Atypical hemolytic uremic syndrome: Consensus of diagnosis and treatment in Taiwan.

Atypical hemolytic uremic syndrome (aHUS), characterized by microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury, is a rare but life-threatening systemic disorder caused by the dysregulation of the complement pathway. Current advances in molecular analysis and pathogenesis have facilitated the establishment of diagnosis and development of effective complement blockade. Based on this recent consensus, we provide suggestions regarding the diagnosis and management of aHUS in Taiwan. The diagnosis of aHUS is made by the presence of TMA with normal ADAMTS13 activity without known secondary causes. Although only 60% of patients with aHUS have mutations in genes involving the compliment and coagulation systems, molecular analysis is suggestive for helping establish diagnosis, clarifying the underlying pathophysiology, guiding the treatment decision-making, predicting the prognosis, and deciding renal transplantation. Complement blockade, anti-C5 monoclonal antibody, is the first-line therapy for patients with aHUS. Plasma therapy should be considered for removing autoantibody in patients with atypical HUS caused by anti-CFH or complement inhibitor is unavailable.

Dysregulation of Immune Cell Subpopulations in Atypical Hemolytic Uremic Syndrome.

Atypical hemolytic uremic syndrome (aHUS) is a rare, life-threatening thrombotic microangiopathy. Definitive biomarkers for disease diagnosis and activity remain elusive, making the exploration of molecular markers paramount. We conducted single-cell sequencing on peripheral blood mononuclear cells from 13 aHUS patients, 3 unaffected family members of aHUS patients, and 4 healthy controls. We identified 32 distinct subpopulations encompassing 5 B-cell types, 16 T- and natural killer (NK) cell types, 7 monocyte types, and 4 other cell types. Notably, we observed a significant increase in intermediate monocytes in unstable aHUS patients. Subclustering analysis revealed seven elevated expression genes, including NEAT1, MT-ATP6, MT-CYB, VIM, ACTG1, RPL13, and KLRB1, in unstable aHUS patients, and four heightened expression genes, including RPS27, RPS4X, RPL23, and GZMH genes, in stable aHUS patients. Additionally, an increase in the expression of mitochondria-related genes suggested a potential influence of cell metabolism on the clinical progression of the disease. Pseudotime trajectory analysis revealed a unique immune cell differentiation pattern, while cell-cell interaction profiling highlighted distinctive signaling pathways among patients, family members, and controls. This single-cell sequencing study is the first to confirm immune cell dysregulation in aHUS pathogenesis, offering valuable insights into molecular mechanisms and potential new diagnostic and disease activity markers.

Discovery of Novel Protein Biomarkers in Urine for Diagnosis of Urothelial Cancer Using iTRAQ Proteomics.

Urothelial carcinoma (UC) is the ninth most prevalent malignancy worldwide. Noninvasive and efficient biomarkers with high accuracy are imperative for the surveillance and diagnosis of UC. CKD patients were enrolled as a control group in this study for the discovery of highly specific urinary protein markers of UC. An iTRAQ-labeled quantitative proteomic approach was used to discover novel potential markers. These markers were further validated with 501 samples by ELISA assay, and their diagnostic accuracies were compared to those of other reported UC markers. BRDT, CYBP, GARS, and HDGF were identified as novel urinary UC biomarkers with a high discrimination ability in a population comprising CKD and healthy subjects. The diagnostic values of the four novel UC markers were better than that of a panel of well-known or FDA-approved urinary protein markers CYFR21.1, Midkine, and NUMA1. Three of our discovered markers (BRDT, HDGF, GARS) and one well-known marker (CYFR21.1) were finally selected and combined as a marker panel having AUC values of 0.962 (95% CI, 0.94-0.98) and 0.860 (95% CI, 0.83-0.89) for the discrimination between UC and normal groups and UC and control (healthy + CKD) groups, respectively.

Plasma miRNA profile is a biomarker associated with urothelial carcinoma in chronic hemodialysis patients.

