Publications by authors named "Jia-Jung Lee"

45 Publications

Low serum iron is associated with anemia in CKD stage 1-4 patients with normal transferrin saturations.

Sci Rep 2021 Apr 16;11(1):8343. Epub 2021 Apr 16.

Division of Nephrology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, 100 Tzyou First Road, San-Ming District, Kaohsiung, 807, Taiwan.

Low transferrin saturation (TSAT), calculated by serum iron divided by total iron-binding capacity (TIBC), indicates iron deficiency. Because malnutrition and inflammation are associated with low TIBC in chronic kidney disease (CKD), TSAT might not reflect iron status or risk for anemia. We examined whether low serum iron was a risk factor for anemia in CKD patients with normal TSAT. Thus we compare the risk for anemia in 2500 CKD stage 1-4 patients divided by TSAT (cutoff: 20%) and serum iron (cutoff: 70 μg/dL in men, 60 μg/dL in women). Our results confirmed low TIBC (< 200 μg/dL) was associated with hypoalbuminemia and high C-reactive protein. In fully-adjusted logistic regression, both "normal TSAT low iron" and "low TSAT low iron" groups were associated with baseline anemia (hemoglobin < 11 g/dL) (odds ratios (OR) 1.56; 95% confidence interval (CI) 1.13-2.16 and OR 2.36; 95% CI 1.76-3.18, respectively) compared with the reference group (normal TSAT normal iron). Sensitivity tests with different cutoffs for TSAT and iron also showed similar results. In patients without anemia, both groups were associated with anemia after 1 year (OR 1.69; 95% CI 1.00-2.83 and OR 1.94; 95% CI 1.11-3.40, respectively). In conclusion, CKD stage 1-4 patients with normal TSAT but low serum iron are still at risk for anemia.
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http://dx.doi.org/10.1038/s41598-021-87401-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8052429PMC
April 2021

Comorbidities in patients with chronic hepatitis C and hepatitis B on hemodialysis.

J Gastroenterol Hepatol 2021 Mar 2. Epub 2021 Mar 2.

Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.

Background And Aim: Hemodialysis patients are at increased risk of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection. Both HBV and HCV infections lead to risks of end-stage liver diseases and extrahepatic manifestations. This study aimed to investigate hepatic and extrahepatic comorbidities in hemodialysis patients with HBV or HCV infections compared with those without viral hepatitis.

Methods: A total of 1910 hemodialysis patients, including 159 HCV viremic patients (HCV group), 217 seropositive for HBV surface antigen (HBsAg, HBV group) and 1534 seronegative for both anti-HCV and HBsAg (non-B and non-C [NBNC] group), from 23 hemodialysis centers were enrolled. Comorbidities were classified into 10 categories by the International Classification of Diseases-10th Revision.

Results: Among the 1910 patients, the mean age was 64.6 years, and 52.7% were male patients. A total of 1834 (96%) patients had at least one comorbidity, and the mean number of comorbidities was 2.9 ± 1.5 per person. The three most common comorbidities were hypertension, diabetes, and ischemic heart diseases. The mean number of comorbidities per person was significantly higher in the HCV group (3.3 ± 1.7) than in the HBV (2.7 ± 1.5, P < 0.001) and NBNC groups (2.9 ± 1.5, P = 0.004), mainly due to the higher prevalence of ischemic heart disease, respiratory disorders, and mental/behavioral disorders. The HBV and NBNC groups exhibited comparable burdens of comorbidities.

Conclusions: Hemodialysis patients had a high prevalence of multiple comorbidities. Hemodialysis patients with HCV exhibited a higher burden of comorbidities, especially ischemic heart diseases, respiratory disorders, and mental/behavioral disorders, than HBV and NBNC patients did.
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http://dx.doi.org/10.1111/jgh.15480DOI Listing
March 2021

Evolutionary seroepidemiology of viral hepatitis and the gap in hepatitis C care cascades among uraemic patients receiving haemodialysis in Taiwan-the Formosa-Like Group.

J Viral Hepat 2021 May 13;28(5):719-727. Epub 2021 Feb 13.

Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.

Uraemic patients undergoing haemodialysis are at high risk of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection. We aimed to evaluate the evolutionary seroprevalence of viral hepatitis and the gap in HCV care cascades in this special population by a large-scale surveillance study in Taiwan. Uraemic patients on maintenance haemodialysis from 22 sites (FORMOSA-LIKE group) in 2012 (n = 1,680) and 2019 (n = 2,326) were recruited for this study. The distributions and sequential changes of viral hepatitis markers were analysed. The prevalence of anti-HCV antibody and hepatitis B surface antigen (HBsAg) seropositivity was 13.6% (316/2326) and 11.5% (267/2326), respectively, in 2019 compared with 17.3% (290/1680, P = .002) and 13.6% (229/1680, P = .046), respectively, in 2012. The HCV-viremic rate among anti-HCV-seropositive patients was significantly lower in 2019 than in 2012 (56.3% [178/316] vs. 73.8% [214/290], P < .001). The HCV treatment rate increased from 2.3% (5/217) in 2012 to 21.7% (49/226) in 2019 (P < .001). In the sequential analysis of the 490 patients who participated in both screens, 17 of the 55 HCV-viremic patients became HCV RNA seronegative, including 13 by antivirals and four spontaneously. By contrast, one anti-HCV-seropositive but nonviremic patient became viremic, and six anti-HCV-seronegative patients became anti-HCV-seropositive in 2019. The annual incidence of new HCV was 0.2%/year. Seven HBsAg-seropositive patients experienced HBsAg loss (1.25%/year). Two patients had new anti-HBc seropositivity (new HBV exposure: 0.57%/year). The seroprevalence of viral hepatitis decreased in an 8-year follow-up but remained prevalent, and the treatment of HCV infection was underutilized in uraemic patients. Additional efforts are needed to enhance the HCV treatment uptake of uraemic patients. Clinical Trial IDs: NCT03803410, NCT01766895.
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http://dx.doi.org/10.1111/jvh.13477DOI Listing
May 2021

Comedications and potential drug-drug interactions with direct-acting antivirals in hepatitis C patients on hemodialysis.

Clin Mol Hepatol 2021 01 3;27(1):186-196. Epub 2020 Dec 3.

Division of Hepatobiliary, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.

