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INTRODUCTION AND OBJECTIVE:Mineralcorticoid receptor antagonist was the first-line treatment in bilateral adrenal hyperplasia (BAH) with primary aldosteronism (PA). Some patients were refractory to...

Context Familial hyperaldosteronism type I (FH-I) or glucocorticoid-remediable aldosteronism (GRA) is caused by unequal crossing over of the steroid 11β-hydroxylase (CYP11B1) and aldosterone synthase (CYP11B2) genes. Somatic KCNJ5 mutations have not been reported in patients with GRA; therefore, the appropriate treatment and prognosis of such concurrent cases remain unknown. Case Description Two siblings of a Taiwanese family with GRA were found to have adrenal adenomas and somatic KCNJ5 mutations. Complete clinical cure was achieved after unilateral adrenalectomy. Furthermore, the conversion site of the chimeric gene was identified by direct sequencing. Conclusions We report the coexistence of a somatic KCNJ5 mutation and GRA. Patients with GRA whose blood pressure management develops resistance to glucocorticoid treatment could therefore benefit from a lateralization test. The promising outcomes after unilateral adrenalectomy presented in this report offer new perspectives for further research into various PA subtypes.

Background/Purpose: This study aims to investigate the safety and feasibility of laparoscopic adrenalectomy for benign adrenal tumor without peri-operative NGT decompression. Methods: From July 2010 to March 2014, 82 consecutive patients with benign unilateral adrenal tumor underwent elective laparoscopic adrenalectomy by a single surgeon were recruited for this study. We compared the clinico-demographic profile, estimated blood loss, operative time, time to full diet, time to ambulate, the length of hospital staying, analgesics use and complications between two groups stratified by the use of NGT. Results: There were no significant differences in the clinico-demographic profile of the two groups, including age, laterality, body mass index, gender, ASA classification, tumor diameter and histologic types between two groups. Peri-operative parameters were similar between NGT and Non-NGT groups (estimated blood loss, 55.85 vs. 54.4 ml; operative time, 110.3 vs. 112.3 min; p > 0.05) The post-operative outcome of interests, including days to full oral intake (3.32 vs. 3.34 days), days to ambulate (2.07 vs. 2.10 days), hospital stay (4.32 vs. 4.34 days), and analgesics use (6.00 vs. 5.83 mg; all p > 0.05) showed no significant difference between NGT and non-NGT group. Conclusion: Laparoscopic adrenalectomy in patients with benign unilateral adrenal tumor without the use of peri-operative nasogastric tube decompression is safe and feasible. Keywords: Nasogastric tube decompression, Outcomes, Laparoscopic adrenalectomy

Objectives Acute kidney disease (AKD), the transition of acute kidney injury to chronic kidney disease, has major clinical significance. Whether mineralocorticoid receptor antagonist will afford target organ protection during this critical stage remains ill-defined. Methods Using a population-based cohort database from January 1999 to July 2011, we identified 7252 AKD patients with hypertension, of whom 2255 were treated with mineralocorticoid receptor antagonist (user) and 4997 were treated by other antihypertensive medication (nonuser). Outcomes were all-cause mortality, major adverse cardiovascular events (MACE), and long-term dialysis dependence. Results With median 13.37 months of follow-up (IQR 30.53 months), users had a lower incidence of dialysis dependence than nonusers (138.3/1000 person-years vs. 267.2/1000 person-years). After matching users and nonusers (1 : 1) with mortality as a competing risk, Cox proportional hazards analyses showed that mineralocorticoid receptor antagonist therapy was associated with lower risk of dialysis dependence [subhazard ratio (sHR) = 0.83, 95% confidence interval (CI) 0.74-0.93, P = 0.001] but higher risk of hyperkalemia (sHR 1.15, 95% CI, 1.04-1.26, P = 0.005) compared with nonusers. Nonetheless, the risks for all-cause mortality [adjusted hazard ratio (aHR) 1.07, 95% CI 0.98-1.17, P = 0.109] and MACE (sHR 1.08, 95% CI 0.95-1.23, P = 0.210) were similar. Conclusion Although carrying the risk of hyperkalemia, mineralocorticoid receptor antagonist therapy is associated with similar risk for incident MACE and death; however, with lower risk of long-term dialysis dependence. Our findings have the potential to provide target-organ protection insights in AKD patients with hypertension.

Background/Purpose: Even with the increasing recognition of primary aldosteronism (PA) as a cause of refractory hypertension and an issue of public health, the consensus of its optimal surgical or medical treatment in Taiwan has not been reached. Our objective was to develop a clinical practice guideline that is feasible for real-world management of PA patients in Taiwan. Methods: The Taiwan Society of Aldosteronism (TSA) Task Force recognized the above-mentioned issues and reached this Taiwan PA consensus at its inaugural meeting, in order to provide updated information of internationally acceptable standards, and also to incorporate our local disease characteristics and constraints into PA management. Results: In patients with lateralized PA, including aldosterone producing adenoma (APA), laparoscopic adrenalectomy is the ‘gold standard’ of treatment. Mini-laparoscopic and laparoendoscopic single-site approaches are feasible only in highly experienced surgeons. Patients with bilateral adrenal hyperplasia or those not suitable for surgery should be treated by mineralocorticoid receptor antagonists. The outcome data of PA patient management from the literature, especially from PA patients in Taiwan, are reviewed. Mental health screening is helpful in early detection and management of psychopathology among PA patients. Conclusion: We hope this consensus will provide a guideline to help medical professionals to manage PA patients in Taiwan to achieve a better quality of care. Keywords: Primary aldosteronism, Guideline, TAIPAI

Objective To focus on the potential beneficial effects of the pleiotropic effects of dipeptidyl peptidase-4 inhibitors (DPP4is) on attenuating progression of diabetic kidney disease in reducing the long-term effect of the acute kidney injury (AKI) to chronic kidney disease (CKD) transition. Patients and Methods Data from the National Health Insurance Research Database from January 1, 1999, to July 31, 2011, were analyzed, and patients with diabetes weaning from dialysis-requiring AKI were identified. Cox proportional hazards models and inverse-weighted estimates of the probability of treatment were used to adjust for treatment selection bias. The outcomes were incident end-stage renal disease (ESRD) and mortality, major adverse cardiovascular events, and hospitalized heart failure. Results Of a total of 6165 patients with diabetes weaning from dialysis-requiring AKI identified, 5635 (91.4%) patients were DPP4i nonusers and 530 (8.6%) patients were DPP4i users. Compared with DPP4i nonusers, DPP4i users had a lower risk of ESRD (hazard ratio, 0.81; 95% CI, 0.70-0.94; P=.04) and all-cause mortality (hazard ratio, 0.28; 95% CI, 0.23-0.34; P

PurposeSomatic KCNJ5 mutation occurs in half of unilateral primary aldosteronism (PA) and is associated with more severe phenotype. Mutation status can only be identified by tissue sample from adrenalectomy. NP-59 adrenal scintigraphy is a noninvasive functional study for disease activity assessment. This study aimed to evaluate the predictive value of NP-59 adrenal scintigraphy in somatic KCNJ5 mutation among PA patients who received adrenalectomy.MethodsSixty-two PA patients who had NP-59 adrenal scintigraphy before adrenalectomy with available KCNJ5 mutation status were included. Two semiquantitative parameters, adrenal to liver ratio (ALR) and lesion to contralateral ratio of bilateral adrenal glands (CON) derived from NP-59 adrenal scintigraphy, of mutated and wild-type patients were compared. Cutoff values calculated by receiver-operating characteristic (ROC) analysis were used as a predictor of KCNJ5 mutation.ResultsTwenty patients had KCNJ5 mutation and 42 patients were wild type. Patients harboring KCNJ5 mutation had both higher ALR and CON (p = 0.0031 and 0.0833, respectively) than wild-type patients. With ALR and CON cutoff of 2.10 and 1.95, the sensitivity and specificity to predict KCNJ5 mutation were 85%, 57% and 45%, 93%, respectively. Among 20 patients with KCNJ5 mutation, 16 showed G151R point mutation (KCNJ5- G151R) and 4 showed L168R point mutation (KCNJ5-L168R), which former one had significantly lower ALR (p=0.0471).ConclusionPA patients harboring somatic KCNJ5 mutation had significantly higher NP-59 uptake regarding to ALR and CON than those without mutation. APAs with KCNJ5-L168R point mutation showed significantly higher ALR than those with KCNJ5-G151R point mutation.

