Measurement Of Renin Research Articles

A-057 Assessing Direct Renin Stability in EDTA Plasma Prior to Separation from Cells and Post-thaw

Abstract Background Renin is an enzyme secreted by the kidneys responsible for blood pressure regulation through the renin-angiotensin-aldosterone axis. Direct renin measurements are frequently used to investigate underlying causes of hypertension, including primary aldosteronism (PA), which is screened for using an aldosterone:renin ratio (ARR). Appropriate handling of renin samples in the preanalytical phase is critical, as cryoactivation of prorenin can occur when samples are refrigerated or cooled for extended periods of time, falsely elevating results. Manufacturer instructions for renin handling are often poorly defined and there is currently no consensus as to best handling practices. Two variables that frequently lead to renin sample rejections in our laboratory are time to centrifugation after collection and time kept at room temperature (RT). The objective of this study was to evaluate the stability of direct renin under ambient and freeze-thaw conditions in an effort to reduce test cancellations due to improper handling. Methods Plasma samples collected from five volunteers with consent in K2EDTA tubes were used for renin stability studies. Baseline renin samples were kept at RT for two hours after collection, centrifuged, measured, and subsequently frozen for post-thaw studies. To assess stability before separation from cells, samples kept at RT for two and four hours prior to centrifugation were assayed in triplicate for direct renin. For post-thaw stability studies, plasma samples were split into two aliquots each and frozen at -20⁰C for at least 24 hours, but no longer than 30 days. After removal from -20⁰C, one set of aliquots was thawed on the benchtop at RT and the second set was thawed in an RT water bath for up to one hour. Samples were centrifuged and assayed for direct renin in triplicate at baseline and six hours post-thaw. Direct renin was measured using the LIAISON XL chemiluminescent immunoassay (Diasorin). Bias was assessed after each treatment. The total allowable error (TEa) was ±2 pg/mL or ±20%. Results Measured renin concentrations ranged from 6.8-29.7 pg/mL. The percent bias in direct renin concentrations when comparing samples stored for two-hour and four-hour timepoints before centrifugation was 2.0% on average. Post-thaw studies comparing renin concentrations at the baseline and six-hour timepoints revealed an average percent bias of 13.1% and 12.2% for RT and water bath thawing methods, respectively. All samples tested were within the TEa. Conclusions Direct renin is stable in lavender K2EDTA tubes at RT for up to four hours, prior to centrifugation and separation from cells. Renin concentrations remained stable after storage at -20⁰C and thawing at RT for up to six hours, regardless of thawing method. By expanding direct renin stability criteria, we hope to reduce the number of cancellations due to preanalytical handling errors and prevent redundant phlebotomy for patients.

Plasma Renin: A Useful Marker for Mineralocorticoid Adjustment in Patients With Primary Adrenal Insufficiency.

Renin is a marker of blood volume. There is no consensus on the validity of plasma renin measurement for adjusting mineralocorticoid (MC) substitution in patients with primary adrenal insufficiency (PAI). This work aimed to investigate if plasma renin could be used to adjust MC substitution in patients with PAI. A total of 150 patients with at least one measurement of plasma renin followed for PAI at 2 tertiary expert centers between 2008 and 2022 were retrospectively included. As supraphysiological hydrocortisone might have additional MC activity, we integrated the individual hydrocortisone dose to obtain the MC equivalent dose (Eq-MC). Renin less than 20 mIU/L was considered oversubstituted, renin between 20 and 60 mIU/L as correctly substituted, and renin over 60 mIU/L as undersubstituted. The mean dose of fludrocortisone was 82.3 ± 46 μg/day. Plasma renin was abnormal in 56.7% of cases (7 patients oversubstituted and 78 patients undersubstituted). Abnormalities in electrolyte levels were observed in only 12.7% of patients. Plasma renin correlated negatively with sodium (P < .01) and systolic blood pressure (P = .026), and positively with potassium (P < .01). Doses changes in Eq-MC had a statistically significant effect on renin levels (P = .0037), with an increase of MC dose correlating with a decrease in renin level and vice versa; no correlation was observed using electrolytes or blood pressure. Plasma renin correlates with electrolytes and blood pressure. While dose changes significantly alter renin levels, electrolytes and blood pressure do not, suggesting that renin may provide more information about MC replacement therapy than electrolytes and blood pressure.