The incidence of urothelial carcinoma (UC) is higher in patients undergoing chronic dialysis than in the general population. This study investigated plasma miRNA profiling as the ancillary diagnosis biomarker associated with UC in patients undergoing chronic hemodialysis. We successfully screened out and detected miRNA expression from plasma in eight patients undergoing dialysis through quantitative real-time PCR array analysis and identified eight candidate miRNAs. The candidate miRNAs were then validated using single quantitative RT-PCR assays from 52 plasma samples. The miRNA classifier for ancillary UC detection was developed by multiple logistic regression analyses. Moreover, we validated the classifier by testing another nine samples. Expression levels of miR-150-5p, miR-150-5p/miR-155-5p, miR-378a-3p/miR-150-5p, miR-636/miR-150-5p, miR-150-5p/miR-210-3p, and miR-19b-1-5p/miR-378a-3p were shown to be significantly different between UC and non-UC samples (P = 0.035, 0.0048, 0.016, 0.024, 0.038, and 0.048). Kaplan-Meier curve analysis also showed that low miR-19b-1-5p expression was associated with a worse prognosis (P = 0.0382). We also developed a miRNA classifier based on five miRNA expression levels to predict UC and found that the area under curve was 0.882. The classifier had a sensitivity of 80% (95% confidence interval: 0.5191% to 0.9567%) and a specificity of 83.7% (95% confidence interval: 0.6799% to 0.9381%). This classifier was tested by nine samples with 100% accuracy. The miRNA classifier offers higher sensitivity and specificity than the existing makers. Thus, this approach will improve the prospective diagnosis of UC in patients undergoing chronic hemodialysis.

Galectin-9 Is Critical for Mucosal Adaptive Immunity through the T Helper 17-IgA Axis.

Impairment of the intestinal mucosal immunity significantly increases the risk of acute and chronic diseases. IgA plays a major role in humoral mucosal immunity to provide protection against pathogens and toxins in the gut. Here, we investigated the role of endogenous galectin-9, a tandem repeat-type ß-galactoside-binding protein, in intestinal mucosal immunity. By mucosal immunization of Lgals9-/- and littermate control mice, it was found that lack of galectin-9 impaired mucosal antigen-specific IgA response in the gut. Moreover, Lgals9-/- mice were more susceptible to developing watery diarrhea and more prone to death in response to high-dose cholera toxin. The results indicate the importance of galectin-9 in modulating intestinal adaptive immunity. Furthermore, bone marrow chimera mice were established, and galectin-9 in hematopoietic cells was found to be critical for adaptive IgA response. In addition, immunized Lgals9-/- mice exhibited lower expression of Il17 and fewer T helper 17 (Th17) cells in the lamina propria, implying that the Th17-IgA axis is involved in this mechanism. Taken together, these findings suggest that galectin-9 plays a role in mucosal adaptive immunity through the Th17-IgA axis. By manipulating the expression or activity of galectin-9, intestinal mucosal immune response can be altered and may benefit the development of mucosal vaccination.

Maximum Glomerular Filtration Decline Rate is Associated with Mortality and Poor Renal Outcome in Chronic Kidney Disease Patients.

BACKGROUND: Glomerular filtrate rate (GFR) decline is associated with increased risk of dialysis in patients with chronic kidney disease (CKD). It is unclear whether the maximum, the minimum, or the average of GFR decline rate is associated with the risk of mortality and the initiation of renal replacement therapy (RRT). We investigated prognostic role of the maximum, the minimum, and the average of GFR decline rate in patients with CKD not yet on dialysis. METHODS: Patients, enrolled in the CKD program of China Medical University Hospital between July 2004 and Aug 2013, with CKD stages 3-5 (estimated GFR [eGFR] < 60 mL/min/1.73 m2) not yet on dialysis were analyzed. Primary outcome was a composite of mortality and RRT. The association between 3 readings of GFR decline rate and primary outcome was analyzed using Cox proportional hazard regression. RESULTS: We analyzed 815 patients aged 75 (interquartile range [IQR] 65-82) years with a median follow-up of 5.2 years (IQR 3.9-6.9). The maximum of eGFR decline rate was associated with the primary outcome (hazard ratio 2.19, 95% CI 1.16-4.12, p = 0.015), independent of age, gender, diabetes, cerebrovascular accident, smoking, baseline eGFR, serum albumin, calcium, urine protein/creatinine ratio, usage of renin-angiotensin system blockade. The minimum and the average of eGFR decline rate were not associated with the primary outcome. CONCLUSIONS: The maximum of GFR decline rate was associated with mortality and poor renal outcome in CKD patients, independent of other contributive confounders.