The aim of this study was to update the information on internationally acceptable standards and clinical practice recommendations for the management of patients with primary aldosteronism (PA). The Taiwan Society of Aldosteronism (TSA) Task Force acknowledged the novel issues of PA and reached a group consensus on PA in Taiwan by collecting the best available evidence and conducting one group meeting, several conference calls, and multiple e-mail communications. Unilateral adrenalectomy is the preferred treatment for patients with aldosterone-producing adenoma (APA). For medical treatment with mineralocorticoid receptor antagonists (MRAs), spironolactone is the first-line treatment, and eplerenone is a reasonable alternative in PA patients intolerant or contraindicated to spironolactone. The dose of MRAs can be titrated according to plasma renin activity (PRA). For screening PA-related comorbidities, we suggest albuminuria to predict a post-treatment decline in renal function, echocardiography as cardiac evaluation, bone mineral density scan for osteoporosis, and obstructive sleep apnea. In tissue and genetic surveys, we suggest immunohistochemical staining and somatic mutation screening for post-operative adrenal specimens in APA patients. With this consensus, we hope to update the information on PA for clinical physicians to facilitate better identification, management and treatment of patients with PA.

The association between regional economic status and the probability of renal recovery among patients with dialysis-requiring AKI (AKI-D) is unknown. The nationwide prospective multicenter study enrolled critically ill adult patients with AKI-D in four sampled months (October 2014, along with January, April, and July 2015) in Taiwan. The regional economic status was defined by annual disposable income per capita (ADIPC) of the cities the hospitals located. Among the 1,322 enrolled patients (67.1 ± 15.5 years, 36.2% female), 833 patients (63.1%) died, and 306 (23.1%) experienced renal recovery within 90 days following discharge. We categorized all patients into high (n = 992) and low economic status groups (n = 330) by the best cut-point of ADIPC determined by the generalized additive model plot. By using the Fine and Gray competing risk regression model with mortality as a competing risk factor, we found that the independent association between regional economic status and renal recovery persisted from model 1 (no adjustment), model 2 (adjustment to basic variables), to model 3 (adjustment to basic and clinical variables; subdistribution hazard ratio, 1.422; 95% confidence interval, 1.022–1.977; p = 0.037). In conclusion, high regional economic status was an independent factor for renal recovery among critically ill patients with AKI-D.

Background Primary aldosteronism ( PA ) is associated with higher atrial fibrillation prevalence and other cardiovascular complications. However, the effect of target treatment to prevent new‐onset atrial fibrillation ( NOAF ) remains unclear. This study investigated incidence of NOAF under different treatment strategies in patients with PA. Methods and Results We analyzed longitudinal data for patients with PA without atrial fibrillation history from 1997 to 2009 within the National Health Insurance Research Database in Taiwan. Patients with essential hypertension matched by propensity score were enrolled as controls. The primary outcome measurement was NOAF , and secondary outcome measurements were mortality, major cardiac and cardiac/cerebrovascular events, and a combined end point of NOAF and mortality. We identified 2202 patients with PA (534 adrenalectomy, 1668 mineralocorticoid receptor antagonist [MRA] therapy) and 8808 essential hypertension controls with mean follow‐up of 4.4 years. In primary outcome measurement, patients with PA who underwent adrenalectomy had a lower incidence of NOAF (adjusted hazard ratio; 0.28, P =0.011) than controls. In contrast, the patients with PA who received MRA therapy had comparable risk of NOAF (adjusted hazard ratio, 1.20; P =0.224). In secondary outcome measurement, patients with PA who underwent adrenalectomy had a lower rate of mortality and combined end point of NOAF and mortality than controls. Patients with PA who received MRA therapy had a higher risk of mortality, major cardiac and cardiac/cerebrovascular events, and combined NOAF with mortality than the essential hypertension controls. Conclusions Compared with patients with essential hypertension, patients with PA who underwent adrenalectomy had a lower incidence of NOAF . However, this finding was not observed in patients with PA who received MRA therapy with a lower dose. Differences between the 2 strategies may reduce with a higher dose of MRA therapy.

Background: In primary aldosteronism (PA), kidney function impairment could be concealed by relative hyperfiltration and emerge after adrenalectomy. We hypothesized transtubular gradient potassium gradient (TTKG), a kidney aldosterone bioactivity indicator, could correlate to end organ damage and forecast kidney function impairment after adrenalectomy. Methods: In the present prospective study, we enrolled lateralized PA patients who underwent adrenalectomy and were followed up 12 months after operation in the Taiwan Primary Aldosteronism Investigation (TAIPAI) registry from 2010 to 2018. The clinical outcome was kidney function impairment, defined as estimated glomerular filtration rate (eGFR) 2 at 12 months after adrenalectomy. End organ damage is determined by microalbuminuria and left ventricular mass. Results: In total, 323 patients [mean, 50.8 ± 10.9 years old; female 178 (55.1%)] were enrolled. Comparing pre-operation and post-operation data, systolic blood pressure, serum aldosterone, urinary albumin to creatinine ratio and eGFR decreased. TTKG ⩾ 4.9 correlated with pre-operative urinary albumin to creatinine ratio >50 mg/g [odds ratio (OR) = 2.42; p = 0.034] and left ventricular mass (B = 20.10; p = 0.018). Multivariate logistic regression analysis demonstrated that TTKG ⩾ 4.9 could predict concealed chronic kidney disease (OR = 5.42; p = 0.011) and clinical success (OR = 2.90, p = 0.017) at 12 months after adrenalectomy. Conclusions: TTKG could predict concealed kidney function impairment and cure of hypertension in PA patients after adrenalectomy. TTKG more than 4.9 as an adverse surrogate of aldosterone and hypokalaemia correlated with pre-operative end organ damage in terms of high proteinuria and cardiac hypertrophy.

Background Previous studies show that patients with primary aldosteronism are associated with higher risk of congestive heart failure ( CHF ). However, the effect of target treatment to the incidental CHF has not been elucidated. We aimed to investigate the risk of new‐onset CHF in patients with aldosterone‐producing adenomas ( APAs ) and explore the effect of adrenalectomy on new onset of CHF . Methods and Results From 1997 to 2009, 688 APA were identified and matched with essential hypertension controls. The risks of developing incidental CHF (hazard ratio, 0.49; 95% CI , 0.31–0.75; P =0.001) and mortality (hazard ratio, 0.29; 95% CI , 0.20–0.44; P APA group after targeted treatment. A total of 605 patients with APAs who underwent adrenalectomy lowered the risks of CHF (subdistribution hazard ratio, 0.55; 95% CI , 0.34–0.90; P =0.017) and mortality (adjusted hazard ratio, 0.27; 95% CI , 0.16–0.44; P Conclusions In conclusion, for patients with APAs, adrenalectomy can be associated with lower risk of incidental CHF and all‐cause mortality in a long‐term follow‐up.

Diabetic kidney disease (DKD) is a major cause of morbidity and mortality in patients with diabetes mellitus and the leading cause of end-stage renal disease in the world. The most characteristic marker of DKD is albuminuria, which is associated with renal disease progression and cardiovascular events. Renal hemodynamics changes, oxidative stress, inflammation, hypoxia and overactive renin-angiotensin-aldosterone system (RAAS) are involved in the pathogenesis of DKD, and renal fibrosis plays the key role. Intensified multifactorial interventions, including RAAS blockades, blood pressure and glucose control, and quitting smoking, help to prevent DKD development and progression. In recent years, novel agents are applied for preventing DKD development and progression, including new types of glucose-lowering agents, pentoxifylline, vitamin D analog paricalcitol, pyridoxamine, ruboxistaurin, soludexide, Janus kinase inhibitors and nonsteroidal minerocorticoid receptor antagonists. In this review, recent large studies about DKD are also summarized. Keywords: Diabetic kidney disease (DKD), Diabetic nephropathy (DN), Diabetes mellitus, Albuminuria

Background Acute kidney injury (AKI) after cardiovascular surgery is a serious complication. Little is known about the ability of novel biomarkers in combination with clinical risk scores for prediction of advanced AKI. Methods In this prospectively conducted multicenter study, urine samples were collected from 149 adults at 0, 3, 6, 12 and 24 h after cardiovascular surgery. We measured urinary hemojuvelin (uHJV), kidney injury molecule-1 (uKIM-1), neutrophil gelatinase-associated lipocalin (uNGAL), α-glutathione S-transferase (uα-GST) and π-glutathione S-transferase (uπ-GST). The primary outcome was advanced AKI, under the definition of Kidney Disease: Improving Global Outcomes (KDIGO) stage 2, 3 and composite outcomes were KDIGO stage 2, 3 or 90-day mortality after hospital discharge. Results Patients with advanced AKI had significantly higher levels of uHJV and uKIM-1 at 3, 6 and 12 h after surgery. When normalized by urinary creatinine level, uKIM-1 in combination with uHJV at 3 h post-surgery had a high predictive ability for advanced AKI and composite outcome (AUC = 0.898 and 0.905, respectively). The combination of this biomarker panel (normalized uKIM-1, uHJV at 3 h post-operation) and Liano’s score was superior in predicting advanced AKI (AUC = 0.931, category-free net reclassification improvement of 1.149, and p