Abstract P310: Subclinical primary aldosteronism is associated with an increased risk of major adverse cardiovascular events

Background: Subclinical primary aldosteronism (PA), defined as renin-independent aldosterone production without overt PA, has recently been associated with adverse cardiac remodelling, unfavorable indices of arterial stiffness and incident hypertension. The objective of this study was to evaluate whether subclinical PA is linked to an increased risk of cardiovascular events. Methods: This study used data from CARTaGENE, a populational cohort of randomly selected individuals aged 40-69 years, with prospective outcomes data obtained from linkage with governmental administrative databases. The outcome of interest was major adverse cardiovascular events (MACE), a composite of cardiovascular death, myocardial infarction, stroke and heart failure, assessed from enrollment (2009-2010) to March 2021. All individuals with available plasma renin and aldosterone measurements, outcomes data and nutritional assessment were included in this study. Cox regression models were used to test the associated between MACE and the log-transformed aldosterone-to-renin ratio (ARR), with adjustments for sex, age, height, weight, race, diabetes, prior cardiovascular disease, smoking status, systolic BP, heart rate, estimated glomerular filtration rate, sodium and potassium levels, LDL- and total-cholesterol, antihypertensive drugs (listed as individual classes), statin and aspirin use, and 24-hour nutritional intake of sodium and potassium. Multiple imputation was used for missing data. Results: In 2,055 participants with available data (45.5% female, mean age 55.6 years, 6.6% diabetes, 2.9% prior cardiovascular disease, mean baseline systolic BP 128.5 mmHg), 58 MACEs occurred over a median follow-up of 10.8 years (IQR 10.6-11.0). In the Cox regression analysis, the log-transformed ARR was predictive of MACE with a hazard ratio (HR) of 2.86 (95% CI 1.34 to 6.10, p=0.007). Results were similar when participants taking any anti-hypertensive drug were excluded (HR 3.05, 95% CI 1.38 to 6.71, p=0.006). Conclusion: In a representative sample of the general population, a higher ARR appears to be highly predictive of adverse cardiovascular events. This indicates that subclinical PA could be an important and yet unrecognized risk factor for cardiovascular diseases, and may warrant screening in a broader population.

Diagnostic Accuracy of Aldosterone and Renin Measurement by Chemiluminescence for Screening of Patients with Primary Aldosteronism.

Primary aldosteronism (PA) is the most common cause of endocrine arterial hypertension, and the suggested screening test for case detection is the aldosterone-to-renin ratio (ARR) or aldosterone-to-direct renin ratio (ADRR) based on radio-immunoassay (RIA) and chemiluminescence assay (CLIA), respectively. The objective of our study was to evaluate the reliability of CLIA for aldosterone and renin measurement and the diagnostic performance of ADRR. A prospective cohort of 1110 patients referred to a single laboratory medicine center underwent measurement of aldosterone and direct renin concentration (DRC) by CLIA and measurement of aldosterone and plasma renin activity (PRA) by RIA. Of 1110 patients, 640 obtained a final diagnosis of hypertension, and 90 of these patients were diagnosed with PA. Overall, between-method correlation was highly significant for aldosterone concentrations (R = 0.945, p < 0.001) and less strong but significant for DRC/PRA (R = 0.422, p < 0.001). Among hypertensive patients, in PA cases, the areas under the receiver operator characteristics (ROC) curves were 0.928 (95% confidence interval 0.904-0.954) for ADRR and 0.943 (95% confidence interval 0.920-0.966) for ARR and were comparable and not significantly different. The highest accuracy was obtained with an ADRR cut-off of 25 (ng/L)/(mIU/L), displaying a sensitivity of 91% and a specificity of 85%. The chemiluminescence assay for aldosterone and DRC is a reliable method for PA diagnosis compared to the classical RIA method.

Selective venous sampling for secondary hypertension.

Selective venous sampling (SVS), an invasive radiographic procedure that depends on contrast media, holds a unique role in diagnosing and guiding the treatment of certain types of secondary hypertension, particularly in patients who may be candidates for curative surgery. The adrenal venous sampling (AVS), in particular, is established as the gold standard for localizing and subtyping primary aldosteronism (PA). Throughout decades of clinical practice, AVS could be applied not only to PA but also to other endocrine diseases, such as adrenal Cushing syndrome (ACS) and Pheochromocytomas (PCCs). Notably, the application of AVS in ACS and PCCs remains less recognized compared to PA, with the low success rate of catheterization, the controversy of results interpretation, and the absence of a standardized protocol. Additionally, the AVS procedure necessitates enhancements to boost its success rate, with several helpful but imperfect methods emerging, yet continued exploration remains essential. We also observed renal venous sampling (RVS), an operation akin to AVS in principle, serves as an effective means of diagnosing renin-dependent hypertension, aiding in the identification of precise sources of renin excess and helping the selection of surgical candidates with renin angiotensin aldosterone system (RAAS) abnormal activation. Nonetheless, further basic and clinical research is needed. Selective venous sampling (SVS) can be used in identifying cases of secondary hypertension that are curable by surgical intervention. Adrenal venous sampling (AVS) and aldosterone measurement for classificatory diagnosis of primary aldosteronism (PA) are established worldwide. While its primary application is for PA, AVS also holds the potential for diagnosing other endocrine disorders, including adrenal Cushing's syndrome (ACS) and pheochromocytomas (PCCs) through the measurements of cortisol and catecholamine respectively. In addition, renal venous sampling and renin measurement can help to diagnose renovascular hypertension and reninoma.

Insight into the status of plasma renin and aldosterone measurement: findings from 526 clinical laboratories in China.

