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DOI: 10.1055/a-1467-2161
Establishing Reference Ranges for Aldosterone, Renin and Aldosterone-to-Renin Ratio for Women in the Third-Trimester of Pregnancy
Funding This study was financially supported by the statutory funds from the Department of Endocrinology and Metabolic Diseases and the Department of Obstetrics, Perinatology and Gynaecology, Polish Mother’s Memorial Hospital - Research Institute, Lodz, Poland.
Abstract
Objective Diagnosis of primary hyperaldosteronism in pregnancy is complicated due to lack of reference ranges for aldosterone, renin and aldosterone-to-renin ratio. We have endeavoured to establish third-trimester reference ranges for the above-mentioned parameters.
Design & Patients We performed postural tests for aldosterone and renin (chemiluminescence immunoassay Liason® DiaSorin Inc., Italy) in 70 healthy pregnant women (age 30.53±4.51 years), at 32.38±4.25 weeks of gestation and in 22 non-pregnant healthy women (age 33.08±8.72 years).
Results Aldosterone reference ranges were 6.51–73.97 ng/dl and 12.33–86.38 ng/dl, for supine and upright positions, respectively and that for renin were 6.25–59.36 µIU/ml and 11.12–82.55 µIU/ml, respectively. Aldosterone and renin concentrations were higher in an upright position (p=0.000459 and p=0.00011, respectively). In contrast, aldosterone-to-renin ratio was not affected by posture (i. e. 0.497–3.084 ng/dl/µIU/ml versus 0.457–3.06 ng/dl/µIU/ml, p=0.12), but was higher (p=0.00081) than in non-pregnant controls. In comparison to manufacturer-provided non-pregnant reference range, supine aldosterone concentrations increased by 556% (lower cut-off) and 313% (upper cut-off), while upright aldosterone concentrations increased by 558% (lower cut-off) and 244% (upper cut-off). The reference range for supine renin concentrations increased by 223% (lower cut-off) and 48.7% (upper cut-off), while upright renin concentrations increased by 253% (lower cut-off) and 79% (upper cut-off).
Conclusions There is an upward shift in aldosterone and renin reference ranges in the third-trimester of pregnancy accompanied by an increase in an aldosterone-to-renin ratio, that is not influenced by posture. It remains to be established whether the aldosterone-to-renin ratio may be used as a screening tool for primary hyperaldosteronism in pregnancy.
Publication History
Received: 01 February 2021
Received: 26 February 2021
Accepted: 16 March 2021
Article published online:
03 February 2022
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References
- 1 Barton JR, O’Brien JM, Bergauer NK. et al. Mild gestational hypertension remote from term: Progression and outcome. Am J Obstet Gynecol 2001; 184: 979-983 DOI: 10.1067/mob.2001.112905.
- 2 Malha L, August P. Secondary hypertension in pregnancy. Curr Hypertens Rep 2015; 17: 53. DOI: 10.1007/s11906-015-0563-z.
- 3 Conn JW. The evolution of primary aldosteronism from 1954 to 1960. Acta Endocrinol Suppl (Copenh) 1960; 34 (Suppl 50): S65-S71 DOI: 10.1530/acta.0.xxxivs065.
- 4 Kaplan N. The current epidemic of primary aldosteronism: causes and consequences. J Hyperten 2004; 22: 863-869 DOI: 10.1097/00004872-200405000-00001.
- 5 Baudrand R, Guarda FJ, Fardella C. et al. Continuum of renin-independent aldosteronism in normotension. hypertension. Hypertension 2017; 69: 950-956 DOI: 10.1161/HYPERTENSIONAHA.116.08952.
- 6 Hsueh WA, Luetscher JA, Carlson EJ. et al. Changes in active and inactive renin thoughout pregnancy. J Clin Endocrinol Metab 1982; 54: 1010-1016 DOI: 10.1210/jcem-54-5-1010.
- 7 Landau E, Amar L. Primary aldosteronism and pregnancy. Ann Endocrinol (Paris) 2016; 77: 148-160 DOI: 10.1016/j.ando.2016.04.009.
- 8 Corsello SM, Paragliola RM. Evaluation and management of endocrine hypertension during pregnancy. Endocrinol Metab Clin North Am 2019; 48: 829-842 DOI: 10.1016/j.ecl.2019.08.011.
- 9 Kline GA. Primary Aldosteronism: Unnecessary complexity in definition and diagnosis as a barrier to wider clinical care. Clin Endocrinol (Oxf) 2015; 82: 779-784 DOI: 10.1111/cen.12798.
- 10 Reddy S, Jim B. Hypertension and pregnancy: Management and future risks. Adv Chronic Kidney Dis 2019; 26: 137-145 DOI: 10.1053/j.ackd.2019.03.017.
- 11 Hutcheon JA, Lisonkova S, Joseph KS. Epidemiology of pre-eclampsia and the other hypertensive disorders of pregnancy. Best Pract Res Clin Obstet Gynaecol 2011; 25: 391-403 doi: 10.1016/j.bpobgyn.2011.01.006
- 12 WHO. World Health Report 2005: make every mother and child count Geneva, Switzerland: World Health Organization, 2005; Day Adv Neonatal Care. 2005. 5. 124
- 13 Braunthal S, Andrei Brateanu A. Hypertension in pregnancy: Pathophysiology and treatment. SAGE Open Med 2019; 7: 1-15 DOI: 10.1177/2050312119843700.
- 14 Prejbisz A, Dobrowolski P, Kosiński P. et al. Management of hypertension in pregnancy - prevention, diagnosis, treatment and long-term prognosis. A position statement based on expert consensus of the Polish Society of Hypertension, Polish Cardiac Society and Polish Society of Gynecologists and Obstetricians. Arterial Hypertens 2019; 23: 117-182 DOI: 10.5603/AH.a2019.0011.