Background/aims: Direct-acting antivirals (DAAs) have been approved for hepatitis C virus (HCV) treatment in patients with end-stage renal disease (ESRD) on hemodialysis. Nevertheless, the complicated comedications and their potential drug-drug interactions (DDIs) with DAAs might limit clinical practice in this special population.

Methods: The number, class, and characteristics of comedications and their potential DDIs with five DAA regimens were analyzed among HCV-viremic patients from 23 hemodialysis centers in Taiwan.

Results: Of 2,015 hemodialysis patients screened in 2019, 169 patients seropositive for HCV RNA were enrolled (mean age, 65.6 years; median duration of hemodialysis, 5.8 years). All patients received at least one comedication (median number, 6; mean class number, 3.4). The most common comedication classes were ESRD-associated medications (94.1%), cardiovascular drugs (69.8%) and antidiabetic drugs (43.2%). ESRD-associated medications were excluded from DDI analysis. Sofosbuvir/velpatasvir/voxilaprevir had the highest frequency of potential contraindicated DDIs (red, 5.6%), followed by glecaprevir/pibrentasvir (4.0%), sofosbuvir/ledipasvir (1.3%), sofosbuvir/velpatasvir (1.3%), and elbasvir/grazoprevir (0.3%). For potentially significant DDIs (orange, requiring close monitoring or dose adjustments), sofosbuvir/velpatasvir/voxilaprevir had the highest frequency (19.9%), followed by sofosbuvir/ledipasvir (18.2%), glecaprevir/pibrentasvir (12.6%), sofosbuvir/velpatasvir (12.6%), and elbasvir/grazoprevir (7.3%). Overall, lipid-lowering agents were the most common comedication class with red-category DDIs to all DAA regimens (n=62), followed by cardiovascular agents (n=15), and central nervous system agents (n=10).

Conclusion: HCV-viremic patients on hemodialysis had a very high prevalence of comedications with a broad spectrum, which had varied DDIs with currently available DAA regimens. Elbasvir/grazoprevir had the fewest potential DDIs, and sofosbuvir/velpatasvir/voxilaprevir had the most potential DDIs.
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http://dx.doi.org/10.3350/cmh.2020.0180DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7820195PMC
January 2021

Establishment of an outreach, grouping healthcare system to achieve microelimination of HCV for uremic patients in haemodialysis centres (ERASE-C).

Gut 2020 Dec 10. Epub 2020 Dec 10.

Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan

Objective: HCV prevails in uremic haemodialysis patients. The current study aimed to achieve HCV microelimination in haemodialysis centres through a comprehensive outreach programme.

Design: The ERASE-C Campaign is an outreach programme for the screening, diagnosis and group treatment of HCV encompassing 2323 uremic patients and 353 medical staff members from 18 haemodialysis centres. HCV-viremic subjects were linked to care for directly acting antiviral therapy or received on-site sofosbuvir/velpatasvir therapy. The objectives were HCV microelimination (>80% reduction of the HCV-viremic rate 24 weeks after the end of the campaign in centres with ≥90% of the HCV-viremic patients treated) and 'No-C HD' (no HCV-viremic subjects at the end of follow-up).

Results: At the preinterventional screening, 178 (7.7%) uremic patients and 2 (0.6%) staff members were HCV-viremic. Among them, 146 (83.9%) uremic patients received anti-HCV therapy (41 link-to-care; 105 on-site sofosbuvir/velpatasvir). The rates of sustained virological response (SVR12, undetectable HCV RNA 12 weeks after the end of treatment) in the full analysis set and per-protocol population were 89.5% (94/105) and 100% (86/86), respectively, in the on-site treatment group, which were comparable with the rates of 92.7% (38/41) and 100% (38/38), respectively, in the link-to-care group. Eventually, the HCV-viremic rate decreased to 0.9% (18/1,953), yielding an 88.3% reduction from baseline. HCV microelimination and 'No-C HD' were achieved in 92.3% (12/13) and 38.9% (7/18) of the haemodialysis centres, respectively.

Conclusion: Outreach strategies with mass screenings and on-site group treatment greatly facilitated HCV microelimination in the haemodialysis population.

Clinicaltrialsgov Identifier: NCT03803410 and NCT03891550.
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http://dx.doi.org/10.1136/gutjnl-2020-323277DOI Listing
December 2020

The applicability of non-invasive methods for assessing liver fibrosis in hemodialysis patients with chronic hepatitis C.

PLoS One 2020 20;15(11):e0242601. Epub 2020 Nov 20.

Faculty of Internal Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.

Background: The accurate assessment of liver fibrosis among hemodialysis patients with chronic hepatitis C (CHC) is important for both treatment and for follow up strategies. Applying the non-invasive methods in general population with viral hepatitis have been successful but the applicability of the aminotransferase/platelet ratio index (APRI) or the fibrosis-4 index (FIB-4) in hemodialysis patients need further evaluation.

Materials And Methods: We conducted a prospective, multi-center, uremic cohort to verify the applicability of APRI and FIB-4 in identifying liver fibrosis by reference with the standard transient elastography (TE) measures.

Results: There were 116 CHC cases with valid TE were enrolled in our analysis. 46 cases (39.6%) were classified as F1, 35 cases (30.2%) as F2, 11 cases (9.5%) as F3, and 24 cases (20.7%) as F4, respectively. The traditional APRI and FIB-4 criteria did not correctly identify liver fibrosis. The optimal cut-off value of APRI was 0.28 and of FIB-4 was 1.91 to best excluding liver cirrhosis with AUC of 76% and 77%, respectively. The subgroup analysis showed that female CHC hemodialysis patients had better diagnostic accuracy with 74.1% by APRI. And CHC hemodialysis patients without hypertension had better diagnostic accuracy with 78.6% by FIB-4.

Conclusions: This study confirmed the traditional category level of APRI and FIB-4 were unable to identify liver fibrosis of CHC hemodialysis patients. With the adjusted cut-off value, APRI and FIB-4 still showed suboptimal diagnostic accuracy. Our results suggest the necessary of TE measures for liver fibrosis in the CHC uremic population.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0242601PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7678992PMC
January 2021

Pyuria, urinary tract infection and renal outcome in patients with chronic kidney disease stage 3-5.

Sci Rep 2020 11 10;10(1):19460. Epub 2020 Nov 10.