Accurate measurements of renin and aldosterone levels play an important role in primary aldosteronism screening, which is of great importance in the management and categorization of hypertension. The objective of this studyis to investigate the current status of plasma renin and aldosterone measurements in China, which is achieved by analyzing the results of 526 clinical laboratories nationwide for three pooled fresh plasma samples derived from more than 2,000 patients. Renin and aldosterone in three pooled plasma samples were measured four times in 526 laboratories employing various measurement systems. The inter- and intra-laboratory %CV were calculated and compared. To determine the source of the substantial inter-laboratory %CV,laboratories were categorized according to the measurement systems they are using, and both the inter- and intra-measurement-system %CV were calculated and compared. Regarding renin, the majority of laboratories use four primary commercial immunoassays. However, for aldosterone, in addition to commercial immunoassays, laboratory-developed liquid chromatography-tandem mass spectrometry (LC-MS) methods are also used by laboratories. The median values of intra-laboratory %CVs, intra-measurement-system %CVs, inter-laboratory %CVs, and inter-measurement systems %CVs varied between 1.6 and 2.6 %, 4.6 and 14.9 %, 8.3 and 25.7 %, and 10.0 and 34.4 % for renin, respectively. For aldosterone, these values ranged from 1.4 to 2.2 %, 2.5-14.7 %, 9.9-31.0 %, and 10.0-35.5 %, respectively. The precision within laboratories and measurement systems for plasma renin and aldosterone measurements is satisfactory. However, the comparability between laboratories using different measurement systems remains lacking, indicating the long way to achieve standardization and harmonization for these two analytes.

The Clinical Impact of Sample Storage at -20 °C on Renin Reference Intervals and Aldosterone-Renin Ratio Calculations.

Cryoactivation is known to occur in whole blood and plasma samples when kept between +4 and -5 °C, leading to falsely high renin concentrations. In 2022 it has been clearly shown that cryoactivation can also occur in samples stored at -20 °C. Based on these new findings, here we discuss how this can influence the clinical diagnosis of patients. First, we show that storage of renin plasma samples can affect the renin measurements and thereby the aldosterone to renin ratio (ARR) calculation, which might explain the high intraindividual variability in ARR also recently demonstrated. Second, we discuss the existing studies on the establishment of renin reference intervals and note the lack of attention given to this recently revealed preanalytical condition. Our literature review of the reference intervals for renin suggest that cryoactivation might have influenced the published data.

A longitudinal study on the effect of obesity upon circulating renin-angiotensin system in normal pregnancy

Background and aimsObesity is the most common health issue in women of reproductive age, which profoundly affects maternal-fetal health. Despite progress in understanding key inflammatory and metabolic changes, the pathogenesis of the cardiovascular phenotype of obese pregnant women remains to be fully understood. This study aimed at: (i) evaluating the changes of the renin-angiotensin system (RAS) throughout pregnancy in obese vs normal weight (control) women, and (ii) evaluating the presence of any associations between maternal hemodynamic status and RAS changes. Methods and resultsThirty-eight normal weight and nineteen obese pregnant women were included. Clinical assessment, blood samples and maternal hemodynamic evaluation were performed at 12, 20, 30, and 36 weeks, while ultrasound assessment was scheduled at 20, 30, and 36 weeks of gestation. Measurements of sFlt-1, PlGF, Angiotensinogen, Renin, AngII, Ang1-7, ACE and ACE2 were performed by ELISA. Our data show that normotensive obese women had lower placental blood supply, as assessed by UV-Q and UV-Q/EFW, as compared to controls, and significantly higher levels of AngII and AngII/Ang1-7 ratio, which were inversely related to placental blood supply. ConclusionsOur study shows for the first time that normotensive obese women exhibited a significant progressive increase of AngII and AngII/Ang1-7 throughout pregnancy, which were inversely related to placental blood supply as assessed by UV-Q and UV-Q/EFW. Our data shed light on the early changes in pregnant obese women and suggest that RAS dysregulation is a prerequisite rather than a consequence of hypertensive disorders of pregnancy and other maternal neonatal complications.

FRI123 Development And Impact Of A Best Practice Alert For Primary Aldosteronism Screening

