 30, 1257–1269 (2008).
    1. Moissl U. M. et al. Body fluid volume determination via body composition spectroscopy in health and disease. Physiol Meas 27, 921–933 (2006).
    1. Wabel P., Chamney P., Moissl U. & Jirka T. Importance of whole-body bioimpedance spectroscopy for the management of fluid balance. Blood Purif 27, 75–80 (2009).
    1. Wu K. D. et al. Preoperative diagnosis and localization of aldosterone-producing adenoma by adrenal venous sampling after administration of metoclopramide. J Formos Med Assoc 100, 598–603 (2001).
    1. Chamney P. W. et al. A whole-body model to distinguish excess fluid from the hydration of major body tissues. Am J Clin Nutr 85, 80–89 (2007).
    1. Wieskotten S. et al. Bioimpedance-based identification of malnutrition using fuzzy logic. Physiol Meas 29, 639–654 (2008).
    1. Zeger S. L. & Liang K. Y. Longitudinal data analysis for discrete and continuous outcomes. Biometrics 42, 121–130 (1986).
    1. Ma Y., Mazumdar M. & Memtsoudis S. G. Beyond repeated-measures analysis of variance: advanced statistical methods for the analysis of longitudinal data in anesthesia research. Reg Anesth Pain Med 37, 99–105 (2012).
    1. Wu V. C. et al. Effect of diuretic use on 30-day postdialysis mortality in critically ill patients receiving acute dialysis. PLoS One 7, e30836 (2012).
    1. Catena C. et al. Cardiovascular outcomes in patients with primary aldosteronism after treatment. Arch Intern Med 168, 80–85 (2008).
    1. Sechi L. A., Colussi G., Di Fabio A. & Catena C. Cardiovascular and renal damage in primary aldosteronism: outcomes after treatment. Am J Hypertens 23, 1253–1260 (2010).
    1. Wu V. C. et al. Primary aldosteronism: changes in cystatin C-based kidney filtration, proteinuria, and renal duplex indices with treatment. J Hypertens 29, 1778–1786 (2011).
    1. Strauch B. et al. Adrenalectomy improves arterial stiffness in primary aldosteronism. Am J Hypertens 21, 1086–1092 (2008).
    1. Mulatero P. et al. Roles of clinical criteria, computed tomography scan, and adrenal vein sampling in differential diagnosis of primary aldosteronism subtypes. J Clin Endocrinol Metab 93, 1366–1371 (2008).
    1. Catena C. et al. Long-term cardiac effects of adrenalectomy or mineralocorticoid antagonists in patients with primary aldosteronism. Hypertension 50, 911–918 (2007).
    1. Reincke M. et al. Observational study mortality in treated primary aldosteronism: the German Conn’s registry. Hypertension 60, 618–624 (2012).
    1. Catena C. et al. Mineralocorticoid antagonists treatment versus surgery in primary aldosteronism. Horm Metab Res 42, 440–445 (2010).
    1. Rossi G. P. et al. Long-term control of arterial hypertension and regression of left ventricular hypertrophy with treatment of primary aldosteronism. Hypertension 62, 62–69 (2013).
    1. Miyake Y. et al. Prognosis of primary aldosteronism in Japan: results from a nationwide epidemiological study. Endocr J 61, 35–40 (2014).
    1. Mulatero P. et al. Long-term cardio- and cerebrovascular events in patients with primary aldosteronism. J Clin Endocrinol Metab 98, 4826–4833 (2013).
    1. Stehr C. B. et al. Increased levels of oxidative stress, subclinical inflammation, and myocardial fibrosis markers in primary aldosteronism patients. J Hypertens 28, 2120–2126 (2010).
    1. Vogt B. & Burnier M. Aldosterone and cardiovascular risk. Curr Hypertens Rep 11, 450–455 (2009).
    1. Kapadia S. R. et al. Hemodynamic regulation of tumor necrosis factor-alpha gene and protein expression in adult feline myocardium. Circ Res 81, 187–195 (1997).
    1. Vega A., Quiroga B., Abad S., Ruiz C. & Lopez-Gomez J. M. Study on overhydration in dialysis patients and its association with inflammation. Nefrologia 34, 579–583 (2014).
    1. O’Lone E. L., Visser A., Finney H. & Fan S. L. Clinical significance of multi-frequency bioimpedance spectroscopy in peritoneal dialysis patients: independent predictor of patient survival. Nephrol Dial Transplant 29, 1430–1437 (2014).
    1. Feldman A. M. et al. The role of tumor necrosis factor in the pathophysiology of heart failure. J Am Coll Cardiol 35, 537–544 (2000).
    1. Torre-Amione G. et al. Proinflammatory cytokine levels in patients with depressed left ventricular ejection fraction: a report from the Studies of Left Ventricular Dysfunction (SOLVD). J Am Coll Cardiol 27, 1201–1206 (1996).
    1. Wu V. C. et al. Kidney impairment in primary aldosteronism. Clin Chim Acta 412, 1319–1325 (2011).
    1. Sechi L. A. et al. Long-term renal outcomes in patients with primary aldosteronism. JAMA 295, 2638–2645 (2006).
    1. Nishimura M. et al. Cardiovascular complications in patients with primary aldosteronism. Am J Kidney Dis 33, 261–266 (1999).
    1. Reincke M. et al. Risk factors associated with a low glomerular filtration rate in primary aldosteronism. J Clin Endocrinol Metab 94, 869–875 (2009).
    1. Danforth D. N. Jr., Orlando M. M., Bartter F. C. & Javadpour N. Renal changes in primary aldosteronism. J Urol 117, 140–144 (1977).

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