Kwan-dun Wu - Academia.edu (original) (raw)

Papers by Kwan-dun Wu

Although statin treatment is recommended for patients with chronic kidney disease (CKD) stages I–... more 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 <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...

Journal of Clinical Medicine, 2018

Ci ji yi xue za zhi = Tzu-chi medical journal

Adverse neurological effects may be common following acute kidney injury (AKI). The purpose of ou... more 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. 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 Patients 18-year-old and older who were withdrawn from temporary dialysis because of AKI and survived for at least 90 days following discharge were included in our acute-dialysis-recovery group.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. 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; = 0.01) compared with the control group. The conditional effects plo...

Critical care (London, England), Jan 26, 2018

Acute kidney injury (AKI) after cardiovascular surgery is a serious complication. Little is known... more 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. 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. 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 ...

PloS one, 2017

Postoperative acute kidney injury (AKI) is common following cardiac surgery (CS). Body weight (BW... more 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. 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. A total of 188 pati...

PLOS ONE, 2017

Background The benefit of alpha-Ketoanalogues (KA) supplementation for chronic kidney disease (CK... more 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

Scientific reports, Sep 7, 2016

Previous studies have shown that sirtuin 1 (Sirt1) is renoprotective; however, details regarding ... more Previous studies have shown that sirtuin 1 (Sirt1) is renoprotective; however, details regarding its distribution and functions in the kidney remain unknown. Here, we demonstrated that Sirt1 was mainly expressed in the tubulointerstitial cells of normal rat kidneys and was co-localized with aquaporin 2, indicating it may be involved in water/salt regulation. Renal Sirt1 expression increased in the non-glomerular cytoplasmic portion of the kidney after a 24-h fast, but no significant changes in Sirt1 expression occurred after water loading (50 mL/kg) or 24-h water deprivation. After consuming a low-salt (0.075%) or 60% calorie restriction diet for 7 days, Sirt1 expression in the rat kidney was significantly increased, whereas a high-salt (8%) diet did not change the level of Sirt1 expression. The low-salt diet also increased Sirt1 expression in the heart, muscle, brain, and fat tissues. The increased Sirt1 that was observed in rats on a low-salt diet was associated with increased ghr...

Journal of the Formosan Medical Association = Taiwan yi zhi, Jan 3, 2016

Vascular calcification can predict cardiovascular (CV) morbidity and mortality in patients with e... more Vascular calcification can predict cardiovascular (CV) morbidity and mortality in patients with end-stage renal disease. We evaluated the prevalence, association factors, and outcomes of chest X-ray-detected aortic arch calcification (AoAC) in patients undergoing peritoneal dialysis (PD). We included 190 patients undergoing PD (mean age, 52.6 ± 14.3 years) for whom chest radiographs were available. AoAC revealed by chest X-ray was graded from 0 to 3 according to an AoAC score (AoACS). Multiple regression analyses were used to determine the factors associated with AoACS. After adjusting for age, sex, PD duration, diabetes mellitus, mean blood pressure, and history of CV disease, the association between AoAC grading and mortality were assessed using the Kaplan-Meier curve and Cox proportional hazard model. Age (p < 0.001), PD duration (p = 0.004), history of CV disease (p < 0.001), and renal Kt/V (p = 0.031) were associated with AoACS. After a mean follow-up of 55.1 ± 32.1 month...

Critical Care, 2015

Acute kidney injury (AKI) has been a global health epidemic problem with soaring incidence, incre... more Acute kidney injury (AKI) has been a global health epidemic problem with soaring incidence, increased long-term risks for multiple comorbidities and mortality, as well as elevated medical costs. Despite the improvement of patient outcomes following the advancements in preventive and therapeutic strategies, the mortality rates among critically ill patients with AKI remain as high as 40–60 %. The distant organ injury, a direct consequence of deleterious systemic effects, following AKI is an important explanation for this phenomenon. To date, most evidence of remote organ injury in AKI is obtained from animal models. Whereas the observations in humans are from a limited number of participants in a relatively short follow-up period, or just focusing on the cytokine levels rather than clinical solid outcomes. The remote organ injury is caused with four underlying mechanisms: (1) “classical” pattern of acute uremic state; (2) inflammatory nature of the injured kidneys; (3) modulating effe...