Abstract Disclosure: S. Charoensri: None. L. Bashaw: None. C. Dehmlow: None. T. Ellies: None. A.F. Turcu: None. Background: Primary aldosteronism (PA) is a common cause of secondary hypertension, affecting up to 25% of patients with treatment-resistant hypertension. PA amplifies the risk of cardiovascular morbidity and mortality above that of equivalent primary hypertension. Despite this, &amp;lt;3% of candidates for PA screening are ever evaluated, including in academic centers with facile access to all required resources for PA subtyping and treatment. Clinical decision support tools, such as best practice alerts (BPA), can leverage electronic medical records technology to support health care delivery improvement efforts. Intervention and Measurements: In collaboration with institutional Informational Technology services, we developed an algorithm that identifies PA screening candidates as adult patients with hypertension and one of the following criteria: ≥ 4 current antihypertensive medications; age &amp;lt; 35 years; hypokalemia (defined by potassium supplements or low serum potassium in the past year); or adrenal mass on problem list. The algorithm excluded patients who had both plasma aldosterone and renin measurements within the past 5 years. A non-disruptive BPA to suggest PA screening was constructed and set to trigger in patients meeting inclusion and exclusion criteria when evaluated in outpatient setting by clinicians who treat hypertension, including Internists, Family Practitioners, Cardiologists, Nephrologists, and Endocrinologists. An order set for PA screening and a link to results interpretation guidance were also embedded within the BPA. The BPA was first piloted between Aug-Sept 2021, and then launched on October 1st, 2021. We assessed the number of unique patients identified by the BPA between Oct 1st, 2021- Dec 14th, 2022, stratified by PA screening indications; attitude towards the BPA; and number of patients who received PA screening orders. Results: In total, the BPA identified 14,443 unique candidates for PA screening, including: 6944 patients with treatment-resistant hypertension; 6583 patients with hypertension and hypokalemia; 1527 patients with hypertension &amp;lt;35 years; and 444 with hypertension and an adrenal mass. During the same time frame, 3614 (25%) patients received orders for plasma aldosterone and renin. Patients tested were on average 57 +/-17 years old, 2000 (55.3%) were women, 2573 (71.2%) were White, 712 (19.7%) Black, and 105 (2.9%) Asian. Of new orders, 1364 (37.7%) were placed by Internists, 685 (18.9%) by Family Medicine physicians, 559 (15.5%) by Endocrinologists, 235 (6.5%) by Cardiologists, and 50 (1.4%) by Nephrologists. Family Practitioners and Internists placed most orders via the embedded BPA order set (66.6% and 46.3%, respectively), while Endocrinologists placed 98.6% of the orders outside of the BPA order set. Conclusions: Non-disruptive BPAs enhance the rates of PA screening, particularly among Internists and Family Practitioners. Presentation: Friday, June 16, 2023

Immunohistochemical staining seems mandatory for individualizing and shortening follow-up in unilateral primary aldosteronism.

The clinical significance of immunohistochemistry (IHC) for unilateral primary aldosteronism (PA) has been unclear. Individualized follow-up of PA patients could be in sight. Long-term outcomes of patients, classified based on IHC, need further investigation. We aimed to assess long-term clinical outcomes for unilateral PA, classifying patients based on IHC. A nationwide observational study, with up to 16 years follow-up, executed in 2007-2016 at Landspitali University Hospital, tertiary referral center. Patients were diagnosed and treated in line with the current guidelines. Haematoxylin and eosin (H&E) tissue slides were stained using CYP11B1 and -B2 antibodies. All cases were re-evaluated and classified according to the HISTALDO consensus. Outcomes were assessed using the PASO criteria. All unilateral PA patients diagnosed in 2007-2016 in Iceland, 26 patients aged 28-73 years, who underwent adrenalectomy, were included. Aldosterone, renin, and cortisol values, use and dosage of antihypertensives, potassium supplementation, blood pressure and serum potassium pre-intervention and throughout follow-up, and histopathology results post-adrenalectomy. Following IHC, an aldosterone-producing nodule was seen in 12 adrenals, an aldosterone-producing adenoma in 10 and multiple aldosterone-producing micronodules in four. IHC altered histopathology from previous H&E diagnosis in 23% (6/26) of the patients. In total, 81% (21/26) of the patients had partial clinical success. Eight percent (2/26) of the patients needed potassium supplementation during follow-up. In the classical group, the AVS results were more determinative with significantly higher lateralization index (median 10.1 vs. 5.3, p = .04) and more contralateral suppression (median nondominant ratio 0.4 vs. 1.0, p = .03). One out of five patients with complete clinical success at 12 months post-op had severe relapse later, the other four were normotensive without antihypertensives for up to 10 years. We found IHC mandatory for accurate histopathologic diagnosis of PA. Our results support the importance of contralateral suppression when interpreting AVS results. Also, the study highlights the complicated assessment of clinical outcome and importance of aldosterone and renin measurements during follow-up.

Nephrectomy for kidney tumor increases the risk of de novo arterial hypertension.