Background/Purpose: Even though the increasing clinical recognition of primary aldosteronism (PA) as a public health issue, its heightened risk profiles and the availability of targeted surgical/medical treatment being more understood, consensus in its diagnosis and management based on medical evidence, while recognizing the constraints of our real-world clinical practice in Taiwan, has not been reached. Methods: The Taiwan Society of Aldosteronism (TSA) Task Force acknowledges the above-mentioned issues and reached this Taiwan PA consensus at its inaugural meeting, in order to provide updated information of internationally acceptable standards, and also to incorporate our local disease characteristics into the management of PA. Results: When there is suspicion of PA, a plasma aldosterone to renin ratio (ARR) should be obtained initially. Patients with abnormal ARR will undergo confirmatory laboratory and image tests. Subtype classification with adrenal venous sampling (AVS) or NP-59 nuclear imaging, if AVS not available, to lateralize PA is recommended when patients are considered for adrenalectomy. The strengths and weaknesses of the currently available identification methods are discussed, focusing especially on result interpretation. Conclusion: With this consensus we hope to raise more awareness of PA among medical professionals and hypertensive patients in Taiwan, and to facilitate reconciliation of better detection, identification and treatment of patients with PA. Index words: Primary aldosteronism, Guideline, TAIPAI, TSA

Discoveries of somatic mutations permit the recognition of subtypes of aldosterone-producing adenomas (APAs) with distinct clinical presentations and pathological features. Catenin β1 (CTNNB1) mutation in APAs has been recently described and discussed in the literature. However, significant knowledge gaps still remain regarding the prevalence, clinical characteristics, pathophysiology, and outcomes in APA patients harboring CTNNB1 mutations. Aberrant activation of the Wnt/β-catenin signaling pathway will further modulate tumorigenesis. We also discuss the recent knowledge of CTNNB1 mutation in adrenal adenomas.

Objective:Abnormal glucose metabolism due to insulin resistance has been linked to aldosterone overproduction. However, the long-term incidence of new-onset diabetes mellitus (NODM) among patients with primary aldosteronism after targeted treatment has not been well documented.Methods:The diagnosis

// Chi-Sheng Hung 1 , Xue-Ming Wu 2 , Ching-Way Chen 3 , Ying-Hsien Chen 1 , Vin-Cent Wu 1 , Che-Wei Liao 4 , Yi-Yao Chang 5 , Ruh-Fang Yen 6 , Ching-Chu Lu 6 , Mao-Yuan M. Su 7 , Kao-Lang Liu 7 , Chin-Chen Chang 7 , Li-Yu Daisy Liu 8 , Kwan-Dun Wu 1 , Yen-Hung Lin 1 and the TAIPAI Study Group 1 Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan 2 Department of Internal Medicine, Taoyuan General Hospital, Taoyuan, Taiwan 3 Department of Internal Medicine, National Taiwan University Hospital Yun-Lin Branch, Yun-Lin, Taiwan 4 Department of Internal Medicine, National Taiwan University Hospital Hsin-Chu Branch, Hsin-Chu, Taiwan 5 Cardiology Division of Cardiovascular Medical Center, Far Eastern Memorial Hospital, New Taipei City, Taiwan 6 Department of Nuclear Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan 7 Department of Medical Imaging, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan 8 Department of Agronomy, Biometry Division, National Taiwan University, Taipei, Taiwan Correspondence to: Yen-Hung Lin, email: austinr34@gmail.com Keywords: primary aldosteronism, salt intake, left ventricular mass, TAIPAI Received: December 08, 2016 Accepted: April 05, 2017 Published: April 28, 2017 ABSTRACT Salt intake is highly associated with cardiac structure in patients with primary aldosteronism (PA). We investigated the association among dietary salt intake, aldosterone and left ventricular mass in patients with PA. We enrolled 158 patients with PA and 158 patients with essential hypertension. We measured 24-hour urinary sodium (UNa) and aldosterone (UAldo) level and echocardiography parameters. In patients with PA, the UAldo level was positively correlated with left ventricular mass index (LVMI; r=0.231, p=0.007). The UNa level was not linearly correlated with left ventricular structural parameters in patients with PA. To test if UNa has a non-linear relationship with LVMI among patients with PA, we categorized the participants according to the tertile of UNa (low, median, and high tertile). PA patients with medium tertile of UNa had significant lower LVMI than the other two groups (LVMI: 144.1 ± 42.9, 121.1 ± 33.4, and 136.7 ± 32.8 g/m2, from the lowest to the highest tertile of Una; analysis of variance p=0.006, post-hoc p

Primary aldosteronism (PA) is associated with increased urinary calcium excretion and osteoporosis prevalence. We studied the long-term effect of hyperaldosterone on fracture risk and possible risk mitigation via treatments, by comparing PA patients and their essential hypertension (EH) counterparts extracted by propensity score match. We used a longitudinal population database from the Taiwan National Health Insurance, and used a validated algorithm to identify PA patients diagnosed in 1997-2010. Our sample included 2533 PA patients, including 921 patients with aldosterone-producing adenoma (APA). Our methods for assessing excessive fracture risk included multivariable Cox regression and the competing risk regression. The incidence rate of fracture at any site was 14.4 per 1000 person-years for PA, and 11.2 per 1000 person-years for APA. In contrast, the incidence rate of fracture at any site was 8.3 per 1000 person-years in EH controls for PA, and 6.5 per 1000 person-years in EH controls for APA. Mineralocorticoid receptor antagonist (MRA) treatment might be associated with higher risk of osteoporotic fracture in the whole female PA cohort (subdistribution hazard ratio [SHR] = 2.12, p = 0.008) as well as female APA patients (SHR = 1.15, p = 0.049). As to fracture at any site, MRA treatment was also associated with higher risk; the SHR was 1.88 (p < 0.001) in the whole female PA cohort, and 2.17 (p = 0.019) in female APA patients. PA is tightly associated with higher risk of bone fracture, even in the case where the competing risk of death was controlled. Particularly, female PA patients treated with MRA were confronted with significantly higher risk in bone fracture than their EH controls. © 2017 American Society for Bone and Mineral Research.

Objective: Adverse neurological effects may be common following acute kidney injury (AKI). The purpose of our study was to investigate the long-term risk of dementia following AKI and temporary dialysis during hospitalization. Materials and Methods: The study was based on data from the National Health Insurance Research Database of Taiwan. Patients 18-year-old and older who were withdrawn from temporary dialysis because of AKI and survived for at least 90 days following discharge were included in our acute-dialysis-recovery group. Patients without AKI and dialysis were the control group. A Cox proportional-hazards regression model was applied to determine the risk of dementia. Results: Of 2905 acute-dialysis patients, 689 (23.7%) survived for at least 90 days following recovery from acute dialysis. The Cox proportional-hazards regression model showed that the acute-dialysis-recovery group had an increased long-term risk of dementia (hazard ratio [HR], 2.01; P = 0.01) compared with the control group. The conditional effects plot showed that the risk of dementia was amplified in patients who were older than 58 years. The development of dementia following recovery from acute dialysis was associated with an increase in all-cause mortality (HR, 2.38; P < 0.001). Conclusions: Patients with acute dialysis have a greater risk for the subsequent development of dementia after recovery than patients without AKI and dialysis, and patients who develop dementia after recovery from temporary dialysis are at increased risk for mortality.

