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There is little comprehensive education for people with end-stage renal disease (ESRD) progress. We investigated the differences in terms of outcomes between patients with CKD stages 3–5 who enrolled and did not enroll in the pre-ESRD care education in Taiwan. This retrospective cohort study was conducted using data from the National Health Insurance Research Database (NHIRD). All patients diagnosed with CKD stages 3–5 who received the pre-ESRD care education through the pay for performance (P4P) program were enrolled. Based on whether or not they participated in the program, they were categorized into P4P or non-P4P groups. All analyses were performed from January 2006 through December 2015. Study outcomes were risk of hemodialysis dependency, hospitalization, and all-cause mortality. In this study of 29,337 patients, those with CKD stages 3–5 in the P4P group had lower events of hemodialysis, hospitalization, and all-cause mortality compared to patients in the non-P4P group. This study suggested that pre-ESRD care education is associated with increased patient outcomes, resulting in lower hemodialysis and hospitalization events and a higher overall survival rate in patients with CKD stages 3–5. Patient education could raise opportunities to improve pre-ESRD care by reaching patients outside the traditional health care setting.

The coronavirus disease 2019 (COVID-19) pandemic is the largest health crisis ever faced worldwide. It has resulted in great health and economic costs because no effective treatment is currently available. Since infected persons vary in presentation from healthy asymptomatic mild symptoms to those who need intensive care support and eventually succumb to the disease, this illness is considered to depend primarily on individual immunity. Demographic distribution and disease severity in several regions of the world vary; therefore, it is believed that natural inherent immunity provided through dietary sources and traditional medicines could play an important role in infection prevention and disease progression. People can boost their immunity to prevent them from infection after COVID-19 exposure and can reduce their inflammatory reactions to protect their organ deterioration in case suffering from the disease. Some drugs with in-situ immunomodulatory and anti-inflammatory activity are also identified as adjunctive therapy in the COVID-19 era. This review discusses the importance of COVID-19 interactions with immune cells and inflammatory cells; and further emphasizes the possible pathways related with traditional herbs, medications and nutritional products. We believe that such pathophysiological pathway approach treatment is rational and important for future development of new therapeutic agents for prevention or cure of COVID-19 infection.

PURPOSE To evaluate whether concomitant use of amiodarone and sulfonylureas is associated with an increased risk of serious hypoglycemia. METHODS We conducted two nested case-control studies by analyzing the Taiwan National Health Insurance Research Database from 2008 to 2013 among diabetic patients continuously receiving sulfonylureas. Cases were defined as patients with severe hypoglycemia and those with a composite outcome of severe hypoglycemia, altered consciousness, and fall-related fracture in the first and second study, respectively. In both studies, each case was individually matched up to 10 randomly-selected controls. Conditional logistic regressions were employed to estimate odds ratios (ORs). RESULTS We identified 1343 cases and 11 597 controls as well as 2848 cases of composite events and 24 808 controls among 46 317 sulfonylurea users. Concurrent use of amiodarone with sulfonylureas was associated with a 1.56-fold (95% CI: 0.98-2.46) increased risk of severe hypoglycemia, despite not statistically significant. Notably, an approximately 2-fold increased risk of severe hypoglycemia was observed with amiodarone therapy lasting for >180 days (adjusted OR: 2.08; 95% CI: 1.01-4.30) or at a daily dose greater than 1 defined daily dose (adjusted OR: 2.21; 95% CI: 1.25-3.91) when concurrently administrating sulfonylureas. A significantly increased risk of hypoglycemia-related composite events was also found with amiodarone concurrently used with sulfonylureas (adjusted OR: 1.59; 95% CI: 1.13-2.24). CONCLUSIONS Concurrent use of amiodarone and sulfonylureas is associated with an increased risk of serious hypoglycemia among diabetic patients, with an elevated risk for amiodarone used in a long-term or at a high daily dose.

Background: The recommended target low-density lipoprotein cholesterol (LDL-C) level for coronary artery disease (CAD) patients has been lowered from 100 to 70 mg/dL in several clinical guidelines for secondary prevention. We aimed to assess whether initiating statin treatment in CAD patients with baseline LDL-C 70–100 mg/dL in Taiwan could be cost-effective. Methods: A Markov model was developed to simulate a hypothetical cohort of CAD patients with a baseline LDL-C level of 90 mg/dL. The incidence and recurrence of MI and stroke related to specific LDL-C levels as well as the statin effect, mortality rate, and health state utilities were obtained from the literature. The direct medical costs and rate of fatal events were derived from the national claims database. The incremental cost-effectiveness ratio (ICER) per quality-adjusted life years (QALYs) was calculated, and sensitivity analyses were performed. Results: Moderate-intensity statin use, a treatment regimen expected to achieve LDL

Background: The long-term effects of statin use on rehospitalization due to ischemic stroke (reHospIS) in hyperlipidemic patients are still unknown. Therefore, we aimed to assess the long-term risks of reHospIS for hyperlipidemic patients who were taking statins and nonstatin lipid-lowering medicines on a regular basis.Methods and Materials: The National Health Insurance Research Database in Taiwan was used to conduct a 6-year cohort study of patients >45 years old (n = 9,098) who were newly diagnosed with hyperlipidemia and hospitalized for the first or second time due to ischemic stroke (IS). The risk of reHospIS was assessed using Cox proportional hazards regression model.Results: Nonstatin lipid-lowering medicines regular users were associated with a higher risk of reHospIS compared to stains users (hazard ratio, HR = 1.29–1.39, p < 0.05). Rosuvastatin was the most preferred lipid-lowering medicine with lower HRs of reHospIS in hyperlipidemic patients whether they developed diabetes or not. Bezafibrate regular users of hyperlipidemic patients developing diabetes (HR = 2.15, p < 0.01) had nearly 50% lower reHospIS risks than those without diabetes (HR = 4.27, p < 0.05). Age, gender, drug dosage, comorbidities of diabetes and heart failure (HF), and characteristics of the first hospitalization due to IS were all adjusted in models. Moreover, increasing trends of HRs of reHospIS were observed from Rosuvastatin, nonstatin lipid-lowering medicines, Lovastatin, and Gemfibrozil to Bezafibrate users.Conclusion: Statins were associated with long-term secondary prevention of reHospIS for hyperlipidemic patients. Rosuvastatin seemed to have the best protective effects. On the other hand, Bezafibrate appears to be beneficial for hyperlipidemic patients developing diabetes. Further research into the combination treatment of statin and nonstatin lipid-lowering medicines in hyperlipidemic patients developing diabetes is warranted.

The coronavirus disease 2019 (COVID-19) pandemic continues to burden healthcare systems worldwide. COVID-19 symptoms are highly heterogeneous, and the patient may be asymptomatic or may present with mild to severe or fatal symptoms. Factors, such as age, sex, and comorbidities, are key determinants of illness severity and progression. Aging is accompanied by multiple deficiencies in interferon production by dendritic cells or macrophages in response to viral infections, resulting in dysregulation of inflammatory immune responses and excess oxidative stress. Age-related dysregulation of immune function may cause a more obvious pathophysiological response to SARS-CoV-2 infection in elderly patients and may accelerate the risk of biological aging, even after recovery. For more favorable treatment outcomes, inhibiting viral replication and dampening inflammatory and oxidative responses before induction of an overt cytokine storm is crucial. Resveratrol is a potent antioxidant with antiviral activity. Herein, we describe the reasons for impaired interferon production, owing to aging, and the impact of aging on innate and adaptive immune responses to infection, which leads to inflammation distress and immunosuppression, thereby causing fulminant disease. Additionally, the molecular mechanism by which resveratrol could reverse a state of excessive basal inflammatory and oxidative stress and low antiviral immunity is discussed.