Kidney is an essential regulator of arterial blood pressure (BP) via the renin-angiotensin system. The impact of kidney surgery on BP is unclear. To evaluate the consequences of kidney surgery for renal tumor on BP. In a multicenter prospective study, we evaluated 200 patients who underwent nephrectomy for renal tumor between 2018 and 2020 at 7 departments of the UROCCR network. All patients had localized cancer without pre-existing hypertension. BP was measured the week before nephrectomy, one month and six months after nephrectomy, according to the recommendations for home blood pressure measurement. Plasmatic renin was measured one week before surgery and 6 months after surgery. The primary endpoint was the occurrence of de novo hypertension (HTN). The secondary endpoint was a clinically significant increase in BP at six months defined by an increase in systolic and / or diastolic ABP ≥10 mmHg or if medical anti-hypertensive treatment was required RESULTS AND LIMITATIONS: BP and renin measurements were available for 182 (91%) and 136 (68%) patients, respectively. We excluded from the analysis 18 patients who had undeclared HTN detected on preoperative measurements. At six months, 31 (19.2%) patients had de novo HTN and 43 (26.3%) patients had a significant increase in their BP. The type of surgery was not associated with an increased risk of HTN (21.7% PN vs 15.7% RN; p=0.59). There was no difference between plasmatic renin levels before and after surgery (18.5 vs. 16, p=0.46). In multivariable analysis, age (O.R 1.07; CI-95 1.02-1.12; p=0.03) and BMI (O.R. 1.14; CI-95 1.03-1.26; p=0.01) were the only predictors of de novo HTN. Surgical treatment of renal tumors is associated with significant changes in BP. These changes are not impacted by the type of surgery (PN vs RN). In this study we evaluated blood pressure changes after surgery for renal tumors. We found that 19% of the patients developed de novo hypertension 6 months after surgery. We feel that patients who are scheduled to undergo kidney cancer surgery should be informed of these findings and have their blood pressure closely monitored after the operation.

PS-BPB04-9: DEVELOPMENT AND VALIDATION OF NEW METHOD TO MEASURE PLASMA ALDOSTERONE AND RENIN ACTIVITY USING LIQUID CHROMATOGRAPHY TANDEM MASS SPECTROMETER (LC-MS/MS)

Objective: Measurement of aldosterone, renin, and aldosterone-renin ratio (ARR), are used to diagnose primary aldosteronism (PA). Immunoassays used to measure plasma aldosterone yield higher results compared to tandem mass spectrometry (LC-MS/MS). This can lead to false positive diagnosis of PA, and potential for unnecessary adrenal vein sampling. We report our development and validation of a novel test using LC-MS/MS, with reduced run time, for measurement of plasma aldosterone concentration (PAC) and plasma renin activity (PRA). Design and method: The detection and quantification of plasma aldosterone and angiotensin 1 (product for the calculation of renin activity) in the mass spectrometer was based on the multiple reaction monitoring of precursor to fragment ions under negative and positive ionization modes, respectively. Validation of the tests were based on the CLSI (Clinical &amp; Laboratory Standards Institute) guidelines. Concurrent measurement for 190 samples were done on our instrument, and on a commercial lab using LC-MS/MS (Mayo Laboratories, USA) for comparison. Results: Our measurements of PAC and PRA was sensitive with a limit of quantification at 3 ng/dL and 0.25 ng/ml/h, respectively, and analytical run times were 6.5 min and 3.5 min, respectively. Both aldosterone and angiotensin 1 calibration curves had excellent linearity in the ranges of 3 - 300 ng/dL and 0.25 - 25 ng/ml/h, respectively, with coefficient of correlation, r2 &gt; 0.994. The intra and inter day accuracy of aldosterone and angiotensin 1 were in the range of 95–110% with CV of &lt; 13%. Reference ranges were established for our local population. Compared with the other LC-MS/MS laboratory, there was good correlation for PAC, r2 = 0.90, 95%CI: 0.86 - 0.92, and PRA, r2 = 0.81, 95% CI: 0.75 - 0.86, using 190 samples. In addition, amongst those with low aldosterone &lt; 6ng/dL, there was good agreement between both labs, with 95 of 122 (77.9%) samples having low aldosterone using both methods, which has been shown to be an ideal threshold to exclude the diagnosis of PA. Conclusions: Our laboratory has developed and validated a sensitive and accurate LC-MS/MS test for PAC and PRA with shortened run time, for the diagnosis PA.

Renin Trajectories and Outcome in Stable Heart Failure with Reduced Ejection Fraction (HFrEF) on Contemporary Therapy: A Monocentric Study from an Austrian Tertiary Hospital Outpatient Clinic

Introduction. The renin-angiotensin system (RAS) is the main target of neurohumoral therapy in heart failure with reduced ejection fraction (HFrEF) effectively reducing mortality. Reasonably, renin might serve as a biomarker for risk prediction and therapy response. Renin indeed bears some additional value to clinical risk models, albeit the effect is not pronounced. Whether assessing renin trajectories can overcome the weaknesses of single renin measurements has not been reported. Methods. A total of 505 patients with stable HFrEF were enrolled prospectively and followed through routine clinical visits. Active plasma renin concentration was documented up to 5 years. Changes in renin were analyzed throughout the disease course, and survival was compared for different renin trajectories within the first year. Results. Baseline renin levels were not related to all-cause mortality (crude HR for an increase of 100 μiE/ml: 1.01 (95% CI: 0.99–1.02), [Formula: see text]) but associated with unplanned HF hospitalizations (crude HR: 1.01 (95% CI: 1.00-1.02), [Formula: see text]). Renin increased during the disease course from baseline to 1-year and 2-year FUP (122.7 vs. 185.6 μIU/ml, [Formula: see text], and 122.7 vs. 258.5 μIU/ml, [Formula: see text]). Both survival and unplanned HF hospitalization rates were comparable for different renin trajectories at 1-year FUP ([Formula: see text], [Formula: see text]). Conclusions. Intriguingly, renin is not a good biomarker to indicate prognosis in HF, while renin trajectories over a 1-year period do not have an additional value. Rapid physiologic plasma renin variations, but also opposing effects of angiotensinogen-derived metabolites under presence of RAS blockade, might obscure the predictive ability of renin.