OBJECTIVE The association between hyperaldosteronism and autoimmune disorders has been postulated. However, long-term incidence of a variety of new-onset autoimmune diseases (NOAD) among patients with primary aldosteronism has not been well investigated. METHODS From Taiwan's National Health Insurance Research Database with a 23-million population insurance registry, the identification of primary aldosteronism, essential hypertension and NOAD as well as all-cause mortality were ascertained by a validated algorithm. RESULTS From 1997 to 2009, 2319 primary aldosteronism patients without previously autoimmune disease were identified and propensity score-matched with 9276 patients with essential hypertension. Among those primary aldosteronism patients, 806 patients with aldosterone-producing adenomas (APA) were identified and matched with 3224 essential hypertension controls. NOAD incidence is augmented in primary aldosteronism patients compared with its matched essential hypertension (hazard ratio 3.82, P

Background Primary aldosteronism is the most common cause of secondary hypertension and is associated with left ventricular hypertrophy. However, whether aldosterone excess is responsible for left ventricular (LV) diastolic dysfunction is unknown. Methods and Results We prospectively enrolled 129 patients with aldosterone‐producing adenoma and 120 patients with essential hypertension, and analyzed their clinical, biochemical, and echocardiographic data, including tissue Doppler images. The patients with aldosterone‐producing adenoma were reevaluated 1 year after adrenalectomy. After propensity score matching, there were 105 patients in each group. The patients with aldosterone‐producing adenoma had worse diastolic function than the patients with essential hypertension, as reflected by lower e′ ( P P =0.003). Multivariate analysis showed that LV diastolic function was significantly correlated with age ( P P P =0.002), systolic blood pressure ( P =0.004), creatinine ( P =0.008), and log‐transformed aldosterone‐renin ratio ( P =0.003). After adrenalectomy, the patients with aldosterone‐producing adenoma had significant improvements in LV diastolic function as reflected by an increase in e′ ( P =0.003) and decrease in E/e′ ( P =0.002). The change in E/e′ was independently correlated with baseline E/e′ ( P P =0.006). Conclusions The patients with primary aldosteronism had worse LV diastolic function than the patients with essential hypertension after propensity score matching, and this could be reversed after adrenalectomy, suggesting that aldosterone excess may induce LV diastolic dysfunction.

Objective Primary aldosteronism (PA) is a common cause of secondary hypertension, and the long-term effect of excess aldosterone on kidney function is unknown. Patients and Methods We used a longitudinal population database from the Taiwan National Health Insurance system and applied a validated algorithm to identify patients with PA diagnosed between 1997 and 2009. Results There were 2699 patients with PA recruited, of whom 761 patients with an aldosterone-producing adenoma (APA) were identified. The incidence rate of end-stage renal disease (ESRD) was 3% in patients with PA after targeted treatments and 5.2 years of follow-up, which was comparable to the rate in controls with essential hypertension (EH). However, after taking mortality as a competing risk, we found a significantly lower incidence of ESRD when comparing patients with PA vs EH [subdistribution hazard ratio (sHR), 0.38; P = 0.007] and patients with APA vs EH (sHR 0.55; P = 0.021) after adrenalectomy; however, we did not see similar results in groups with mineralocorticoid receptor antagonist (MRA)‒treated PA vs EH. There was also a significantly lower incidence of mortality in groups with PA and APA who underwent adrenalectomy than among EH controls (P < 0.001). Conclusion Regarding incident ESRD, patients with PA were comparable to their EH counterparts after treatment. After adrenalectomy, patients with APA had better long-term outcomes regarding progression to ESRD and mortality than hypertensive controls, but MRA treatments did not significantly affect outcome.

We sought to measure the clinical benefits of adrenal venous sampling (AVS), a test recommended by guidelines for primary aldosteronism (PA) patients seeking surgical cure, in a large registry of PA patients submitted to AVS. Data of 1625 consecutive patients submitted to AVS in 19 tertiary referral centers located in Asia, Australia, Europe, and North America were collected in a large multicenter international registry. The primary end points were the rate of bilateral success, ascertained lateralization of PA, adrenalectomy, and of cured arterial hypertension among AVS-guided and non AVS-guided adrenalectomy patients. AVS was successful in 80.1% of all cases but allowed identification of unilateral PA in only 45.5% by the criteria in use at each center. Adrenalectomy was performed in 41.8% of all patients and cured arterial hypertension in 19.6% of the patients, 2-fold more frequently in women than men ( P P =0.027). Compared with surgical cases, patients treated medically needed more antihypertensive medications ( P P The low rate of adrenalectomy and cure of hypertension in PA patients seeking surgical cure indicates suboptimal AVS use, possibly related to issues in patient selection, technical success, and AVS data interpretation. Given the better outcomes of AVS-guided adrenalectomy, these results call for actions to improve the diagnostic use of this test that is necessary for detection of surgical PA candidates. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT01234220.

Background Superior performance of surgical treatment over medical treatment for primary aldosteronism (PA) has been reported in small-scale clinical studies with diverse clinical outcomes, but no solid conclusion has been drawn as results of large randomized trials are lacking. Methods: We performed a search of PubMed, MEDLINE, Embase and Cochrane Library for randomized or observational studies that investigated cardiovascular outcomes in patients with primary aldosteronism undergoing medical versus surgical treatment. - Composite outcomes including persistence of hypertension (HT) and incidence of significant clinical events (e.g. major adverse cardiovascular events [MACE] and all-cause mortality) after treatment was considered. 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. Findings: A total of 368 related citations were reviewed and 11 studies that fulfilled the inclusion criteria, with altogether 5,994 PA patients, were included in the meta-analysis. Evaluation showed that there were low-moderate risks of bias in (63.64%) 7 of the included studies. The results of meta-analyses demonstrated lower incidence of composite outcomes among PA patients who underwent surgical treatment over medical treatment (Odds Ratio (OR): 0.49, 95% CI: 0.29-0.83 in random effects model). Surgical treatment also led to less incidence of persistence of HT (OR of non-cure of HT: 0.31, 95% CI: 0.11-0.85 in random effects model). Fewer major cardiovascular events and mortality events after surgical treatment were observed in the fixed effect model (OR: 0.47, 95% CI: 0.39-0.56), but failed to reach significant statistical levels in random effects model (OR: 0.71, 95% CI: 0.33-1.52) when compared to medical treatment. Interpretation: Superior performance of surgical treatment over medical treatment for PA patients is confirmed with meta-analyses in terms of lower incidences of composite outcomes and non-cure of HT. Hence, adrenalectomy could now be concluded as the treatment of choice for lateralized PA. Funding Statement: This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Declaration of Interests: All authors declare no competing interests Ethics Approval Statement: The pre-defined review protocol was registered at the PROSPERO international prospective register of systematic reviews (PROSPERO registration number CRD42019119175). The protocol for this trial and supporting CONSORT checklist are available as supporting information.

Aim Acute kidney injury (AKI) carries an increasing incidence rate worldwide and increases the risk of developing end-stage renal disease (ESRD) as well as the medical expenses during the post-AKI course. The Taiwan Consortium for Acute Kidney Injury and Renal Diseases (CAKs) has thus launched a nationwide epidemiology and prognosis of dialysis-requiring acute kidney injury (NEP-AKI-D) study, which prospectively enrols critically ill patients with AKI. Through thoroughly evaluating the risk and prognostic factors of AKI, we hope to lower the incidence of AKI and ESRD from the perspective of AKI-ESRD interaction. Methods The CAKs includes 30 hospitals which distribute widely through the four geographical regions (north, middle, south, and east) of Taiwan, and have a 1:1 ratio of medical centres to regional hospitals in each region. The NEP-AKI-D study enrols intensive care unit-based AKI patients who receive dialysis in the four seasonal sampled months (October 2014, along with January, April, and July 2015) in the included hospitals. The collected data include demographic information, pertaining laboratory results, dialysis settings and patient outcomes. The data are uploaded in a centre website and will be audited by on-site principal investigators, computer logic gates, and the CAKs staffs. The outcomes of interest are in-hospital mortality, dialysis-dependency and readmission rate within 90 days after discharge. Conclusion The NEP-AKI-D study enrols a large number of representative AKI patients throughout Taiwan. The results of the current study are expected to provide more insight into the risk and prognostic factors of AKI and further attenuated further chronic kidney disease transition.

Primary aldosteronism has been associated with myocardial fibrosis, and is the most common cause of secondary hypertension. We previously showed that aldosterone can induce the secretion of galectin-3. The aim of this study was to investigate the association between myocardial fibrosis and plasma galectin-3 level in patients with primary aldosteronism. We prospectively analyzed 11 patients with aldosterone-producing adenoma (APA) who received adrenalectomy from December 2006 to October 2008, and 17 patients with essential hypertension as controls. Levels of plasma galectin-3 were determined in both groups, and both groups underwent echocardiography with cyclic variations of integrated backscatter (CVIBS) to characterize tissue initially and 1 year after surgery in the APA group. Diastolic blood pressure, concentration of plasma aldosterone and aldosterone-renin ratio were significantly higher, and serum potassium level and plasma renin activity significantly lower in the APA group compared to the controls. In addition, left ventricular mass index was significantly higher and CVIBS significantly lower in the APA group (7.3±2.0 vs 9.2±1.7 dB, p=0.015). Furthermore, the concentration of plasma galectin-3 was significantly higher in the APA group (2.1±0.9 vs 1.1±0.6 ng/mL, p=0.005) compared to the controls. CVIBS was correlated to plasma galectin-3 level. In the APA group, CVIBS increased significantly (7.3±2.0 to 9.2±2.4 dB, p=0.032) and plasma galectin-3 decreased (2.1±0.9 to 1.2±0.6, p=0.049) 1 year postadrenalectomy. The patients with APA had increased myocardial fibrosis, and this was associated with a higher plasma galectin-3 level. Both increased myocardial fibrosis and plasma galectin-3 level recovered at least partially after adrenalectomy. Trial registration number 200611031R; Results.