Study Objectives: Smoking and sleep are modifiable factors associated with the chronic kidney diseases. However, the interaction of smoking and sleep on the renal function are still unclear. Therefore, we aimed to evaluate the interactive impacts of smoking and sleep on the renal function.Methods: Data were obtained from the National Health and Nutrition Examination Survey. The study population were categorized into nine subgroups by smoking (smoking every day, sometimes, and non-smokers recently) and sleep duration (short duration ≤ 6 h, normal duration 6–9 h, and longer duration ≥ 9 h on the weekdays).Results: The study group with a short sleep duration had significantly higher serum cotinine and hydrocotinine levels compared with the other two sleep groups. After adjusting the demographic characteristics (age, race, body mass index, and marital status), sleep quality (snoring or breathing cessation), and comorbidities (diabetes mellitus, hypertension, high cholesterol, anemia, congestive heart failure, coronary heart disease, and stroke), non-smokers with short or long sleep duration had significant lower estimated glomerular filtration rate (eGFR) levels than the study group who smoked every day and slept ≤ 6 h. The effects of sleep duration on eGFR levels varied with smoking status. For the study group smoking every day, eGFR levels increased as sleep duration decreased, whereas for the study group smoking sometimes, eGFR levels increased as sleep duration increased. The U-shaped effects of eGFR levels were observed among non-smokers whose normal sleep duration was associated with better eGFR levels. Normal sleep duration was an important protective factor of the renal function for non-smokers than smokers.Conclusions: The effects of sleep duration on eGFR levels varied with smoking status. Normal sleep duration was a protective factor and more crucial for non-smokers than for smokers.

Renal osteodystrophy (ROD) represents bone disorders related to chronic kidney disease (CKD) and several bone biomarkers are used clinically to predict ROD in CKD and hemodialysis (HD) patients. Serum albumin associates with inflammation other than nutritional status in these patients. Chronic inflammation is proved to relate with bone loss, however, the influence of hypoalbuminemia on bone biomarkers is still unclear. In this study, we evaluated the pattern of bone biomarker changes and further studied the influence of hypoalbuminemia on these biomarkers. A total of 300 maintenance HD patients were evaluated and 223 HD patients were included in the study. The patients were grouped according to serum parathyroid hormone (PTH) levels (PTH ≤150 pg/mL, PTH 150-300 pg/mL, PTH 300-600 pg/mL and PTH >600 pg/mL). Bone biomarkers and inflammatory markers were measured and their relation with PTH levels was determined. Significantly increased interleukin-6 (IL-6) and lower albumin levels were noted among PTH>600 pg/mL group. Bone turnover markers were significantly higher in PTH >600 pg/mL group (p< 0.05). Hypoalbuminemia significantly increased the fibroblast growth factor-23 (FGF-23) and procollagen type 1N-terminal propeptide (P1NP) in PTH ≤150 pg/mL, PTH 150-300 pg/mL, PTH 300-600 pg/mL groups, whereas no such relation was noted among PTH> 600 ng/dL group. In conclusion, hypoalbuminemia represents a chronic inflammation which differently relates to bone turnover markers according to serum PTH levels in SHPT patients. Thus, serum albumin measurement should be considered in determining bone disorders among these patients.

Background: Sleeping disorder has been associated with chronic kidney disease (CKD); however, the correlation between sleeping pills use and CKD has not been investigated in-depth yet. This study elucidated the potential association of sleeping pill use with the risk of CKD and CKD progression to end-stage renal disease (ESRD) requiring dialysis.Methods: This study was based on a population-based cohort that included 209,755 sleeping pill users among 989,753 individuals. After applying the exclusion criteria, 186,654 sleeping pill users and 373,308 nonusers were enrolled to monitor the occurrence of CKD. Using a cumulative daily dose, we analyzed the types of sleeping pills related to the risk of CKD and ESRD. Propensity score matching and analysis using Cox proportional hazards regression were performed with adjustments for sex, age, and comorbidities.Results: Sleeping pill use was related to increased CKD risk after adjusting for underlying comorbidities (adjusted hazard ratio [aHR] = 1.806, 95% confidence interval [CI]: 1.617–2.105, p < 0.001). With the exception of hyperlipidemia, most comorbidities correlated with an increased risk of CKD. Persistent use of sleeping pills after CKD diagnosis increased the risk of concurrent ESRD (aHR = 7.542; 95% CI: 4.267–10.156; p < 0.001). After the subgroup analysis for sleeping pill use, brotizolam (p = 0.046), chlordiazepoxide (p < 0.001), clonazepam (p < 0.001), diazepam (p < 0.001), dormicum (p < 0.001), estazolam (p < 0.001), fludiazepam (p < 0.001), flunitrazepam (p < 0.001), nitrazepam (p < 0.001), trazodone (p < 0.001), zolpidem (p < 0.001), and zopiclone (p < 0.001) were found to have significant correlation with increased CKD risk.Conclusion: Sleeping pill use was related to an increased risk of CKD and ESRD. Further studies are necessary to corroborate these findings.

Introduction: Patients with carbon monoxide poisoning (COP) commonly have long-term morbidities. However, it is not known whether patients with COP exhibit an increased risk of developing chronic kidney disease (CKD) and whether hyperbaric oxygen therapy (HBOT) alters this risk. Methods: This study identified 8,618 patients who survived COP and 34,464 propensity score-matched non-COP patients from 2000 to 2013 in a nationwide administrative registry. The primary outcome was the development of CKD. The association between COP and the risk of developing CKD was estimated using a Cox proportional hazards regression model; the cumulated incidence of CKD among patients stratified by HBOT was evaluated using a Kaplan-Meier analysis. Results: After adjusting for covariates, the risk of CKD was 6.15-fold higher in COP patients than in non-COP controls. Based on the subgroup analyses, regardless of demographic characteristics, environmental factors, and comorbidities, the COP cohort exhibited an increased risk of developing CKD compared with the controls. The cumulative incidence of CKD in COP patients did not differ between the HBOT and non-HBOT groups (p = 0.188). Conclusions: COP might be an independent risk factor for developing CKD. Thus, clinicians should enhance the postdischarge follow-up of kidney function among COP patients.

Chronic kidney disease-mineral bone disorders (CKD-MBD) exhibit abnormalities in the circulating mineral levels, vitamin D metabolism, and parathyroid function that contribute to the formation of a bone lesion. The uremic toxin, indoxyl sulfate (IS), accumulates in the blood in cases of renal failure and leads to bone loss. The bone and renal responses to the action of the parathyroid hormone (PTH) are progressively decreased in CKD in spite of increasing PTH levels, a condition commonly called PTH resistance. There is a high prevalence of low bone turnover or adynamic bone disease in the early stages of CKD. This could be due to the inhibition of bone turnover, such as in PTH resistance, reduced active vitamin D levels, diabetes, aluminum, and, increased IS. With an increase in IS, there is a decrease in the osteoblast Wnt/b-catenin signaling and increase in the expression of Wnt signaling inhibitors, such as sclerostin and Dickkopf-1 (DKK1). Thus, a majority of early CKD patients exhibit deterioration of bone quality owing to the action of IS, this scenario could be termed uremic osteoporosis. However, this mechanism is complicated and not fully understood. With progressive deterioration in the renal function, IS accumulates along with persistent PTH secretion, potentially leading to high-turnover bone disease because high serum PTH levels have the ability of overriding peripheral PTH resistance and other inhibitory factors of bone formation. Finally, it leads to deterioration in bone quantity with prominent bone resorption in end stage renal disease. Uremic toxins adsorbents may decelerate oxidative stress and improve bone health in CKD patients. This review article focuses on IS and bone loss in CKD patients.