Scientific reports, Jan 3, 2015

The risk for herpes zoster (HZ) in acute kidney injury (AKI) survivors was never explored. We ide... more The risk for herpes zoster (HZ) in acute kidney injury (AKI) survivors was never explored. We identified 2,387 adults in the Taiwan National Health Insurance Research Database who recovered from dialysis-requiring AKI and matched them with non-recovery and non-AKI patients by propensity score. During a mean follow-up of 2.7 years, the incidences of HZ were 6.9, 8.2 and 4.8 episodes per 1,000 person-years in AKI-non-recovery, AKI-recovery and non-AKI group, respectively. The recovery group was more likely to develop herpes zoster than those without acute kidney injury [incidence-rate ratios 1.71, 95% confidence interval 1.16-2.52; p = 0.007]. Patients without acute kidney injury were less likely to develop herpes zoster than those AKI, recovered from dialysis or not (hazard ratio HR 0.66, 95% CI 0.46-0.95). Dialysis-requiring acute kidney injury poses a long-term risk of herpes zoster after hospital discharge. Even patients who have recovered from dialysis still carry a significantly...

PLOS ONE, 2015

Discontinuation of acute, unplanned dialysis is always an important therapeutic goal in dialysis-... more Discontinuation of acute, unplanned dialysis is always an important therapeutic goal in dialysis-requiring patients with existing chronic kidney disease. Only a limited proportion of patients could be weaned off dialysis and remained dialysis-free. Here we performed a multicenter, observational study to investigate factors associated with successful weaning from acute dialysis, and to explore the potential impact of weaning itself on outcomes of patients with chronic kidney disease following urgent-start dialysis. We recruited 440 chronic kidney disease patients with a baseline estimated glomerular filtration rate <45 ml/min per 1/73 m2, and used propensity score-adjusted Cox regression analysis to measure the effect of weaning from acute dialysis on death during the index hospitalization and death or readmission after discharge. Over 2 years, 64 of 421 (15.2%) patients who survived >1 month died, and 36 (8.6%) were removed from dialysis, with 26 (6.2%) remaining alive and dialysis-free. Logistic regression analysis found that age ≧ 65 years, ischemic acute tubular necrosis, nephrotoxic exposure, urinary obstruction, and higher predialysis estimated glomerular filtration rate and serum hemoglobin were predictors of weaning off dialysis. After adjustment for propensity scores for dialysis weaning, Cox proportional hazards models showed successful weaning from dialysis (adjusted hazard ratio 0.06; 95% confidence interval 0.01 to 0.35), along with a history of hypertension and serum albumin, were independent protectors for early death. Conversely, a history of stroke, peripheral arterial disease and cancer predicted the occurrence of early mortality. In conclusion, this prospective cohort study shows that compared to patients with chronic kidney disease who became end-stage renal disease after acute dialysis, patients who could be weaned off acute dialytic therapy were associated with reduced risk of premature death over a 2-year observation period.

Journal of the American Heart Association, Jan 15, 2014

The incidence of acute kidney injury (AKI) requiring dialysis in hospitalized patients is increas... more The incidence of acute kidney injury (AKI) requiring dialysis in hospitalized patients is increasing; however, information on the long-term incidence of stroke in patients surviving to discharge after recovering from AKI after dialysis has not been reported. Patients that survived after recovery from dialysis-requiring AKI during index hospitalizations from 1999 to 2008 were identified in nationwide administrative registries. The risk of de novo stroke and death were analyzed with time-varying Cox proportional hazard models. The results were validated by a critical care database. We enrolled 4315 patients in the AKI-recovery group (men, 57.7%; mean age, 62.8±16.8 years) and matched 4315 control subjects as the non-AKI group by propensity scores. After a median follow-up period of 3.36 years, the incident stroke rate was 15.6 per 1000 person-years. The AKI-recovery group had higher risk (hazard ratio: 1.25; P=0.037) and higher severity of stroke events than the non-AKI group, regardl...

