Immunoglobulin A nephropathy (IgAN) is an autoimmune disease characterized by abnormal IgA deposi... more Immunoglobulin A nephropathy (IgAN) is an autoimmune disease characterized by abnormal IgA deposition in glomerulus. Current diagnosis of IgAN still depends on renal biopsy, an invasive method that might increase the risk of clinical outcomes. Therefore, we aimed to explore the characteristics of T cell repertoire in IgAN from peripheral blood samples for identifying innovative diagnostic biomarkers. Herein, we included 8 IgAN patients, 25 non-IgAN patients, and 10 healthy controls in the study. A high-throughput immune repertoire sequencing was conducted to investigate the T-cell receptor beta-chain (TCRβ) repertoire of peripheral blood. Characteristics of TCRβ repertoire were assessed for these three distinct groups. A reduced TCRβ repertoire diversity was observed in IgAN patients compared to non-IgAN and healthy individuals. A skewed distribution toward shorter TCRβ complementarity determining region (CDR3) length was found in non-IgAN relative to IgAN patients. In addition, the differences in usages of five TRBV genes (TRBV5-4, TRBV6-4, TRBV12-1, TRBV16, and TRBV21-1) were identified between IgAN, non-IgAN, and healthy subjects. Of note, the TRBV6-4 gene, which is associated with mucosal-associated invariant T (MAIT) cells, exhibited higher usage in IgAN patients, suggesting potential importance of MAIT cells in IgAN. In short, our findings supported TCR repertoire characteristics as potential biomarkers for IgAN diagnosis.
Background. Real-time three-dimensional echocardiography (RT3DE) has emerged as a more accurate a... more Background. Real-time three-dimensional echocardiography (RT3DE) has emerged as a more accurate and effective tool for assessing left ventricular (LV) function, compared to traditional two-dimensional (2D) methods. In this study, we used this new tool to revise the controversial relationship between LV function and intra-dialytic hypotension. Methods. This study enrolled 29 intra-dialytic hypotensive patients (the IDH group) and 34 controls (the CON group) on regular maintenance haemodialysis. The RT3DEand 2D-derived ejection fraction (EF), stroke volume index (SVI) and ratio of early transmitral inflow velocity to diastolic early tissue velocity were assessed at pre-dialysis and mid-dialysis. The intravascular volume was assessed by the inferior vena cava collapsibility index. Results. Pre-dialysis evaluation showed no difference in RT3DE-and 2D-derived parameters between the two groups. At mid-dialysis, the IDH group had a lower 2D EF (54 ± 9.1 versus 62 ± 6.8% in the CON group, P < 0.001), RT3DE EF (53 ± 6 versus 60 ± 7% in the CON group, P < 0.001) and SVI (24.3 ± 8 versus 30.6 ± 12.2 mL in the CON group, P = 0.02). From pre-dialysis to middialysis, the IDH group had greater decrease in the change in 2D EF (−4.8% ± 12.6% versus 5% ± 13.7% in the CON group, P = 0.004), RT3DE EF (−11.8 ± 10.3 versus −3.4 ± 11.5% in the CON group, P = 0.003) and SVI (−17.3 ± 18.5 versus −9.2 ± 19.8% in the CON group, P = 0.004). The calculated cardiac index change also showed a greater decrease in the IDH group (−17.8 ± 20.2 versus −5.7 ± 18.5% in the CON group, P = 0.02). No significant difference in the ratio of early transmitral inflow velocity to diastolic early tissue velocity, heart rate, systemic vascular resistance index or inferior vena cava collapsibility index was found between the two groups at the baseline or mid-dialysis. A lack of an increase in heart rate and the systemic vascular resistance index in the IDH group during the hypotensive episodes implies that these patients have autonomic dysfunction. Multivariate analysis showed that the RT3DE EF change of < −9.5% (odds ratio = 6, P = 0.003) and the presence of diabetes (odds ratio = 4.4, P = 0.013) had significant and independent associations with intra-dialytic hypotension. Conclusions. By adopting RT3DE to assess LV performance, our data demonstrated that an inadequate compensation in the LV systolic function is the main mechanism mediating the occurrence of intra-dialytic hypotension in patients with autonomic dysfunction.