Supplemental Digital Content is available in the text, The prevalence of chronic kidney disease (CKD) in Taiwan is 11.9%, and the incidence and prevalence of end-stage renal disease (ESRD) is ranked first in the world. The severity of CKD progression to ESRD is dependent on glomerular filtration rate and proteinuria. However, the risk factors for ESRD also include diabetes, hypertension, hyperlipidemia, age, sex, and so on, and predicting CKD progression using few variables is insufficient. Currently, there are no models with high accuracy and high explanatory power that could predict the risk of progression to dialysis in CKD patients in Taiwan. Our aim was to establish an optimal prediction model for CKD progression in patients This study was a retrospective cohort study, which reviewed data from the “Public health insurance Pre-ESRD preventive program and patient health education program” that was implemented by the National Health Insurance Administration, Ministry of Health and Welfare. From 2006 to 2013, data of CKD patients from the Tri-Service General Hospital in Neihu District, Taipei City was examined. The data collected in this study included demographic variables, past medical history, and blood biochemical values. After exclusion of variables with >30% missing data, the remaining variables were interpolated using multiple imputations and inputted into the prediction model for analysis. The Cox proportion hazard model was used to investigate the influence of CKD risk factors on progression to dialysis. The strengths of various models were evaluated using likelihood ratios (LR), in order to identify a model which uses the least factors but has the strongest explanatory power. The study results included 1549 CKD patients, of whom 1017 eventually had dialysis. This study found that in the prediction model with the best explanatory power, the influencing factors and hazard ratios (HR) were: age 0.95 (0.91–0.99), creatinine 1.03 (1.02–1.05), urea nitrogen 1.18 (1.14–1.23), and comorbid systemic diabetes 1.65 (1.45–1.88). A prediction model was developed in this study, which could be used to carry out predictions based on blood biochemical values from patients, in order to accurately predict the risk of CKD progression to dialysis.

Secondary hyperparathyroidism (SHPT) relates to high turnover bone loss and is responsible for most bone fractures among chronic kidney disease (CKD) patients. Changes in the Wingless/beta-catenin signaling (Wnt/&beta, catenin) pathway and Wnt inhibitors have been found to play a critical role in CKD related bone loss. A calcimimetic agent, cinacalcet, is widely used for SHPT and found to be similarly effective for parathyroidectomy clinically. A significant decrease in hip fracture rates is noted among US hemodialysis Medicare patients since 2004, which is probably related to the cinacalcet era. In our previous clinical study, it was proven that cinacalcet improved the bone mineral density (BMD) even among severe SHPT patients. In this study, the influence of cinacalcet use on bone mass among CKD mice was determined. Cinacalcet significantly reduced the cortical porosity in femoral bones of treated CKD mice. It also improved the whole-bone structural properties through increased stiffness and maximum load. Cinacalcet increased femoral bone wingless 10b (Wnt10b) expression in CKD mice. In vitro studies revealed that cinacalcet decreased osteoclast bone resorption and increased Wnt 10b release from osteoclasts. Cinacalcet increased bone mineralization when culturing the osteoblasts with cinacalcet treated osteoclast supernatant. In conclusion, cinacalcet increased bone quantity and quality in CKD mice, probably through increased bone mineralization related with osteoclast Wnt 10b secretion.

Vitamin D has been demonstrated to lessen proteinuria severity in chronic kidney disease (CKD). Compared with healthy populations, patients with CKD may have lower serum levels of 1,25-dihydroxy vitamin D (1,25-(OH)2 D) and 25-hydroxy vitamin D (25-(OH) D). We investigated the effect of oral low-dose active vitamin D (calcitriol at 0.25 μg, 3 times weekly) on urinary protein excretion.We conducted a nonblinded and non-placebo-controlled study. In total, 60 patients with CKD (average estimated glomerular filtration rate of15 mL/min) who received a stable dose of angiotensin receptor blocker (ARB) or angiotensin-converting enzyme inhibitor (ACEI) were enrolled in this 24-week study. We randomly assigned these patients to the vitamin D group (oral calcitriol at 0.25 μg 3 times weekly with an ACEI or ARB) or the control group (ACEI or ARB). Change in the urine protein/creatinine ratio (uPCR) was the primary endpoint in this study.The mean baseline uPCRs of the 2 groups were comparable (1.84 ± 0.83 g/g vs. 2.02 ± 0.97 g/g, control vs. vitamin D group; P = .46). After the 24-week treatment, the uPCRs were significantly lower than the baseline values in the vitamin D group (1.35 ± 0.64 g/g; P .05) but not in the control group. The values of uPCR decreased significantly at 8, 16, and 24 weeks (P .05 vs. baseline) in the vitamin D group. The values of uPCRs were significantly lower in the vitamin D group than in the control group at 8, 16, and 24 weeks (P .05). A positive correlation was discovered between reduction in uPCRs at 24-week and baseline 25-(OH) D serum level in the vitamin D group (r = 0.738, P .001).Supplementary low-dose active vitamin D could reduce proteinuria in CKD patients with low serum 25-(OH) D levels.

The catastrophic coronavirus disease 2019 (COVID-19) pandemic is currently a critical global issue. One well-known complication of COVID-19 in severe cases is acute kidney injury, but no research has given a description of its impact on the kidney in patients with mild symptoms. We explore the renal function changes in mild COVID-19 patients. This retrospective, single-center study included 27 participants with laboratory-detected severe acute respiratory syndrome coronavirus two (SARS-CoV-2) infection who were admitted to the Tri-Service General Hospital from 4 February to 26 May 2020 and analyzed their clinical features, radiological findings, and laboratory data. Data collected upon admission and discharge showed a median estimated glomerular filtration rate (eGFR) of 106.7 mL/min/1.732 m2 and 112.2 mL/min/1.732 m2, respectively, with a p-value of 0.044. A correlation between renal function and the severity of infection was also found and was statistically significant upon admission. Patients with a lower lymphocyte count or higher C-reactive protein, neutrophil count, and neutrophil-to-lymphocyte ratio presented with a decreased eGFR during their early infection phase. The biomarkers (CRP and NLR) may be linked with dynamic changes of renal function in COVID-19 patients who are asymptomatic or have mild symptoms.

Background Acute water intoxication after hysteroscopy is a rare, life-threatening condition, often accompanied with delayed diagnosis owing to masked symptoms because of general anesthesia. Case presentation Herein we presented a 39-year-old female who presented with cardiac arrest after hysteroscopic myomectomy because of acute water intoxication and survived after extracorporeal membrane oxygenation, continuous venous–venous hemofiltration, and aggressive high sodium fluid resuscitation. Conclusion Failure to recognize and treat this condition appropriately may lead to potentially lethal cardiopulmonary complications.