Yu-Feng Lin,1,2 Tao-Min Huang,2,3 Shuei-Liong Lin,2,4 Vin-Cent Wu,2 Kwan-Dun Wu2 1Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan; 2Division of Nephrology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; 3Graduate Institute of Epidemiology and Preventive Medicine, National Taiwan University College of Public Health, Taipei, Taiwan; 4Graduate Institute of Physiology, National Taiwan University College of Medicine, Taipei, Taiwan Objective: Prompt assessment of perioperative complications is critical for the comprehensive care of surgical patients. Acute kidney injury requiring dialysis (AKI-D) is associated with high mortality, yet little is known about how long-term outcomes of patients have evolved. The association of AKI-D with postsurgical outcomes has not been well studied.Methods: We investigated patients from the National Health Insurance Research Database and validated by the multicenter Clinical Trial Consortium for Renal Diseases cohort. All patients with AKI-D 18 years or older undergoing four major surgeries (cardiothoracic, esophagus, intestine, and liver) were retrospectively investigated (N=106,573). Patient demographics, surgery type, comorbidities before admission, and postsurgical outcomes, including the in-hospital, 30-day, and long-term mortality together with dialysis dependence were collected.Results: AKI-D is the top risk factor for 30-day and long-term mortality after major surgery. Of 1,664 individuals with AKI-D and 6,656 matched controls, AKI-D during the hospital stay was associated with in-hospital (adjusted hazard ratio [aHR]=3.04, 95% CI 2.79–3.31), 30-day (aHR=3.65, 95% CI 3.37–3.94), and long-term (aHR=3.22, 95% CI 3.01–3.44) mortality. Patients undergoing cardiothoracic surgery (CTS) showed less in-hospital (aHR=0.85, 95% CI 0.75–0.97), 30-day (aHR=0.79, 95% CI 0.70–0.89), and long-term (aHR=0.80, 95% CI 0.72–0.90) mortality compared with non-CTS patients with AKI-D. CTS patients had a high risk of 30-day dialysis dependence (subhazard ratio [sHR]=1.67, 95% CI 1.18–2.38), but the risk of long-term dialysis dependence was similar (sHR=1.38, 95% CI 0.96–2.00) after AKI-D by taking mortality as a competing risk. Non-CTS patients had more comorbidities of sepsis, azotemia, hypoalbuminemia, and metabolic acidosis compared with CTS patients.Conclusion: AKI exhibits paramount effects on postsurgical outcomes that extend well beyond discharge from the hospital. The goal of the perioperative assessment should include the reassurance of enhancing renal function recovery among different surgeries, and optimized follow-up is warranted in attenuating the complications after postsurgical AKI has occurred. Keywords: major surgery, acute kidney injury, postsurgical complication, dialysis dependence, mortality

The use of statin therapy on the prevention of atherosclerotic cardiovascular disease (ASCVD) is recommended by the American College of Cardiology (ACC) and the American Heart Association (AHA), nevertheless, its validation on primary aldosteronism (PA) patients has not been reported. We investigated the risk of incident ASCVD in middle-aged patients with PA compared with essential hypertension (EH) based on ACC/AHA recommendations. We enrolled 461 PA patients and 553 EH patients. Even though the ratio of metabolic syndrome in each group was similar, the PA group had higher systolic blood pressures, higher low-density lipoprotein levels, higher plasma aldosterone concentration (PAC), lower high-density lipoprotein levels, and higher 10-year ASCVD compared to the EH group. The discriminative power for predicting ASCVD by the recommended statin use from the ACC/AHA guidelines was proper in the PA group (i.e., under the receiver operating characteristic curve (95% confidence interval, 0.94 (0.91–0.96)). The generalized additive model showed patients with PAC higher than 60 ng/dL accompanying the standard timing of the statin use suggested by the ACC/AHA. The ACC/AHA guidelines have good discriminative power in the prediction of middle-aged high-risk hypertensive patients, while PAC identifies those high-risk individuals who may benefit from early statin therapy.

Accumulated evidence has shown that low renin hypertension is common in patients with diabetic nephropathy. However, the performance of aldosterone to renin ratio (ARR) in primary aldosteronism (PA) patients with diabetes has not been well validated. Here, we report the performance of screening ARR in PA patients with diabetes. The study enrolled consecutive patients and they underwent ARR testing at screening. Then the diagnosis of PA was confirmed from the Taiwan Primary Aldosteronism Investigation registration dataset. Generalized additive model smoothing plot was used to validate the performance of screening ARR in PA patients with or without diabetes. During this study period, 844 PA patients were confirmed and 136 (16.0%) among them had diabetes. Other 816 patients were diagnosed with essential hypertension and used as the control group and 89 (10.9%) among them had diabetes. PA patients with diabetes were older and had a longer duration of hypertensive latency, higher systolic blood pressure and lower glomerular filtration rate than those PA patients without diabetes. The cut-off value of ARR in the generalized additive model predicting PA was 65 ng/dL per ng/mL/h in diabetic patients, while 45 ng/dL per ng/mL/h in non-diabetic patients. There was a considerable prevalence of diabetes among PA patients, which might be capable of interfering with the conventional screening test. The best cut-off value of ARR, more than 65 ng/dL per ng/mL/h in PA patients with diabetes, was higher than those without diabetes.

Although statin treatment is recommended for patients with chronic kidney disease (CKD) stages I–IV, its potential benefits have not been reported in advanced CKD patients. Non-diabetic patients with advanced CKD (pre-dialysis patients, estimated glomerular filtration rate &lt, 15 mL/min/1.73 m2) were enrolled from a National Health Insurance Research Database with a population of 23 million. Statin users and non-users were matched using propensity scoring and analyzed using Cox proportional hazards models, taking mortality as a competing risk with subsequent end-stage renal disease (ESRD) and statin doses as time-dependent variables. A total of 2551 statin users and 7653 matched statin non-users were identified from a total 14,452 patients with advanced CKD. Taking mortality as a competing risk, statin use did not increase the risk of new-onset diabetes mellitus (NODM) or decrease the risk of de novo major adverse cardiovascular events (MACE), but reduced all-cause mortality (hazard ratio (HR) = 0.59 [95% CI 0.42–0.84], p = 0.004) and sepsis-related mortality (HR = 0.53 [95% CI 0.32–0.87], p = 0.012). For advanced CKD patients, statin was neither associated with increased risks of developing NODM, nor with decreased risk of de novo MACE occurrence, but with a reduced risk of all-cause mortality, mainly septic deaths.

Background An elevated plasma aldosterone level has been reported as an independent risk factor for severe erectile dysfunction in men. The aim of this study was to explore whether primary hyperaldosteronism patients experience erectile dysfunction after targeted treatment. Methods We conducted a population-based cohort study of men with newly identified primary hyperaldosteronism/aldosterone-producing adenoma from January 1, 1997, to December 31, 2009. Men with essential hypertension and normotension were matched to the primary hyperaldosteronism group according to propensity score matching. Results We identified 1,067 men with primary hyperaldosteronism (mean age, 46.7 ± 12.8 years) and matched them with the same number of men with essential hypertension or normotension. During the mean follow-up interval of 5.4 years, the incident rates of total erectile dysfunction were 5.7, 3.9, and 3.1 per 1,000 person-years for the primary hyperaldosteronism, essential hypertension, and normotension groups, respectively. Men with primary hyperaldosteronism exhibited a higher risk of erectile dysfunction compared with men with normotension (competing risks hazard ratio, 1.83), and no difference was seen in comparison with men who have essential hypertension. After adrenalectomy, men who have primary hyperaldosteronism had a higher risk of exhibiting severe erectile dysfunction compared with men who have essential hypertension (competing risks hazard ratio, 2.44) or normotension (competing risks hazard ratio, 2.90). Conclusion Men with primary hyperaldosteronism reported a higher incidence of severe erectile dysfunction than normotension controls despite targeted treatment. The risk of severe erectile dysfunction increased after men who have primary hyperaldosteronism underwent adrenalectomy. This result raises the possibility of severe erectile dysfunction after adrenalectomy and calls for a prospective large-scale study of men who have aldosterone-producing adenoma regarding their erectile function both before and after adrenalectomy.

