Hong-Wei Chang

Bilateral aldosterone-producing adenomas: differentiation from bilateral adrenal hyperplasia

BACKGROUND Primary aldosteronism (PA) is a common curable disease of secondary hypertension. Most such patients have either idiopathic bilateral adrenal hyperplasia (BAH) or unilateral aldosterone-producing adenoma (APA). Bilateral APAs are reportedly extremely rare. AIM To compare the distinctive characteristics, clinical course, and outcomes of bilateral APA vs. BAH. DESIGN Retrospective record review. METHODS From July 1994 to Jan 2007, 190 patients diagnosed with PA underwent surgical intervention at our hospital. Bilateral APA was diagnosed in 7/164 patients with histologically-proven APA. Twenty-one patients diagnosed as BAH, and 21 randomly selected of unilateral APA patients, matched by age and sex served as controls. RESULTS Patients with bilateral APA had similar blood pressure, arterial blood gas analysis, spot urinary potassium to creatinine ratio and clinical symptoms to those with BAH, but lower serum potassium levels (p = 0.027), lower plasma renin activity (p = 0.037), and higher plasma aldosterone concentrations (p = 0.029). Aldosterone-renin ratio (ARR) after administration of 50 mg captopril was higher in bilateral APA than in BAH patients (p = 0.023), but not different between unilateral APA and BAH (p = 0.218). A cut-off of ARR >100 ng/dl per ng/ml/h and plasma aldosterone >20 ng/dl after captopril significantly differentiated bilateral APA from BAH. Bilateral subtotal adrenalectomy normalized blood pressure and biochemistry in all patients with bilateral APA. DISCUSSION Bilateral APA, presenting simultaneously or sequentially, may not be a rare disease, accounting for 4.3% of APA in this sample. The clinical presentations of bilateral functional adenoma are not different from BAH, but patients with low serum potassium and ARR >100 after captopril should be carefully evaluated for bilateral adenoma.

Restless legs syndrome in end‐stage renal disease: a multicenter study in Taiwan

Restless legs syndrome (RLS) is an underestimated movement disorder in patients with end‐stage renal disease (ESRD). Several clinical and laboratory factors were inconsistently reported to associate with RLS. We aim to perform a large‐scale multicenter study to investigate the possible associated risk factors of RLS in patients with ESRD in Taiwan, a country with the highest incidence of uremia in the world.

Restless legs syndrome is associated with cardio/cerebrovascular events and mortality in end‐stage renal disease

Earlier studies suggested an association between idiopathic restless legs syndrome (RLS) and cardiovascular diseases. However, the risk of cardiovascular events in patients with secondary RLS due to end‐stage renal disease (ESRD) is unclear. Our aim was to examine whether ESRD patients with RLS had an increased risk of cardio/cerebrovascular events and mortality.

Association of candidate genetic variants with restless legs syndrome in end stage renal disease: a multicenter case−control study in Taiwan

Recent genome‐wide association studies have shown associations between multiple genetic variants and primary restless legs syndrome (RLS). Their roles in end stage renal disease (ESRD) related secondary RLS are not clear and studies in Asian populations are scarce. The association between candidate genetic variants and uremic RLS was investigated in a large cohort of Taiwanese dialysis patients.

Renal hypouricemia is an ominous sign in patients with severe acute respiratory syndrome