Background. Although amino acid peritoneal dialysate (AAPD) substitution is thought to improve pr... more Background. Although amino acid peritoneal dialysate (AAPD) substitution is thought to improve proteinenergy malnutrition in patients undergoing peritoneal dialysis (PD), it may also increase plasma homocysteine (Hcy) levels due to the methionine load in the dialysate. However, it is still unclear which factors are important for elevating Hcy in patients treated with AAPD. Methods. Sixteen malnourished PD patients (age 48±18 years) were treated daily with one exchange of 1.1% AAPD for 3 months. The effects of AAPD on nutrition, Hcy, methionine, leptin and insulin resistance were studied. We also analysed factors that influenced plasma Hcy levels. Results. We found a transient increase in serum albumin (P<0.01) after 1 month treatment, especially in patients with serum albumin 3.5 g/dl. Total plasma Hcy increased markedly after AAPD (the peak at month 2, P<0.001) and returned to baseline after ceasing AAPD, despite no changes in dietary methionine intake and serum methionine levels. Eight patients with Hcy increments >5.65 mM (the median) had lesser dietary intakes of protein (P ¼ 0.01) and methionine (P ¼ 0.028), lower body fat mass (P ¼ 0.05) and lower aspartate transaminase (AST) (P ¼ 0.008) before AAPD treatment than patients with lower increments. ÁHcy was inversely correlated with baseline dietary methionine intake (r ¼ À 0.61), protein intake (r ¼ À 0.54) and AST (r ¼ À 0.51) (all P<0.05). There was no change in leptin or insulin resistance. AAPD treatment significantly increased Kt/V urea (P<0.001), weekly creatinine clearance (P<0.05) and peritoneal glucose transport (P<0.05). Conclusions. Treatment with 1.1% AAPD transiently increased serum albumin in malnourished PD patients. However, the methionine load from the dialysate in this study significantly elevated plasma Hcy levels, especially in patients with lower protein and methionine intakes, and lower AST levels. Further long-term studies will be needed to clarify potential nutritional benefits and adverse effects of AAPD.
die. Conclusion: In this CKD cohort, patients were more likely to develop ESRD than cardiovascula... more die. Conclusion: In this CKD cohort, patients were more likely to develop ESRD than cardiovascular death. The rate of GFR decline and predictors of ESRD were comparable to those reported in Western countries. Thus, the high incidence of ESRD in Taiwan may be attributed, at least in part, to lower cardiovascular mortality.
Background: Estimated glomerular filtration rate (eGFR) using the Modification of Diet in Renal D... more Background: Estimated glomerular filtration rate (eGFR) using the Modification of Diet in Renal Disease (MDRD) study or the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations may not be accurate for Asians; thus, we developed modified eGFR equations for Taiwanese adults. Methods: This cross-sectional study compared the Taiwanese eGFR equations, the MDRD study, and the CKD-EPI equations with inulin clearance (C in). A total of 695 adults including 259 healthy volunteers and 436 CKD patients were recruited. Participants from the Kaohsiung Medical University Hospital were used as the development set (N = 556) to develop the Taiwanese eGFR equations, whereas participants from the National Taiwan University Hospital were used as the validation set (N = 139) for external validation. Results: The Taiwanese eGFR equations were developed by using the extended Bland-Altman plot in the development set. The Taiwanese MDRD equation was 1.3096MDRD 0.912 , Taiwanese CKD-EPI was 1.2626CKD-EPI 0.914 and Taiwanese four-level CKD-EPI was 1.2056four-level CKD-EPI 0.914. In the validation set, the Taiwanese equations had the lowest bias, the Taiwanese equations and the Japanese CKD-EPI equation had the lowest RMSE, whereas the Taiwanese and the Japanese equations had the best precision and the highest P 30 among all equations. However, the Taiwanese MDRD equation had higher concordance correlation than did the Taiwanese CKD-EPI, the Taiwanese four-level CKD-EPI and the Japanese equations. Moreover, only the Taiwanese equations had no proportional bias among all of the equations. Finally, the Taiwanese MDRD equation had the best diagnostic performance in terms of ordinal logistic regression among all of the equations. Conclusion: The Taiwanese MDRD equation is better than the MDRD, CKD-EPI, Japanese, Asian, Thai, Taiwanese CKD-EPI, and Taiwanese four-level CKD-EPI equations for Taiwanese adults.
Journal of The American Society of Nephrology, Jun 1, 2014
The mechanism of vascular calcification in CKD is not understood fully, but may involve collagen ... more The mechanism of vascular calcification in CKD is not understood fully, but may involve collagen deposition in the arterial wall upon osteo/chondrocytic transformation of vascular smooth muscle cells (VSMCs). Increased levels of circulating angiopoietin-2 correlate with markers of CKD progression and angiopoietin-2 regulate inflammatory responses, including intercellular and vascular adhesion and recruitment of VSMCs. Here, we investigate the potential role of angiopoietin-2 in the pathogenesis of arterial stiffness associated with CKD. In a cohort of 416 patients with CKD, the plasma level of angiopoietin-2 correlated independently with the severity of arterial stiffness assessed by pulse wave velocity. In mice subjected to 5/6 subtotal nephrectomy or unilateral ureteral obstruction, plasma levels of angiopoietin-2 also increased. Angiopoietin-2 expression markedly increased in tubular epithelial cells of fibrotic kidneys but decreased in other tissues, including aorta and lung, after 5/6 subtotal nephrectomy. Expression of collagen and profibrotic genes in aortic VSMCs increased in mice after 5/6 subtotal nephrectomy and in mice producing human angiopoietin-2. Angiopoietin-2 stimulated endothelial expression of chemokines and adhesion molecules for monocytes, increased Ly6C low macrophages in aorta, and increased the expression of the profibrotic cytokine TGF-b1 in aortic endothelial cells and Ly6C low macrophages. Angiopoietin-2 blockade attenuated expression of monocyte chemokines, profibrotic cytokines, and collagen in aorta of mice after 5/6 subtotal nephrectomy. This study identifies angiopoietin-2 as a link between kidney fibrosis and arterial stiffness. Targeting angiopoietin-2 to attenuate inflammation and collagen expression may provide a novel therapy for cardiovascular disease in CKD.
