Hung-Wei Chang

Association of Kidney Function With Residual Hypertension After Treatment of Aldosterone-Producing Adenoma

BACKGROUND Autonomous secretion of aldosterone in patients with primary aldosteronism increases glomerular filtration rate and causes kidney damage. The influence of a mild decrease in kidney function on residual hypertension after adrenalectomy is unexplored. STUDY DESIGN Nonconcurrent prospective study. SETTING & PARTICIPANTS The study was based on the Taiwan Primary Aldosteronism Investigation (TAIPAI) database. 150 patients (61 men; overall mean age, 47.2 +/- 11.6 years) with a diagnosis of aldosterone-producing adenoma had undergone unilateral adrenalectomy at National Taiwan University Hospital from July 1999 to January 2007. PREDICTOR Presurgery estimated glomerular filtration rate (eGFR). OUTCOMES & MEASUREMENTS Residual hypertension after adrenalectomy, defined either as less than 75% of recorded blood pressure measurements with systolic blood pressure less than 140 mm Hg and diastolic blood pressure less than 90 mm Hg or requiring antihypertensive medications during the first year after surgery. RESULTS Before surgery, 27 (18%), 72 (48%), and 51 (34%) patients had moderately to severely decreased (<60 mL/min/1.73 m(2)), mildly decreased (60 <or= eGFR < 90 mL/min/1.73 m(2)), or nondecreased eGFR (>or=90 mL/min/1.73 m(2)), respectively. After surgery, 16 (59.3%), 29 (40.3%), and 10 (19.3%) patients in each category had postsurgery residual hypertension. Compared with patients without decreased eGFR before surgery, adjusted odds ratios for postsurgery residual hypertension were 2.7 (95% confidence interval, 1.03 to 7.0; P = 0.04) and 2.8 (95% confidence interval, 1.05 to 9.3) for mildly and moderately to severely decreased eGFR, respectively. LIMITATIONS Arbitrary definition for residual hypertension. CONCLUSIONS Two-thirds of patients with aldosterone-producing adenoma were cured of hypertension by means of unilateral adrenalectomy. Kidney function impairment, even mild, appears to be associated with a high incidence of postsurgery residual hypertension.

Kidney impairment in primary aldosteronism

BACKGROUND Kidney impairment is noted in primary aldosteronism (PA), and probably initiated by glomerular hyperfiltration. METHODS A prospectively defined survey was conducted on 602 patients who were suspected of PA in the multiple-center Taiwan Primary Aldosteronism Investigation (TAIPAI) database. Estimated glomerular filtration rate (eGFR) was calculated and followed up at 1 yr after treatment. RESULTS The diagnosis of PA was confirmed in 330 patients. Among them 17% of these patients had kidney impairment (eGFR<60 ml/min/1.73 m²). Patients with PA had a higher prevalence of estimated hyperfiltration than those with essential hypertension (EH) (14.5% vs. 7.0%, p=0.005). The eGFR independently predicted PA (OR, 1.017) in the propensity-adjusted multivariate logistic model. In PA, plasma renin activity and lower serum potassium (p=0.018) was correlated with kidney impairment (p=0.001), while this relationship was not significant in patients with EH. Either unilateral adrenalectomy or treatment of spironolactone for PA patients caused a decrease of eGFR (p<0.001). Pre-operative hypokalemia (p=0.013) and the long latency of hypertension (p=0.016) could enhance the significant decrease of eGFR after adrenalectomy. CONCLUSIONS Patients with aldosteronism had relative estimated hyperfiltration than patients with EH. Calculation of eGFR may increase the specificity in identifying patients with PA. Our findings demonstrate the correlation of serum potassium and renin with estimated hyperfiltration in PA and their relationship to kidney damage. These results provide a high priority for future renal protective strategies and methods for the early diagnosis and prompt treatment of PA.

Primary Aldosteronism: Diagnostic Accuracy of the Losartan and Captopril Tests

BACKGROUND To assess whether angiotensin-II receptor blockers (ARBs) offer any additional advantage in confirming the diagnosis of primary aldosteronism (PA) and their use in the differentiation of PA subtypes. METHODS A prospective, cohort, head-to-head study was conducted between July 2003 and July 2006. A total of 135 patients received captopril and losartan tests to confirm the diagnosis of PA in the TAIPAI (Taiwan Primary Aldosteronism Investigation) intervention. RESULTS In total, 71 patients were diagnosed with PA. The area under the receiver-operating characteristic (ROC) curve of the postcaptopril plasma aldosterone concentration (PAC) was significantly less than that of the postlosartan PAC (0.744 vs. 0.829, P = 0.038). Using an aldosterone-renin ratio (ARR, ng/dl per ng/ml/h) >35 with a PAC >10 ng/dl, the specificity was 89.1% vs. 93.8% and the sensitivity was 66.2% vs. 84.5 % for the captopril test vs. the losartan test, respectively. With respect to the losartan test, the accuracy was 88.9%, the agreement was good (k = 0.778), and there was no disagreement with the McNemar test (P = 0.118). Losartan had the advantage of a better negative predictive value to exclude PA when patients were referred with a serum potassium (SK) level <3.8 mmol/l. When a postlosartan ARR >60 was the cutoff value, the positive predictive value was 82% with a negative predictive value of 57% in distinguishing aldosterone-producing adenomas (APAs) from idiopathic hyperaldosteronism (IHA). CONCLUSIONS The postlosartan ARR and PAC were shown to have better accuracy for the diagnosis of PA than the captopril test. With a postlosartan ARR >60, APAs can be adequately differentiated from IHA.