Nephron Clinical Practice, 2008

Background: Taiwan has the highest incidence of end-stage renal disease (ESRD) in the world, but ... more Background: Taiwan has the highest incidence of end-stage renal disease (ESRD) in the world, but little is known about the outcomes of patients with chronic kidney disease (CKD) before ESRD in Taiwan. This study investigated the rate of renal progression and predictors for ESRD and death in a prospective cohort of patients under usual nephrologic care at a single center. Methods: A total of 433 patients at CKD stage 3–5 short of dialysis were recruited from nephrology clinics. Patients were monitored for up to 36 months or until ESRD, death or loss to follow-up. Glomerular filtration rates (GFR) were calculated by the Modification of Diet in Renal Disease abbreviated formula. Results: At baseline, mean age was 65.6 years, 61.7% were male, 33.3% were diabetic and 29.1% had cardiovascular diseases (CVD). At the end of follow-up, 123 patients (28.4%) had advanced to ESRD and 41 (9.5%) had died. Mean annual declines in GFR were 2.24, 4.22, and 3.23 ml/min/1.73 m2 for stages 3, 4, and 5,...

PLoS ONE, 2012

Background: The impact of diuretic usage and dosage on the mortality of critically ill patients w... more Background: The impact of diuretic usage and dosage on the mortality of critically ill patients with acute kidney injury is still unclear. Methods and Results: In this prospective, multicenter, observational study, 572 patients with postsurgical acute kidney injury receiving hemodialysis were recruited and followed daily. Thirty-day postdialysis mortality was analyzed using Cox's proportional hazards model with time-dependent covariates. The mean age of the 572 patients was 60.8616.6 years. Patients with lower serum creatinine (p = 0.031) and blood lactate (p = 0.033) at ICU admission, lower predialysis urine output (p = 0.001) and PaO 2 /FiO 2 (p = 0.039), as well as diabetes (p = 0.037) and heart failure (p = 0.049) were more likely to receive diuretics. A total of 280 (49.0%) patients died within 30 days after acute dialysis initiation. The analysis of 30-day postdialysis mortality by fitting propensity score-adjusted Cox's proportional hazards models with time-dependent covariates showed that higher 3-day accumulated diuretic doses after dialysis initiation (HR = 1.449, p = 0.021) could increase the hazard rate of death. Moreover, higher time-varying 3-day accumulative diuretic doses were associated with hypotension (p,0.001) and less intense hemodialysis (p,0.001) during the acute dialysis period. Background and Significance: Higher time-varying 3-day accumulative diuretic dose predicts mortality in postsurgical critically ill patients requiring acute dialysis. Higher diuretic doses are associated with hypotension and a lower intensity of dialysis. Caution should be employed before loop diuretics are administered to postsurgical patients during the acute dialysis period.

PLoS ONE, 2012

Aims: Preoperative proteinuria is associated with post-operative acute kidney injury (AKI), but w... more Aims: Preoperative proteinuria is associated with post-operative acute kidney injury (AKI), but whether it is also associated with increased long-term mortality and end-stage renal disease (ESRD) is unknown. Methods and Results: We studied 925 consecutive patients undergoing CABG. Demographic and clinical data were collected prospectively, and patients were followed for a median of 4.71 years after surgery. Proteinuria, according to dipstick tests, was defined as mild (trace to 1+) or heavy (2+ to 4+) according to the results of the dipstick test. A total of 276 (29.8%) patients had mild proteinuria before surgery and 119 (12.9%) patients had heavy proteinuria. During the follow-up, the Cox proportional hazards model demonstrated that heavy proteinuria (hazard ratio [HR], 27.17) was an independent predictor of long-term ESRD. There was a progressive increased risk for mild proteinuria ([HR], 1.88) and heavy proteinuria ([HR], 2.28) to predict all-cause mortality compared to no proteinuria. Mild ([HR], 2.57) and heavy proteinuria ([HR], 2.70) exhibited a stepwise increased ratio compared to patients without proteinuria for long-term composite catastrophic outcomes (mortality and ESRD), which were independent of the baseline GFR and postoperative acute kidney injury (AKI). Conclusion: Our study demonstrated that proteinuria is a powerful independent risk factor of long-term all-cause mortality and ESRD after CABG in addition to preoperative GFR and postoperative AKI. Our study demonstrated that proteinuria should be integrated into clinical risk prediction models for long-term outcomes after CABG. These results provide a high priority for future renal protective strategies and methods for post-operative CABG patients.