Background and Aims The substantial mortality and morbidity burden of chronic kidney disease (CKD... more Background and Aims The substantial mortality and morbidity burden of chronic kidney disease (CKD) is well described, with the highest burden associated with progression to end-stage kidney disease (ESKD), where kidney replacement therapy (dialysis or kidney transplantation) is indicated. CKD is known to have a detrimental effect on patient health-related quality of life (HRQoL). However, there is a lack of data comparing the impact of CKD on patient and caregiver HRQoL versus the general population. This study aimed to administer validated HRQoL instruments using a quantitative online survey to estimate the HRQoL of patients with CKD and their caregivers compared to the general population. Method A non-interventional survey enrolled adult patients with CKD and caregivers. Patients with a diagnosis of CKD for at least 3 months were included. ESKD was defined as patients with CKD stage 5 or receiving dialysis or a kidney transplant. Caregivers were required not to receive formal paym...
The purpose of this phase I clinical trial is to assess the safety and tolerability of allogeneic... more The purpose of this phase I clinical trial is to assess the safety and tolerability of allogeneic adipose tissue-derived stem cells (ADSCs) among chronic kidney disease (CKD) patients. 12 eligible CKD patients with an estimated glomerular filtration rate (eGFR) of 15-44 ml/min/1.73 m2 received one dose of intravenous allogeneic ADSCs (ELIXCYTE® ), as 3 groups: 3 low dose (6.4 × 107 cells in total of 8 ml), 3 middle dose (19.2 × 107 cells in total of 24 ml) and 6 high dose (32.0 × 107 cells in total of 40 ml) of ELIXCYTE® and evaluated after 48 weeks. Primary endpoint was the safety profiles in terms of incidence of adverse events (AEs) and serious adverse event (SAE). Two subjects in high dose group experienced a total of 2 treatment-related AEs which are Grade 1 slow speech and Grade 1 bradyphrenia after the infusion. One subject in middle dose group experienced an SAE unlikely related to treatment, grade 2 proteinuria. No fatal AE was reported in this study. An increase in eGFR was observed in 7 out of 12 subjects (58%) at Week 24 and in 6 of 12 subjects (50%) by Week 48. By Week 24, an increase in eGFR by more than 20% among all CKD patients with baseline eGFR ≧ 30 ml/min/1.73 m2 as compared to only 2 subjects in baseline eGFR < 30 ml/min/1.73 m2 group. No significant reduction in proteinuria was noted among all subjects. This phase I trial demonstrated single-dose intravenous ELIXCYTE was well tolerated in moderate-to-severe CKD patients and its preliminary efficacy warrants future studies.
Nitric oxide plays an important role in mediating the inflammatory process. The aim of this study... more Nitric oxide plays an important role in mediating the inflammatory process. The aim of this study was to evaluate if nitric oxide production was increased during peritonitis in patients receiving continuous ambulatory peritoneal dialysis (CAPD), and the association with the prognosis. The study population comprised 21 patients with 22 episodes of peritonitis. Fifteen patients without peritonitis were controls. Nitrate was measured by HPLC and nitrite by the Griess method, to reflect nitric oxide production. Peritoneal dialysate effluent and plasma were collected from six patients during peritonitis and 1 week after treatment to study changes in dialysate:plasma ratio. In 15 patients, nitrite was measured during peritonitis and every 3 days for 2 weeks or until normalized for evolutional changes. The dialysate: plasma ratios of nitrate and nitrite during peritonitis were reduced 26% and 41.5%, respectively, after 1 week of treatment, indicating the peritoneal production of nitric oxide during peritonitis. In the evolutional study, a 5.1-fold increase of peak nitrite levels in bacterial peritonitis (H = 1 3) and a 2.5-fold increase in fungal peritonitis (« = 3) were observed compared to controls. Nitrite gradually declined to control levels (9.3 ±7.2 days) after effective antibiotic treatment, but took longer than to normalize leukocyte count in the peritoneal dialysate effluent (3.9+ 1.9 days). In four patients with refractory peritonitis (Candida infection in three, Acinetobacter infection in one), the nitrite levels remained elevated 2-fold despite treatment, and the catheters were removed. It is concluded that nitrite levels in peritoneal dialysate effluent may serve as a marker to assess treatment efficacy in CAPD patients with peritonitis.
