Aldosterone/direct renin concentration ratio as a screening test for primary aldosteronism: a systematic review and meta-analysis.

Background: Primary aldosteronism (PA) refers to a spontaneous increase in adrenal aldosterone secretion, and is considered the main cause of secondary hypertension. The main aldosterone screening methods include plasma aldosterone-to-renin ratio (ARR) and plasma aldosterone/direct renin concentration ratio (ADRR). The ARR method has many limitations such as complex operation, several influencing factors, and difficulty in standardization. Relatively speaking, ADRR has gradually attracted attention due to its simple operation, stable results, and easy standardization. However, different research results have suggested that the diagnostic efficacy of ADRR in the screening of primary aldosteronism varies greatly. Meta-analysis may be a way to provide evidence-based medicine. Therefore, it is necessary to conduct a meta-analysis of the diagnostic efficacy of ADRR in primary aldosteronism to clarify the role of ADRR in the screening of PA. Methods: The words "primary aldosteronism", "primary hyperaldosteronism", "aldosterone", "renin concentration", "hypertension" and "screening test" were used as search terms. Literature searches were conducted in the databases of PubMed, Embase, Cochrane Library, and China National Knowledge Infrastructure (CNKI), Wanfang, and Weipu. According to the PICOS principles studies exploring the effectiveness of ADRR in screening for PA were included in the analysis. The research data were independently extracted and analyzed by 2 researchers. Quality assessment of diagnostic accuracy studies (QUADAS-2) was used to analyze the risk bias of the included studies. Results: The results showed that 10 studies met the inclusion criteria, with a total of 2,806 subjects. The meta-analysis found that the overall sensitivity and specificity were 0.87 [95% confidence interval (CI): 0.85-0.89], 0.85 (95% CI: 0.83-0.86), respectively. The area under the curve (AUC) of the summary receiver operating characteristic (SROC) curve was 0.9333. The pooled positive likelihood ratio (PLR), pooled negative likelihood ratio (NLR), and pooled diagnostic odds ratio (DOR) were 5.84 (3.67-9.30), 0.16 (0.12-0.22), and 39.82 (22.84-69.44), respectively. Discussion: This study confirmed that ADRR screening for PA has good sensitivity and specificity. Therefore, ADRR can be used to screen for PA. But the risk and problematic control should be considered.

Changes in plasma aldosterone level after weight loss by bariatric surgery in morbidly obese patients.

BACKGROUND: Overactivation of renin-aldosterone-angiotensin system (RAS) is part of the pathogenesis of obesity-associated hypertension. Evidences have shown that weight loss can result in reduction in blood pressure and RAS. This study was aim to investigate changes of plasma aldosterone concentration (PAC) after bariatric surgery. METHODS: A prospective study was done in 14 morbidly obese patients undergoing bariatric surgery. Patients who were taking medications that can interfere with PAC and renin levels were excluded. Collection of blood samples were done at baseline and at 3 and 6-month post-bariatric surgery. RESULTS: Four out of 14 patients had hypertension at baseline. Mean body mass index (BMI) was 56.7 ± 13.5 kg/m2. PAC were significantly decreased at 3-and 6-month post-bariatric surgery from 14.3 ± 8.0 to 7.5 ± 5.5 [reduction of 36% from baseline (P < 0.01)] and 8.0 ± 6.6 ng/dl [reduction of 32% from baseline (P < 0.05)] respectively. The reduction of PAC at 3-month post-surgery was correlated with the reduction of body weight (r = 0.46, P < 0.05), waist circumference (r = 0.73, P < 0.05) and percent of body fat (r = 0.58, P < 0.05). CONCLUSIONS: Maximal reduction of PAC in obese patients underwent bariatric surgery occurred during the first 3 months after bariatric surgery. The reduction of PAC was associated with the reduction of body weight, waist circumference and percent of body fat suggesting the link between RAS and obesity-mediated hypertension.

Analytical validation and investigation on reference intervals of aldosterone and renin in Chinese Han population by using fully automated chemiluminescence immunoassays.

BACKGROUND: The aldosterone/renin ratio (ARR) is recommended to screen for primary aldosteronism (PA) in hypertension. We estimated fully automated chemiluminescence immunoassays (CLIA) for plasma aldosterone concentrations (PAC) and plasma direct renin concentrations (PRC) and investigated their reference intervals in Chinese Han population. METHODS: PAC and PRC were measured on a fully automated analyzer (LIAISON XL, DiaSorin, Italy). Performance characteristics were estimated according to CLSI approved guidelines. 328 healthy individuals were selected for reference intervals investigation. Results simultaneously tested by CLIA and radioimmunoassays were reviewed from 123 patients with hypertension and/or adrenal space-occupying lesion. PAC/PRC ratio (ARRprc) was compared to PAC/plasma renin activity (PRA) ratio (ARRpra). RESULTS: Within-laboratory imprecision was 5.6%-6.7% for PAC and 3.0%-3.3% for PRC. The LoQ was 72.2 pmol/L for PAC and 1.27 mIU/L for PRC. Linearity was excellent in the range of concentrations between 94 and 2708 pmol/L for PAC and 1.3-461.8 mIU/L for PRC. Interferences of hemoglobin, unconjugated bilirubin and lipaemia could be acceptable, but not of conjugated-bilirubin when renin and aldosterone at low concentrations. The central 95% reference intervals for males: PAC: 76-722 pmol/L, PRC: 3.3-92.7 mIU/L, ARR: 2.2-46.0 pmol/mIU; for females: PAC: 85-1010 pmol/L, PRC: 3.7-99.8 mIU/L, ARR: 3.6-68.4 pmol/mIU. Upper reference limits for ARR of younger and older men were lower than women. ARRprc and ARRpra showed almost perfect agreement (kappa = 0.815) for screening PA. CONCLUSION: The DiaSorin tests are valuable analytical options for PAC and PRC measurements. We recommend sex-specific and age-specific reference intervals of these items should be estimated.