Abdominal aortic calcification score predicts the occurrence of coronary artery disease in middle-aged peritoneal dialysis patients.

AIM: Abdominal aortic calcification (AAC) score in dialysis patients was associated with coronary artery disease (CAD) in cross-sectional study, but the use of AAC score in the CAD prediction was not clear. We aimed to use AAC score in the estimation of CAD occurrence in middle-aged peritoneal dialysis (PD) patients. METHODS: Middle-aged (45-65 years old) PD patients were recruited and followed up until CAD occurrence, patient mortality, or PD failure. We quantified AAC score by lateral lumbar radiography, and used receiver operation curve (ROC) analysis to find the cut-off value for CAD prediction. RESULTS: There were 187 patients recruited for study with a mean follow-up of 1027 ± 427 days. AAC score in patients with CAD during follow-up period (9.7 ± 7.6, n = 41) was higher than in patients without CAD occurrence (5.5 ± 6.1, n = 146) (P < 0.001). Multivariate hazard ratio of AAC score for CAD was 1.07 (P = 0.044). ROC showed that AAC score of 5.5 had a sensitivity of 0.667 and a specificity of 0.581 in the prediction of CAD occurrence. Patients with AAC score above 5.5 had significantly higher cumulative incidence of CAD than patients with AAC score below 5.5 (Log-rank test, P = 0.003). Age (P = 0.002), diabetes (P = 0.002), hypertension (P = 0.032), longer dialysis vintage (P < 0.001) and lower serum potassium (P = 0.012) were parameters significantly associated with higher AAC score. CONCLUSION: AAC score can predict CAD occurrence in PD patients. Age, diabetes, hypertension, dialysis vintage and serum potassium level are factors associated with higher AAC score.

IL-17 and CD40 ligand synergistically stimulate the chronicity of diabetic nephropathy.

Background: Early stages of diabetic nephropathy (DN) are characterized by an influx of inflammatory cells. Interactions between infiltrating T cells and podocytes may play an important role in the ongoing inflammatory response and remodelling. The aim of this study was to explore the role of IL-17 and CD40 ligand (CD40L) in DN. Methods: The study design involved a case series. Kidney biopsy samples of 69 patients with type 2 diabetes were assessed for the presence of CD4+ IL-17+ T cells. The number of CD4+ IL-17+ T cells were counted and correlated with clinical and laboratory findings. Additionally, advanced glycation end-products (AGEs) were added to cultured podocytes to imitate diabetic conditions and thus to elucidate the role of CD4+ IL-17+ T cells in renal sclerosis. Results: CD80 expression was detected in early phases of DN but was absent during diffused glomerurosclerosis in DN kidney specimens. In DN samples, CD40 expression was not only observed in most of the infiltrating cells, but also increased in podocytes and tubular epithelial cells. CD40L is locally expressed on infiltrating cells. CD4+ IL-17+ T cells were found in DN, and the number of CD4+ IL-17+ T cells was positively correlated with the deterioration in glomerular filtration rate (GFR). IL-17A was the key cytokine produced by CD4+ IL-17+ T cells. IL-17A levels were elevated in DN renal tissue and were correlated with declining GFR. IL-17 and CD40L synergistically enhanced IL-6, monocyte chemoattractant protein-1 (MCP-1), regulated on activation, normal T cell expressed and secreted (RANTES), transforming growth factor beta 1 (TGF-ß1) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) production in vitro. AGEs induced podocyte activation with increasing expression of IL-17A, CD40 and TGF-ß1 in vitro. Blockade with an anti-IL-17 monoclonal antibody reduced the expression of CD40 and TGF-ß1, but increased the viability of cultured podocytes. Conclusions: IL-17 and CD40L synergistically mediate the inflammatory response and remodelling associated with tissue injury and glomerular sclerosis in DN.