Background: The malnutrition-inflammation score (MIS) is an indicator of malnutrition-inflammatio... more Background: The malnutrition-inflammation score (MIS) is an indicator of malnutrition-inflammation complex syndrome and an outcome predictor in maintenance hemodialysis patients. However, its utility in peritoneal dialysis (PD) patients and its association with the Charlson comorbidity index (CCI) have not yet been examined. Methods: All chronic stable PD outpatients in the PD center of the National Taiwan University Hospital in January 2006 were studied and followed for up to 18 months. The baseline MIS and CCI at the beginning of the study and the dates and causes of mortality or hospitalization during the study period were obtained. Results: A total of 141 PD patients were enrolled. During the study period, 8 patients died and 40 patients had at least one fatal or nonfatal major cardiovascular or infection event. The CCI correlated positively and significantly with the MIS (r = +0.344, p < 0.001). The MIS and CCI were both independent predictors of cardiovascular and infection...
In Taiwan, most first-time dialysis was started without the creation of an arteriovenous shunt. H... more In Taiwan, most first-time dialysis was started without the creation of an arteriovenous shunt. Here, we aimed to elucidate the transitions of dialysis status in the unplanned first dialysis patients and determine factors associated with their outcomes. A total of 50,315 unplanned first dialysis patients aged more than 18 years were identified from the National Health Insurance Dataset in Taiwan between 2001 and 2012. All patients were followed for 5 years for the transitions in dialysis status, including robust (dialysis-free), sporadic dialysis, continued dialysis, and death. Furthermore, factors associated with the development of continued dialysis and death were examined by the Cox proportional hazard models. After 5 years after the first dialysis occurrence, there were 5.39% with robust status, 1.67% with sporadic dialysis, 8.45% with continued dialysis, and 84.48% with death. Notably, we have identified common risk factors for developing maintenance dialysis and deaths, includ...
This retrospective study aimed to investigate the effect of diabetes mellitus (DM) on the risks o... more This retrospective study aimed to investigate the effect of diabetes mellitus (DM) on the risks of end-stage kidney disease (ESKD) and post-liver transplantation (post-LT) mortality. Using data from the National Health Insurance Research Database, Taiwan, 3,489 patients who received a LT between 1 January 2005, and 31 December 2015, were enrolled in this study and divided into the pre-existing DM, post-LT DM (PLTDM), and without DM groups. All subjects were followed up from 1 year after LT to the index date for ESKD, and the occurrence of death, or until 31 December 2016. Of the 3,489 patients with LT, 1,016 had pre-existing DM, 215 had PLTDM, and 2,258 had no DM pre- or post-LT. The adjusted HRs of ESKD were 1.77 (95% Confidence Interval [CI], .78–3.99) and 2.61 (95% CI, 1.63–4.18) for PLTDM group and pre-existing DM group compared to without DM group, respectively. For the risk of death, the adjusted HRs were 1.05 (95% CI, .72–1.55) and 1.28 (95% CI, 1.04–1.59) for PLTDM group and...
ObjectivesOver the past two decades, debates on whether the profit status of dialysis facilities ... more ObjectivesOver the past two decades, debates on whether the profit status of dialysis facilities influences patient prognosis have been popular in the USA. Taiwan is one of the regions with the highest rate per capita of kidney replacement therapy worldwide, but no similar research has been conducted to date. This is the first study to address this issue.DesignThis was a nationwide retrospective cohort study based on the Taiwan Renal Registry Data System.SettingPatients were categorised into two groups based on the profit status (for-profit, not-for-profit (NFP)) of dialysis facilities, with 31 350 patients in each group. The patients were followed up from 2005 to 2012.ParticipantsPatients with uraemia who underwent long-term haemodialysis in private dialysis facilities and public facilities were excluded.Primary and secondary outcome measuresSurvival analyses were performed to compare prognosis between the two groups. Adjustments to patients’ basic profile, and facilities’ geograph...
Background and objectives: Chronic musculoskeletal (MS) pain is common in chronic kidney disease ... more Background and objectives: Chronic musculoskeletal (MS) pain is common in chronic kidney disease (CKD) patients. The association of chronic MS pain and CKD progression has not yet been established. Method: We conducted a prospective cohort study to evaluate the association of chronic MS pain and CKD progression of pre-dialysis CKD patients. Result: A total of 53.2% of pre-dialysis CKD patients had chronic MS pain. Patients classified as progression and non-progression had a similar prevalence of chronic MS pain at baseline, and similar baseline use of NSAIDs and Chinese herbal medicines. Univariate Cox analysis indicated that chronic MS pain and baseline NSAID or Chinese herbal medicine use were not significantly associated with progression of CKD. But multivariate Cox regression found chronic MS pain was independently significantly associated with all-cause mortality (HR, 2.912, 95% CI, 1.004-8.444; p ¼ .049). However, serum levels of hs-CRP were similar between those chronic MS pain patients and without chronic MS pain patients (4.96 ± 9.4 vs. 4.25 ± 13.3 mg/L, p ¼ .535). Conclusion: The CKD patients with chronic MS pain was independently and significantly associated with all-cause mortality, but not independently and significantly associated with CKD progression and composite endpoints. The inflammatory marker-hs-CRP was similar between CKD patients with and without chronic MS pain.