Division of Nephrology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, 100 Tzyou First Road, Kaohsiung, 807, Taiwan.

Pyuria is common in chronic kidney disease (CKD), which could be due to either urinary tract infection (UTI) or renal parenchymal inflammation. Only little is known regarding the association of pyuria or UTI with renal outcomes. We investigated 3226 patients with stage 3-5 CKD. Pyuria was defined as ≥ 50 WBC per high-power field (hpf) and was correlated to old age, female, diabetes, hypoalbuminemia, lower eGFR, and higher inflammation status. In Cox regression, patients with more than one episode of pyuria in the first year (11.8%) had increased risks for end-stage renal disease (ESRD) [hazard ratio (95% CI): 1.90 (1.58-2.28); p < 0.001], rapid renal function progression [odds ratio (95% CI): 1.49 (1.13-1.95); p = 0.001], and all-cause mortality [hazard ratio: 1.63 (1.29-2.05); p < 0.001], compared to those without pyuria. In a subgroup analysis, the risk of pyuria for ESRD was modified by CKD stages. We investigated the effects of UTI (urinary symptoms and treated by antibiotics) and pyuria without UTI (urine WBC < 50 to ≥ 10/hpf without any episodes of ≥ 50 WBC/hpf or UTI), while both groups were associated with clinical outcomes. In conclusion, CKD stage 3-5 patients with frequent pyuria or UTI episodes have increased risks of renal outcomes.
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http://dx.doi.org/10.1038/s41598-020-76520-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7655801PMC
November 2020

Review of the present features and the infection control challenges of COVID-19 pandemic in dialysis facilities.

Kaohsiung J Med Sci 2020 Jun 3;36(6):393-398. Epub 2020 Jun 3.

Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.

The COVID-19 has swept the world causing suffering, death, loss, and massive economy damage. The dialysis population is vulnerable and the dialysis facility is critical in maintaining operations and avoiding disease transmission. The present information regarding the clinical features of COVID-19 infection in the dialysis population was collected, and the useful measures of COVID-19 infection prevention and infection control in the dialysis facilities were summarized. Leadership, education, preparedness, management, and recovery phase were determined to be the critical procedures. It is hoped this updated interim review might provide information for medical professionals to take proactive action to best prepare and mitigate damage when facing the COVID-19 pandemic challenge.
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http://dx.doi.org/10.1002/kjm2.12239DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7300887PMC
June 2020

Generation of a gene corrected human isogenic IBMS-iPSC-014-C from polycystic-kidney-disease induced pluripotent stem cell line using CRISPR/Cas9.

Stem Cell Res 2020 05 20;45:101784. Epub 2020 Apr 20.

Division of Nephrology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Faculty of Renal Care, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Regenerative Medicine and Cell Therapy Research Center, Kaohsiung Medical University, Kaohsiung, Taiwan. Electronic address:

We report the engendering an isogenic iPSC line from the IBMS-iPSC-014-05 with homozygous correction of the R803X, Chr4: 88989098C > T in PKD2, using CRISPR/Cas9 technology. The results from the isogenic control, IBMS-iPSC-014-05C, showed that mutation had been corrected, while maintaining normal morphology, pluripotency, and differentiation capacity into three germ layers.
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http://dx.doi.org/10.1016/j.scr.2020.101784DOI Listing
May 2020

Take proactive measures for the pandemic COVID-19 infection in the dialysis facilities.

J Formos Med Assoc 2020 05 11;119(5):895-897. Epub 2020 Apr 11.

Division of Nephrology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Faculty of Renal Care, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan. Electronic address:

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http://dx.doi.org/10.1016/j.jfma.2020.03.022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7151404PMC
May 2020

Blood pressure modifies outcomes in patients with stage 3 to 5 chronic kidney disease.

Kidney Int 2020 02 7;97(2):402-413. Epub 2019 Nov 7.

Division of Nephrology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; Faculty of Renal Care, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.

Observational studies have demonstrated that low blood pressure is related to poor clinical outcomes in patients with chronic kidney disease (CKD). Subgroup analyses from the SPRINT trial showed that targeting systolic blood pressure under 120 mmHg is less beneficial for patients with CKD. Although malnutrition and inflammation are common in patients with advanced CKD, such patients are usually excluded from clinical trials. Therefore, we hypothesized that malnutrition-inflammation-cachexia syndrome could explain this J-shaped relationship. To test this, we studied 2441 patients with CKD stages 3-5 who received anti-hypertensive treatment for at least one year. Averaged blood pressures of the first year were used in the analyses. Fine-Gray competing risks regression showed a J-shaped relationship between continuous systolic blood pressure and end-stage kidney disease (ESKD) with a nadir risk at a systolic blood pressure of 120 mmHg. Adjusted sub-distribution hazard ratios of categorical systolic blood pressure 100-109 and 110-119 mmHg were 2.17 (95% confidence interval: 1.21-3.89) and 1.37 (0.94-1.99) for ESKD, respectively, compared with systolic blood pressures of 120-129 mmHg. Cox regression also showed J-shaped relationships between continuous systolic or diastolic blood pressures, and the composite outcomes of cardiovascular events and all-cause mortality. Logistic regression demonstrated the odds ratios of blood pressure components for Malnutrition-Inflammation Scores over 4 were J-shaped. Sub-distribution hazard ratios of systolic blood pressure 100-119 mmHg for ESKD was higher in those with a Malnutrition-Inflammation Score over 4, compared to 0.93 (0.53-1.63) in those with a score of 4 or under with significant interaction. Thus, malnutrition-inflammation-cachexia syndrome is associated with low blood pressure and modifies the J-shaped relationship in patients with advanced CKD.
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http://dx.doi.org/10.1016/j.kint.2019.10.021DOI Listing
February 2020

Ratio of Early Mitral Inflow Velocity to the Global Diastolic Strain Rate and Global Left Ventricular Longitudinal Systolic Strain Predict Overall Mortality and Major Adverse Cardiovascular Events in Hemodialysis Patients.

Dis Markers 2019 5;2019:7512805. Epub 2019 Sep 5.

Division of Nephrology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.

Background: The ratio of early mitral inflow velocity to the global diastolic strain rate (E/E'sr) and global longitudinal systolic strain (GLS) of the left ventricle (LV) are emerging indices of diastolic and systolic functions, respectively, for the LV. Their prognostic significance in the prediction of mortality and cardiovascular (CV) outcomes remains underexplored in hemodialysis (HD) patients.

