Overestimation of Aldosterone by Immunoassay in Renal Impairment

Lam, Leo; Chiu, Weldon; Davidson, James S.

doi:10.1373/clinchem.2016.255737

Cited by 10 publications

(9 citation statements)

References 5 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This also meant we were unable to measure renin in all patients, due to the more specific sample requirements. The previously described correlation between the aldosterone method discrepancy and eGFR ( 16 ) was not demonstrable in this cohort, and marked discordance was also evident in some patients with well-preserved eGFR. This may be due to another mechanism contributing to the excess polar metabolite in this cohort but could also be due to the limited power of the study to detect a renal threshold effect or due to the shortcomings of eGFR as a marker of renal function ( 29 ).…”

Section: Discussioncontrasting

confidence: 63%

“…To the best of our knowledge, all published studies measuring aldosterone in COVID-19 patients have used non-extraction immunoassays. These methods lack specificity and are prone to interference, for example, the polar aldosterone metabolite aldosterone-18-glucuronide has been shown to cross-react in a non-extraction assay commonly used in clinical laboratories ( 15 , 16 ). This is more apparent in patients with renal failure as hydrophilic metabolites accumulate.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Unquantifiably low aldosterone concentrations are prevalent in hospitalised COVID-19 patients but may not be revealed by chemiluminescent immunoassay

Wiegand

Halsall

Cowan

et al. 2022

Endocrine Connections

View full text Add to dashboard Cite

Objective: Previous studies have reported conflicting findings regarding aldosterone levels in patients hospitalised with COVID-19. We therefore used the gold-standard technique of liquid chromatography tandem mass-spectrometry (LCMSMS) to address this uncertainty. Design: All patients admitted to Addenbrooke’s Hospital Cambridge with COVID-19 between March 10, 2020 and May 13, 2021, and in whom a stored blood sample was available for analysis, were eligible for inclusion. Methods: Aldosterone was measured by LCMSMS and by immunoassay; cortisol and renin were determined by immunoassay. Results: Using LCMSMS, aldosterone was below the limit of detection (<70 pmol/L) in 74 (58.7%) patients. Importantly, this finding was discordant with results obtained using a commonly employed clinical immunoassay (Liaison Diasorin®), which over-estimated aldosterone compared to the LCMSMS assay (intercept 14.1 [95% CI -34.4 to 54.1] + slope 3.16 [95% CI 2.09 to 4.15] pmol/L). The magnitude of this discrepancy did not clearly correlate with markers of kidney or liver function. Solvent extraction prior to immunoassay improved the agreement between methods (intercept -14.9 [95% CI -31.9 to -4.3] and slope 1.0 [95% CI 0.89 to 1.02] pmol/L) suggesting the presence of a water-soluble metabolite causing interference in the direct immunoassay. We also replicated a previous finding that blood cortisol concentrations were often increased, with increased mortality in the group with serum cortisol levels >744 nmol/L (p=0.005). Conclusion: When measured by LCMSMS, aldosterone was found to be profoundly low in a significant proportion of patients with COVID-19 at the time of hospital admission. This has likely not been detected previously due to high levels of interference with immunoassays in patients with COVID-19, and this merits further prospective investigation.

show abstract

Section: Discussioncontrasting

confidence: 63%

Section: Introductionmentioning

confidence: 99%

Unquantifiably low aldosterone concentrations are prevalent in hospitalised COVID-19 patients but may not be revealed by chemiluminescent immunoassay

Wiegand

Halsall

Cowan

et al. 2022

Endocrine Connections

View full text Add to dashboard Cite

show abstract

“…Sixth, the aldosterone assay employed may lead to mild overestimation, particularly among individuals with kidney impairment. 48 However, kidney impairment was rare in this population-based cohort, kidney function via eGFR was adjusted for in the analyses, and the impact of any overestimation would therefore be expected to be similar across all study participants. In addition, as the analyses focused on differences in aldosterone rather than comparison of absolute values or thresholds, the absolute aldosterone levels were less important than the relationship of aldosterone with renin and inter-individual comparisons.…”

Section: Discussionmentioning

confidence: 99%

Subclinical Primary Aldosteronism and Cardiovascular Health: A Population-Based Cohort Study