Intra-individual Variability of Serum Aldosterone and Implications for Primary Aldosteronism Screening.

Primary aldosteronism (PA) screening relies on an elevated aldosterone to renin ratio with a minimum aldosterone level, which varies from 10 to 15 ng/dL (277-415.5 pmol/L) using immunoassay. To evaluate intra-individual coefficient of variation (CV) of aldosterone and aldosterone to direct renin concentration ratio (A/DRC) and its impact on PA screening. A total of 671 aldosterone and DRC measurements were performed by the same chemiluminescence assays in a large cohort of 216 patients with confirmed PA and at least 2 screenings. The median intra-individual CV of aldosterone and A/DRC was 26.8% and 26.7%. Almost 40% of the patients had at least one aldosterone level <15 ng/dL, 19.9% had at least 2 aldosterone levels <15 ng/dL, and 16.2% had mean aldosterone levels <15 ng/dL. A lower cutoff of 10 ng/dL was associated with false negative rates for PA screening of 14.3% for a single aldosterone measurement, 4.6% for 2 aldosterone measurements, and only 2.3% for mean aldosterone levels. Considering the minimum aldosterone, true positive rate of aldosterone thresholds was 85.7% for 10 ng/dL and 61.6% for 15 ng/dL. An A/DRC >2 ng/dL/µIU/mL had a true positive rate for PA diagnosis of 94.4% and 98.4% when based on 1 or 2 assessments, respectively. CV of aldosterone and A/DRC were not affected by sex, use of interfering antihypertensive medications, PA lateralization, hypokalemia, age, and number of hormone measurements. Aldosterone concentrations had a high CV in PA patients, which results in an elevated rate of false negatives in a single screening for PA. Therefore, PA screening should be based on at least 2 screenings with concomitant aldosterone and renin measurements.

The Importance of Correlation between Aldosterone and Parathyroid Hormone in Patients with Primary Hyperparathyroidism.

In primary hyperparathyroidism, an increased risk of developing the cardiovascular disease may exist due to increased activity of the renin-angiotensin-aldosterone system. The aim of this study was to evaluate the relationship between parathyroid hormone and aldosterone in patients with primary hyperparathyroidism. The study included 48 patients with primary hyperparathyroidism and 30 healthy subjects who matched age and gender to the study group. This study was conducted at the Center for Laboratory medicine, Clinical center of Vojvodina, Novi Sad, Serbia. In addition to clinical data and laboratory determination of the concentration of total and ionized calcium, phosphorus, measurements of parathyroid hormone, vitamin D, direct renin, and aldosterone were performed by the method of chemiluminescent technology. Compared to the controls, the study group had statistically significantly higher values of aldosterone (p=0.028), total calcium (p=0.01), ionized calcium (p=0.003) and parathyroid hormone (P ≤ 0.001) Serum aldosterone and parathyroid hormone levels were correlated positively in patients with primary hyperparathyroidism (r=0.509, p < 0.05). A statistically significant positive correlation between renin and parathyroid hormone (r=0.688, p < 0.05) and renin and calcium (r=0.673, p < 0.05) was determined in hyperparathyroid patients. In multivariate regression analysis, the strongest predictive variable of aldosterone secretion was parathyroid hormone (p=0.011). An independent relationship between parathyroid hormone and aldosterone in patients with primary hyperparathyroidism and the correlation between renin and parathyroid hormone as well as with calcium indicate not only the direct but also the indirect associations between parathyroid hormone and aldosterone in primary hyperparathyroidism. These findings may represent another possible model of renin-angiotensin-aldosterone-induced organ damage.

RF32 | PSUN49 To Repeat or Not to Repeat: The Question of Aldosterone and Renin Variability