PLoS ONE, 2013

Although cardiovascular disease (CVD) is the leading cause of mortality in patients with chronic ... more Although cardiovascular disease (CVD) is the leading cause of mortality in patients with chronic kidney disease (CKD), the pathophysiology is not thoroughly understood. Given that elevated albuminuria or circulating angiopoietin-2 associates with CVD and mortality in CKD patients, we were intrigued by the relationship between albuminuria and angiopoietin-2. A total of 416 patients with CKD stages 3 to 5 were stratified by urine albumin-creatinine ratio as normoalbuminuria (,30 mg/ g), microalbuminuria (30-300 mg/g), or macroalbuminuria (.300 mg/g). The levels of plasma angiopoietin-2 and vascular endothelial growth factor (VEGF) increased, and soluble Tie-2 decreased in the subgroups of albuminuria; whereas angiopoietin-1 did not change. Linear regression showed a positive correlation between urine albumin-creatinine ratio (ACR) and plasma angiopoietin-2 (correlation coefficient r = 0.301, 95% confidence interval 0.211-0.386, P,0.0001), but not between ACR and VEGF or soluble Tie-2. Multivariate linear regression analysis showed that plasma angiopoietin-2 was independently associated with ACR (P = 0.025). Furthermore, plasma angiopoietin-2 was positively correlated with high sensitive C-reactive protein (r = 0.114, 95% confidence interval 0.018-0.208, P = 0.020). In conclusion, plasma angiopoietin-2 was associated with albuminuria and markers of systemic microinflammation in CKD patients. Although previous evidence has shown that angiopoietin-2 destabilizes vasculature and induces inflammation in different scenarios, further study will be required to delineate the role of angiopoietin-2 in albuminuria and microinflammation in CKD patients.

Journal of the Renin-Angiotensin-Aldosterone System, 2012

Introduction: The hereditability of insulin resistance has been demonstrated in both familial and... more Introduction: The hereditability of insulin resistance has been demonstrated in both familial and twin studies. The effects of renin-angiotensin-aldosterone system gene polymorphisms on insulin resistance remain inconclusive. Methods: This is a sibling-based association study. Polymorphisms of renin-angiotensin-aldosterone system genes were examined in 1113 hypertension and 676 normotension siblings from Chinese and Japanese hypertensive families. The generalized estimation equations method was used to compare the differences in metabolic variables between hypertension and normotensive siblings. Results: For the G-6A polymorphism of AGT, GG siblings had lower 2-h insulin than siblings carrying the A allele (p=0.006). Siblings with different variants of the angiotensin II type 1 receptor A1166C had no difference in metabolic variables. Siblings carrying the D allele of the angiotensin converting enzyme gene had higher levels of fasting glucose, fasting insulin, area under the curve of insulin levels and the homeostasis model assessment of insulin resistance than II siblings (all p<0.05). Lower levels of fasting glucose and 2-h glucose were observed in siblings with the T allele than their CC homozygotes for the C-344T polymorphism of CYP11B2 (p<0.05). Siblings carrying three high-risk genotypes of the angiotensin converting enzyme, angiotensinogen and CYP11B2 had higher fasting glucose level than siblings carrying no high-risk genotypes (p=0.011). Conclusion: Our comprehensive analysis of renin-angiotensin-aldosterone system gene polymorphisms demonstrates that the angiotensin converting enzyme and CYP11B2 gene polymorphisms are associated with insulin resistance in hypertensive families.

Journal of the Formosan Medical Association, 2014

Background/Purpose: Several studies have shown the renoprotective effects of pentoxifylline in th... more Background/Purpose: Several studies have shown the renoprotective effects of pentoxifylline in the treatment of chronic kidney disease (CKD). This study was conducted to examine whether there was an increased benefit of including pentoxifylline with angiotensinconverting enzyme inhibitor (ACEI) or angiotensin II receptor blocker (ARB) in the treatment of CKD. Methods: A single-center retrospective analysis was conducted. A total of 661 Stage 3B-5 CKD patients who received ACEI or ARB treatment were recruited. The patients were divided into the pentoxifylline use group and the no pentoxifylline group. Renal survival analysis of the two groups was compared. Subgroup analysis was performed by dividing the patients into lower [urine protein to creatinine ratio (UPCR) < 1 g/g] and higher (UPCR ! 1 g/g) proteinuria subgroups. Results: There was no between-groups difference regarding mortality and cardiovascular events. Addition of pentoxifylline showed a better renal outcome (p Z 0.03). The protective effect of add-on pentoxifylline was demonstrated in the higher proteinuria subgroup (p Z 0.005). In the multivariate Cox regression model, pentoxifylline use also showed a better renal outcome [hazard ratio (HR): 0.705; 95% confidence interval (CI): 0.498e0.997; p Z 0.048]. This effect was more prominent in the higher proteinuria subgroup (HR: 0.602; 95% CI: 0.413e0.877; p Z 0.008).