Canonical Wnt (Wingless/Integrated) signaling is crucial in bone development and the Wnt ligand can promote osteoblast differentiation from mesenchymal progenitor cells. Calcitriol, an active vitamin D3, is used clinically for treatment of secondary hyperparathyroidism (SHPT) in chronic kidney disease (CKD) patients. The bone effects of calcitriol in SHPT remains uncertain. We hypothesized that calcitriol improves bone mass by suppressing osteoclast activity, and simultaneously promoting Wnt ligand secretion. We designed a cross-sectional study in maintenance hemodialysis patients to explore the effects of calcitriol on different bone turnover markers and specifically emphasized the Wnt 10b levels. Then, we explored the source of Wnt 10b secretion by using osteoclasts and osteoblasts treated with calcitriol in cell culture studies. Finally, we explored the effects of calcitriol on bone microarchitectures in CKD mice, using the 5/6 nephrectomy CKD animal model with analysis using micro-computed tomography. Calcitriol promoted the growth of both trabecular and cortical bones in the CKD mice. Wnt 10b and Procollagen 1 N-terminal Propeptide (P1NP) significantly increased, but Tartrate-resistant acid phosphatase 5b (Trap 5b) significantly decreased in the calcitriol-treated maintenance hemodialysis patients. Calcitriol enhanced Wnt 10b secretion from osteoclasts in a dose-dependent manner. Treatment of SHPT with calcitriol improved the bone anabolism by inhibiting osteoclasts and promoting osteoblasts that might be achieved by increasing the Wnt 10b level.

Osteoporosis is a systemic skeletal disorder characterized by a decrease in bone mass and microarchitectural deterioration of bone tissue. The World Health Organization has defined osteoporosis as a decrease in bone mass (50%) and bony quality (50%). Vitamin D, a steroid hormone, is crucial for skeletal health and in mineral metabolism. Its direct action on osteoblasts and osteoclasts and interaction with nonskeletal tissues help in maintaining a balance between bone turnover and bone growth. Vitamin D affects the activity of osteoblasts, osteoclasts, and osteocytes, suggesting that it affects bone formation, bone resorption, and bone quality. At physiological concentrations, active vitamin D maintains a normal rate of bone resorption and formation through the RANKL/OPG signal. However, active vitamin D at pharmacological concentration inhibits bone resorption at a higher rate than that of bone formation, which influences the bone quality and quantity. Nutritional vitamin D rather than active vitamin D activates osteoblasts and maintains serum 25(OH)D 3 concentration. Despite many unanswered questions, much data support nutritional vitamin D use in osteoporosis patients. This article emphasizes the role of nutritional vitamin D replacement in different turnover status (high or low bone turnover disorders) of osteoporosis together with either anti-resorptive (Bisphosphonate, Denosumab et.) or anabolic (Teriparatide) agents when osteoporosis persists.

Background: The endothelial progenitor cells (EPCs) dysfunction is a critical event in the initiation of atherosclerotic plaque development and the level of circulating EPCs can be considered a biomarker of cardiovascular events. The level and functional change in EPCs has been investigated in hemodialysis patients, but the effect of absolute number of EPCs on risk of death has not yet been explored. We hypothesized that the number of EPCs predicted death from cardiovascular and all-cause mortality in hemodialysis patients. Methods: We evaluate the association between endothelial progenitor cells and clinical outcome in 154 patients on maintenance hemodialysis. The blood sample was drawn at the time of patient enrollment and EPCs were identified by flow cytometry using triple staining for CD34/CD133/KDR. Results: The median duration of follow-up was 4.19 years. There were 79 (51.3%) deaths during the follow-up period, 41 of whom died due to a confirmed cardiovascular cause. The cumulative survival was greater in the high-EPC group than the low-EPC group for all-cause and cardiovascular mortality. Decreased EPCs levels were associated with a significant increase in the risk of cardiovascular and all-cause mortality after adjusting for age, gender, current smokers, diabetes mellitus, and hypertension. Conclusions: The level of circulating EPCs independently predicts the clinical outcome in patients on maintenance hemodialysis. Thus, the EPCs levels may be a useful predictive tool for evaluating the risk of death in maintenance hemodialysis patients.

Object Traumatic intracranial hemorrhage (TICH) patients with acute kidney injury (AKI) were reported to have a high mortality rate. Renal replacement therapy (RRT) is indicated for patients with a severe kidney injury. This study aimed to compare the effects of different RRT modalities regarding chronic dialysis rate among adult TICH patients with AKI. Methods A retrospective search of computerized hospital records from 2000 to 2010 for patients with a discharge diagnosis of TICH was conducted to identify the index cases. We collected the data of TICH patients with increased intracranial pressure combined with severe AKI who received intermittent hemodialysis (IHD) or continuous veno-venous hemofiltration (CVVH) as RRT. The outcome was dialysis dependence between 2000 and 2010. Results From a total of 310 patients who were enrolled in the study, 134 (43%) received CVVH and 176 (57%) received IHD. The risk of dialysis dependency was significantly lower in the CVVH group than in the IHD group (adjusted hazard ratio: 0.368, 95% CI, 0.158–0.858, P = 0.034). Diabetes mellitus and coronary artery disease were risk factors for dialysis dependency. CVVH compared with IHD modality was associated with lower dialysis dependency rate in TICH patients combined with AKI and diabetes mellitus and those with an injury severity score (ISS) ≥16. Conclusion CVVH may yield better renal outcomes than IHD among TICH patients with AKI, especially those with diabetes mellitus and an ISS ≥16. The beneficial impact of CVVH on TICH patients needs to be clarified in a large cohort study in future.

To determine the influence of physicochemical parameters on survival in metabolic acidosis (MA) and acute kidney injury (AKI) patients.Seventy-eight MA patients were collected and assigned to AKI or non-AKI group. We analyzed the physiochemical parameters on survival at 24 h, 72 h, 1 week, 1 month, and 3 months after AKI.Mortality rate was higher in the AKI group. AKI group had higher anion gap (AG), strong ion gap (SIG), and apparent strong ion difference (SIDa) values than non-AKI group. SIG value was higher in the AKI survivors than nonsurvivors and this value was correlated serum creatinine, phosphate, albumin, and chloride levels. SIG and serum albumin are negatively correlated with Acute Physiology and Chronic Health Evaluation IV scores. AG was associated with mortality at 1 and 3 months post-AKI, whereas SIG value was associated with mortality at 24 h, 72 h, 1 week, 1 month, and 3 months post-AKI.Whether high or low SIG values correlate with mortality in MA patients with AKI depends on its correlation with serum creatinine, chloride, albumin, and phosphate (P) levels. AG predicts short-term mortality and SIG value predicts both short- and long-term mortality among MA patients with AKI.

A 33-year-old woman was admitted to our emergency department in a state of unconsciousness after attempting suicide with unknown substances. Severe metabolic acidosis (pH: 6.81), with a high anion gap (36.2) and high lactate level (20.2 mmol/L), was observed. After four hours of intensive medical treatment, the patient regained consciousness, with a return of the arterial pH to 7.42. Finally, cyanide intoxication was diagnosed based on the detection of a serum cyanide level of 3.5 mg/L. The presence of a high anion gap associated with severe lactic acidosis is a clue for making a rapid differential diagnosis of acute cyanide intoxication. Providing intensive and immediate supportive management is also crucial, even in cases without obtainable specific antidotes.