Adrenalectomy reverses myocardial fibrosis in patients with primary aldosteronism.

Objective: Primary aldosteronism is the most frequent cause of secondary hypertension and is associated with more prominent left ventricular hypertrophy and increased myocardial fibrosis. However, the reversibility of cardiac fibrosis is still unclear. Our objective was to investigate myocardial fibrosis in primary aldosteronism patients and its change after surgery. Method: We prospectively analyzed 20 patients with aldosterone-producing adenoma (APA) who received adrenalectomy from December 2006 to October 2008 and 20 patients with essential hypertension were enrolled as the control group. Plasma carboxy-terminal propeptide of procollagen type I (PICP) determination and echocardiography including ultrasonic tissue characterization by cyclic variation of integrated backscatter (CVIBS) were performed in both groups and 1 year after operation in the APA group. Results: APA patients had significantly higher SBP and DBP, higher plasma aldosterone concentration (PAC), higher aldosterone–renin ratio (ARR), lower serum potassium levels, and lower plasma renin activity (PRA) than patients with essential hypertension. In echocardiography, APA patients had a higher left ventricular mass index than essential hypertension patients. APA patients had significantly lower CVIBS (6.2 ± 1.5 vs. 8.7 ± 2.0 dB, P < 0.001) and higher plasma PICP levels (107 ± 27 vs. 85 ± 24 &mgr;g/l, P = 0.009) than essential hypertension patients. In the correlation study, CVIBS is correlated with log-transformed PRA and log-transformed ARR and PICP is correlated with log-transformed PRA, log-transformed PAC, and log-transformed ARR. One year after adrenalectomy, CVIBS increased significantly (6.2 ± 1.5 to 7.3 ± 1.7 dB, P = 0.033) and plasma PICP levels decreased (107 ± 27 vs. 84 ± 28 &mgr;g/l, P = 0.026). Conclusion: Increases in collagen content in the myocardium of APA patients may be reversed by adrenalectomy.

Primary aldosteronism: changes in cystatin C-based kidney filtration, proteinuria, and renal duplex indices with treatment.

Objectives To obtain information about the effect of prolonged aldosterone excess on kidney function. Methods We determined kidney function changes defined by cystatin C-based estimations of glomerular filtration rate (CysC-GFR). Pretreatment proteinuria and intrarenal Doppler velocimetric indices in primary aldosteronism were examined and followed after adrenalectomy or spironolactone treatment. Results This prospective, multicenter study included 130 primary aldosteronism patients (56 men; age, 49.9 ± 13.4 years: 100 with adenoma and 30 with idiopathic hyperaldosteronism) and 73 essential hypertension patients (36 men; age, 51.4 ± 14.8 years) as controls. Patients with primary aldosteronism had higher CysC-GFR (P < 0.05) and heavier proteinuria (0.042) than those with essential hypertension. With primary aldosteronism, a higher aldosterone–renin ratio (odds ratio, OR = 7.85, P = 0.008) was independently related to pretreatment CysC-GFR. The factors related to pretreatment proteinuria included CysC-GFR (OR, −0.006, P = 0.001), plasma aldosterone concentration (OR, 0.004, P = 0.002), and duration of hypertension (OR, 0.016, P = 0.032). Duration of hypertension was also independently correlated with the pretreatment resistive index among primary aldosteronism patients (OR, 0.004, P = 0.035). CysC-GFR (all, P < 0.05), proteinuria (P < 0.001), and resistive index (P < 0.001) decreased 1 year after adrenalectomy but not with spironolactone treatment. Conclusion Our data suggest that prolonged hyperaldosteronism will cause relative kidney hyperfiltration and reversible intrarenal vascular structural changes, which disguise the consequent renal injury, including declining GFR and proteinuria. Adrenalectomy and spironolactone treatment exert different clinical impacts toward kidney damage even with a similar blood pressure-lowering effect.

Strong luminescence from strain relaxed InGaN/GaN nanotips for highly efficient light emitters

Semiconductor heterostructures represent the most important building block for current optoelectronic devices. One of the common features of semiconductor heterostructures is the existence of internal strain due to lattice mismatch. The internal strain can tilt the band alignment and significantly alter the physical properties of semiconductor heterostructures, such as reducing the internal quantum efficiency of a light emitter. Here, we provide a convenient route to release the internal strain by patterning semiconductor heterostructures into nanotip arrays. The fabrication of the nanotip arrays was achieved by self-masked dry etching technique, which is simple, low cost and compatible with current semiconductor technologies. By implementing our approach to InGaN/GaN multiple quantum wells, we demonstrate that the light emission can be enhanced by up to 10 times. Our approach renders an excellent opportunity to manipulate the internal strain, and is very useful to create highly efficient solid state emitters.

