The clinical characteristics and outcomes in patients with clinical aldosterone-producing adenomas harboring KCNJ5 mutations with or without subclinical hypercortisolism remain unclear. This ...prospective study is aimed at determining factors associated with subclinical hypercortisolism in patients with clinical aldosterone-producing adenomas. Totally, 82 patients were recruited from November 2016 to March 2018 and underwent unilateral laparoscopic adrenalectomy with at least a 12-month follow-up postoperatively. Standard subclinical hypercortisolism (defined as cortisol >1.8 μg/dL after 1 mg dexamethasone suppression test DST) was detected in 22 (26.8%) of the 82 patients. Intriguingly, a generalized additive model identified the clinical aldosterone-producing adenoma patients with 1 mg DST>1.5 μg/dL had significantly larger tumors (P=0.02) than those with 1 mg DST<1.5 μg/dL. Multivariable logistic regression showed that the presence of KCNJ5 mutations (odds ratio, 0.22, P=0.010) and body mass index (odds ratio, 0.87, P=0.046) were negatively associated with 1 mg DST>1.5 μg/dL, whereas tumor size was positively associated with it (odds ratio, 2.85, P=0.014). Immunohistochemistry revealed a higher degree of immunoreactivity for CYP11B1 in adenomas with wild-type KCNJ5 (P=0.018), whereas CYP11B2 was more commonly detected in adenomas with KCNJ5 mutation (P=0.007). Patients with wild-type KCNJ5 and 1 mg DST>1.5 μg/dL exhibited the lowest complete clinical success rate (36.8%) after adrenalectomy. In conclusion, subclinical hypercortisolism is common in clinical aldosterone-producing adenoma patients without KCNJ5 mutation or with a relatively larger adrenal tumor. The presence of serum cortisol levels >1.5 μg/dL after 1 mg DST may be linked to a lower clinical complete success rate.
Abstract Context Investigating the co-occurrence of obstructive sleep apnea (OSA) and primary aldosteronism (PA) is crucial for understanding their interrelation. Objective This work aimed to ...evaluate the prevalence of OSA in individuals diagnosed with PA and to assess the prevalence of PA within the OSA population, with a specific focus on hypertensive individuals. Methods An exhaustive search was performed across PubMed, Embase, CINAHL, Scopus, and Web of Science up to September 2023, without restrictions on language or publication date. Studies were selected based on their focus on the prevalence of OSA in PA patients and vice versa, specifically in hypertensive individuals. Data were extracted using standard guidelines, focusing on patient characteristics, prevalence rates, and other relevant clinical parameters. Results Proportional meta-analysis using a random-effects model revealed a 59.8% prevalence of OSA in hypertensive PA patients, with 45.4% exhibiting moderate-to-severe OSA. Meta-regression showed no significant effect of age, sex, body mass index, antihypertensive medication, systolic blood pressure, diastolic blood pressure, or serum potassium on OSA prevalence. However, a significant positive association was found with the glomerular filtration rate (GFR) (P < .001). Subgroup analysis also revealed that a hyperfiltration rate (GFR ≥ 100 mL/min per 1.73 m2) may be associated with a higher prevalence of OSA (71%, P value for interaction < .01). Among hypertensive OSA patients, 11.2% had PA. Conclusion A substantial prevalence of OSA in individuals with PA was identified, demonstrating a complex interplay between these conditions in hypertensive patients. Notably, the prevalence of OSA was significantly associated with kidney hyperfiltration.