Methods: This prospective study included 190 maintenance HD patients. The E/E'sr ratio and GLS were assessed using two-dimensional speckle tracking echocardiography. The clinical outcomes included overall mortality, CV mortality, and major adverse cardiovascular events (MACE). The associations between the E/E'sr ratio, GLS, and clinical outcomes were evaluated using multivariate Cox regression analysis. The incremental values of the E/E'sr ratio and GLS in outcome prediction were assessed by changes in Cox models.

Results: Over a median follow-up period of 3.7 years, there were 35 overall deaths, 16 CV deaths, and 45 MACE. Impaired diastolic function with a higher E/E'sr ratio was associated with overall mortality (HR, 1.484; 95% CI, 1.201-1.834; < 0.001), CV mortality (HR, 1.584; 95% CI, 1.058-2.371; = 0.025), and MACE (HR, 1.205; 95% CI, 1.040-1.397; = 0.013) in multivariate adjusted Cox analysis. Worsening GLS was associated with overall mortality (HR, 1.276; 95% CI, 1.101-1.480; = 0.001), CV mortality (HR, 1.513; 95% CI, 1.088-2.104; = 0.014), and MACE (HR, 1.214; 95% CI, 1.103-1.337; < 0.001). The E/E'sr ratio and GLS had better outcome prediction than the E to early diastolic mitral annular velocity (E/E') ratio and left ventricular ejection fraction (LVEF). Moreover, adding the E/E'sr ratio and GLS to Cox models containing relevant clinical and conventional echocardiographic parameters improved the prediction of overall mortality ( < 0.001), CV mortality ( < 0.001), and MACE ( < 0.001).

Conclusion: The E/E'sr ratio and GLS, as emerging indices of LV diastolic and systolic functions, significantly predict mortality and CV outcomes and outperform conventional echocardiographic parameters in outcome prediction in HD patients.
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http://dx.doi.org/10.1155/2019/7512805DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6748193PMC
February 2020

Primary cardiac manifestation of autosomal dominant polycystic kidney disease revealed by patient induced pluripotent stem cell-derived cardiomyocytes.

EBioMedicine 2019 Feb 11;40:675-684. Epub 2019 Jan 11.

Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan; Cellular and Molecular Arrhythmia Research Program, University of Wisconsin-Madison, Madison, WI, United States; Department of Medicine, University of Wisconsin-Madison, Madison, WI, United States. Electronic address:

Background: Mutations in PKD1 or PKD2 gene lead to autosomal dominant polycystic kidney disease (ADPKD). The mechanism of ADPKD progression and its link to increased cardiovascular mortality is still elusive.

Methods: We differentiated ADPKD patient induced pluripotent stem cells (iPSCs) to cardiomyocytes (CMs). The electrophysiological properties at the cellular level were analyzed by calcium imaging and whole cell patch clamping.

Findings: The ADPKD patient iPSC-CMs had decreased sarcoplasmic reticulum calcium content compared with Control-CMs. Spontaneous action potential of the PKD2 mutation line-derived CMs demonstrated slower beating rate and longer action potential duration. The PKD1 mutation line-derived CMs showed a comparable dose-dependent shortening of phase II repolarization with the Control-CMs, but a significant increase in beating frequency in response to L-type calcium channel blocker. The PKD1-mutant iPSC-CMs also showed a relatively unstable baseline as a greater percentage of cells exhibited delayed afterdepolarizations (DADs). Both the ADPKD patient iPSC-CMs showed more β-adrenergic agonist-elicited DADs compared with Control-CMs.

Interpretation: Characterization of ADPKD patient iPSC-CMs provides new insights into the increased clinical risk of arrhythmias, and the results enable disease modeling and drug screening for cardiac manifestations of ADPKD. FUND: Ministry of Science and Technology, National Health Research Institutes, Academia Sinica Program for Technology Supporting Platform Axis Scheme, Thematic Research Program and Summit Research Program, and Kaohsiung Medical University Hospital, Taiwan.
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http://dx.doi.org/10.1016/j.ebiom.2019.01.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6413318PMC
February 2019

Hematuria and Renal Outcomes in Patients With Diabetic Chronic KidneyDisease.

Am J Med Sci 2018 09 12;356(3):268-276. Epub 2018 Jun 12.

Division of Nephrology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan. Electronic address:

Background: Hematuria may indicate nondiabetic renal disease in diabetic chronic kidney disease (CKD). However, some studies have reported that hematuria is noted in diabetic nephropathy and is associated with albuminuria. Hematuria is a risk factor for end-stage renal disease in glomerulonephritis, but its prognostic value in diabetic CKD is unknown. We investigated the factors associated with hematuria and the prognostic value of hematuria in patients with diabetic CKD.

Material And Methods: We included 1958 patients with type 2 diabetes and CKD stages 1-5, and 111 patients underwent renal biopsy. Patients in the biopsied cohort were younger and had more severe proteinuria, compared with those in the total cohort; hematuria was associated with nondiabetic renal disease.

Results: In the total cohort, hematuria was observed in 15.0% of the patients and was associated with young age, a lower estimated glomerular filtration rate, proteinuria, high blood pressure and short diabetes duration. Hematuria was significantly associated with an increased risk (hazard ratio 1.39, 95% CI: 1.10-1.76, P < 0.001) of end-stage renal disease, particularly in patients with CKD stages 1-3 or a urine protein-to-creatinine ratio of <1,500mg/g (P for interaction < 0.05). The odds ratio of hematuria for rapid renal progression was 1.81 (95% CI: 1.29-2.53, P < 0.001).

Conclusions: Hematuria is associated with nondiabetic renal disease in biopsied patients with diabetic CKD and is associated with an increased risk of end-stage renal disease in patients with early diabetic CKD.
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http://dx.doi.org/10.1016/j.amjms.2018.06.005DOI Listing
September 2018

Independent Association of Overhydration with All-Cause and Cardiovascular Mortality Adjusted for Global Left Ventricular Longitudinal Systolic Strain and E/E' Ratio in Maintenance Hemodialysis Patients.

Kidney Blood Press Res 2018 10;43(4):1322-1332. Epub 2018 Aug 10.