Abstract Plasma aldosterone concentration (PAC), renin levels and aldosterone-renin ratio (ARR) are used to screen for primary aldosteronism (PA). A recent study (Yozamp et al. Hypertension 2021) reported substantial intraindividual variability of PAC and ARR (using plasma renin activity) in the context of usual antihypertensive therapy. The intraindividual variability of PAC and direct renin concentration (DRC), a more widely used measurement of renin, in the absence of interfering medications is unknown but important where a single ARR is used to screen for PA. The aim of this study was to evaluate the intraindividual variability of PAC, DRC and ARR in a cohort of patients with and without PA. Patients who attended an Endocrine Hypertension Service from May 2017 to July 2021 with at least two ARR measurements off interfering medications were retrospectively evaluated. While the measurements were performed at several hospital and community laboratories, the same analyser was used. PA was confirmed using the seated saline suppression test following an abnormal ARR &amp;gt;70 pmol/L: mU/L. PAC and DRC variability was calculated as coefficient of variation (CV=standard deviation/mean×100) and percent difference (PD=difference between highest and lowest values/mean×100). A total of 223 patients were analysed (55% female, median age 52 years), including 162 with PA (25% with unilateral disease). Significant variability in both PAC and DRC was observed in the PA group (CV: 24%, 41%; PD: 46%, 76% respectively) and non-PA group (CV: 22%, 40%; PD: 38%, 65% respectively), which was higher than the assays’ analytical variability. The ARR was also highly variable within individuals, in both the PA group (CV: 42%; PD: 74%) and non-PA group (CV: 37%; PD: 61%). Variability was not significantly different between PA subtypes, and persisted irrespective of age, gender and degree of hypertension. Sixty-two patients (39%) with PA could have had a missed diagnosis if the ARR had not been repeated, i.e., had at least one ARR &amp;lt;70 pmol/L: mU/L, while 28 (46%) without PA had at least one abnormal ARR &amp;gt; 70. Intraindividual variability in PAC, DRC and ARR occurs in a significant number of patients being investigated for PA. These results support the need for at least two ARR on separate occasions before PA is excluded or further investigated. Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m., Monday, June 13, 2022 1:06 p.m. - 1:11 p.m.

Renin: Measurements, Correlates, and Associations With Long-Term Adverse Kidney Outcomes.

The association of renin with adverse kidney outcomes is largely unknown, and renin measurement strategies vary. We aimed to measure the clinical correlates of different renin measurements and the association between renin and incident chronic kidney disease (CKD), end-stage kidney disease (ESKD), and mortality. We performed a prospective cohort analysis of 9,420 participants in the Atherosclerosis Risk in Communities study followed from 1996 to 1998 through 2019. We estimated longitudinal associations of renin measured using SomaScan modified nucleotide aptamer assay with incident CKD, ESKD, and death using Cox proportional hazards models. Using samples from a subsequent study visit, we compared SomaScan renin with plasma renin activity (PRA) and renin level from Olink, and estimated associations with covariates using univariate and multivariable regression. Higher SomaScan renin levels were associated with a higher risk of incident CKD (hazard ratio per two-fold higher [HR], 1.14; 95% confidence interval [CI], 1.09 to 1.20), ESKD (HR, 1.20; 95% CI, 1.03 to 1.41), and mortality (HR, 1.08; 95% CI, 1.04 to 1.13) in analyses adjusted for demographic, clinical, and socioeconomic covariates. SomaScan renin was moderately correlated with PRA (r = 0.61) and highly correlated with Olink renin (r = 0.94). SomaScan renin and PRA had similar clinical correlates except for divergent associations with age and beta-blocker use, both of which correlated positively with SomaScan renin but negatively with PRA. SomaScan aptamer-based renin level was associated with a higher risk of CKD, ESKD, and mortality. It was moderately correlated with PRA, sharing generally similar clinical covariate associations.

Role of α1-blockers in the current management of hypertension.

There is emerging evidence that α1‐blockers can be safely used in the treatment of hypertension. These drugs can be used in almost all hypertensive patients for blood pressure control. However, there are several special indications. Benign prostatic hyperplasia is a compelling indication of α1‐blockers, because of the dual treatment effect on both high blood pressure and lower urinary tract symptoms. Many patients with resistant hypertension would require α1‐blockers as add‐on therapy. Primary aldosteronism screen is a rapidly increasing clinical demand in the management of hypertension, where α1‐blockers are useful for blood pressure control in the preparation for the measurement of plasma aldosterone and renin. Nonetheless, α1‐blockers have to be used under several considerations. Among the currently available agents, only long‐acting α1‐blockers, such as doxazosin gastrointestinal therapeutic system 4–8 mg daily and terazosin 2–4 mg daily, should be chosen. Orthostatic hypotension is a concern with the use of α1‐blockers especially in the elderly, and requires careful initial bedtime dosing and avoiding overdosing. Fluid retention is potentially also a concern, which may be overcome by combining an α1‐blocker with a diuretic.