Background The clinical consequences of starting chronic peritoneal dialysis (PD) after emergent dialysis via a temporary hemodialysis (HD) catheter has rarely been evaluated within a full spectrum of treated end-stage renal disease (ESRD). We investigated the longer-term outcomes of patients undergoing emergent-start PD in comparison with that of other practices of PD or HD in a prospective cohort of new-onset ESRD. Methods This was a 2-year prospective observational study. We enrolled 507 incident ESRD patients, among them 111 chose PD (43 planned-start, 68 emergent-start) and 396 chose HD (116 planned-start, 280 emergent-start) as the long-term dialysis modality. The logistic regression model was used to identify variables associated with emergent-start dialysis. The Kaplan–Meier survival analysis was used to determine patient survival and technique failure. The propensity score-adjusted Cox regression model was used to identify factors associated with patient outcomes. Results During the 2-year follow-up, we observed 5 (4.5%) deaths, 15 (13.5%) death-censored technique failures (transfer to HD) and 3 (2.7%) renal transplantations occurring in the PD population. Lack of predialysis education, lower predialysis estimated glomerular filtration rate and serum albumin were predictors of being assigned to emergent dialysis initiation. The emergent starters of PD displayed similar risks of patient survival, technique failure and overall hospitalization, compared with the planned-start counterparts. By contrast, the concurrent planned-start and emergent-start HD patients with an arteriovenous fistula or graft were protected from early overall death and access infection-related mortality, compared with the emergent HD starters using a central venous catheter. Conclusions In late-referred chronic kidney disease patients who have initiated emergent dialysis via a temporary HD catheter, post-initiation PD can be a safe and effective long-term treatment option. Nevertheless, due to the potential complications and cost concerns, such practice of PD initiation would better be replaced with a planned-start mode by employing more effective predialysis therapeutic education and timely catheter placement.

Aims: There is a trend toward deferring the initiation of chronic dialysis until absolutely indicated. This strategy, however, might lead to increased uncertainties in the timing of dialysis access creation prior to dialysis onset for patients approaching end-stage renal disease (ESRD), and the impact of which on hard end points remains largely unclear. We hereby investigated the effect of varied patterns of dialysis initiation on outcomes of new-onset hemodialysis (HD) patients. Methods: Four hundred sixty-two prospectively recruited patients were stratified into planned elective (n = 117, 25%), planned urgent (n = 65, 14%) or unplanned urgent (n = 280, 61%) starters based on the timing of access creation with respect to dialysis initiation. The outcome measures were all-cause mortality, hospitalization and access reconstruction over 2 years. Results: The mean estimated glomerular filtration rate (eGFR) was higher in the planned elective than in the planned urgent or unplanned urgent starters at access creation (5.3 vs. 4.4 or 4.3 ml/min/1.73 m2), but not at dialysis initiation (4.2 vs. 3.9 or 4.3 ml/min/1.73 m2). During the follow-up, the planned elective population exhibited the lowest rates of overall mortality and hospitalization, but not access reconstruction. Multivariate Cox's regression analysis showed that the planned urgent and the unplanned urgent groups, comparing to the planned elective population, displayed a greater risk of early death (hazards ratio [HR] 3.324, 95% CI 1.409-7.840; HR 2.510, 95% CI 1.177-5.355, respectively) and early hospitalization (sub-hazards ratio [SubHR] 2.238, 95% CI 1.530-3.274; SubHR 1.529, 95% CI 1.096-2.133, respectively). Conclusion: Incident ESRD patients undergoing planned elective start of HD, compared to their planned or unplanned urgent counterparts, showed reduced risk of overall mortality and hospitalization in the first 2 years after commencing long-term dialysis at a mean eGFR 2.

The effect of aldosterone on vascular smooth muscle cell function is still unclear. One method to measure vascular smooth muscle cell function is endothelial-independent vascular dilation, for which the key factor is sarcoplasmic reticulum calcium adenosine triphosphatase (SERCA).Our objective was to investigate the effect of aldosterone on vascular smooth muscle cell function and SERCA regulation.We prospectively analyzed 35 patients with primary aldosteronism (PA; 32 patients with aldosterone-producing adenoma and three patients with idiopathic hyperaldosteronism) and 30 patients with essential hypertension (EH) who were enrolled as the control group. Flow and nitrate-mediated dilation were performed in both groups and 1 year after adrenalectomy in the patients with aldosterone-producing adenoma. In addition, we investigated the effect of aldosterone on SERCA regulation in human aortic smooth muscle cells.This study took place in an academic clinical research center.Participants included 35 patients with PA and 30 patients with EH.Adrenalectomy was undertaken in patients with aldosterone-producing adenoma.The PA patients had significantly lower flow-mediated dilation (FMD) and nitrate-mediated dilation (NMD) values than the patients with EH (FMD: 13 ± 6 vs 16 ± 4; NMD: 16 ± 6 vs 19 ± 5; both P.05). FMD/NMD were significantly correlated with log 24 hour-urine aldosterone (FMD: r = -0.287, P = .048; NMD: r = -0.402, P = .005) but not blood pressure. The impaired FMD and NMD values were significantly restored 1 year after adrenalectomy (FMD: 11 ± 4 to 19 ± 7; NMD: 15 ± 6 to 21 ± 6; both P.01). Under confocal microscopy, aldosterone was shown to suppress the expression of SERCA2a of human aortic smooth muscle cells. Aldosterone significantly suppressed the expression of SERCA2a from 10(-8) M in mRNA and protein levels. This suppression was through down-regulation of mineralocorticoid receptor dependent mitochondrial transcription factors A and B2.Aldosterone impairs vascular smooth muscle cell function and suppresses SERCA 2a expression.

Background Primary aldosteronism (PA) is one of the major etiologies for secondary hypertension featuring more prominent left ventricular hypertrophy. The purpose of the study was to investigate the predictive factors of left ventricular mass index (LVMI) regression in patients with PA after adrenalectomy. Methods We prospectively analyzed 30 patients with aldosterone-producing adenoma (APA) who received adrenalectomy from October 2006 to September 2008. Echocardiography was performed preoperation and 1 year after operation. Results Thirty patients with aldosterone-producing adenoma undergoing adrenalectomy were enrolled. In a 1-year follow-up, LVMI decreased significantly by an average of 18.6%. Net LVMI decrease (ΔLVMI) was associated with preoperative LVMI, preoperative serum potassium level, baseline systolic blood pressure (SBP), baseline diastolic blood pressure, net SBP decrease (ΔSBP), net diastolic blood pressure decrease, preoperative/postoperative change of log-transformed plasma aldosterone concentration, preoperative/postoperative change of log-transformed plasma renin activity, and preoperative/postoperative change of serum potassium level (Δserum potassium level). In a multiple regression analysis, preoperative LVMI (β = −0.287, P = 0.049), ΔSBP (β = 0.518, P = 0.01), and Δserum potassium level (β = −20.471, P = 0.014) were significantly correlated with ΔLVMI. Conclusions The LVMI in patients with PA regressed significantly after adrenalectomy. Preoperative LVMI, ΔSBP, and Δserum potassium levels are independent factors associated with the degree of LVMI regression.

In adults, membranous nephropathy (MN) is a major cause of nephrotic syndrome. However, the etiology of approximately 75% of MN cases is idiopathic. Secondary causes of MN are autoimmune diseases, infection, drugs, and malignancy. The pathogenesis of MN involves formation of immune complex in subepithelial sites, but the definite mechanism is still unknown. There are three hypotheses about the formation of immune complex, including preformed immune complex, in situ immune-complex formation, and autoantibody against podocyte membrane antigen. The formation of immune complex initiates complement activation, which subsequently leads to glomerular damage. Recently, the antiphospholipase A2 receptor antibody was found to be associated with idiopathic MN. This finding may be useful in the diagnosis and prognosis of MN. The current treatment includes best supportive care, which consists of the use of angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers, lipid-lowering agents, and optimal control of blood pressure. Immunosuppressive agents should be used for patients who suffer from refractory proteinuria or complications associated with nephrotic syndrome. Existing evidence supports the use of a combination of steroid and alkylating agents. This article reviews the epidemiology, pathogenesis, diagnosis, and the treatment of MN.