Division of Nephrology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.

Background/aims: Fluid overload is common and associated with morbidity and mortality in patients with end-stage renal disease. The relationship between fluid overload and cardiac function is complex, and whether fluid overload is associated with adverse outcomes in patients undergoing hemodialysis (HD) independently of systolic and diastolic function of the left ventricle (LV) remains unclear.

Methods: The present study aimed to investigate the relationship between overhydration and all-cause and cardiovascular (CV) mortality after adjusting for LV function in 178 maintenance HD patients. The relative hydration status (overhydration/ extracellular water, ∆HS) was measured using a body composition monitor, and then used to assess the fluid status. A ∆HS ≥7% was defined as fluid overload. Global left ventricular longitudinal systolic strain (GLS), and the early filling and early diastolic mitral annular velocity (E/E') ratio were assessed using speckle-tracking and tissue Doppler echocardiography.

Results: During a mean follow-up period of 2.7 years, 24 patients died, including 11 CV deaths. An increased ∆HS was significantly associated with all-cause and CV mortality in the univariate analysis. This prognostic significance remains after multivariate adjusting for GLS and E/E' ratio for all-cause (HR, 1.123; 95% CI, 1.063-1.186; p-value < 0.001) and CV (HR, 1.088; 95% CI, 1.005-1.178; p-value =0.037) mortality. Moreover, ∆HS significantly improved the prognostic value beyond conventional clinical and echocardiographic parameters.

Conclusion: A higher ∆HS was independently associated with increased all-cause and CV mortality after adjusting for systolic and diastolic function of the LV. This suggests that ∆HS may be a relevant target for improving outcomes in maintenance HD patients.
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http://dx.doi.org/10.1159/000492591DOI Listing
November 2018

Anemia modifies the prognostic value of glycated hemoglobin in patients with diabetic chronic kidney disease.

PLoS One 2018 22;13(6):e0199378. Epub 2018 Jun 22.

Division of Nephrology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.

A common complication of chronic kidney disease (CKD), anemia can influence glycated hemoglobin (HbA1c) levels. In diabetic patients, anemia occurs earlier and with higher severity over the course of CKD stages. To elucidate the effect of hemoglobin (Hb) on the predictive value of HbA1c, we enrolled 1558 diabetic patients with stages 3-4 CKD, categorized according to baseline Hb and HbA1c quartiles. Linear regression revealed that higher HbA1c correlated significantly with higher Hb in the Hb < 10 g/dL group (β = 0.146, P = 0.004). A fully-adjusted Cox regression model revealed worse clinical outcomes in patients with higher HbA1c quartiles in the Hb ≥ 10 g/dL group. Hazard ratios for end-stage renal disease (ESRD), all-cause mortality, and composite endpoint (cardiovascular events and all-cause mortality) in patients with Hb ≥ 10 g/dL and the highest HbA1c quartile were 1.92 (95% confidence interval [CI], 1.17-3.15), 1.76 (95% CI, 1.02-3.03), and 1.54 (95% CI, 1.03-2.31), respectively. By contrast, HbA1c was not associated with clinical outcomes in the Hb < 10 g/dL group. In conclusion, in stages 3-4 diabetic CKD, higher HbA1c is associated with a higher risk of poor clinical outcomes in patients with Hb ≥ 10 g/dL.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0199378PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6014665PMC
April 2019

Angiopoietin-2, Renal Deterioration, Major Adverse Cardiovascular Events and All-Cause Mortality in Patients with Diabetic Nephropathy.

Kidney Blood Press Res 2018 6;43(2):545-554. Epub 2018 Apr 6.

Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.

Background/aims: Diabetic nephropathy is the leading cause of end-stage renal disease and accounts for 30∼40% of patients requiring maintenance dialysis, thereby increasing the burden on health insurance programs. Diabetic nephropathy is also the strongest predictor of cardiovascular morbidity and mortality. The aim of this study was to examine whether angiopoietin-2 (Angpt2), a modulator of endothelial function, affects the clinical outcomes of diabetic patients.

Methods: This study enrolled 236 patients with diabetes mellitus with estimated glomerular filtration rate (eGFR) < 60ml/min/1.73m2 from January 2006 to December 2011, who were followed until June 2017. Clinical outcomes included renal outcomes (commencing dialysis and rapid decline in renal function (eGFR decline > 3 ml/min per 1.73 m2/year)), major adverse cardiovascular events (MACEs), and all-cause mortality.

Results: Over a mean follow-up period of 3.9±2.7 years, 135 (57.2%) patients commenced dialysis, 106 (44.9%) had rapid decline in renal function, and 50 (21.2%) had MACEs or died from all-causes. Log-formed Angpt2 was significantly associated with increased risks of commencing dialysis (HR: 3.91, 95% CI: 1.56-9.76), rapid renal function decline (OR: 6.81, 95% CI: 1.06-43.88), and MACEs or all-cause mortality (HR: 6.34, 95% CI: 1.18-33.97) in the adjusted analysis. Patients in the highest quartile had hazard ratios of 2.90 and 3.11 for commencing dialysis and rapid renal function decline, respectively, compared to those in the lowest quartile after adjustments. Similar significant dose-response results were found in composite outcomes of either MACEs or all-cause mortality.

Conclusion: Angpt2 is an independent predictor of adverse clinical outcomes in diabetic patients. Further studies are needed to identify the pathogenic role of Angpt2 in renal deterioration and cardiovascular complications of diabetes mellitus.
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http://dx.doi.org/10.1159/000488826DOI Listing
October 2018

Association of type 2 diabetes mellitus and ratio of transmitral E wave velocity to early diastole mitral velocity with cardiovascular events in chronic kidney disease.

Oncotarget 2017 Nov 10;8(55):94407-94416. Epub 2017 Oct 10.

Department of Medical Laboratory Science and Biotechnology, College of Health Sciences, Kaohsiung Medical University, Kaohsiung, Taiwan.