Hypothyroidism is associated with all-cause mortality in a national cohort of chronic haemodialysis patients.

AIM: The prevalence of hypothyroidism is high in haemodialysis (HD) patients and hypothyroidism increases all-cause mortality in HD patients. Comorbidities are common in HD patients and are associated with both mortality and hypothyroidism. The aim of the study is to explore the effect of the interactions of comorbidities and hypothyroidism on all-cause mortality in HD patients. METHOD: Patients with hypothyroidism (ICD-9-CM 244.0, 244.1, and 244.9) and matched patients without hypothyroidism in the Registry for Catastrophic Illness Patient Database of Taiwan Health Insurance from 2000 to 2010 were analyzed. The association of hypothyroidism and risk of all-cause mortality was analyzed using Cox proportional hazard regression. RESULT: Nine hundred and eight HD patients with hypothyroidism and 3632 sex-, age-, gender- matched HD patients without hypothyroidism were analyzed. Hypothyroidism was associated with increased all-cause mortality with an adjusted hazard ratio of 1.22 [95% confidence interval (CI): 1.10-1.36, P < 0.001]. TRT may decrease mortality associated with hypothyroidism (P < 0.001). There was a significant interaction (P = 0.04) between diabetes and hypothyroidism. There was no significant interaction found in hypothyroidism and the following comorbidities: hyperlipidaemia, hypertension, chronic obstructive pulmonary disease, coronary artery disease, stroke, peripheral arterial disease, asthma, congestive heart failure and cancer. CONCLUSION: Hypothyroidism is associated with increased all-cause mortality in chronic HD patients. The interaction of hypothyroidism and diabetes, but not other common comorbidities in HD patients, has an effect on mortality risks.

Abdominal aortic calcification score can predict future coronary artery disease in hemodialysis patients: a 5-year prospective cohort study.

BACKGROUND: Abdominal aortic calcification (AAC) has been known to be associated with cardiovascular mortality in hemodialysis. However, the association between AAC and future coronary artery disease (CAD) occurrence is not clear. We aimed to clarify the association of AAC severity and the occurrence of future CAD events in hemodialysis patients. METHODS: Hemodialysis (HD) patients were recruited in this prospective cohort study. AAC severity was quantified by AAC score, which was measured by lateral lumbar radiography. We used receiver operation curve (ROC) analysis to find the cutoff AAC value for CAD prediction. CAD-free survival was analyzed by Kaplan-Meier study. RESULTS: There were 303 patients recruited for study with a median (interquartile range) follow-up of 95 (65-146) months. The AAC score in patients with occurrence of new CAD [9 (3-15.25), n = 114] was higher than in patients without new CAD occurrence [5 (1-9) n = 189], p < 0.001. Multivariate hazard ratio of AAC score for CAD was 1.039 (p = 0.016). ROC study showed that an AAC score of 5.5 had a sensitivity of 0.658 and a specificity of 0.587 in the prediction of new CAD occurrence. Patients with AAC score above 5.5 had significantly higher cumulative incidence of CAD than patients with AAC score below 5.5. Age, diabetes, prior history of CAD, and longer dialysis vintage were major factors associated with higher AAC score. CONCLUSIONS: AAC score can predict the occurrence of future CAD events in HD patients. The best cut-off value of AAC score is 5.5. AAC score greater than 5.5 is a reliable abdominal aortic calcification marker, and can predict future CAD in ESRD patients. Major contributive factors for higher AAC score were age, presence of diabetes, prior history of CAD, and longer dialysis vintage.

Prolonged QT interval is linked to all-cause and cardiac mortality in chronic peritoneal dialysis patients.