Verification and evaluation of aldosteronism demographics in the Taiwan Primary Aldosteronism Investigation Group (TAIPAI Group)

Objective: Current data on primary aldosteronism (PA) from Asian populations are scarce. This cohort study clarifies the attributes of patients with PA in a typical Chinese population. Design: An observational cohort study. Methods: The records of patients referred to the Hypertension Clinic from a multi-centre registration in Taiwan from January 1995 to December 2007 were reviewed. All patients with PA were classified into two subtypes: aldosterone-producing adenomas (APA) and idiopathic hyperaldosteronism (IHA); their characteristics were compared. Results: Our cohort consisted of 346 patients with PA, 255 with APA and 91 with IHA. The initial hypokalaemia (59% in APA vs. 27.5% in IHA, p < 0.0001) and transtubular potassium gradient (TTKG) (6.30 ± 2.41 in APA vs. 4.91 ± 2.03 in IHA, p = 0.01) were higher in the APA group. Baseline plasma aldosterone concentration (PAC) was also significantly different between the two subgroups (49.96 ± 38.15 ng/dl in APA vs. 34.24 ± 21.47 in IHA, p < 0.0001). Conclusions: In typical Chinese PA patients, the APA subgroup had a higher proportion of hypokalaemia with elevated TTKG and higher PAC as compared with the IHA subgroup. This largest Asian database also demonstrated major differences between the Caucasian and Chinese populations including female predilection, frequent hypokalaemia, and common paralytic myopathy.

Diagnosis of primary aldosteronism: Comparison of post-captopril active renin concentration and plasma renin activity

BACKGROUND A common pharmacologic test for the diagnosis of primary aldosteronism (PA) is the administration of captopril to determine whether an abnormal plasma aldosterone concentration (PAC) to plasma renin activity (PRA) ratio(ARR) persists, although active renin concentration (ARC) may offer advantages with regard to processing and standardization. METHODS A prospective, head-to-head study was conducted between Feb 2008 and Dec 2008. One hundred and fourteen patients enrolled and received captopril to aid in the diagnosis of PA in the TAIPAI intervention. RESULTS Fifty-one patients were diagnosed with PA. Post-captopril ARC was significantly correlated with PRA. The area under the receiver operating characteristic curve of the post-captopril ARR was not different in PRA vs ARC measurements. When post-captopril ARC-based ARR (ARR(ARC))>35.5 as the cut-off value, we obtained sensitivity of 75.0% and specificity of 86.4% to differentiate PA from essential hypertension. CONCLUSIONS The correlation of individual PRA and ARC after administration of captopril was excellent; especially at the lower PRA levels. Post-captopril ARR(ARC) values used to diagnose PA are not different from post-captopril PRA-based (ARR(PRA)) values in patients without kidney, liver and heart failures. Primary aldosteronism can be diagnosed with a post-captopril cut-off value of ARR(ARC)>35.5 pmol/ng.

Optical properties of InGaN quantum dots grown by SiNx nanomasks

InGaN quantum dots (QDs) deposited on SiNx nanomasks have been investigated by atomic force microscopy, photoluminescence (PL), and photoluminescence excitation (PLE) measurements. It was found that the size of QDs can be well controlled by SiNx nanomasks, enabling the manipulation of quantum confinement effect. The PL spectra of InGaN QDs contain several fine structures, and the main peaks can be attributed to families of QDs with different sizes. The emission arising from InGaN QDs and GaN buffer layer can be clearly distinguished based on PLE measurement, which can be used to improve the interpretation in the previous reports. Our study indicates that the quantum confined Stark effect due to piezoelectric field plays a very important role in the optical properties of InGaN QDs, which is very useful for the application of optoelectronic devices.

Optoelectronic properties of ZnSe/ZnMgSSe multiple quantum wells

Optoelectronic properties of undoped ZnSe/ZnMgSSe multiple quantum wells (MQWs) grown by molecular beam epitaxy on (001) GaAs substrates have been investigated by photoluminescence, photoconductivity, and persistent photoconductivity (PPC) measurements. The features related to the band-to-band excitonic and impurity-related transitions of ZnSe/ZnMgSSe MQWs are observed and discussed. In addition, the parameters that describe the temperature dependence of the interband transition energy and broadening function of the excitonic feature are evaluated. PPC has been observed in undoped ZnSe/ZnMgSSe MQWs. The decay kinetics of the PPC effect can be described by a stretched-exponential function, Ippc(t)=Ippc(0)exp[−(t/τ)β], (0<β<1). Through the study of the PPC effect under various conditions, such as different temperature, different photon energy of photoexcitation, and different ZnSe well width, we identify that the carrier excitation from the defect level in ZnMgSSe barrier layer into the ZnSe well layer is t...