The association between DM and left ventricular diastolic dysfunction, assessed using the ratio of peak early transmitral filling wave velocity (E) to early diastolic velocity of mitral annulus (Ea), with cardiovascular (CV) outcomes in patients with chronic kidney disease (CKD) remains uncertain. This study included 356 CKD stage 3-5 patients underwent echocardiography. All patients were classified into four groups based on the presence of DM and E/Ea ≤ or > 9. CV events included CV death, hospitalization for heart failure, unstable angina or nonfatal myocardial infarction, sustained ventricular arrhythmia, transient ischemic attack, and stroke. There were 58 CV events during the mean observation period of 25.0 months. A combination of the presence of DM and E/Ea > 9 (vs a combination of non-DM and E/Ea ≤ 9) was associated with CV events in unadjusted model (hazard ratio [HR], 6.990; 95% confidence interval [CI], 2.753-17.744; < 0.001), and in a multivariate adjusted model (HR, 3.037; 95% CI, 2.088-7.177; = 0.025). In the patients without DM, the E/Ea ratio ( = 0.033) improved the prediction of CV events, compared to the E/Ea ratio ( = 0.018), left atrial diameter ( = 0.016) and left ventricular mass index ( = 0.001) in the patients with DM. The combination of DM and left ventricular diastolic dysfunction was associated with CV events in patients with CKD stage 3-5. Assessments of DM status and E/Ea ratio may facilitate identifying high-risk patient population of unfavorable CV outcomes.
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http://dx.doi.org/10.18632/oncotarget.21768DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5706883PMC
November 2017

Induced pluripotent stem cells derived from an autosomal dominant polycystic kidney disease patient carrying a PKD1 Q533X mutation.

Stem Cell Res 2017 12 28;25:83-87. Epub 2017 Oct 28.

Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan. Electronic address:

Autosomal Dominant Polycystic Kidney Disease (ADPKD) is the most prevalent monogenic kidney disorder leading to kidney failure. We generated induced pluripotent stem cells (iPSCs) from a 37-year-old man carrying a PKD1 Q533X mutation who suffered from kidney failure and a myocardial infarction. The iPSCs were reprogrammed from the patient's peripheral blood mononuclear cells using the Sendai virus system, and were confirmed to possess the specific PKD1 Q533X mutation and normal karyotype. Pluripotency was confirmed using in vitro and in vivo assays. This iPSC line will be useful for studying the mechanisms driving the complicated pathophysiology of ADPKD.
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http://dx.doi.org/10.1016/j.scr.2017.10.026DOI Listing
December 2017

Generation of an induced pluripotent stem cell line, IBMS-iPSC-014-05, from a female autosomal dominant polycystic kidney disease patient carrying a common mutation of R803X in PKD2.

Stem Cell Res 2017 12 10;25:38-41. Epub 2017 Oct 10.

Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan. Electronic address:

Autosomal dominant polycystic kidney disease (ADPKD) is one of the most commonly inherited forms of polycystic kidney disease, and is characterized by the growth of numerous cysts in both kidneys. Here we generated an induced pluripotent stem cell (iPSC) line from the peripheral blood mononuclear cells (PBMCs) of a 63-year-old female ADPKD patient carrying an R803X mutation in the PKD2 gene using the Sendai-virus delivery system. Downstream characterization of these iPSCs showed that they possessed normal karyotyping, were free of genomic integration, retained the disease-causing PKD2 mutation, expressed pluripotency markers and could differentiate into three germ layers.
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http://dx.doi.org/10.1016/j.scr.2017.10.005DOI Listing
December 2017

Generation of induced pluripotent stem cells derived from an autosomal dominant polycystic kidney disease patient with a p.Ser1457fs mutation in PKD1.

Stem Cell Res 2017 10 15;24:139-143. Epub 2017 Sep 15.

Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan. Electronic address:

Autosomal dominant polycystic kidney disease is one of the most prevalent forms of inherited cystic kidney disease, and can be characterized by kidney cyst formation and enlargement. Here we report the generation of a Type 1 ADPKD disease iPS cell line, IBMS-iPSC-012-12, which retains the conserved deletion of PKD1, normal karyotype and exhibits the properties of pluripotent stem cells such as ES-like morphology, expression of pluripotent markers and capacity to differentiate into all three germ layers. Our results show that we have successfully generated a patient-specific iPS cell line with a mutation in PKD1 for study of renal disease pathophysiology.
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http://dx.doi.org/10.1016/j.scr.2017.09.004DOI Listing
October 2017

The interaction between fluid status and angiopoietin-2 in adverse renal outcomes of chronic kidney disease.

PLoS One 2017 23;12(3):e0173906. Epub 2017 Mar 23.

Division of Nephrology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.

Background: Fluid overload is not only the characteristic but also an important complication in chronic kidney disease (CKD) patients. Angiopoietin-2 (Angpt2) disturbs endothelium and vessel permeability, which may induce fluid overload. The aim of this study is to examine the interaction between fluid status and Angpt2 in adverse renal outcomes of CKD.

Methods: This cohort study enrolled 290 patients with CKD stages 3-5 from January 2011 to December 2011 and followed up until December 2015. Fluid status was presented as overhydration (OH) value measured by body composition monitor, while OH>1.1L was defined as fluid overload. Renal outcomes were defined as commencing dialysis and rapid renal function decline (the slope of estimated glomerular filtration rate < -5 ml/min/1.73 m2/y).

Results: During a mean follow-up of 38.6±18.3 months, 125 (43.1%) patients progressed to commencing dialysis and 99(34.7%) patients presented rapid renal function decline. All patients were stratified by OH of 1.1L and the median of circulating Angpt2. These patients with both OH>1.1L and high circulating Angpt2 were more likely to reach commencing dialysis compared to other groups. The risks for commencing dialysis and rapid renal function decline were significantly higher in patients with OH>1.1L and high circulating Angpt2 level compared to those with OH≦1.1L and low circulating Angpt2 (2.14, 1.21-3.78, P = 0.009; 4.96, 1.45-16.97, P = 0.01). There was a significant interaction between OH level and circulating Angpt2 in entering dialysis (P-interaction = 0.02).

Conclusions: Fluid overload and Angpt2 might have a synergistic effect on adverse renal outcomes in CKD patients.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0173906PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5363828PMC
August 2017

Heart Rate Variability Predicts Major Adverse Cardiovascular Events and Hospitalization in Maintenance Hemodialysis Patients.

Kidney Blood Press Res 2017 17;42(1):76-88. Epub 2017 Mar 17.

Division of Nephrology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.

Background/aims: Heart rate variability (HRV) has been linked to mortality in maintenance hemodialysis (HD) patients, but it is less clear whether HRV is associated with major adverse cardiovascular events (MACEs) and hospitalization.