Journal of the American Society of Nephrology, 2010

Whether preoperative proteinuria associates with adverse renal outcomes after cardiac surgery is ... more Whether preoperative proteinuria associates with adverse renal outcomes after cardiac surgery is unknown. Here, we performed a secondary analysis of a prospectively enrolled cohort of adult patients undergoing coronary artery bypass grafting (CABG) at a medical center and its two affiliate hospitals between 2003 and 2007. We excluded patients with stage 5 CKD or those who received dialysis previously. We defined proteinuria, measured with a dipstick, as mild (trace to 1ϩ) or heavy (2ϩ to 4ϩ). Among a total of 1052 patients, cardiac surgery-associated acute kidney injury (CSA-AKI) developed in 183 (17.4%) patients and required renal replacement therapy (RRT) in 50 (4.8%) patients. In a multiple logistic regression model, mild and heavy proteinuria each associated with an increased odds of CSA-AKI, independent of CKD stage and the presence of diabetes mellitus (mild: OR 1.66, 95% CI 1.09 to 2.52; heavy: OR 2.30, 95% CI 1.35 to 3.90). Heavy proteinuria also associated with increased odds of postoperative RRT (OR 7.29, 95% CI 3.00 to 17.73). In summary, these data suggest that preoperative proteinuria is a predictor of CSA-AKI among patients undergoing CABG.

The Journal of Clinical Endocrinology & Metabolism, 2007

Context: The mechanism associated with the overproduction of aldosterone by aldosterone-producing... more Context: The mechanism associated with the overproduction of aldosterone by aldosterone-producing adenomas (APA) is unknown. Objective: The objective of the study was to explore the role of the D2 dopamine receptor (D2R) on aldosterone synthesis and secretion and clarify the clinical importance of this role on aldosterone overproduction in APA. Results: D2R expression in APA was examined in 24 patients and was much less than that in the nontumorous adrenal cortex. D2R mRNA levels in APA were inversely correlated with CYP11B2 mRNA levels and the patient's plasma aldosterone concentration. Angiotensin II (AII)-stimulated aldosterone secretion and CYP11B2 mRNA expression in human adrenocarcinoma cells (H295R) was attenuated by the D2 agonist, bromocriptine (BMC). BMC selectively attenuated AII-induced protein kinase C (PKC)-phosphorylation and its trans-location to the cell membrane. PKC-specific short-hairpin RNA significantly decreased AII-induced CYP11B2 mRNA expression and aldosterone secretion. BMC also attenuated the AII-induced increase in cytoplasmic calcium, partially through an inhibition of cytoplasmic inositol 1,4,5 triphosphate production. Despite similar total PKC levels in APA and the nontumorous adrenal cortex, expression of phosphorylated PKC in APA was much higher. Conclusion: This is the first study to demonstrate that the D2R modulated aldosterone secretion and synthesis through a specific attenuation of PKC activity, as well as the intracellular calcium level. Down-regulation of the D2R in APA, in turn, increased PKC activity and led to overproduction of aldosterone in affected patients. The D2R may thus serve as a potential treatment target for primary aldosteronism.

Journal of Clinical Medicine, 2018

Ci ji yi xue za zhi = Tzu-chi medical journal

Critical care (London, England), Jan 26, 2018

PloS one, 2017

PLOS ONE, 2017

Scientific reports, Sep 7, 2016

Journal of the Formosan Medical Association = Taiwan yi zhi, Jan 3, 2016

Critical Care, 2015

Scientific reports, Jan 3, 2015

PLOS ONE, 2015

Journal of the American Heart Association, Jan 15, 2014

Nephron Clinical Practice, 2008

PLoS ONE, 2012

PLoS ONE, 2013

Journal of the Renin-Angiotensin-Aldosterone System, 2012

Journal of the Formosan Medical Association, 2014

Journal of the American Society of Nephrology, 2010

The Journal of Clinical Endocrinology & Metabolism, 2007