Background: The purpose of this study is to determine the incidence and significance of hypouricemia in patients with severe acute respiratory syndrome (SARS). Pulmonary lesions in patients with SARS are thought to result from proinflammatory cytokine dysregulation. Acute renal failure has been reported in patients with SARS, but whether cytokines can injure renal tubules is unknown. Methods: Sixty patients diagnosed with SARS in Taiwan in April 2003 were studied. Patients were identified as hypouricemic when their serum uric acid (UA) level was less than 2.5 mg/dL (<149 μmol/L) within 15 days after fever onset. Urine UA and creatinine levels were available for 43 patients; the serum cytokines interleukin-6 (IL-6), IL-8, and tumor necrosis factor-α (TNF-α) were measured in 16 patients. Results: Sixteen patients (26.7%) had hypouricemia (UA, 1.68 ± 0.52 mg/dL [100 ± 31 μmol/L]). No differences in age, sex, symptoms, vital signs, hemogram, or other biochemistry data existed between the hypouricemic and normouricemic groups. Fractional excretion (FE) of UA (FEUA) in 12 hypouricemic patients was 39.6% ± 23.4%, significantly greater than that of 31 normouricemic patients (16.4% ± 11.4%; P < 0.0001). After adjustments for age and sex, high FEUA was significantly associated with the lowest blood oxygenation (P = 0.001; r = −0.624). The number of catastrophic outcomes (endotracheal intubation and/or death) adjusted for older age and sex showed that hypouremic patients had an odds ratio of 10.57 (confidence interval, 2.33 to 47.98; P = 0.002). Kaplan-Meier curves for catastrophic outcome–free results showed significant differences between patients with normouricemia or hypouricemia (P = 0.01). Serum IL-8 levels correlated significantly with FEUA (P < 0.001; r = 0.785) and inversely with serum UA level (P = 0.044; r = −0.509); neither IL-6 nor TNF-α level showed such correlations. Conclusion: One fourth of patients with SARS developed hypouricemia, which might result from a defect in renal UA handling and was associated with a high serum IL-8 level. Renal hypouricemia is an ominous sign in patients with SARS.

Role of D2 dopamine receptor in adrenal cortical cell proliferation and aldosterone-producing adenoma tumorigenesis

Aldosterone-producing adenoma (APA) and bilateral adrenal hyperplasia are the two characteristic types of primary aldosteronism. Dysregulation of adrenal cortical cell proliferation contributes to both diseases. We previously demonstrated that APA expressed less dopamine D2 receptor than the respective non-tumor tissue and might contribute to the overproduction of aldosterone. As activation of D2 receptor inhibits the proliferation of various cells, downregulation of D2 receptor in APA may play a role in the tumorigenesis of APA. In this study, we demonstrate that D2 receptor plays a role in angiotensin II (AII)-stimulated adrenal cortical cell proliferation. The D2 receptor agonist, bromocriptine, inhibited AII-stimulated cell proliferation in primary cultures of the normal human adrenal cortex and APA through attenuating AII-induced phosphorylation of PK-stimulated cyclin D1 protein expression and cell proliferation. D2 receptor also inhibited AII-induced ERK1/2 phosphorylation. Our results demonstrate that, in addition to inhibiting aldosterone synthesis/production, D2 receptor exerts an anti-proliferative effect in adrenal cortical and APA cells by attenuating PKCμ and ERK phosphorylation. The lower level of expression of D2 receptor in APA may augment cell proliferation and plays a crucial role in the tumorigenesis of APA. Our novel finding suggests a new therapeutic target for primary aldosteronism.

Impact of Spiritual and Religious Activity on Quality of Sleep in Hemodialysis Patients

Background: Sleep disorders are common in hemodialysis (HD) patients. This study examined the relationship between quality of sleep (QoS) and religious/spiritual activity in HD patients. Methods: The study subjects were 861 HD patients from 14 dialysis clinics in Taiwan. QoS and religious/spiritual activity were evaluated by the Pittsburgh Sleep Quality Index (PSQI) questionnaire and the Royal Free Questionnaire respectively. Results: There was no difference in clinical parameters between the good and poor sleepers. Although total scores of religious and spiritual activity did not correlate with global PSQI score, patients who held strong ‘spiritual’ beliefs reported more problems in ‘sleep disturbances’, while those who exercised religious beliefs more strongly reported less trouble in ‘daytime dysfunction’. Conclusion: There is no significant correlation between QoS and religious/spiritual activity globally. However, the spiritual and religious activity did associate with different components of QoS.

In rat renal fibroblasts, mycophenolic acid inhibits proliferation and production of the chemokine CCL2, stimulated by tumour necrosis factor-α

BACKGROUND AND PURPOSE Renal fibroblasts play a pivotal role in the development of tubulointerstitial fibrosis, a condition highly predictive of progression towards end‐stage renal disease. The present study investigated the anti‐mitogenic and anti‐inflammatory effects of an inhibitor of inosine monophosphate dehydrogenase, mycophenolic acid (MPA) and the mechanisms underlying its action in normal rat kidney fibroblasts (49F cells).