Immunoglobulin A nephropathy (IgAN) is an autoimmune disease characterized by abnormal IgA deposi... more Immunoglobulin A nephropathy (IgAN) is an autoimmune disease characterized by abnormal IgA deposition in glomerulus. Current diagnosis of IgAN still depends on renal biopsy, an invasive method that might increase the risk of clinical outcomes. Therefore, we aimed to explore the characteristics of T cell repertoire in IgAN from peripheral blood samples for identifying innovative diagnostic biomarkers. Herein, we included 8 IgAN patients, 25 non-IgAN patients, and 10 healthy controls in the study. A high-throughput immune repertoire sequencing was conducted to investigate the T-cell receptor beta-chain (TCRβ) repertoire of peripheral blood. Characteristics of TCRβ repertoire were assessed for these three distinct groups. A reduced TCRβ repertoire diversity was observed in IgAN patients compared to non-IgAN and healthy individuals. A skewed distribution toward shorter TCRβ complementarity determining region (CDR3) length was found in non-IgAN relative to IgAN patients. In addition, the differences in usages of five TRBV genes (TRBV5-4, TRBV6-4, TRBV12-1, TRBV16, and TRBV21-1) were identified between IgAN, non-IgAN, and healthy subjects. Of note, the TRBV6-4 gene, which is associated with mucosal-associated invariant T (MAIT) cells, exhibited higher usage in IgAN patients, suggesting potential importance of MAIT cells in IgAN. In short, our findings supported TCR repertoire characteristics as potential biomarkers for IgAN diagnosis.
Background. Real-time three-dimensional echocardiography (RT3DE) has emerged as a more accurate a... more Background. Real-time three-dimensional echocardiography (RT3DE) has emerged as a more accurate and effective tool for assessing left ventricular (LV) function, compared to traditional two-dimensional (2D) methods. In this study, we used this new tool to revise the controversial relationship between LV function and intra-dialytic hypotension. Methods. This study enrolled 29 intra-dialytic hypotensive patients (the IDH group) and 34 controls (the CON group) on regular maintenance haemodialysis. The RT3DEand 2D-derived ejection fraction (EF), stroke volume index (SVI) and ratio of early transmitral inflow velocity to diastolic early tissue velocity were assessed at pre-dialysis and mid-dialysis. The intravascular volume was assessed by the inferior vena cava collapsibility index. Results. Pre-dialysis evaluation showed no difference in RT3DE-and 2D-derived parameters between the two groups. At mid-dialysis, the IDH group had a lower 2D EF (54 ± 9.1 versus 62 ± 6.8% in the CON group, P < 0.001), RT3DE EF (53 ± 6 versus 60 ± 7% in the CON group, P < 0.001) and SVI (24.3 ± 8 versus 30.6 ± 12.2 mL in the CON group, P = 0.02). From pre-dialysis to middialysis, the IDH group had greater decrease in the change in 2D EF (−4.8% ± 12.6% versus 5% ± 13.7% in the CON group, P = 0.004), RT3DE EF (−11.8 ± 10.3 versus −3.4 ± 11.5% in the CON group, P = 0.003) and SVI (−17.3 ± 18.5 versus −9.2 ± 19.8% in the CON group, P = 0.004). The calculated cardiac index change also showed a greater decrease in the IDH group (−17.8 ± 20.2 versus −5.7 ± 18.5% in the CON group, P = 0.02). No significant difference in the ratio of early transmitral inflow velocity to diastolic early tissue velocity, heart rate, systemic vascular resistance index or inferior vena cava collapsibility index was found between the two groups at the baseline or mid-dialysis. A lack of an increase in heart rate and the systemic vascular resistance index in the IDH group during the hypotensive episodes implies that these patients have autonomic dysfunction. Multivariate analysis showed that the RT3DE EF change of < −9.5% (odds ratio = 6, P = 0.003) and the presence of diabetes (odds ratio = 4.4, P = 0.013) had significant and independent associations with intra-dialytic hypotension. Conclusions. By adopting RT3DE to assess LV performance, our data demonstrated that an inadequate compensation in the LV systolic function is the main mechanism mediating the occurrence of intra-dialytic hypotension in patients with autonomic dysfunction.