Aldosterone/direct renin concentration ratio as a screening test for primary aldosteronism: A meta-analysis.

OBJECTIVE: The accuracy of aldosterone/direct renin concentration ratio (ADRR) as a screening test in patients with primary aldosteronism (PA) varies widely across the studies. Therefore, we conducted a meta-analysis to assess the accuracy of ADRR. METHODS: A literature search was performed in PubMed, Embase, and the Cochrane library published between April 1971-February 2016. Studies focusing on the accuracy of ADRR for PA screening were included. Two authors independently extracted information regarding patient characteristics, antihypertensives status, true positives, true negatives, false positives, and false negatives. The random-effects model was used for statistical analysis. Heterogeneity was explored by subgroup analysis and meta-regression. RESULTS: Nine studies involving 974 patients were included. The overall sensitivity, specificity, area under the curve, and diagnostic odds ratio of ADRR were 0.89 (95% confidence interval (CI) 0.84-0.93), 0.96 (95% CI 0.95-0.98), 0.985 and 324 respectively, with substantial heterogeneity. Meta-regression showed that antihypertensive status affects the ADRR and may account for the heterogeneity (p=0.03). Subgroup analysis of patients who discontinued the antihypertensives revealed a sensitivity of 0.99 (95% CI, 0.95-1.00) and a specificity of 0.98 (95% CI, 0.96-0.99). CONCLUSIONS: This study demonstrates the efficacy of ADRR as a screening test for PA. However, as antihypertensive drugs can interfere with the interpretation of ADRR, it is recommended to interrupt therapy or at least replace with analogues that do not significantly affect the ADRR value.

The ratios of aldosterone / plasma renin activity (ARR) versus aldosterone / direct renin concentration (ADRR).

Primary aldosteronism (PA) is estimated to occur in 5-12% of patients with hypertension. Assessment of aldosterone / plasma renin activity (PRA) ratio (ARR) has been used as a screening test in patients suspected of PA. Direct determination of renin (DRC) and calculation of aldosterone / direct renin concentration ratio (ADRR) could be similarly useful for screening patients suspected of PA. The study included 62 patients with indication for evaluation of the renin-angiotensin-aldosterone system and 35 healthy volunteers. In all participants we measured concentrations of serum aldosterone, plasma direct renin, and PRA after a night's rest and again after walking for two hours. The concentrations of aldosterone, direct renin, and PRA were measured by isotopic methods (radioimmunoassay (RIA) / immunoradiometric assay (IRMA)). Correlations of ARR with ADRR in the supine position were r = 0.9162, r(2) = 0.8165 (p < 0.01); and in the up-right position were r = 0.7765, r(2) = 0.9153 (p < 0.01). The cut-off values of ARR and ADRR ≥ 100 presented highest specificity (99%) for the diagnosis of PA; however, quite acceptable specificity and sensitivity (> 80% and 100%, respectively) appeared for the ratios ≥ 30. We suggest that for practical and economic reasons ARR can be replaced by ADRR.

The effect of blood collection procedure on plasma renin activity (PRA) and concentrations of direct renin (DRC) and aldosterone.

INTRODUCTION: Performing measurements of plasma renin activity (PRA) or direct renin concentration (DRC) and aldosterone concentration, we should be well informed about requirements concerning blood sample processing. MATERIAL AND METHODS: Forty-seven patients had blood collected in the supine and upright positions. Blood was withdrawn into two EDTA2K tubes and one with clot activator. One EDTA2K tube was cooled at +4 °C and centrifuged at +4 °C whereas the other was prepared at room temperature. PRA and DRC were measured by radioimmunoassay (RIA) and radioimmunometry (IRMA), respectively, in both cooled and not cooled plasma samples, and aldosterone was measured by RIA in not cooled plasma and in serum. RESULTS: In all the groups, with low, medium, and high values of PRA and direct renin, the temperature of sample processing within 30 minutes had no marked influence on the final result (correlation coefficient for renin was 0.9994, and for PRA, 0.8297). The measured concentrations of aldosterone also showed high correlation (r = 0.9790) but were markedly higher in plasma. CONCLUSION: The measurements of DRC, and to a lesser extent PRA, were similar regardless of temperature condition during the 20-30 minutes necessary for blood sample processing. Aldosterone concentrations in plasma vs serum samples appeared to be markedly higher.