Background We evaluated the risk of osteoporosis in patients with primary biliary cirrhosis (PBC) using a nationwide population-based dataset. Methods In a cohort study of 986,713 individuals, we selected 2,493 PBC patients who were aged 18 years or older and had been diagnosed with PBC, based on the International Classification of Disease (ICD-9-CM) codes 571.6, during 20002010. The control cohort comprised 9,972 randomly selected, propensity matched patients (by age, gender, and index date), without PBC. Using this adjusted data, a possible association between PBC and the risk of developing osteoporosis was estimated using a Cox proportional hazard regression model. Results During the follow-up period, osteoporosis was diagnosed in 150 (6.02%) patients in the PBC cohort and in 539 (5.41%) patients in the non-PBC cohort. After adjusting for covariates, osteoporosis risk was found to be 3.333 times greater in the PBC cohort than in the non-PBC cohort when measured over 6 years after PBC diagnosis. Stratification revealed that the use of ursodeoxycholic acid (UDCA) had no significance in decreasing the risk of osteoporosis when comparing the PBC cohorts with the non-PBC cohorts (P = 0.124). Additionally, osteoporosis risk was significantly higher in PBC patients with steroid use (aHR: 6.899 vs 3.333). Moreover, when comparing the PBC cohorts to the non-PBC cohorts, the non-cirrhotic patients were prone to osteoporosis at a younger age compared to those in the cirrhotic cohorts. We also found that the associated risk of fractures is only prominent for vertebral and wrist fractures in the PBC cohort compared to that in the non-PBC cohort. Conclusion A significant association exists between PBC and subsequent risk for osteoporosis. Therefore, PBC patients, particularly those treated with steroids, should be evaluated for subsequent risk of osteoporosis.

Introduction Pulmonary embolism is a potentially life-threatening complication of nephrotic syndrome. Syncope is rarely reported as an initial presentation of pulmonary embolism in nephrotic patients. Case presentation We describe a 35-year-old man who was taking steroids and diuretics for relapse of minimal change disease who presented after a syncopal event. The patient was hypotensive and had distended neck veins. The major laboratory findings were hypoalbuminemia with mild proteinuria. The findings on electrocardiography, chest radiography, and echocardiography and the elevated plasma D-dimer level raised suspicion of pulmonary embolism. Thrombi in the bilateral main pulmonary arteries on chest computed tomography together with compromised hemodynamics were consistent with the diagnosis of massive pulmonary embolism. He received anticoagulant treatment and the disease resolved. Conclusion Pulmonary embolism should be considered as a cause of syncope in patients with nephrotic syndrome, despite the absence of severe hypoalbuminemia and proteinuria, especially in patients taking concurrent steroid and diuretic therapy.

Constrictive pericarditis due to secondary hyperparathyroidism occurs in up to 4% of patients with end-stage renal disease.

Background/Aims: End-stage renal disease (ESRD) is simultaneously associated with immune activation, systemic inflammation and immune deficiency. Toll-like receptor 3 (TLR3), a receptor for viral double-stranded RNA, is involved in immune cell activation in renal diseases and may contribute to chronic inflammatory disease progression. To date, effects of TLR3 polymorphisms on ESRD remain unknown. Therefore, we determined the predictive value of TLR3 polymorphisms and further functionally studied ESRD. Methods: We performed a case-control association study and genotyped 616 ESRD patients and 813 healthy controls. Patients were genotyped for -7C/A, 1377C/T and 1234C/T polymorphisms of TLR3 using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. The Haplotype association analysis was performed using the Haploview package. A luciferase reporter assay and real-time PCR were used to test the function of the -7C/A promoter polymorphism in TLR3 expression in human embryonic kidney 293 (HEK293) cells. Results: Genotype distributions of -7C/A and 1377C/T in TLR3 were significantly different in ESRD patients and healthy controls. The ATC haplotype of TLR3 was associated with a decreased risk of ESRD. We also found significant differences in TLR3 expression by dexamethasone treatment between various genotypes of -7C/A (p = 0.02). TLR3 transcriptional activity of the variant -7 C allele was higher than that of the -7 A allele after dexamethasone treatment. Conclusion: Results indicate that, in our population, the presence of the C allele of -7C/A in TLR3 increases the susceptibility to ESRD. In vitro studies demonstrated that -7C/A may be involved in ESRD development through transcriptional modulation of TLR3.

Background/Aims: Secondary hyperparathyroidism may worsen after the administration of pamidronate in postmenopausal hemodialysis (HD) patients. The aim of this study was to evaluate the short-term effect of coadministration of calcitriol and pamidronate on dynamic parathyroid hormone (PTH) secretion. Methods: Fifteen postmenopausal women undergoing regular HD with serum intact PTH levels of >200 pg/ml were enrolled. The PTH-ionized calcium (iCa) curve was evaluated by the response to hypo- and hypercalcemia induced with 1 and 4 mEq/l of dialysate calcium, respectively. Parameters were compared after pamidronate was administered and after coadministration of pamidronate and calcitriol. Changes in serum levels of maximal serum PTH (PTHmax), basal PTH (PTHbase) and minimal PTH (PTHmin) were evaluated. Results: Pamidronate therapy resulted in a decrease in predialysis basal plasma iCa (p < 0.05) and an increase in PTHmax (p < 0.01), PTHbase (p < 0.01) and PTHmin (p < 0.01). The change in serum iCa and PTH was reversed after the coadministration of calcitriol and pamidronate. Conclusion: Our study demonstrated that pamidronate therapy is associated with a reduced plasma iCa and increased PTH secretion. These adverse effects may be reversed by calcitriol. These findings suggest that in considering pamidronate treatment in postmenopausal patients with osteoporosis receiving HD, it might be safer to add calcitriol to prevent the increased PTH secretion.

Background: Several polymorphisms in the angiotensin-converting enzyme (ACE) and ACE2 genes are associated with the development of end-stage renal disease (ESRD). Certain genetic polymorphisms may modify the deleterious effects of environmental factors such as cigarette smoking and may also modify the inherited risk. We investigated the association of six ACE and ACE2 polymorphisms with ESRD to determine whether a relationship exists between gene–smoking interactions and ESRD. Materials and methods: We performed a case-control association study and genotyped 683 ESRD patients and 653 healthy controls. All subjects were genotyped for ACE (I/D, G2350A and A-240T) and ACE2 (G8790A, A1075G and G16854C) gene polymorphisms by polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP) analysis. Results: Significant associations were observed between ACE I/D and G2350A polymorphisms and ESRD. There was no difference in ACE2 genotype distribution between ESRD patients and healthy controls. Haplotype analysis showed that DAA and DAT haplotypes were risk factors for ESRD. Moreover, a gene–environment interaction was observed between ACE I/D polymorphism and cigarette smoking. Conclusion: ACE I/D and ACE G2350A polymorphisms were associated with the development of ESRD. The interaction between ACE I/D polymorphism and smoking is also associated with an enhanced risk of ESRD.