Background. Although amino acid peritoneal dialysate (AAPD) substitution is thought to improve pr... more Background. Although amino acid peritoneal dialysate (AAPD) substitution is thought to improve proteinenergy malnutrition in patients undergoing peritoneal dialysis (PD), it may also increase plasma homocysteine (Hcy) levels due to the methionine load in the dialysate. However, it is still unclear which factors are important for elevating Hcy in patients treated with AAPD. Methods. Sixteen malnourished PD patients (age 48±18 years) were treated daily with one exchange of 1.1% AAPD for 3 months. The effects of AAPD on nutrition, Hcy, methionine, leptin and insulin resistance were studied. We also analysed factors that influenced plasma Hcy levels. Results. We found a transient increase in serum albumin (P<0.01) after 1 month treatment, especially in patients with serum albumin 3.5 g/dl. Total plasma Hcy increased markedly after AAPD (the peak at month 2, P<0.001) and returned to baseline after ceasing AAPD, despite no changes in dietary methionine intake and serum methionine levels. Eight patients with Hcy increments >5.65 mM (the median) had lesser dietary intakes of protein (P ¼ 0.01) and methionine (P ¼ 0.028), lower body fat mass (P ¼ 0.05) and lower aspartate transaminase (AST) (P ¼ 0.008) before AAPD treatment than patients with lower increments. ÁHcy was inversely correlated with baseline dietary methionine intake (r ¼ À 0.61), protein intake (r ¼ À 0.54) and AST (r ¼ À 0.51) (all P<0.05). There was no change in leptin or insulin resistance. AAPD treatment significantly increased Kt/V urea (P<0.001), weekly creatinine clearance (P<0.05) and peritoneal glucose transport (P<0.05). Conclusions. Treatment with 1.1% AAPD transiently increased serum albumin in malnourished PD patients. However, the methionine load from the dialysate in this study significantly elevated plasma Hcy levels, especially in patients with lower protein and methionine intakes, and lower AST levels. Further long-term studies will be needed to clarify potential nutritional benefits and adverse effects of AAPD.
die. Conclusion: In this CKD cohort, patients were more likely to develop ESRD than cardiovascula... more die. Conclusion: In this CKD cohort, patients were more likely to develop ESRD than cardiovascular death. The rate of GFR decline and predictors of ESRD were comparable to those reported in Western countries. Thus, the high incidence of ESRD in Taiwan may be attributed, at least in part, to lower cardiovascular mortality.
Background: Estimated glomerular filtration rate (eGFR) using the Modification of Diet in Renal D... more Background: Estimated glomerular filtration rate (eGFR) using the Modification of Diet in Renal Disease (MDRD) study or the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations may not be accurate for Asians; thus, we developed modified eGFR equations for Taiwanese adults. Methods: This cross-sectional study compared the Taiwanese eGFR equations, the MDRD study, and the CKD-EPI equations with inulin clearance (C in). A total of 695 adults including 259 healthy volunteers and 436 CKD patients were recruited. Participants from the Kaohsiung Medical University Hospital were used as the development set (N = 556) to develop the Taiwanese eGFR equations, whereas participants from the National Taiwan University Hospital were used as the validation set (N = 139) for external validation. Results: The Taiwanese eGFR equations were developed by using the extended Bland-Altman plot in the development set. The Taiwanese MDRD equation was 1.3096MDRD 0.912 , Taiwanese CKD-EPI was 1.2626CKD-EPI 0.914 and Taiwanese four-level CKD-EPI was 1.2056four-level CKD-EPI 0.914. In the validation set, the Taiwanese equations had the lowest bias, the Taiwanese equations and the Japanese CKD-EPI equation had the lowest RMSE, whereas the Taiwanese and the Japanese equations had the best precision and the highest P 30 among all equations. However, the Taiwanese MDRD equation had higher concordance correlation than did the Taiwanese CKD-EPI, the Taiwanese four-level CKD-EPI and the Japanese equations. Moreover, only the Taiwanese equations had no proportional bias among all of the equations. Finally, the Taiwanese MDRD equation had the best diagnostic performance in terms of ordinal logistic regression among all of the equations. Conclusion: The Taiwanese MDRD equation is better than the MDRD, CKD-EPI, Japanese, Asian, Thai, Taiwanese CKD-EPI, and Taiwanese four-level CKD-EPI equations for Taiwanese adults.
Journal of The American Society of Nephrology, Jun 1, 2014
The mechanism of vascular calcification in CKD is not understood fully, but may involve collagen ... more The mechanism of vascular calcification in CKD is not understood fully, but may involve collagen deposition in the arterial wall upon osteo/chondrocytic transformation of vascular smooth muscle cells (VSMCs). Increased levels of circulating angiopoietin-2 correlate with markers of CKD progression and angiopoietin-2 regulate inflammatory responses, including intercellular and vascular adhesion and recruitment of VSMCs. Here, we investigate the potential role of angiopoietin-2 in the pathogenesis of arterial stiffness associated with CKD. In a cohort of 416 patients with CKD, the plasma level of angiopoietin-2 correlated independently with the severity of arterial stiffness assessed by pulse wave velocity. In mice subjected to 5/6 subtotal nephrectomy or unilateral ureteral obstruction, plasma levels of angiopoietin-2 also increased. Angiopoietin-2 expression markedly increased in tubular epithelial cells of fibrotic kidneys but decreased in other tissues, including aorta and lung, after 5/6 subtotal nephrectomy. Expression of collagen and profibrotic genes in aortic VSMCs increased in mice after 5/6 subtotal nephrectomy and in mice producing human angiopoietin-2. Angiopoietin-2 stimulated endothelial expression of chemokines and adhesion molecules for monocytes, increased Ly6C low macrophages in aorta, and increased the expression of the profibrotic cytokine TGF-b1 in aortic endothelial cells and Ly6C low macrophages. Angiopoietin-2 blockade attenuated expression of monocyte chemokines, profibrotic cytokines, and collagen in aorta of mice after 5/6 subtotal nephrectomy. This study identifies angiopoietin-2 as a link between kidney fibrosis and arterial stiffness. Targeting angiopoietin-2 to attenuate inflammation and collagen expression may provide a novel therapy for cardiovascular disease in CKD.