Background: Glomerular hyperfiltration has been recently noticed as an important issue in primary aldosteronism (PA) patients. However, its effect on the cardiovascular system remains unknown. Methods: We prospectively analyzed 47 PA patients including 11 PA patients with estimated glomerular filtration rate (eGFR) > 130 ml/min per 1.73 m2 (group 1), and 36 PA patients with eGFR 90-110 ml/min per 1.73 m2 (group 2). Fourteen essential hypertension (EH) patients with eGFR 90-110 ml/min per 1.73 m2 were included as the control group (group 3). Echocardiography including left ventricular mass index (LVMI) measurement and tissue Doppler imaging (TDI) was performed. Predicted left ventricular mass (LVM) was calculated. Inappropriate LVM was defined as an excess of > 35% from the predicted value. Results: The value of LVMI decreased significantly in order from groups 1 to 3 (group 1>2>3). While group 2 had a significantly higher percentage of inappropriate LVM than group 3, the percentage of inappropriate LVM were comparable in groups 1 and 2. Group 1 had a higher mitral E velocity, E/A ratio than that of group 2. In the TDI study, the E/E' ratio also decreased significantly in order from groups 1 to 3 (group 1>2>3). Group 2 had lower E' than that of group 3, although the E' of group 1 and 2 were comparable. Conclusions: Although PA patients with glomerular hyperfiltration were associated with higher LVMI, higher mitral E velocity, higher E/E' ratio, they had comparable E' with PA patients with normal GFR. This phenomenon may be explained by higher intravascular volume in this patient group.

High aldosterone concentrations are associated with the risk of stroke that is independent of blood pressure levels. We investigated the risk of ischemic stroke in primary aldosteronism (PA) patients.This retrospective case-control study was based on the Taiwan Primary Aldosteronism Investigation (TAIPAI) database from 2004 to 2010. The study group comprised the patients who developed ischemic stroke after the diagnosis of PA. The PA patients who did not develop stroke were matched according to age and sex as the control group. A multivariate logistic regression model was performed to determine the risk factors of ischemic stroke.Of 339 patients diagnosed with PA, 22 patients (6.5%) developed de novo ischemic stroke. The PA patients with stroke suffered from a longer hypertensive period (11.0±6.5 vs 7.8±8.3, P=.007) and a higher prevalence of proteinuria than those who did not develop stroke (40.9% vs 12.9%, P=.002). A multivariate logistic regression model showed that PA patients with proteinuria (HR 3.58, P=.02), preexisting coronary artery disease (HR 11.12, P.001) or left ventricular hypertrophy (HR 3.09, P=.047) were associated with an increased risk of ischemic stroke.Proteinuria, a medical history of coronary artery disease or left ventricular hypertrophy, was associated with an increased risk of ischemic stroke in PA patients. Our results suggest that a public health initiative is necessary to enhance the follow-up of proteinuria and to manage subsequent stroke among patients with aldosteronism.

OBJECTIVE Acute kidney injury (AKI) is related to a high prevalence of insulin resistance. However, information is lacking on the sequelae of further metabolic change among AKI requiring dialysis in patients who could be weaned off dialysis (acute kidney disease [AKD]). RESEARCH DESIGN AND METHODS Using the National Health Insurance Research Database from 2000 to 2010, with the exclusion of those with diabetes at the start, we identified 3,307 subjects with AKD and 9,921 matched control subjects from 963,037 hospitalized patients for the comparison of the outcomes, including new-onset diabetes and all-cause mortality. RESULTS Within the median follow-up period of 5.99 years, AKD patients had a higher incidence of new-onset diabetes than the matched control patients (5.16% vs. 4.17% per person-year, P = 0.001). AKD patients were at higher risk of mortality than control patients (adjusted hazard ratio [aHR] 1.27 [95% CI 1.18–1.36], P < 0.001). With mortality as a competing risk, a Cox proportional hazards analysis showed that AKD patients had a higher risk of subsequent diabetes (subhazard ratio [sHR] 1.18 [95% CI 1.07–1.30], P < 0.001) compared with the matched control patients. Subgroup analysis showed that patients with baseline hypertension (aHR 1.15 [95% CI 1.04–1.28]), hyperlipidemia (aHR 1.23 [95% CI 1.02–1.48]), and gout (aHR 1.23 [95% CI 1.03–1.46]) had increased odds of developing new-onset diabetes during follow-up. CONCLUSIONS Patients who experienced AKI had a higher incidence of developing new-onset diabetes and mortality. This observation adds evidence regarding potential metabolic dysregulation after AKI.

BACKGROUND Postoperative acute kidney injury (AKI) is common following cardiac surgery (CS). Body weight (BW) may be an amenable variable by representing the summation of the nutritional and the fluid status. However, the predictive role of perioperative BW changes in CS patients with severe postoperative AKI is never explored. This study aimed to evaluate this association. METHODS This study was conducted using a prospectively collected multicenter cohort, NSARF (National Taiwan University Hospital Study Group on Acute Renal Failure) database. The adult CS patients with postoperative AKI requiring renal replacement therapy (RRT), who had clear initial consciousness, received CS within 14 days of hospitalization, and underwent RRT within seven days after CS in intensive care units from January 2001 to January 2014 were enrolled. With the endpoint of 30-day postoperative mortality, we evaluated the association between the clinical factors denoting fluid status and patients outcomes. RESULTS A total of 188 patients (70 female, mean age 63.7 ± 15.2 years) were enrolled. Comparing with the survivors (n = 124), the non-survivors (n = 64) had a significantly higher perioperative BW change [3.6 ± 6.1% versus 0.1 ± 8.3%, p = 0.003] but not the postoperative and pre-RRT BW changes. By using multivariate Cox proportional hazards model, the independent indicators of 30-day postoperative mortality included perioperative BW change (p = 0.026) and packed red blood cells transfusion (p = 0.007), postoperative intra-aortic balloon pump (p = 0.001) and central venous pressure level (p = 0.005), as well as heart rate (p = 0.022), sequential organ failure assessment score (p < 0.001), logistic organ dysfunction score (p = 0.001), and blood total bilirubin level (p = 0.044) at RRT initiation. The generalized additive models further demonstrated, in a multivariate manner, that the mortality risk rose significantly during a perioperative BW change of 2% to 15%. CONCLUSIONS Perioperative BW change was independently associated with an increased risk for 30-day postoperative mortality in CS patients with RRT-requiring AKI.

// Vin-Cent Wu 1, * , Che-Hsiung Wu 2, 3, * , Ya-Wen Yang 4 , Kuo-How Huang 5 , Chia-Hui Chang 2 , Shao-Yu Yang 1 , Yen-Hung Lin 1 , Kwan-Dun Wu 1 and The NRPB Kidney Consortium 6 1 Division of Nephrology, National Taiwan University Hospital, Taipei, Taiwan 2 Division of Nephrology, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Taipei, Taiwan 3 School of Medicine, Tzu Chi University, Hualien, Taiwan 4 Division of General Surgery, Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan 5 Department of Internal Medicine, Urology, National Taiwan University Hospital, Taipei, Taiwan 6 NRPB, National Research Program for Biopharmaceuticals, Taipei, Taiwan * These authors have contributed equally to this article Correspondence to: Kwan-Dun Wu, email: kdwu@ntuh.gov.tw Keywords: primary aldosteronism, bromocriptine, spironolactone Received: May 01, 2017 Accepted: June 20, 2017 Published: September 06, 2017 ABSTRACT Background: Dopamine D2-like receptors are attenuated in aldosterone producing adenoma, lead to overproduction of aldosterone in affected patients, and thus reported to serve as a potential treatment target for primary aldosteronism. The D2 dopamine receptor agonist bromocriptine has been used clinically for reducing tumor mass of pituitary adenomas of lactotroph origin. The aim of the present study was to assess the efficacy of adding bromocriptine to spironolactone in the biochemical control of primary aldosteronism. Methods: Thirty patients (15 aldosterone producing adenoma) received bromocriptine treatment with dose titration to a daily dose of 7.5mg. Urine aldosterone and potassium excretion ratio of all patients were compared based on the result of metoclopramide test at baseline. Results: On the basis of response to metoclopramide at baseline, the proportions of patients with lower urine aldosterone and urine potassium level after taking bromocriptine for six months were higher in the high metoclopramide response group. Initial aldosterone-renin ratio and high metoclopramide response at baseline were independent predictors of a decrease in aldosterone secretion after a six–month course of bromocriptine. The effects of bromocriptine added to spironolactone to reduce aldosterone secretion and potassium excretion in primary aldosteronism dissipated at 9 month after the initial treatment. Conclusions: In this pilot study, we found that short-term addition of bromocriptine to spironolactone improved the biochemical control of primary aldosteronism. Dopamine agonist is more effective in patients with high baseline aldosterone-renin ratio and those sensitive to metoclopramide stimulation. However, this effect dissipated after 9 months. Clinical trial registry information: ClinicalTrials. Gov number: NCT00451672; https://www.clinicaltrial.gov/ct2/show/NCT00451672?term=NCT00451672r trial registry name: The Therapeutic Effect of Bromocriptin in Patients With Primary Aldosteronism.