AIM: Prolonged QT interval is related to changes of electrolytes in haemodialysis (HD) and is associated with all-cause mortality in HD patients. It is unknown if prolonged QT interval is associated with all-cause mortality in peritoneal dialysis (PD) patients as the electrolytes were relatively stable in PD. We therefore investigated the association of prolonged QT interval and all-cause mortality in chronic PD patients. METHODS: The QT intervals were measured in 2003 and all patients were followed to December 2012. A prolonged QT interval was defined as a QT interval > 450 ms. The association of prolonged QT interval with all-cause and cardiac-specific mortality was analyzed using Cox regression and Kaplan-Meier analysis. RESULTS: Of 306 patients, 196 (64%) patients had prolonged QT interval. The incidence density rate was 9.7 per 100 persons-years for all-cause mortality and 5.6 for cardiac specific mortality in patients with prolonged QT interval. Prolonged QT interval was associated with all-cause mortality with a hazard ratio (HR) of 1.59 (95% confidence interval (CI): 1.06-2.39, P = 0.03] and cardiac mortality (HR: 1.66, 95% CI: 1.00-2.78, P = 0.05) with adjustments for age, gender, diabetes, and vintage of dialysis. Longer QT interval (>500 ms, 450-500 ms, and < 450 ms) was significantly associated with a worse overall survival (P = 0.03, log-rank test) and cardiac mortality free survival (P = 0.05, log-rank test). CONCLUSIONS: Prolonged QT interval was associated with all-cause and cardiac mortality in patients on peritoneal dialysis. The association is independent of patient's age and diabetes.

Transformation of 5-D itch scale and numerical rating scale in chronic hemodialysis patients.

BACKGROUND: Pruritus is a common and frustrating symptom in hemodialysis (HD) patients and 5-D itch scale is proposed as a reliable measurement of pruritus. However, information regarding 5-D itch scale categories is currently unavailable. We explored optimal cut-offs 5-D itching scale based on numerical rating scale (NRS) categories in HD patients. METHODS: Four hundred and nine HD patients in China Medical University Hospital in December 2014 were included and severity of pruritus was estimated using NRS and 5-D itch scale. The association of NRS and 5-D itch scale was analyzed by linear regression. The optimal cut-offs for 5-D itch scale based on NRS categories were generated. RESULTS: The average NRS was 3.4 ± 3.0 and the average 5-D itch scale was 10.9 ± 4.8. The 5-D score was strongly correlated with the NRS: r = 0.831 (p < 0.001). NRS = -2.31 + 0.52 × (5-D scale). The averages of 5-D scales were 6.4 ± 1.5, 9.6 ± 2.2, 13.1 ± 3.2, 15.7 ± 4.4, 19.5 ± 4.4 for no, mild, moderate, severe, and very severe pruritus based on categorized NRS. A 5-D itch scale categories were proposed, ≤ 8 for NRS = 0, 9-11 for mild pruritus, 12-17 for moderate pruritus, 18-21 for severe pruritus and ≥ 22 for very severe pruritus. CONCLUSIONS: Categories for the 5-D itch scale were proposed based on the measurements of pruritus severity in HD patients. This information provides a simple solution that enables transformation between the 5-D itch scale and the numerical rating scale.

Seasonal influenza vaccination is associated with reduced morbidity and mortality in peritoneal dialysis patients.

BACKGROUND: Studies on the effectiveness of seasonal influenza vaccination in peritoneal dialysis (PD) patients are limited. The aim of the present study is to evaluate the effectiveness of seasonal influenza vaccination in reducing morbidity and mortality in incident end-stage renal disease patients on PD. METHODS: From Taiwan's National Health Insurance Research Database, we identified 2089 incident PD patients with seasonal influenza vaccination and 2089 propensity score matched incident PD patients without the vaccination during 1998-2010. Each study subject was followed up to measure the 12-month incident cardiovascular and infectious diseases, and deaths. The effects of multi-year vaccinations were also estimated. RESULTS: Compared with the non-vaccinated cohort, the vaccinated cohort had a lower hospitalization rate (68.5 versus 80.2 per 100 person-years) with an adjusted hazard ratio (aHR) of 0.85 [95% confidence interval (CI) = 0.78-0.92]. Hazards of hospitalization were significantly reduced for sepsis (aHR = 0.79, 95% CI = 0.65-0.96), heart disease (aHR = 0.74, 95% CI = 0.63-0.89) and intensive care (aHR = 0.85, 95% CI = 0.73-0.99). In addition, hazards of peritonitis (aHR = 0.84, 95% CI = 0.73-0.97) and overall mortality (aHR = 0.66, 95% CI = 0.55-0.78) were also reduced. The aHR of mortality was reduced much further to 0.28 (95% CI = 0.22-0.35) for those with multiple-year vaccinations. CONCLUSIONS: Seasonal influenza vaccination for PD patients is associated with significant reduction in morbidities and a 34% reduction in mortality. Multi-year vaccinations could reduce the death hazard further to 72%.