Background and Aims The substantial mortality and morbidity burden of chronic kidney disease (CKD... more Background and Aims The substantial mortality and morbidity burden of chronic kidney disease (CKD) is well described, with the highest burden associated with progression to end-stage kidney disease (ESKD), where kidney replacement therapy (dialysis or kidney transplantation) is indicated. CKD is known to have a detrimental effect on patient health-related quality of life (HRQoL). However, there is a lack of data comparing the impact of CKD on patient and caregiver HRQoL versus the general population. This study aimed to administer validated HRQoL instruments using a quantitative online survey to estimate the HRQoL of patients with CKD and their caregivers compared to the general population. Method A non-interventional survey enrolled adult patients with CKD and caregivers. Patients with a diagnosis of CKD for at least 3 months were included. ESKD was defined as patients with CKD stage 5 or receiving dialysis or a kidney transplant. Caregivers were required not to receive formal paym...
The purpose of this phase I clinical trial is to assess the safety and tolerability of allogeneic... more The purpose of this phase I clinical trial is to assess the safety and tolerability of allogeneic adipose tissue-derived stem cells (ADSCs) among chronic kidney disease (CKD) patients. 12 eligible CKD patients with an estimated glomerular filtration rate (eGFR) of 15-44 ml/min/1.73 m2 received one dose of intravenous allogeneic ADSCs (ELIXCYTE® ), as 3 groups: 3 low dose (6.4 × 107 cells in total of 8 ml), 3 middle dose (19.2 × 107 cells in total of 24 ml) and 6 high dose (32.0 × 107 cells in total of 40 ml) of ELIXCYTE® and evaluated after 48 weeks. Primary endpoint was the safety profiles in terms of incidence of adverse events (AEs) and serious adverse event (SAE). Two subjects in high dose group experienced a total of 2 treatment-related AEs which are Grade 1 slow speech and Grade 1 bradyphrenia after the infusion. One subject in middle dose group experienced an SAE unlikely related to treatment, grade 2 proteinuria. No fatal AE was reported in this study. An increase in eGFR was observed in 7 out of 12 subjects (58%) at Week 24 and in 6 of 12 subjects (50%) by Week 48. By Week 24, an increase in eGFR by more than 20% among all CKD patients with baseline eGFR ≧ 30 ml/min/1.73 m2 as compared to only 2 subjects in baseline eGFR < 30 ml/min/1.73 m2 group. No significant reduction in proteinuria was noted among all subjects. This phase I trial demonstrated single-dose intravenous ELIXCYTE was well tolerated in moderate-to-severe CKD patients and its preliminary efficacy warrants future studies.
Nitric oxide plays an important role in mediating the inflammatory process. The aim of this study... more Nitric oxide plays an important role in mediating the inflammatory process. The aim of this study was to evaluate if nitric oxide production was increased during peritonitis in patients receiving continuous ambulatory peritoneal dialysis (CAPD), and the association with the prognosis. The study population comprised 21 patients with 22 episodes of peritonitis. Fifteen patients without peritonitis were controls. Nitrate was measured by HPLC and nitrite by the Griess method, to reflect nitric oxide production. Peritoneal dialysate effluent and plasma were collected from six patients during peritonitis and 1 week after treatment to study changes in dialysate:plasma ratio. In 15 patients, nitrite was measured during peritonitis and every 3 days for 2 weeks or until normalized for evolutional changes. The dialysate: plasma ratios of nitrate and nitrite during peritonitis were reduced 26% and 41.5%, respectively, after 1 week of treatment, indicating the peritoneal production of nitric oxide during peritonitis. In the evolutional study, a 5.1-fold increase of peak nitrite levels in bacterial peritonitis (H = 1 3) and a 2.5-fold increase in fungal peritonitis (« = 3) were observed compared to controls. Nitrite gradually declined to control levels (9.3 ±7.2 days) after effective antibiotic treatment, but took longer than to normalize leukocyte count in the peritoneal dialysate effluent (3.9+ 1.9 days). In four patients with refractory peritonitis (Candida infection in three, Acinetobacter infection in one), the nitrite levels remained elevated 2-fold despite treatment, and the catheters were removed. It is concluded that nitrite levels in peritoneal dialysate effluent may serve as a marker to assess treatment efficacy in CAPD patients with peritonitis.