Background The benefit of alpha-Ketoanalogues (KA) supplementation for chronic kidney disease (CKD) patients that followed low-protein diet (LPD) remains undetermined. Methods We extracted longitudinal data for all CKD patients in the Taiwan National Health Insurance from January 1, 2000 through December 31, 2010. A total of 1483 patients with anemic advanced CKD treated with LPD, who started KA supplementation, were enrolled in this study. We analyzed the risks of end stage renal disease and all-cause mortality using Cox proportional hazard models with influential drugs as time-dependent variables. Results A total of 1113 events of initiating long-term dialysis and 1228 events of the composite outcome of long-term dialysis or death occurred in patients with advanced CKD after a mean follow-up of 1.57 years. Data analysis suggests KA supplementation is associated with a lower risk for long-term dialysis and the composite outcome when daily dosage is more than 5.5 tablets. The beneficial effect was consistent in subgroup analysis, independent of age, sex, and comorbidities. Conclusions Among advanced CKD patients that followed LPD, KA supplementation at an appropriate dosage may substantially reduce the risk of initiating long-term dialysis or of developing the composite outcome. KA supplementation represents an additional therapeutic strategy to slow the progression of CKD.

Acute kidney injury (AKI) is an independent risk factor for ensuing chronic kidney disease (CKD). Animal studies have demonstrated that renin-angiotensin system (RAS) inhibitor can reduce ensuing CKD after functional recovery from AKI. Here we study the association between ensuing CKD and use of RAS inhibitor including angiotensin converting enzyme inhibitor or angiotensin II type 1a receptor blocker starting after renal functional recovery in our prospectively collected observational AKI cohort. Adult patients who had cardiac surgery–associated AKI (CSA-AKI) are studied. Patients with CKD, unrecovered AKI, and use of RAS inhibitor before surgery are excluded. Among 587 eligible patients, 94 patients are users of RAS inhibitor which is started and continued after complete renal recovery during median follow-up period of 2.99 years. The users of RAS inhibitor show significantly lower rate of ensuing CKD (users vs. non-users, 26.6% vs. 42.2%) and longer median CKD-free survival time (users vs. non-users, 1079 days vs. 520 days). Multivariate Cox regression analyses further demonstrate that use of RAS inhibitor is independently associated with lower risk of ensuing CKD (hazard ratio = 0.46, P

Scientific Reports 6: Article number: 32103; published online: 02 September 2016; updated: 24 March 2017 The original version of this Article contained an error in the Abstract. “While need for receptor antagonist (MRA) MRA after diagnosis suggests that a defined daily dose (DDD) of MRA between 12.5and 50 mg may alleviate risk of death in a U-shape pattern”.

Aims An excess of aldosterone results in cardiac remodelling and fibrosis. Interleukin-6 (IL-6) is a key mediator in the fibrotic process; however, the effect of aldosterone on the expression of IL-6 remains unclear. We investigated whether aldosterone induces the expression of IL-6 and thereby contributes to the fibrotic process. Methods and results In this clinical study, we prospectively enrolled 25 patients with primary aldosteronism (PA) and 26 patients with essential hypertension (EH). The PA patients had higher plasma IL-6 levels, left ventricular mass index, degree of myocardial fibrosis, and more impaired diastolic function than the EH patients. In addition, plasma IL-6 levels were positively correlated with 24-h urinary aldosterone and echocardiographic parameters. In cell studies, we investigated the possible molecular mechanism how aldosterone-induced IL-6 secretion and the further effects of collagen production. Aldosterone significantly induced IL-6 protein and mRNA production in human umbilical vein endothelial cells. Intracellular signalling occurred through the mineralocorticoid receptor/PI3K/Akt/NF-kB pathway. In cardiac fibroblasts, IL-6 trans-signalling played a critical role in aldosterone-induced IL-6-enhanced fibrosis-related factor expression. To further investigate the role of IL-6 trans-signalling in aldosterone-induced cardiac fibrosis, we measured the severity of myocardial fibrosis in aldosterone infusion mice models including an IL-6 chemical inhibitor and Sgp130 Knockin Transgenic Mice. Mice receiving recombinant soluble gp130 and Sgp130 Knockin Transgenic Mice prevented myocardial fibrosis and cardiac hypertrophy by aldosterone infusion. Conclusions IL-6 trans-signalling contributes to aldosterone-induced cardiac fibrosis.

C-reactive protein (CRP) encoded by CRP gene is a reflection of systemic inflammation. Many studies associated CRP level with diabetes and glucose levels, but the association of CRP gene with these traits is unclear. We conducted a cross-sectional study consisting of 945 siblings from 330 families collected by the Stanford Asian Pacific Program in Hypertension and Insulin Resistance (SAPPHIRe) to investigate associations between CRP polymorphisms, circulating CRP, diabetes, and glucose levels. Five single-nucleotide polymorphisms were analyzed: rs3093059, rs2794521, rs1417938, rs1800947, and rs1205. The generalized estimating equation approach was used to deal with correlated data within families. CRP level was positively correlated with diabetes prevalence and levels of fasting and 2-hour glucose (each P C at rs3093059 and G at rs1205 were associated with elevated CRP level (each P −6). Allele C at rs3093059 was associated with fasting glucose (β = 0.20, P = 0.045) and G at rs1205 was associated with 2-hour glucose (β = 0.46, P = 0.00090) post oral glucose tolerance test, but only the latter passed Bonferroni correction. No polymorphism was associated with diabetes. Since 2-hour glucose is an indicator of glucose tolerance, this study indicated CRP gene is associated with glucose intolerance.

Constitutive activation of the Wnt pathway/β-catenin signaling may be important in aldosterone-producing adenoma (APA). However, significant gaps remain in our understanding of the prevalence and clinical outcomes after adrenalectomy in APA patients harboring CTNNB1 mutations. The molecular expression of CYP11B2 and gonadal receptors in adenomas were also explored. Adenomas from 219 APA patients (95 men; 44.2%; aged 50.5 ± 11.9 years) showed a high rate of somatic mutations (n = 128, 58.4%). The majority of them harbored KCNJ5 mutations (n = 116, 52.9%); 8 patients (3.7%, 6 women) had CTNNB1 mutations. Patients with APAs harboring CTNNB1 mutations were older and had shorter duration of hypertension. After adrenalectomy, CTNNB1 mutation carriers had a higher possibility (87.5%) of residual hypertension than other APA patients. APAs harboring CTNNB1 mutations have heterogeneous staining of β-catenin and variable expression of gonadal receptors and both CYP11B1 and CYP11B2. This suggests that CTNNB1 mutations may be more related to tumorigenesis rather than excessive aldosterone production.

We aimed to examine the association between preoperative use of statins and postoperative acute kidney injury (AKI) in patients undergoing major surgery by performing a systemic review and meta-analysis. MEDLINE and EMBASE, from inception to April 2013, and the reference lists of related articles were searched for relevant studies. Trials comparing preoperative statin therapy with no preoperative statin in patients undergoing major surgery were included. Outcome measures of interest were the risk of cumulative postoperative AKI and postoperative AKI requiring renal replacement therapy (RRT). Fixed or random effect meta-analysis was performed to derive summary effect estimates. In five randomized controlled trials (RCTs) and 19 observational studies, comprising a total of 989 173 patients undergoing major surgery, 112 840 patients (11.41%) received preoperative statin therapy. The specific type, dosage, and duration of statin therapy were not available in most studies. Preoperative statin therapy was associated with a significant risk reduction for cumulative postoperative AKI (weighted summary odds ratio (OR) 0.87, 95% CI 0.79 to 0.95). The effect of risk reduction was also significant when considering postoperative AKI requiring RRT (OR 0.80, 95% CI 0.72 to 0.90). When restricting the analysis to the five RCTs, preoperative statin therapy did not show significant protective effect on postoperative AKI (OR 0.49, 95% CI 0.22 to 1.09). In patients undergoing major surgery, preoperative statin therapy could associate with a reduced risk for postoperative AKI. However, considerable heterogeneity existed among included studies. Future randomized trials were warranted for this critical clinical question.