Hundemer,

Agharazii,

Madore

et al. 2024

Circulation

View full text Add to dashboard Cite

BACKGROUND: Primary aldosteronism, characterized by overt renin-independent aldosterone production, is a common but underrecognized form of hypertension and cardiovascular disease. Growing evidence suggests that milder and subclinical forms of primary aldosteronism are highly prevalent, yet their contribution to cardiovascular disease is not well characterized. METHODS: This prospective study included 1284 participants between the ages of 40 and 69 years from the randomly sampled population-based CARTaGENE cohort (Québec, Canada). Regression models were used to analyze associations of aldosterone, renin, and the aldosterone-to-renin ratio with the following measures of cardiovascular health: arterial stiffness, assessed by central blood pressure (BP) and pulse wave velocity; adverse cardiac remodeling, captured by cardiac magnetic resonance imaging, including indexed maximum left atrial volume, left ventricular mass index, left ventricular remodeling index, and left ventricular hypertrophy; and incident hypertension. RESULTS: The mean (SD) age of participants was 54 (8) years and 51% were men. The mean (SD) systolic and diastolic BP were 123 (15) and 72 (10) mm Hg, respectively. At baseline, 736 participants (57%) had normal BP and 548 (43%) had hypertension. Higher aldosterone-to-renin ratio, indicative of renin-independent aldosteronism (ie, subclinical primary aldosteronism), was associated with increased arterial stiffness, including increased central BP and pulse wave velocity, along with adverse cardiac remodeling, including increased indexed maximum left atrial volume, left ventricular mass index, and left ventricular remodeling index (all P <0.05). Higher aldosterone-to-renin ratio was also associated with higher odds of left ventricular hypertrophy (odds ratio, 1.32 [95% CI, 1.002–1.73]) and higher odds of developing incident hypertension (odds ratio, 1.29 [95% CI, 1.03–1.62]). All the associations were consistent when assessing participants with normal BP in isolation and were independent of brachial BP. CONCLUSIONS: Independent of brachial BP, a biochemical phenotype of subclinical primary aldosteronism is negatively associated with cardiovascular health, including greater arterial stiffness, adverse cardiac remodeling, and incident hypertension.

show abstract

“…For most patients, their hypertensive status and control was assessed through in-clinic BP measurements which may be prone to a greater degree of variability than standardised 24-h ambulatory blood pressure measurements. For patients who underwent screening for PA, plasma aldosterone concentration was measured using chemiluminescent immunoassays which may give falsely high values in patients with chronic renal disease due to accumulating cross-reacting steroid metabolites [ 47 , 48 ]. Furthermore, patients with CKD have been found to have increasing plasma aldosterone and renin concentrations as creatinine clearance declines which could confound the interpretation of the ARR in this patient group [ 49 , 50 ].…”

Section: Discussionmentioning

confidence: 99%

Screening for primary aldosteronism is underutilised in patients with chronic kidney disease

et al. 2022

View full text Add to dashboard Cite

Background Primary aldosteronism (PA) is the most common and potentially curable endocrine cause of secondary hypertension, and carries a worse prognosis than essential hypertension. Despite the high prevalence of hypertension in patients with chronic kidney disease (CKD), the screening rates for primary aldosteronism in CKD are unknown. Methods In this study, we retrospectively reviewed medical records of 1627 adults who presented to the nephrology clinics of 2 tertiary hospitals in Melbourne, Australia, between 2014 and 2019. In addition to assessing the pattern of screening, we also evaluated patient-specific factors associated with the decision to test for primary aldosteronism. Patients were excluded from the final analysis if they did not have CKD, had an organ transplant, had end stage renal failure, or had insufficient data or follow-up. Results Of the 600 patients included in the analysis, 234 (39%) had an indication for screening for primary aldosteronism based on recommendations made by the Endocrine Society. However, only 33 (14%) were tested. They were younger, had a higher mean systolic blood pressure, better renal function, and lower mean serum potassium than those who were indicated but not screened. Of the 33 screened patients, an elevated aldosterone-to-renin ratio was noted in 8 patients and a diagnosis of primary aldosteronism was made in 4 patients. Conclusions The screening rate for primary aldosteronism is low in a CKD population, especially in patients who are older, have a lower eGFR and normal serum potassium. The consequences of undiagnosed primary aldosteronism in this select population may be substantial due to the cardiovascular and renal sequelae associated with untreated disease. Graphical abstract

show abstract

Overestimation of Aldosterone by Immunoassay in Renal Impairment

Cited by 10 publications

References 5 publications

Unquantifiably low aldosterone concentrations are prevalent in hospitalised COVID-19 patients but may not be revealed by chemiluminescent immunoassay

Unquantifiably low aldosterone concentrations are prevalent in hospitalised COVID-19 patients but may not be revealed by chemiluminescent immunoassay

Subclinical Primary Aldosteronism and Cardiovascular Health: A Population-Based Cohort Study

Screening for primary aldosteronism is underutilised in patients with chronic kidney disease

Contact Info

Product

Resources

About