- 15 Solanki P, Gwini SM, Doery JSG. et al. Age- and sex-specific reference ranges are needed for the aldosterone/renin ratio. Clin Endocrinol (Oxf) 2020; 93: 221-228 DOI: 10.1111/cen.14199.
- 16 Malha L, Chapman AB, August P. Renal physiology and pathophysiology in pregnancy. In: Schrier RW, editor Renal and Electrolyte Disorders. Philadelphia, PA: Lippincott Williams & Wilkins; 2016
- 17 August P, Lenz T, Ales KL. et al. Longitudinal study of the renin-angiotensin-aldosterone system in hypertensive pregnant women: Deviations related to the development of superimposed preeclampsia. Am J Obstet Gynecol 1990; 163: 1612-1621 DOI: 10.1016/0002-9378(90)90639-o.
- 18 Ledoux F, Genest J, Nowaczynski W. et al. Plasma progesterone and aldosterone in pregnancy. Can Med Assoc J 1975; 112: 943-947
- 19 Cugini P, Letizia C, Murano G. et al. Increased serum aldosterone in diabetic pregnancy. Diabetologia 1987; 30: 166-168 DOI: 10.1007/BF00274222.
- 20 Vulkova A, Maleeva A. Secretory levels of plasma cortisol and aldosterone in normal pregnancy. Vutr Boles 1977; 16: 102-105
- 21 Xu Z, Yang J, Hu J. et al. Primary aldosteronism in patients in China with recently detected hypertension. J Am Coll Cardiol 2020; 75: 1913-1922 DOI: 10.1016/j.jacc.2020.02.052.
- 22 Monticone S, Burrello J, Tizzani D. et al. Prevalence and clinical manifestations of primary aldosteronism encountered in primary care practice. J Am Coll Cardiol 2017; 69: 1811-1820 DOI: 10.1016/j.jacc.2017.01.052.
- 23 Brown JM, Siddiqui M, Calhoun DA. et al. The unrecognized prevalence of primary aldosteronism: a cross-sectional study. Ann Intern Med 2020; 173: 10-20 DOI: 10.7326/M20-0065.
- 24 Tsiavos V, Markou A, Papanastasiou L. et al. A new highly sensitive and specific overnight combined screening and diagnostic test for primary aldosteronism. Eur J Endocrinol 2016; 175: 21-28 DOI: 10.1530/EJE-16-0003.
- 25 Markou A, Pappa T, Kaltsas G. et al. Evidence of primary aldosteronism in a predominantly female cohort of normotensive individuals: a very high odds ratio for progression into arterial hypertension. J Clin Endocrinol Metab 2013; 98: 1409-1416 DOI: 10.1210/jc.2012-335.
- 26 Vaidya A, Carey RM. Evolution of the primary aldosteronism syndrome: updating the approach. J Clin Endocrinol Metab 2020; 105: 3771-3783 DOI: 10.1210/clinem/dgaa606.
- 27 Bentley-Lewis R, Graves SW, Seely EW. The renin-aldosterone response to stimulation and suppression during normal pregnancy. Hypertens Pregnancy 2005; 24: 1-16 DOI: 10.1081/PRG-45765.
- 28 Wang K, Hu J, Yang J. et al. Development and validation criteria for sparing confirmatory tests in diagnosing primary aldosteronism. J Clin Endocrinol Metab 2020; 105: 1-8 DOI: 10.1210/clinem/dgaa282.
- 29 Weinberger MH, Kramer NJ, Grim CE. et al. The effect of posture and saline loading on plasma renin activity and aldosterone concentration in pregnant, non-pregnant and estrogen-treated women. J Clin Endocrinol Metab 1977; 44: 69-77 DOI: 10.1210/jcem-44-1-69.
- 30 Affinati AH, Auchus RJ. Endocrine causes of hypertension in pregnancy. Gland Surg 2020; 9: 69-79 DOI: 10.21037/gs.2019.12.04.
- 31 Eguchi K, Hoshide S, Nagashima S. et al. An adverse pregnancy-associated outcome due to overlooked primary aldosteronism. Intern Med 2014; 53: 2499-2504 DOI: 10.2169/internalmedicine.53.2762.
- 32 Okawa T, Asano K, Hashimoto T. et al. Diagnosis and management of primary aldosteronism in pregnancy: case report and review of the literature. Am J Perinatol 2002; 19: 31-36 DOI: 10.1055/s-2002-20170.
- 33 Zelinka T, Petrak O, Rosa J. et al. Primary aldosteronism and pregnancy. Kidney Blood Press Res 2020; 45: 275-285 DOI: 10.1159/000506287.
- 34 GD Searle LLC INSPRA oral tablets, eplerenone oral tablets (2002) https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/021437s013lbl.pdf
- 35 Saito J, Mito A, Yakuwa N. et al. Eplerenone levels in maternal serum, cord blood, and breast milk during pregnancy and lactation. Hypertens Res 2021; DOI: 10.1038/s41440-021-00621-5.. Online ahead of print.
- 36 Riester A, Reincke M. Progress in primary aldosteronism: mineralocorticoid receptor antagonists and management of primary aldosteronism in pregnancy. Eur J Endocrinol 2015; 172: R23-R30
- 37 Ma L, Song Y, Mei M. et al. Age-related cut-offs of plasma aldosterone/renin concentrations for primary aldosteronism screening. Int J Endocrinol 2018; 2018: 8647026 DOI: 10.1155/2018/8647026.