The viral spike coat protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) engages the human ACE (angiotensin-converting enzyme) 2 cell surface receptor to infect the host cells. ...Thus, concerns arose regarding theoretically higher risk for coronavirus disease-19 (COVID-19) in patients taking ACE inhibitors/angiotensin II type 1 receptor antagonists (angiotensin receptor blockers ARBs). We systematically assessed case-population and cohort studies from MEDLINE (Ovid), Cochrane Database of Systematic Reviews PubMed, Embase, medRXIV, the World Health Organization database of COVID-19 publications, and ClinicalTrials.gov through June 1, 2020, with planned ongoing surveillance. We rated the certainty of evidence according to Cochrane methods and the Grading of Recommendations Assessment, Development and Evaluation approach. After pooling the adjusted odds ratios from the included studies, no significant increase was noted in the risk of SARS-CoV-2 infection by the use of ACE inhibitors (adjusted odds ratio, 0.95 95% CI, 0.86–1.05) or ARBs (adjusted odds ratio, 1.05 95% CI, 0.97–1.14). However, the random-effects meta-regression revealed that age may modify the SARS-CoV-2 infection risk in subjects with the use of ARBs (coefficient, −0.006 95% CI, −0.016 to 0.004), that is, the use of ARBs, as opposed to ACE inhibitors, specifically augmented the risk of SARS-CoV-2 infection in younger subjects (<60 years old). The use of ACE inhibitors might not increase the susceptibility of SARS-CoV-2 infection, severity of disease, and mortality in case-population and cohort studies. Additionally, we discovered for the first time that the use of ARBs, as opposed to ACE inhibitors, specifically augmented the risk of SARS-CoV-2 infection in younger subjects, without obvious effects on COVID-19 outcomes.
Superior outcomes after surgical treatment over medical treatment for primary aldosteronism (PA) has been reported in small-scale clinical studies, but no solid conclusion has been drawn as results ...of large randomized trials are lacking.
We performed a search of PubMed, MEDLINE, Embase and Cochrane Library for randomized or observational studies that investigated cardiovascular outcomes in patients with PA undergoing medical
surgical treatment. Meta-analyses of both composite and individual outcomes were conducted. Risks of bias of the included studies were assessed with Risk Of Bias In Non-randomized Studies of Interventions (ROBINS-I) checklist. Trial sequential analysis (TSA) was performed to control the risk of random errors and assess whether the results in our meta-analysis were conclusive.
A total of 12 studies, including a total of 6148 PA patients, were included in the meta-analysis. The results of meta-analyses demonstrated lower incidence of composite cardiovascular outcomes among PA patients who underwent surgical treatment over medical treatment (odds ratio (OR): 0.49). Surgical treatment also led to less incidence of persistence of hypertension (OR of non-cure hypertension: 0.31). Fewer major cardiovascular events and mortality events were observed (OR: 0.60) after surgical treatment. TSA result showed that the required information size was 2151 and the cumulative Z curve crossed the futility boundary and reached the required information size.
Superior performance of surgical treatment over medical treatment is confirmed with meta-analyses in terms of lower incidences of composite cardiovascular outcomes and non-cure of hypertension. Hence, adrenalectomy could now be concluded as the treatment of choice for lateralized PA.
Abstract
For women with recurrent urinary tract infection (UTI), previous U101 study has shown that pentosan polysulfate sodium (PPS) monotherapy for 16 weeks significantly reduced UTI episodes in ...the treatment group throughout the trial period. In this follow-up study, we aimed to assess whether the effects of PPS would last after completion of the trial to prevent recurrent UTIs. Conducted from 2018 to 2019, the U101 study was a multicenter, prospective, phase 2a, randomized trial, enrolling women with recurrent UTI to study the effects of a 16-week oral PPS monotherapy. After approximately two years, the follow-up was conducted by phone interview, obtaining data including self-reported UTI events, quality of life questionnaire, and adverse events. The primary endpoint of follow-up study was UTI recurrence-free survival and the secondary endpoints were quality of life and adverse events. Approximately two years after completion of the trial, the rate of recurrent UTI was 25% (3 of the 12 patients) in the PPS group and 85.7% (12 of the 14 patients) in the control group. Over the entire follow-up period, the UTI recurrence-free survival was significantly better in the PPS group than in the control group (log-rank test
p
< 0.001). The quality of life at two years was significantly improved in the PPS when compared to the control group (91.7 vs. 77.5,
p
< 0.001). No late adverse event was observed after cessation of the treatment. In this study, sixteen weeks of PPS monotherapy in women with recurrent UTI significantly reduced the numbers of recurrent UTI episodes during the 2-year follow-up.