Background: It is intriguing and imperative that the comparison of the iron preparations in hemodialysis (HD) patients. Th is study aimed to observe the short-term effi cacy of parenteral iron sucrose and ferric chloride in HD patients. Materials and Methods: This was a consecutive 10-week single-blind study in Taiwan. An intravenous iron supplement of 100 mg/week was administered as an infusion in 100 ml of normal saline, until a total dose of 1000 mg was achieved. Th e primary outcome was evaluated by the changes in serum hematocrit (Hct) levels. Th e changes in serum Hct and iron indices were evaluated every 2 weeks for 10 weeks. Th e results were collected from 21 April to 4 July 2013. Results: A total of 56 HD patients completed the study. Subjects were randomized into an iron sucrose group (26 patients) and a ferric chloride group (30 patients). Between the two treatment groups, there were no statistically signifi cant diff erences in the change in serum Hct, ferritin, iron, or total iron binding capacity (P > 0.05). In the iron sucrose group, the increase in Hct levels was statistically signifi cant at weeks 4, 8, and 10. In the ferric chloride group, the increase in Hct levels was statistically signifi cant at week 8. No obvious major side eff ects were observed in both groups. Conclusion: In the study subjects, parenteral iron sucrose was as eff ective and safe as ferric chloride for treating anemia in HD patients. Key words: Anemia, ferric chloride, hemodialysis, intravenous iron, iron sucrose

Inflammation, endothelial dysfunction, and mineral bone disease are critical factors contributing to morbidity and mortality in hemodialysis (HD) patients. Physical exercise alleviates inflammation and increases bone density. Here, we investigated the effects of intradialytic aerobic cycling exercise on HD patients. Forty end-stage renal disease patients undergoing HD were randomly assigned to either an exercise or control group. The patients in the exercise group performed a cycling program consisting of a 5-minute warm-up, 20 minutes of cycling at the desired workload, and a 5-minute cool down during 3 HD sessions per week for 3 months. Biochemical markers, inflammatory cytokines, nutritional status, the serum endothelial progenitor cell (EPC) count, bone mineral density, and functional capacity were analyzed. After 3 months of exercise, the patients in the exercise group showed significant improvements in serum albumin levels, the body mass index, inflammatory cytokine levels, and the number of cells positive for CD133, CD34, and kinase insert domain-conjugating receptor. Compared with the exercise group, the patients in the control group showed a loss of bone density at the femoral neck and no increases in EPCs. The patients in the exercise group also had a significantly greater 6-minute walk distance after completing the exercise program. Furthermore, the number of EPCs significantly correlated with the 6-minute walk distance both before and after the 3-month program. Intradialytic aerobic cycling exercise programs can effectively alleviate inflammation and improve nutrition, bone mineral density, and exercise tolerance in HD patients.

Type 2 diabetes mellitus (DM) and associated complications are common in patients with chronic kidney disease (CKD) and can increase morbidity and mortality. A longitudinal 5-year observational study was conducted to investigate whether the use of anti-diabetic medications or not affected survival rates of diabetic dialysis patients. Using a data sample of a million patients from Taiwan’s National Health Insurance Database, a retrospective cohort study surveyed patients with type 2 DM who began dialysis between 2002 and 2007. The study population was classified into groups using or not using anti-diabetic drugs. The group using anti-diabetic drugs was then categorized into 3 subgroups, including use of only oral hypoglycemic agents (OHAs), only insulin, and OHAs-combined insulin groups. Subjects of these four groups were followed 5 years or to date of death. Three major areas were analyzed: (1) demographic data and medical history; (2) survival prognosis and causes of death; and (3) effects on survival prognosis of different classes of OHAs. A total of 912 patients fitting inclusion criteria were enrolled and followed-up for 5 years or to date of death. A total 465 patients died, and those not using anti-diabetic drugs (67.34 %) had a higher mortality rate than those using anti-diabetic drugs (46.42 %). After the multivariate analysis, group of OHAs-combined insulin had the lowest risk of death (HR 0.36, 95 % CI 0.27–0.47), followed by OHAs alone (HR 0.49, 95 % CI 0.38–0.63) and then insulin alone (HR 0.67, 95 % CI 0.51–0.88). To clarify four classes of OHAs (sulfonylurea, α-glucosidase inhibitors, meglitinide, and thiazolidinedione) are used in Taiwan for uremia patient with type 2 DM, and in our study, there were no significant differences in survival prognosis for the four drugs. Finally, the most common cause of death was infectious disease and there were no significant differences among the four groups. This 5-year observational study results suggested that diabetic dialysis patients with anti-diabetic drugs had a lower risk of death compared with those without anti-diabetic drugs. Despite insulin therapy, appropriate OHAs should play an important role in treating these patients.

Chronic hyperglycemia results in a non-enzymatic glycation of proteins, and produces Amadori products, such as glycated albumin (GA), glycosylated hemoglobin (HbA1c), and fructosamine. In current clinical practice, long-term glycemic control is assessed by quarterly measurements of HbA1c. Since the degree of hemoglobin glycosylation depends not only on the level of glycemic control, but also on the lifespan of red blood cells, patients with hemoglobin disorders or anemia of any cause may have erroneous HbA1c levels, and consequently receive insufficient treatment. Patients with chronic kidney disease (CKD) often suffer from various types of anemia, and consequently, they are frequently treated with iron and/or erythropoietin therapy or frequent blood transfusion. Thus, serum GA is a potentially useful glycemic index in diabetic patients with CKD, since it is not influenced by anemia and associated treatments. GA may also reflect the status of blood glucose more rapidly (2-3 weeks) than HbA1c (2-3 months), and is beneficial in those with wide variations in blood glucose or at higher risk for hypoglycemia. If clinical investigations support its utility, it may be applicable as a screening tool for all patients with diabetes during routine health examinations. Serum GA levels are also associated with AGE-related fluorescence and the number of glycation sites, and it may influence the structural and functional changes inalbumin. Since end-stage renal disease is an extreme microvascular complication of diabetic nephropathy, CKD patients with diabetes should be carefully managed to prevent disease progression. In this review, the clinical aspects of GA were discussed, including a comparison of GA with other glycated proteins, the utility and limitations of GA as a glycemic index, its influence on the therapeutic effects of hypoglycemic agents, its correlations with vascular complications, and its potential role in pathogenesis, specifically in diabetic patients with CKD.

Summary Objective Patients on long-term dialysis may develop secondary hyperparathyroidism (SHPT), which causes varying degrees of bone mass loss. This condition is treated with parathyroidectomy (PTX). We investigated whether serial serum bone turnover markers could predict changes in bone mineral density (BMD) after PTX. Design and patients Renal patients on maintenance haemodialysis who received PTX for refractory SHPT (n = 26, male/female: 13/13; mean age: 48·6 ± 10·7 year) and control subjects without SHPT (n = 25) were prospectively followed for 1 year at two tertiary hospitals in Taiwan. Measurements Serum intact parathyroid hormone (iPTH), bone-specific alkaline phosphatase (BAP) and type 5b tartrate-resistant acid phosphatase (TRAP) were measured serially. Additionally, femoral neck (FN) and lumbar spine (LS) BMD were measured before and 1 year after PTX. Results After PTX, iPTH levels decreased markedly and persistently. BMDs increased in both the FN and LS, but particularly in the LS. Serum BAP progressively increased to a peak at 2 weeks after PTX. Serum TRAP levels progressively decreased over 6 months after PTX. In univariate correlation analyses, baseline iPTH correlated positively with T-score changes in FN (r = 0·45, P = 0·021) and LS (r = 0·48, P = 0·013). In multivariate regression models, changes in FN T-scores were negatively predicted by baseline BAP levels (r = −0·615, P = 0·005) and baseline FN T-scores (r = −0·563, P = 0·012), and they were positively predicted by baseline TRAP(r = 0·6, P = 0·007). Changes in LS T-scores were positively predicted by baseline TRAP values (r = 0·528, P = 0·01) and negatively predicted by the percentage change in BAP after 2 weeks (r = −0·501, P = 0·015). Conclusions Parathyroidectomy provided marked, sustained improvements in BMD for up to 1 year. Furthermore, markers of bone turnover predicted 1-year changes in FN and LS BMDs after PTX.