Methods: This study enrolled 179 maintenance HD patients. HRV was measured to assess its prognostic significance in relation to MACEs and hospitalization.

Results: During the follow-up period of 33.3 ± 6.7 months, 36 (20.1%) patients had a MACE, and 98 (54.7%) experienced hospitalization. In multivariate adjusted Cox regression analysis, low very low frequency (VLF) power (hazard ratio [HR], 0.727; 95% confidence interval [CI], 0.624-0.848; p < 0.001), a history of coronary artery disease, high ultrafiltration rate, the use of angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers, and the use of beta-blockers were all significantly associated with MACEs. Low VLF power (HR, 0.873; 95% CI, 0.785-0.971; p = 0.012), low serum albumin, low serum creatinine, low Kt/V levels, and high serum calcium-phosphorus product levels significantly predicted hospitalization in maintenance HD patients.

Conclusions: Reduced VLF power is linked to an increased risk of MACEs and hospitalization in maintenance HD patients. Assessing cardiac autonomic function through HRV is of pivotal prognostic significance for this patient population.
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http://dx.doi.org/10.1159/000469716DOI Listing
March 2018

Glycosuria and Renal Outcomes in Patients with Nondiabetic Advanced Chronic Kidney Disease.

Sci Rep 2016 12 23;6:39372. Epub 2016 Dec 23.

Division of Nephrology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.

Sodium glucose cotransporter 2 inhibitors have shown a potential for renoprotection beyond blood glucose lowering. Glycosuria in nondiabetic patients with chronic kidney disease (CKD) is sometimes noted. Whether glycosuria in CKD implies a channelopathy or proximal tubulopathy is not known. The consequence of glycosuria in CKD is also not studied. We performed a cross-sectional study for the association between glycosuria and urine electrolyte excretion in 208 nondiabetic patients. Fractional excretion (FE) of glucose >4% was 3.4%, 6.3% and 62.5% in CKD stage 3, 4 and 5, respectively. These patients with glycosuria had higher FE sodium, FE potassium, FE uric acid, UPCR, and urine NGAL-creatinine ratio. We conducted a longitudinal study for the consequence of glycosuria, defined by dipstick, in 769 nondiabetic patients with stage 4-5 CKD. Glycosuria was associated with a decreased risk for end-stage renal disease (adjusted hazard ratio: 0.77; CI = 0.62-0.97; p = 0.024) and for rapid renal function decline (adjusted odds ratio: 0.63; CI = 0.43-0.95; p = 0.032); but glycosuria was not associated with all-cause mortality or cardiovascular events. The results were consistent in the propensity-score matched cohort. Glycosuria is associated with increased fractional excretion of electrolytes and is related to favorable renal outcomes in nondiabetic patients with stage 5 CKD.
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http://dx.doi.org/10.1038/srep39372DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5180243PMC
December 2016

Hyponatremia is Associated with Fluid Imbalance and Adverse Renal Outcome in Chronic Kidney Disease Patients Treated with Diuretics.

Sci Rep 2016 11 14;6:36817. Epub 2016 Nov 14.

Division of Nephrology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.

Chronic kidney disease (CKD) is frequently complicated with hyponatremia, probably because of fluid overload or diuretic usage. Hyponatremia in CKD population is associated with increased mortality, but the effect on renal outcome was unknown. We investigated whether hyponatremia is associated with fluid status and is a prognostic indicator for adverse outcomes in a CKD cohort of 4,766 patients with 1,009 diuretic users. We found that diuretic users had worse clinical outcomes compared with diuretic non-users. Hyponatremia (serum sodium <135 mEq/L) was associated with excessive volume and volume depletion, measured as total body water by bioimpedance analysis, in diuretic users, but not in diuretic non-users. Furthermore, in Cox survival analysis, hyponatremia was associated with an increased risk for renal replacement therapy (hazard ratio, 1.45; 95% CI, 1.13-1.85, P < 0.05) in diuretic users, but not in diuretic non-users (P for interaction <0.05); restricted cubic spline model also showed a similar result. Hyponatremia was not associated with all-cause mortality or cardiovascular event whereas hypernatremia (serum sodium >141 mEq/L) was associated with an increased risk for all-cause mortality. Thus, hyponatremia is an indicator of fluid imbalance and also a prognostic factor for renal replacement therapy in CKD patients treated with diuretics.
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http://dx.doi.org/10.1038/srep36817DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5108044PMC
November 2016

Glycated Hemoglobin and Outcomes in Patients with Advanced Diabetic Chronic Kidney Disease.

Sci Rep 2016 Jan 28;6:20028. Epub 2016 Jan 28.

Division of Nephrology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.

Diabetes is the major risk factor for end-stage renal disease (ESRD) worldwide. In advanced chronic kidney disease (CKD), less is known about the predictive value of HbA1c. We enrolled 2401 diabetic patients with stage 3-4 and stage 5 CKD, who were classified into 4 groups according to their baseline HbA1c values (<6%, 6%-7%, 7%-9%, and >9%). During the median follow-up of 3 years, 895 patients developed ESRD, and 530 died. In linear regression analysis, higher HbA1c correlated with higher eGFR in patients with stage 5 CKD but not in stage 3-4 CKD. In Cox regression analysis, a trend toward worse clinical outcomes existed when the HbA1c level exceeded 6% in stage 3-4 CKD, but the significance was only observed for >9%. The hazard ratios (HRs) for ESRD, all-cause mortality and combined CV events with mortality in the group of HbA1c >9% were 1.6 (95% CI, 1.07 to 2.38), 1.52 (95% CI, 0.97 to 2.38) and 1.46 (95% CI, 1.02 to 2.09), respectively. This study demonstrates that the higher HbA1c level is associated higher risks for clinical outcomes in diabetic patients with stage 3-4 CKD but not in stage 5 CKD.
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http://dx.doi.org/10.1038/srep20028DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4730215PMC
January 2016

Use of HLA-B*58:01 genotyping to prevent allopurinol induced severe cutaneous adverse reactions in Taiwan: national prospective cohort study.

BMJ 2015 Sep 23;351:h4848. Epub 2015 Sep 23.

Kaohsiung Medical University Hospital and Kaohsiung Medical University, Kaohsiung, Taiwan Kaohsiung Municipal Hsiaokang Hospital, Kaohsiung Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung.