Nationwide epidemiology and prognosis of dialysis-requiring acute kidney injury (NEP-AKI-D) study: Design and methods.

AIM: Acute kidney injury (AKI) carries an increasing incidence rate worldwide and increases the risk of developing end-stage renal disease (ESRD) as well as the medical expenses during the post-AKI course. The Taiwan Consortium for Acute Kidney Injury and Renal Diseases (CAKs) has thus launched a nationwide epidemiology and prognosis of dialysis-requiring acute kidney injury (NEP-AKI-D) study, which prospectively enrols critically ill patients with AKI. Through thoroughly evaluating the risk and prognostic factors of AKI, we hope to lower the incidence of AKI and ESRD from the perspective of AKI-ESRD interaction. METHODS: The CAKs includes 30 hospitals which distribute widely through the four geographical regions (north, middle, south, and east) of Taiwan, and have a 1:1 ratio of medical centres to regional hospitals in each region. The NEP-AKI-D study enrols intensive care unit-based AKI patients who receive dialysis in the four seasonal sampled months (October 2014, along with January, April, and July 2015) in the included hospitals. The collected data include demographic information, pertaining laboratory results, dialysis settings and patient outcomes. The data are uploaded in a centre website and will be audited by on-site principal investigators, computer logic gates, and the CAKs staffs. The outcomes of interest are in-hospital mortality, dialysis-dependency and readmission rate within 90 days after discharge. CONCLUSION: The NEP-AKI-D study enrols a large number of representative AKI patients throughout Taiwan. The results of the current study are expected to provide more insight into the risk and prognostic factors of AKI and further attenuated further chronic kidney disease transition.

Factors associated with serum fetuin-A concentrations after long-term use of different phosphate binders in hemodialysis patients.

BACKGROUND: Fetuin-A is known as a circulating inhibitor of vascular calcification. Factors associated with serum fetuin-A concentrations after long-term use of different phosphate binders in hemodialysis patients is still uncertain. METHODS: In the post-hoc study, we analyzed serum fetuin-A and biochemical factors (Ca, P, i-PTH, hsCRP, TG, LDL-C) in 50 hemodialysis patients, who completed a 48-week, open-Label, controlled randomized parallel-group study. 23 patients received sevelamer and 27 patients received calcium carbonate. RESULTS: After the 48-week treatment, the sevelamer group had less serum calcium increment, less iPTH decrement, more ALK-P increment, more hsCRP decrement and more LDL-C decrement. There was no significant difference in the serum fetuin-A decrement between two groups. Decreased serum fetuin-A levels were found after 48-week treatment in both groups: from 210.61 (104.73) to 153.85 (38.64) ug/dl, P = 0.003 in sevelamer group, from 203.95 (107.87) to 170.90 (58.02) ug/mL, P =0.002 in calcium group. The decrement in serum fetuin-A (Δfetuin-A) levels was associated with ΔCa (ρ = - 0.230, P = 0.040), ΔiPTH (ρ = 0.306, P = 0.031) and Δalbumin (ρ = 0.408, P = 0.003), not associated with sevelamer use, ΔP and ΔhsCRP. CONCLUSION: After long-term sevelamer or calcium carbonate treatment, both groups of maintenance HD patients had lower serum fetuin-A levels. Serum levels of increased calcium, decreased iPTH and decreased albumin were associated with the serum fetuin-A decrement.