Background: The malnutrition-inflammation score (MIS) is an indicator of malnutrition-inflammatio... more Background: The malnutrition-inflammation score (MIS) is an indicator of malnutrition-inflammation complex syndrome and an outcome predictor in maintenance hemodialysis patients. However, its utility in peritoneal dialysis (PD) patients and its association with the Charlson comorbidity index (CCI) have not yet been examined. Methods: All chronic stable PD outpatients in the PD center of the National Taiwan University Hospital in January 2006 were studied and followed for up to 18 months. The baseline MIS and CCI at the beginning of the study and the dates and causes of mortality or hospitalization during the study period were obtained. Results: A total of 141 PD patients were enrolled. During the study period, 8 patients died and 40 patients had at least one fatal or nonfatal major cardiovascular or infection event. The CCI correlated positively and significantly with the MIS (r = +0.344, p < 0.001). The MIS and CCI were both independent predictors of cardiovascular and infection...
In Taiwan, most first-time dialysis was started without the creation of an arteriovenous shunt. H... more In Taiwan, most first-time dialysis was started without the creation of an arteriovenous shunt. Here, we aimed to elucidate the transitions of dialysis status in the unplanned first dialysis patients and determine factors associated with their outcomes. A total of 50,315 unplanned first dialysis patients aged more than 18 years were identified from the National Health Insurance Dataset in Taiwan between 2001 and 2012. All patients were followed for 5 years for the transitions in dialysis status, including robust (dialysis-free), sporadic dialysis, continued dialysis, and death. Furthermore, factors associated with the development of continued dialysis and death were examined by the Cox proportional hazard models. After 5 years after the first dialysis occurrence, there were 5.39% with robust status, 1.67% with sporadic dialysis, 8.45% with continued dialysis, and 84.48% with death. Notably, we have identified common risk factors for developing maintenance dialysis and deaths, includ...
This retrospective study aimed to investigate the effect of diabetes mellitus (DM) on the risks o... more This retrospective study aimed to investigate the effect of diabetes mellitus (DM) on the risks of end-stage kidney disease (ESKD) and post-liver transplantation (post-LT) mortality. Using data from the National Health Insurance Research Database, Taiwan, 3,489 patients who received a LT between 1 January 2005, and 31 December 2015, were enrolled in this study and divided into the pre-existing DM, post-LT DM (PLTDM), and without DM groups. All subjects were followed up from 1 year after LT to the index date for ESKD, and the occurrence of death, or until 31 December 2016. Of the 3,489 patients with LT, 1,016 had pre-existing DM, 215 had PLTDM, and 2,258 had no DM pre- or post-LT. The adjusted HRs of ESKD were 1.77 (95% Confidence Interval [CI], .78–3.99) and 2.61 (95% CI, 1.63–4.18) for PLTDM group and pre-existing DM group compared to without DM group, respectively. For the risk of death, the adjusted HRs were 1.05 (95% CI, .72–1.55) and 1.28 (95% CI, 1.04–1.59) for PLTDM group and...
ObjectivesOver the past two decades, debates on whether the profit status of dialysis facilities ... more ObjectivesOver the past two decades, debates on whether the profit status of dialysis facilities influences patient prognosis have been popular in the USA. Taiwan is one of the regions with the highest rate per capita of kidney replacement therapy worldwide, but no similar research has been conducted to date. This is the first study to address this issue.DesignThis was a nationwide retrospective cohort study based on the Taiwan Renal Registry Data System.SettingPatients were categorised into two groups based on the profit status (for-profit, not-for-profit (NFP)) of dialysis facilities, with 31 350 patients in each group. The patients were followed up from 2005 to 2012.ParticipantsPatients with uraemia who underwent long-term haemodialysis in private dialysis facilities and public facilities were excluded.Primary and secondary outcome measuresSurvival analyses were performed to compare prognosis between the two groups. Adjustments to patients’ basic profile, and facilities’ geograph...
Background and objectives: Chronic musculoskeletal (MS) pain is common in chronic kidney disease ... more Background and objectives: Chronic musculoskeletal (MS) pain is common in chronic kidney disease (CKD) patients. The association of chronic MS pain and CKD progression has not yet been established. Method: We conducted a prospective cohort study to evaluate the association of chronic MS pain and CKD progression of pre-dialysis CKD patients. Result: A total of 53.2% of pre-dialysis CKD patients had chronic MS pain. Patients classified as progression and non-progression had a similar prevalence of chronic MS pain at baseline, and similar baseline use of NSAIDs and Chinese herbal medicines. Univariate Cox analysis indicated that chronic MS pain and baseline NSAID or Chinese herbal medicine use were not significantly associated with progression of CKD. But multivariate Cox regression found chronic MS pain was independently significantly associated with all-cause mortality (HR, 2.912, 95% CI, 1.004-8.444; p ¼ .049). However, serum levels of hs-CRP were similar between those chronic MS pain patients and without chronic MS pain patients (4.96 ± 9.4 vs. 4.25 ± 13.3 mg/L, p ¼ .535). Conclusion: The CKD patients with chronic MS pain was independently and significantly associated with all-cause mortality, but not independently and significantly associated with CKD progression and composite endpoints. The inflammatory marker-hs-CRP was similar between CKD patients with and without chronic MS pain.
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Papers by Mai-szu Wu