Objective: To evaluate the use of prospective screening for the HLA-B*58:01 allele to identify Taiwanese individuals at risk of severe cutaneous adverse reactions (SCARs) induced by allopurinol treatment.

Design: National prospective cohort study.

Setting: 15 medical centres in different regions of Taiwan, from July 2009 to August 2014.

Participants: 2926 people who had an indication for allopurinol treatment but had not taken allopurinol previously. Participants were excluded if they had undergone a bone marrow transplant, were not of Han Chinese descent, and had a history of allopurinol induced hypersensitivity. DNA purified from 2910 participants' peripheral blood was used to assess the presence of HLA-B*58:01.

Main Outcome Measures: Incidence of allopurinol induced SCARs with and without screening.

Results: Participants who tested positive for HLA-B*58:01 (19.6%, n=571) were advised to avoid allopurinol, and were referred to an alternate drug treatment or advised to continue with their prestudy treatment. Participants who tested negative (80.4%, n=2339) were given allopurinol. Participants were interviewed once a week for two months to monitor symptoms. The historical incidence of allopurinol induced SCARs, estimated by the National Health Insurance research database of Taiwan, was used for comparison. Mild, transient rash without blisters developed in 97 (3%) participants during follow-up. None of the participants was admitted to hospital owing to adverse drug reactions. SCARs did not develop in any of the participants receiving allopurinol who screened negative for HLA-B*58:01. By contrast, seven cases of SCARs were expected, based on the estimated historical incidence of allopurinol induced SCARs nationwide (0.30% per year, 95% confidence interval 0.28% to 0.31%; P=0.0026; two side one sample binomial test).

Conclusions: Prospective screening of the HLA-B*58:01 allele, coupled with an alternative drug treatment for carriers, significantly decreased the incidence of allopurinol induced SCARs in Taiwanese medical centres.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4579807PMC
http://dx.doi.org/10.1136/bmj.h4848DOI Listing
September 2015

Peritoneal Dialysis-Associated Peritonitis Caused by Mycobacterium abscessus.

Perit Dial Int 2015 May-Jun;35(3):369-71

Division of Nephrology Department of Internal Medicine Kaohsiung Medical University Hospital Kaohsiung Medical University, Kaohsiung, Taiwan Faculty of Medicine College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan Faculty of Renal Care College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.

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http://dx.doi.org/10.3747/pdi.2014.00012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4444000PMC
April 2016

Low serum calcium is associated with poor renal outcomes in chronic kidney disease stages 3-4 patients.

BMC Nephrol 2014 Nov 21;15:183. Epub 2014 Nov 21.

Division of Nephrology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, No, 100, Tzyou 1st Road, Kaohsiung 807, Taiwan.

Background: Mineral disorders are associated with adverse renal outcomes in chronic kidney disease (CKD) patients. Previous studies have associated hypercalcemia and hypocalcemia with mortality; however, the association between serum calcium and renal outcome is not well-described. Whether adding calcium besides phosphorus or in the form of calcium-phosphorus (Ca×P) product into the model of survival analysis could improve the prediction of renal outcomes is not known.

Methods: A prospective cohort of 2144 outpatients with CKD stages 3-4 was evaluated. Cox proportional hazard analysis was performed according to calcium quartiles.

Results: The mean calcium level was 9.2±0.7 mg/dL. Low serum calcium (<9.0 mg/dL) was associated with increased risk of requiring renal replacement therapy (RRT) (hazards ratio [HR]:2.12 (95% CI: 1.49-3.02, P<0.05) and rapid renal function progression (odds ratio [OR]: 1.65 (95% CI: 1.19-2.27, P<0.05) compared with high serum calcium (>9.8 mg/dL). Adding calcium into the survival model increased the integrated discrimination improvement by 0.80% (0.12%-1.91%) while calcium-phosphorus product did not improve risk prediction.The combination of high serum phosphorus (>4.2 mg/dL) and low serum calcium (<9.1 mg/dL) was associated with the highest risk of RRT (HR:2.31 (95% CI: 1.45-3.67, P<0.05).

Conclusion: Low serum calcium is associated with increased risk of RRT and rapid renal function progression in CKD stage 3-4 patients. The integration of serum calcium and phosphorus, but not calcium-phosphorus product should be considered in a predictive model of renal outcome.
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http://dx.doi.org/10.1186/1471-2369-15-183DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4255427PMC
November 2014

Hepatitis C virus infection increases risk of developing end-stage renal disease using competing risk analysis.

PLoS One 2014 27;9(6):e100790. Epub 2014 Jun 27.

Division of Nephrology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Faculty of Renal Care, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.

Background: Chronic kidney disease (CKD) and hepatitis C virus (HCV) infection are closely linked and both increase patient mortality. The association of HCV and risk of developing end-stage renal disease (ESRD) has not been analyzed with competing risk model.

Method: We enrolled a prospective cohort of 4,185 patients (mean age, 62 years; 41% female) registered in the CKD integrated care program at two affiliated hospitals of Kaohsiung Medical University in Taiwan between November 11, 2002 and May 31, 2009. With competing risk model, we analyzed the association of HCV infection, defined by seropositive of anti-HCV antibody, and hepatitis B virus (HBV) infection, defined by seropositive of HBV surface antigen, with the risk of entering ESRD.

Results: The prevalence of HCV infection was 7.6% and it increased with the CKD stages (trend test, P<0.001), while the prevalence of HBV infection was 7.4% and no specific trend among CKD stages (tend test, P = 0.1). During the 9,101 person-year follow-up period, there were 446 death and 1,205 patients entering ESRD. After adjusting death as the competing risk, the estimated 5-year cumulative incidence rate of ESRD among patients with and without HCV infection were 52.6% and 38.4%, respectively (modified log-rank, P<0.001). Multivariable analysis showed that HCV infection, but not HBV infection, had higher risk of developing ESRD compared with cases without infection (HCV, HR: 1.32, 95% CI: 1.07-1.62; HBV, HR: 1.10, 95% CI: 0.89-1.35). Subgroup analyses showed consistent results.

Conclusions: With death-adjusted competing risk analysis, HCV infection is associated with an increased risk of developing ESRD in CKD cohort.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0100790PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4074067PMC
October 2015