Icodextrin decreases technique failure and improves patient survival in peritoneal dialysis patients.

AIM: It remains unclear whether long-term daily icodextrin use can decrease technique failure and improve survival in peritoneal dialysis (PD) patients. The aim of the present study was to investigate whether icodextrin use, once daily, can decrease technique failure and prolong patient survival in incident PD patients. METHODS: Incident PD patients who survived more than 90 days were recruited from the China Medical University Hospital, Taiwan, between 1 January 2007 and 31 December 2011. All patients were followed until transfer to haemodialysis (HD), renal transplantation, transfer to another centre, death, or 31 December 2011. RESULTS: A total of 306 incident PD patients (89 icodextrin users, 217 icodextrin non-users) were recruited during the study period. Icodextrin users were more likely to have hypertension, diabetes and high or high-average peritoneal transport compared with non-users. During the follow-up period, 43 patients were transferred to HD: seven (7.87%) of the icodextrin group, and 36 (16.59%) of the non-icodextrin group. Thirty-two patients died during the follow-up period: five (5.62%) of the icodextrin group, and 27 (12.44%) of the non-icodextrin group. Icodextrin use was significantly associated with a better prognosis, in terms of technique failure (adjusted HR = 0.32; 95% CI = 0.14-0.72). With regard to patient survival, icodextrin use (adjusted HR = 0.33; 95% CI = 0.12-0.87) was associated with a significantly lower risk of death. CONCLUSION: The use of icodextrin once daily may decrease technique failure and improve survival in incident PD patients.

Patients with diabetes as the primary kidney disease have a worse survival than patients with comorbid diabetes in chronic haemodialysis patients.

AIM: Diabetes is the leading cause of chronic kidney disease (CKD) that requires dialysis. It is not clear if survival of patients with diabetes as primary kidney disease (DKD) is different from the survival of patients with diabetes as comorbidity (DCM). We investigated the survival of patients with DKD and patients with DCM in patients on maintenance haemodialysis (HD) using propensity score matching approach. METHODS: All patients on maintenance HD in Taiwan Renal Registry Database from 1997 to 2005 were analyzed and were prospectively followed to 31 December 2008. Patients' survival was determined using Cox proportional-hazards regression. RESULTS: We analyzed the survival of 2632 patients with DCM and 13,160 matched patients with DKD. The first year mortality rate was 11.9% in patients with DCM and 13.9% in patients with DKD. The incidence density rate of overall mortality was 11.2 per 100 patient-years in patients with DCM and 12.9 in patients with DKD. Patients with DKD had a worse survival than patients with DCM (P < 0.01). Compared to patients with DCM, the odds ratio (95% confidence interval [CI]) for first year mortality was 1.27 (1.10-1.47) and the hazard ratio for overall mortality was 1.18 (1.12-1.25) in patients with DKD. Patients' age, male gender, comorbid liver cirrhosis, higher fasting blood glucose, lower haematocrit, and lower serum phosphorus were independently associated with higher mortality. CONCLUSIONS: Patients with diabetes as primary kidney disease are associated with higher first year and overall mortality, compared to patients with diabetes as comorbidity in patients on maintenance haemodialysis.

Trends of cost and mortality of patients on haemodialysis with end stage renal disease.

AIM: The prevalence of end-stage renal disease in Taiwan is among the highest in the world. Treatment reimbursement for haemodialysis was capped in 1996 in order to contain costs. This study evaluated temporal changes in the costs and utilization of medical care and mortality in patients receiving haemodialysis following capped reimbursement. METHODS: Using insurance claims data in Taiwan between 1998 to 2009, we established eight annual subcohorts of patients with incident haemodialysis, increasing from 6099 in 1998 to 7745 in 2005. With a 4-year follow-up paradigm for each subcohort, we evaluated resources use and costs of medical services, as well as mortality trends. RESULTS: The annual mean cost for each haemodialysis patient increased from US $431 to $737 for emergency visits, US $9007 to $13,280 for hospitalizations and US $79,141 to $92,416 (16.8% increase) for total costs, from the initial to final subcohorts, respectively. Compared to the 1998 subcohort, the adjusted hazard ratio of deaths declined from 0.97 (95% CI 0.91 to 1.02) for the 1999 subcohort to 0.86 (95% CI 0.82 to 0.91) for the 2005 subcohort (P for trend <0.001). The corresponding cumulative probability of deaths decreased from 45.5% to 35.4%. CONCLUSIONS: The mortality for patients with haemodialysis decreased annually, whereas the overall annual cost increased despite capped reimbursement for haemodialysis. These results encourage further study on reasons of increased uses of emergency service and hospitalization.