PD56-04 ASSESSMENT OF CHANGES IN ARTERIAL BLOOD PRESSURE AFTER NEPHRECTOMY FOR KIDNEY CANCER VAPANCR (UROCCR 26)_PROSPECTIVE STUDY

You have accessJournal of UrologyCME1 May 2022PD56-04 ASSESSMENT OF CHANGES IN ARTERIAL BLOOD PRESSURE AFTER NEPHRECTOMY FOR KIDNEY CANCER VAPANCR (UROCCR 26)_PROSPECTIVE STUDY Pierre Bigot, Jean-Christophe Bernhard, Nicolas Doumerc, François-Xavier Nouhaud, Idir Ouzaid, Patrick Saulnier, Arnaud Mejean, Morgan Rouprêt, and Karim Bensalah Pierre BigotPierre Bigot More articles by this author , Jean-Christophe BernhardJean-Christophe Bernhard More articles by this author , Nicolas DoumercNicolas Doumerc More articles by this author , François-Xavier NouhaudFrançois-Xavier Nouhaud More articles by this author , Idir OuzaidIdir Ouzaid More articles by this author , Patrick SaulnierPatrick Saulnier More articles by this author , Arnaud MejeanArnaud Mejean More articles by this author , Morgan RouprêtMorgan Rouprêt More articles by this author , and Karim BensalahKarim Bensalah More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002636.04AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Kidney is an essential regulator of arterial blood pressure (ABP) via the renin-angiotensin system. The impact of kidney surgery on ABP is debated. Our objective was to evaluate the consequences of kidney surgery for cancer on ABP. METHODS: We carried out a multicenter prospective study (NCT03218319) and included 200 patients who underwent nephrectomy for cancer between January 2018 and September 2020 at 7 academic centers from the UROCCR network. The study obtained approval from Ethical Committee (2017-A00127-46). Inclusions criteria were a localized cancer eligible to nephrectomy and the absence of pre-existing hypertension. ABP was monitored according to the recommendations for home blood pressure measurement. Four measurements were taken after 5 minutes of sitting rest, before breakfast and four additional measurements were taken in the evening before bedtime. Measurements were done during three consecutive days (average of 18 values). ABP evaluation was done the week before nephrectomy, one month and six months after nephrectomy. A renin assessment was done one week before surgery and 6 months after surgery. The primary endpoint was the occurrence of a clinically significant change in ABP at 6 months. A change in ABP was considered clinically significant if the variation in systolic and / or diastolic ABP was ≥ 5 mmHg or if medical anti-hypertensive treatment was required. RESULTS: ABP and renin measurements were evaluable for 182 (91%) and 136 (68%) patients, respectively. There were 112 males and 88 females with a median age of 54 years. Radical (RN) and Partial nephrectomy (PN) were performed in 42 (21%) and 158 (79%) patients, respectively. At 6 months, 55 (30.2%) patients had a significant increase in their ABP and 12 (6.5%) patients started an antihypertensive treatment. Type of surgery was not associated with increases in ABP (31.6 % PN vs 25% RN; p=0.559) nor prescription of antihypertensive drug (4.79% PN vs 12.5 % RN; p=0.089). At 6 months, renin was not significantly higher than before surgery (16.098 vs 15.231, p=0.686). In multivariable analysis, type of surgery, age, sex, BMI, smoking, diabetes and dyslipidemia were not associated with significant changes in ABP. CONCLUSIONS: Renal surgery for cancer induces significant variations in ABP in 30% of patients. Type of surgery is not associated with ABP outcomes. ABP after surgery seems not be related to renin secretion. Longer follow-up and additional patients will be necessary to determine whether this rise in ABP can have a consequence on the occurrence of cardio-vascular events. Source of Funding: This study was granted by the French Association of Urology (AFU) © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e954 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Pierre Bigot More articles by this author Jean-Christophe Bernhard More articles by this author Nicolas Doumerc More articles by this author François-Xavier Nouhaud More articles by this author Idir Ouzaid More articles by this author Patrick Saulnier More articles by this author Arnaud Mejean More articles by this author Morgan Rouprêt More articles by this author Karim Bensalah More articles by this author Expand All Advertisement PDF DownloadLoading ...

Serum renin and major adverse kidney events in critically ill patients: a multicenter prospective study

BackgroundPreliminary studies have suggested that the renin-angiotensin system is activated in critical illness and associated with mortality and kidney outcomes. We sought to assess in a larger, multicenter study the relationship between serum renin and Major Adverse Kidney Events (MAKE) in intensive care unit (ICU) patients.MethodsProspective, multicenter study at two institutions of patients with and without acute kidney injury (AKI). Blood samples were collected for renin measurement a median of 2 days into the index ICU admission and 5–7 days later. The primary outcome was MAKE at hospital discharge, a composite of mortality, kidney replacement therapy, or reduced estimated glomerular filtration rate to ≤ 75% of baseline.ResultsPatients in the highest renin tertile were more severely ill overall, including more AKI, vasopressor-dependence, and severity of illness. MAKE were significantly greater in the highest renin tertile compared to the first and second tertiles. In multivariable logistic regression, this initial measurement of renin remained significantly associated with both MAKE as well as the individual component of mortality. The association of renin with MAKE in survivors was not statistically significant. Renin measurements at the second time point were also higher in patients with MAKE. The trajectory of the renin measurements between time 1 and 2 was distinct when comparing death versus survival, but not when comparing MAKE versus those without.ConclusionsIn a broad cohort of critically ill patients, serum renin measured early in the ICU admission is associated with MAKE at discharge, particularly mortality.