Abstract
Context
Primary aldosteronism (PA) leads to kidney function deterioration after treatment, but the effects of the estimated glomerular filtration rate (eGFR) dip following adrenalectomy and ...its long-term implications are unclear.
Objective
This study aims to examine eGFR dip in patients with unilateral PA (uPA) after adrenalectomy and clarify their long-term prognosis.
Methods
This multicenter prospective population-based cohort study, enrolled patients with uPA who underwent adrenalectomy. Patients were divided into 4 groups based on their eGFR dip ratio. Outcomes investigated included mortality, cardiovascular composite events, and major adverse kidney events (MAKEs).
Results
Among 445 enrolled patients, those with an eGFR dip ratio worse than −30% (n = 74, 16.6%) were older, had higher blood pressure, higher aldosterone concentration, and lower serum potassium levels. During 5.0 ± 3.6 years of follow-up, 2.9% died, 14.6% had cardiovascular composite events, and 17.3% had MAKEs. The group with eGFR dip worse than −30% had a higher risk of MAKEs (P < .001), but no significant differences in mortality (P = .295) or new-onset cardiovascular composite outcomes (P = .373) were found. Multivariate analysis revealed that patients with an eGFR dip ratio worse than −30% were significantly associated with older age (odds ratio OR, 1.04), preoperative eGFR (OR, 1.02), hypokalemia (OR, 0.45), preoperative systolic blood pressure (OR, 1.03), and plasma aldosterone concentration (OR, 0.99).
Conclusion
Within 5 years post adrenalectomy, 17.3% of patients had reduced kidney function. Notably, individuals with an eGFR dip ratio worse than −30% faced higher MAKE risks, underscoring the need to monitor kidney function in PA patients after surgery.
Background In patients with primary aldosteronism (PA), long-term cardiovascular and mortality outcomes after adrenalectomy vs mineralocorticoid receptor antagonist (MRA) have not been compared yet. ...We aim to compare the clinical outcomes of these patients after treatment. Design and Methods A systematic review and meta-analysis was conducted by searching PubMed, Cochrane library, and Embase from no start date restriction to 18 December 2021. Our composite primary outcomes were long-term all-cause mortality and/or major adverse cardiovascular events (MACE), including coronary artery disease (CAD), stroke, arrhythmia, and congestive heart failure. We adopted the random-effects model and performed subgroup analyses, meta-regression, and trial sequential analysis (TSA). Results A total of 9 studies with 8473 adult patients with PA (≥18 years) were enrolled. A lower incidence of composite primary outcomes was observed in the adrenalectomy group (odds ratio (OR): 0.46 (95% CI: 0.38–0.56), P < 0.001). We found a lower incidence of all-cause mortality (OR: 0.33 (95% CI: 0.15–0.73), P = 0.006) and MACE (OR: 0.55, (95% CI: 0.40–0.74), P = 0.0001) in the adrenalectomy group. The incidence of CAD (OR: 0.33 (95% CI: 0.15–0.75), P = 0.008), arrhythmias (OR: 0.46 (95% CI: 0.27–0.81), P = 0.007), and congestive heart failure (OR: 0.52 (95% CI: 0.33–0.81), P = 0.004) was also lower in adrenalectomy group. The metaregression showed patient’s age may attenuate the benefits of adrenalectomy on composite primary outcomes (coefficient: 1.084 (95% CI: 1.005–1.169), P = 0.036). TSA demonstrated that the accrued sample size and effect size were sufficiently large to draw a solid conclusion, and the advantage of adrenalectomy over MRA was constant with the chronological sequence. Conclusions In conclusion, adrenalectomy could be preferred over MRA for patients with PA in reducing the risk of all-cause mortality and/or MACE and should be considered as the treatment of choice. That patients with PA could get less benefit from adrenalectomy as they age warrants further investigation.