Increased risk of Parkinson's disease in patients with end-stage renal disease: a retrospective cohort study.

BACKGROUND: Studies on dyskinesia and Parkinson's syndrome associated with chronic kidney disease or end-stage renal disease (ESRD) have been mainly limited to case reports or case series studies. This population-based study investigated the risk of Parkinson's disease in patients with ESRD. METHODS: From a universal insurance claims database of Taiwan, we established a cohort of 8,325 adults with newly diagnosed ESRD from 1997 to 2010 without a history of Parkinson's disease. A control cohort of 33,382 insured subjects without a history of kidney disease or Parkinson's disease was also selected, with frequency matched for age, sex and index date of the patients with ESRD. Both cohorts were followed up until the end of 2010. RESULTS: The Parkinson's disease incidence was 1.55-fold higher in the cohort with ESRD than in the comparison cohort (48.8 vs. 31.7 per 10,000 person-years) with an adjusted hazard ratio of 1.73 (95% confidence interval, 1.39-2.15). Sex-specific and age-specific analysis showed a higher relative risk for women and younger patients with ESRD compared to the control cohort. CONCLUSIONS: ESRD is significantly associated with an increased risk of Parkinson's disease. Close surveillance for Parkinson's disease should be considered for patients with ESRD.

Long-term sevelamer treatment lowers serum fibroblast growth factor 23 accompanied with increasing serum Klotho levels in chronic haemodialysis patients.

AIMS: Fibroblast growth factor 23 (FGF23) and Klotho are associated with vascular calcification and cardiovascular disease in dialysis patients. Sevelamer has been shown to reduce progression of vascular calcification. This study aimed to determine the long-term effect of sevelamer treatment on serum FGF23 and Klotho levels in chronic haemodialysis (HD) patients. METHODS: In the post-hoc analysis, we measured serum FGF23, Klotho and other biochemical factors (Ca, P, i-PTH, hsCRP, LDL-C) in 50 haemodialysis patients, who completed a 48-week, open-Label, controlled randomized parallel-group study. Twenty-three patients received sevelamer and 27 patients received calcium carbonate. RESULTS: After 48-week sevelamer treatment, there were significant changes with lower LDL-C (from 2.82 ± 0.78 to 1.65 ± 0.53 mmol/L, P = 0.000), lower FGF23 (from 2465.97 (2568.88) to 795.61 (1098.39), P = 0.000) and higher s-Klotho levels (from 189.35 (161.88) to 252.94 (517.80) pg/mL, P = 0.000). In calcium carbonate group, there were no significant changes of LDL-C and FGF23, but with a borderline significant increase of s-Klotho level (from 142.34 (265.24) to 188.57 (252.38) pg/mL, P = 0.054). Multivariate analysis showed that FGF23 decrement was associated with sevelamer treatment (ß = -0.277, P = 0.005), change of serum phosphate (ß = 0.609, P = 0.000) and calcium levels (ß = 0.635, P = 0.000). The increase of serum Klotho was associated with the decrease of serum phosphate (ß = 0.490, P = 0.019). CONCLUSION: Maintenance HD patients had lower serum FGF23 levels, accompanied with significantly increased serum Klotho levels, after 48-week sevelamer treatment. The FGF23 decrement was associated with sevelamer use, the change of serum phosphate and calcium levels. The serum Klotho increment was proportional to the phosphate-lowering power of the binders.