Membranous nephropathy (MN) is a leading cause of adult nephrotic syndrome but lacks adequate treatment. Different extracts ofAngelica sinensis(AS) and one of its active compounds, ferulic acid (FA), were used to evaluate the therapeutic effects in a MN mouse model. The MN model was grouped into three subgroups: no treatment (N-T), treatment at induction of MN (Pre-T), and treatment after full-blown MN (Post-T). The results showed that the methanol (ME) layer of AS extract exhibited a therapeutic effect on MN-induced proteinuria. The ME layer-enriched compound, FA, improved the hypoalbuminemia, hyperlipidemia, and proteinuria in both Pre-T and Post-T groups. Ferulic acid also reduced the formation of oxidative protein products and increased the synthesis of antioxidant enzymes in groups Pre-T and Post-T. Regarding angiogenesis factors, the antiangiogenic factors in renal glomeruli were increased in group N-T, but, after FA treatment, only one of the antiangiogenic factors, thrombospondin-1, showed a significant decrease. Furthermore, the expression of Th2 predominant showed significant decrease in both Pre-T and Post-T groups when compared to that of N-T group. In summary, FA retarded the progression of MN, and the mechanisms involved the regulation of oxidative stresses, angiogenic and antiangiogenic factors, and attenuation of Th2 response.

Secondary hyperparathyroidism (SHP) is characterized by high bone turnover, which may, in turn, result in increased release of lead from bone stores. This study investigated the effects of intravenous calcitriol on blood lead (BL) levels in patients with SHP.Intravenous calcitriol therapy was administered for 16 wk to 28 patients who were on maintenance hemodialysis (HD) and had intact parathyroid hormone (iPTH) plasma levels of300 pg/mL. Blood was drawn at baseline and every 4 wk for 16 wk to determine the levels of iPTH; bone remodeling markers, including bone-specific alkaline phosphatase (bAP) and type 5b tartrate-resistant acid phosphatase (TRAP); and BL.Of the 28 patients, 25 responded to calcitriol therapy; they exhibited significant decrements in serum iPTH levels by the end of 4 wk of therapy and thereafter. After 16 wk of therapy, these patients had significant reductions in serum iPTH levels (p0.01) and significant and parallel decreases in the levels of bAP (p0.01), TRAP (p0.01), and BL (p0.01). Further analysis showed a significant positive correlation between the levels of BL and serum iPTH (r=0.34, p0.01) and BL and serum TRAP (r=0.22, p0.05). However, there was no significant correlation between the levels of BL and serum bAP.Elevated levels of BL and serum bone remodeling markers, which are common features of SHP, can be effectively suppressed by calcitriol therapy. This indicates that hyperparathyroidism not only accelerates bone remodeling but may also enhance bone lead mobilization in patients on maintenance HD.

Type 2 diabetic nephropathy (DN) is the most common cause of end-stage renal disease and is increasingly considered as an inflammatory disease characterized by leukocyte infiltration at every stage of renal involvement. Inflammation and activation of the immune system are closely involved in the pathogenesis of diabetes and its microvascular complications. Macrophage has been well recognized to play an important role in type 2 DN, leukocyte infiltration, and participated in process of DN, as was proposed recently. Th1, Th2, Th17, T reg, and cytotoxic T cells are involved in the development and progression of DN. The purpose of this review is to assemble current information concerning the role of T cells in the development and progression of type 2 DN. Specific emphasis is placed on the potential interaction and contribution of the T cells to renal damage. The therapeutic strategies involving T cells in the treatment of type 2 DN are also reviewed. Improving knowledge of the recognition of T cells as significant pathogenic mediators in DN reinforces the possibility of new potential therapeutic targets translated into future clinical treatments.

Background Metabolic acidosis, especially when induced by multiple drug poisoning, often makes rapid and accurate differential diagnosis of the condition challenging. Methods We closely followed anion and osmolal gaps to differentiate among the aetiologies of metabolic acidosis caused by poisoning with unknown drugs. Results The patient was admitted to our emergency department (ED) in an alert and consciousness state after attempting suicide by ingestion of an uncertain quantity of rodenticides combined with an unknown liquid. Initially, metabolic acidosis (pH 7.23) with normal anion gap (12.8) was observed. However, a change in consciousness and hypotension subsequently developed 6 h later, combined with severe metabolic acidosis (pH 7.16), high anion gap (25.5), and high osmolal gap (83). A presumed diagnosis of methanol intoxication was suspected. After 4 h of high-flux haemodialysis (HD), the serum bicarbonate returned to 23 mmol/l, and the patient regained consciousness. The serum level of methanol before HD was 193.8 mg/dl. The patient was discharged nine days later without sequelae. Conclusions Delayed high anion gap metabolic acidosis may occur in the ED. Frequent monitoring of anion and osmolal gaps is a feasible method to perform a rapid differential diagnosis, particularly in response to drug poisoning.

Background Diabetic nephropathy (DN) occurs in 20% to 30% of all patients with type 2 diabetes mellitus (DM) and is the most common cause of end-stage renal disease. However, the definite pathogenesis, especially the role of immune response, is still unclear. Methods We studied the production and expression of Th1 (IFN-γ, IL-2R), Th2 (IL-4, IL-10), proinflammatory cytokines (IL-1β, and TNF-α), and chemokines (MCP-1, and RANTES) in patients with DN. The correlation among cytokines, chemokines, and clinical parameters were examined. Results A patient with DN presented with longer disease duration, heavy proteinuria, and impaired renal function. Our results demonstrated increased proinflammatory cytokines, Th1 cytokines and chemokines, but not Th2 cytokines, in the plasma and urine of patients with DN as compared to patients with DM without overt nephropathy. Enhanced cytokine/chemokine activation in DN was also demonstrated by positive immunohistochemical staining of kidney tissue. We found a positive correlation between daily protein loss and plasma IFN-γ and IL-2R, and urinary MCP-1, as well as a negative correlation between creatinine clearance and plasma TNF-α and urinary MCP-1. Conclusions There were aberrant cytokines/chemokines production correlated with the degree of proteinuria in patient with overt DN and gross proteinuria. Inflammation may be important in the pathogenesis of DN.

