Establishing Reference Ranges for Aldosterone, Renin and Aldosterone-to-Renin Ratio for Women in the Third-Trimester of Pregnancy

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.

Association of Elevated Serum Aldosterone Concentrations in Pregnancy with Hypertension

“…Mean plasma aldosterone concentrations were approximately 20 ng/dL (or converted to 555 pmol/L) in normal, healthy pregnancy at the 12th gestational week, and approximately 45 ng/dL (or converted to 1250 pmol/L) at the 28th gestational week [20]. We report here median and interquartile ranges of aldosterone concentrations in a cohort of 128 high-risk pregnant patients (a considerable sample size, comparatively [44][45][46]) at gestational weeks 12 (387 pmol/L, 204-705 pmol/L) and 28 (724 pmol/L, 376-1197 pmol/L) of pregnancy quantified via LC-MS/MS (the gold standard for determination of aldosterone in clinical assays; aldosterone concentrations derived from immunoassay-based methods are typically higher and more variable that when derived via mass spectrometry-based methods [47]). For reference, aldosterone concentrations outside of pregnancy measured using LC-MS/MS range between 100-300 pmol/L [47], and the median and interquartile range for aldosterone concentrations in 33 non-pregnant patients with confirmed aldosteronism were 392 pmol/L and 331 to 468 pmol/L [26].…”

“…The clinical utility of the aldosterone-to-renin ratio for detection of primary aldosteronism in pregnancy is unclear. First, the timing of determination of aldosterone and renin for detection of aldosteronism matters during pregnancy; there is an upward shift in the aldosterone and renin ranges compared to non-pregnant states [44], which rises over gestation, but the rise in aldosterone concentrations is proportionally greater than the rise in renin activity over the course of pregnancy (reflected in our study by a doubling in the aldosterone-to-angiotensin II ratio from the first to third trimester of pregnancy in the whole cohort). Second, outside of pregnancy, the elevated aldosterone-to-renin ratio in patients with primary aldosteronism results from renin-independent secretion of aldosterone leading to suppression of renin (as part of a regulatory negative feedback loop) [8].…”