Concurrent autonomous cortisol secretion (ACS) in patients with primary aldosteronism (PA patients) is not uncommon. This work aimed to determine the effect of cortisol levels on incident new-onset ...type 2 diabetes mellitus (NODM) in PA patients. Using the prospectively designed observational TAIPAI cohort, the PA patients were grouped by cortisol level after an overnight low-dose dexamethasone suppression test (1-mg DST). Of the 476 PA patients, 387 (43.7% men; mean age 52.8 years) did not have baseline DM. After a mean follow-up of 4.3 ± 2.9 years, 32 patients (8.3%) developed NODM. The cutoff value obtained via a generalized additive model showed that a serum cortisol level ≥ 2.65 µg/dL after 1-mg DST was a risk factor for developing NODM (HR, 3.5, p = 0.031) by Cox proportional- hazards model.. In PA patients with a higher body mass index (>25 kg/m
; HR, 3.16), lower estimated glomerular filtration rate (<90 ml/min/1.73 m
; HR, 3.18), longer hypertension duration (>7 years; HR, 3.34), and higher waist-to-hip ratio (>0.9; HR, 3.07), a concomitant cortisol level ≥ 2.65 μg/dL after 1-mg DST were more likely to develop NODM. The high-cortisol group of patients with aldosterone-producing adenoma (APA) using mineralocorticoid receptor antagonist (MRA) was associated with an increased risk of NODM (HR, 5.72). Our results showed that PA patients with a concomitant cortisol level ≥ 2.65 µg/dL after 1-mg DST, independent of the aldosterone level, had a higher incidence of NODM. Such PA patients should be carefully evaluated and managed to achieve better glucose control and prevent metabolic syndrome.
Acute kidney injury (AKI) may increase the risk of chronic kidney disease (CKD), development of end-stage renal disease (ESRD), and mortality. However, the impact of exposure to ...angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker (ACEi/ARB) in patients experiencing AKI/acute kidney disease (AKD) is still unclear.
In this systematic review, we searched all relevant studies from PubMed, Embase, Cochrane, Medline, Collaboration Central Register of Controlled Clinical Trials, Cochrane Systematic Reviews, and ClinicalTrials.gov until July 21, 2020. We evaluated whether the exposure to ACEi/ARB after AKI onset alters recovery paths of AKD and impacts risks of all-cause mortality, recurrent AKI, or incident CKD. We rated the certainty of evidence according to Cochrane methods and the GRADE approach.
A total of seven articles, involving 70,801 patients, were included in this meta-analysis. The overall patient mortality rate in this meta-analysis was 28.4%. Among AKI patients, all-cause mortality was lower in ACEi/ARB users than in ACEi/ARB nonusers (log odds ratio (OR) -0.37, 95% confidence interval (CI): -0.42--0.32, p < 0.01). The risk of recurrent adverse kidney events after AKI was lower in ACEi/ARB users than in nonusers (logOR -0.25, 95% CI: -0.33--0.18, p < 0.01). The risk of hyperkalemia was higher in ACEi/ARB users than in nonusers (logOR 0.43, 95% CI: 0.27-0.59, p < 0.01). Patients with continued use of ACEi/ARB after AKI also had lower mortality risk than those prior ACEi/ARB users but who did not resume ACEi/ARB during AKD (logOR -0.36, 95% CI: -0.4--0.31, p < 0.01).
Exposure to ACEi/ARB after AKI is associated with lower risks of all-cause mortality, recurrent AKI, and progression to incident CKD. Patients with AKI may have a survival benefit by continued use of ACEi/ARB; however, a higher incidence of hyperkalemia associated with ACEi/ARB usage among these patients deserves close clinical monitoring.
PDF