We evaluated the improvement of intact parathyroid hormone (iPTH) levels and bone parameters by supplementing nutritional vitamin D (cholecalciferol) to combined calcimimetic (cinacalcet) and active vitamin D analog (calcitriol) among severe secondary hyperparathyroidism (SHPT) hemodialysis (HD) patients. A randomized, controlled open-label study was undertaken in 60 HD patients with serum iPTH > 1000 pg/mL or persistently high iPTH ≥ 600 pg/mL even after >3 months of calcitriol (3 μg/week). The study group received oral cholecalciferol (5000 IU/ day) and the control group received a placebo. All patients received fixed dose cinacalcet (30 mg/day, orally) and calcitriol. Calcitriol was reduced if iPTH ≤ 300 pg/mL and cinacalcet was withdrawn if serum iPTH was persistently low (iPTH ≤ 300 pg/mL) for 4 weeks after the reduction of calcitriol. A significantly lower iPTH level was noted from the 20th week in the study group compared to the placebo group, and the target iPTH ≤ 300 pg/mL was achieved at the 24th week in the study group. Most patients achieved serum 25-(OH)D3 ≥ 30 ng/mL in the study group. Nearly 40% of study patients gained >10% improvement in femoral neck (FN) bone mineral density (BMD). We conclude that cholecalciferol additively reduced serum iPTH levels, improved 25-(OH)D3 levels and improved FN BMD when used together with cinacalcet/calcitriol in severe SHPT HD patients.

Chronic kidney disease (CKD) patients experience bone loss and fracture because of a specific CKD-related systemic disorder known as CKD-mineral bone disorder (CKD-MBD). The bone turnover, mineralization, and volume (TMV) system describes the morphological bone lesions in renal osteodystrophy related to CKD-MBD. Bone turnover and bone volume are defined as high, normal, or low, and bone mineralization is classified as normal or abnormal. All types of bone histology related to TMV are responsible for both bone quantity and bone quality losses in CKD patients. This review focuses on current bone quantity and bone quality losses in CKD patients and finally discusses potential therapeutic measures.

Background: In patients with advanced renal dysfunction undergoing maintenance hemodialysis, glycated albumin (GA) levels may be more representative of blood glucose levels than hemoglobin A1C levels. The aim of this study was to determine the predictive power of GA levels on long-term survival in hemodialysis patients. Methods: A total of 176 patients with a mean age of 68.2 years were enrolled. The median duration of follow-up was 51.0 months. Receiver-operating characteristic curve analysis was utilized to determine the optimal cutoff value. We examined the cumulative survival rate by Kaplan-Meier estimates and the influence of known survival factors with the multivariate Cox proportional-hazard regression model. Results: In the whole patient group, cumulative survival in the low GA group was better than in the high GA group (p=0.030), with more prominence in those aged

Low 25(OH)D levels are common in chronic kidney disease (CKD) patients and are implicated in all-cause mortality and morbidity risks. Furthermore, the progression of CKD is accompanied by a gradual decline in 25(OH)D production. Vitamin D deficiency in CKD causes skeletal disorders, such as osteoblast or osteoclast cell defects, bone turnover imbalance, and deterioration of bone quality, and nonskeletal disorders, such as metabolic syndrome, hypertension, immune dysfunction, hyperlipidemia, diabetes, and anemia. Extra-renal organs possess the enzymatic machinery for converting 25(OH)D to 1,25(OH)2D, which may play considerable biological roles beyond the traditional roles of vitamin D. Pharmacological 1,25(OH)2D dose causes hypercalcemia and hyperphosphatemia as well as adynamic bone disorder, which intensifies vascular calcification. Conversely, native vitamin D supplementation reduces the risk of hypercalcemia and hyperphosphatemia, which may play a role in managing bone and cardio-renal health and ultimately reducing mortality in CKD patients. Nevertheless, the combination of native vitamin D and active vitamin D can enhance therapy benefits of secondary hyperparathyroidism because of extra-renal 1α-hydroxylase activity in parathyroid gland. This article emphasizes the role of native vitamin D replacements in CKD, reviews vitamin D biology, and summarizes the present literature regarding native vitamin D replacement in the CKD population.

Background Chronic kidney disease (CKD) is highly prevalent in Taiwan. More than two-thirds of end-stage renal disease is associated with diabetes mellitus (DM) or hypertension (HTN). Therefore, the formulation of a special preventative policy of CKD in these patients is essential. This study surveyed 14 traditional risk factors and identified their effects on CKD in patients with HTN/DM and compared these with their effects in the general population. Methods This study included 5328 cases and 5135 controls in the CKD/HTN/DM outpatient and health centres of 10 hospitals from 2008 to 2010. Fourteen common effect factors were surveyed (four demographic, five disease and five lifestyle), and their effects on CKD were tested. Significance tests were adjusted by the Bonferroni method. Results of the stratified analyses in the variables were presented with significant heterogeneity between patients with different comorbidities. Results Male, ageing, low income, hyperuricemia and lack of exercise habits were risk factors for CKD, and their effects in people with different comorbidities were identical. Anaemia was a risk factor, and there was an additive effect between anaemia and HTN on CKD. Patients with anaemia had a higher risk when associated with HTN [odds ratio (OR) = 6.75, 95 % confidence limit (95 % CI) 4.76–9.68] but had a smaller effect in people without HTN (OR 2.83, 95 % CI 2.16–3.67). The association between hyperlipidaemia-related factors and CKD was also moderated by HTN. It was a significant risk factor in people without HTN (OR = 1.67, 95 % CI 1.38–2.01) but not in patients with HTN (OR =1.03, 95 % CI 0.89–1.19). Hepatitis B, hepatitis C, betel nut chewing, smoking, alcohol intake and groundwater use were not associated with CKD in multivariate analysis. Conclusions We considered that patients with HTN and anaemia were a high CKD risk population. Physicians with anaemic patients in outpatient clinics need to recognise that patients who also have HTN might be latent CKD cases. Electronic supplementary material The online version of this article (doi:10.1186/s12882-015-0065-x) contains supplementary material, which is available to authorized users.

Background There is increased oxidative stress in patients undergoing haemodialysis (HD); however, little is known of how different dialysis membranes contribute to the oxidative stress induced by the dialysis procedure per se. We therefore studied the influence of two different dialysis membranes on oxidative stress during HD. Methods Eight patients undergoing HD three times per week were enrolled in this cross-controlled study. Patients sequentially received HD using polysulphone (PS) and regenerated cellulose (RC) dialysis membranes for 1 week each. Blood samples were collected in the last section of each hollow fibre 0, 15, 120 and 240 min after starting HD. We determined superoxide anion production derived from neutrophils, superoxide dismutase (SOD) and glutathione peroxidase (GPx) derived from washed red cells, plasma myeloperoxidase (MPO), plasma thiobarbituric acid-reactive substances (TBARS), plasma advanced oxidation protein products (AOPP) and serum 8-hydroxy-2'-deoxyguanosine (8-OHdG). Results Leukocyte numbers, including neutrophils, lymphocytes and monocytes, decreased significantly after 15 min of dialysis, more so with RC than with PS membrane. For both membranes, superoxide anion production transiently increased during the first 15 min whereas the post-dialysis production was decreased. Plasma MPO levels persistently increased during dialysis with the two membranes. Moreover, the increase was more marked with RC than with PS membrane. AOPP and 8-OHdG levels increased progressively when using RC membranes. There were no significant differences in SOD, GPx, TBARS, AOPP and 8-OHdG levels between the two membranes. Conclusions The biocompatibility of the dialyser affects oxidative stress production during a single dialysis session. The measurement of MPO may serve as a reliable marker of the degree of oxidative stress induced using dialysis membranes of different biocompatibilities.