Potentially Inappropriate Medication Use in Older Adults With Multimorbidity in Taiwan.

BACKGROUND: Medication-related problem is a concerning issue in older adults with multimorbidity due to complexity of disease conditions and polypharmacy, and may lead to increase in risk for adverse health outcomes. This study aims to investigate the prevalence and associated factors of potentially inappropriate medication use among the growing population of older adults with multimorbidity in Taiwan. METHOD: The study population was composed of patients who were aged 65 years or older with multimorbidity (two or more chronic diseases) and had at least one outpatient clinic visit with drug prescription in 2018 identified from the Taiwan National Health Insurance Research Database. Potentially inappropriate medication use was defined using the 2019 Beers criteria for drugs to be avoided for older adults. Multiple logistic regression model was conducted to examine patient-related and prescriber-related factors associated with PIM use. RESULTS: A total of 2 432 416 patients (69.7% of the entire older adult population) had multimorbidity and received at least one drug prescription at the outpatient clinic in Taiwan in 2018. The prevalence of having at least one PIM in this population was found to be 85.6%. Patient-related factors (age, sex, specific chronic diseases, frequency of outpatient visits) and prescriber-related factors (physician characteristics, healthcare setting, total number of medications, prior PIM use) were found to be associated with use of PIM. CONCLUSION: High prevalence of PIM use was found in older patients with multimorbidity in Taiwan. Both patient-related and prescriber-related factors had been found to be predictors of PIM use, and should be addressed when trying to improve the medication quality in this population.

Decipher the Immunopathological Mechanisms and Set Up Potential Therapeutic Strategies for Patients with Lupus Nephritis.

Lupus nephritis (LN) is one of the most severe complications in patients with systemic lupus erythematosus (SLE). Traditionally, LN is regarded as an immune complex (IC) deposition disease led by dsDNA-anti-dsDNA-complement interactions in the subendothelial and/or subepithelial basement membrane of glomeruli to cause inflammation. The activated complements in the IC act as chemoattractants to chemically attract both innate and adaptive immune cells to the kidney tissues, causing inflammatory reactions. However, recent investigations have unveiled that not only the infiltrating immune-related cells, but resident kidney cells, including glomerular mesangial cells, podocytes, macrophage-like cells, tubular epithelial cells and endothelial cells, may also actively participate in the inflammatory and immunological reactions in the kidney. Furthermore, the adaptive immune cells that are infiltrated are genetically restricted to autoimmune predilection. The autoantibodies commonly found in SLE, including anti-dsDNA, are cross-reacting with not only a broad spectrum of chromatin substances, but also extracellular matrix components, including α-actinin, annexin II, laminin, collagen III and IV, and heparan sulfate proteoglycan. Besides, the glycosylation on the Fab portion of IgG anti-dsDNA antibodies can also affect the pathogenic properties of the autoantibodies in that α-2,6-sialylation alleviates, whereas fucosylation aggravates their nephritogenic activity. Some of the coexisting autoantibodies, including anti-cardiolipin, anti-C1q, anti-ribosomal P autoantibodies, may also enhance the pathogenic role of anti-dsDNA antibodies. In clinical practice, the identification of useful biomarkers for diagnosing, monitoring, and following up on LN is quite important for its treatments. The development of a more specific therapeutic strategy to target the pathogenic factors of LN is also critical. We will discuss these issues in detail in the present article.

The Effectiveness of Pay-for-Performance Program of Diabetes Care for Psychiatric Patients: A Regional Psychiatric Hospital Experience.

BACKGROUND: The Pay-for-performance (P4P) program of diabetes care has demonstrated successful outcomes in patients with type 2 diabetes. However, the effectiveness of this multidisciplinary care model for psychiatric patients has never been evaluated. The objective of this study is to examine the effectiveness of P4P program of diabetes for psychiatric patients with diabetes. METHODS: This study utilized a retrospective cohort design to examine the effectiveness of P4P program of diabetes care for psychiatric patients with diabetes. The participants' HbA1c (hemoglobin A1c) data of the fourth quarter in 2018 were used as baseline value, while P4P program was not applied yet. HbA1c data of every quarter in 2019 were collected. Generalized estimating equations (GEE) was used to analyze the change of HbA1c level. RESULTS: The HbA1c level increased slightly in the first quarter, and then decreased gradually since the second quarter. The HbA1c level was significantly lower in the fourth quarter after P4P program intervention (p < 0.05). CONCLUSION: P4P program of diabetes care is also effective on psychiatric patients with diabetes, and this multidisciplinary care model could be encouraged and promoted for psychiatric patients with diabetes.

Sirtuin-1 and Its Relevance in Vascular Calcification.

Vascular calcification (VC) is highly associated with cardiovascular disease and all-cause mortality in patients with chronic kidney disease. Dysregulation of endothelial cells and vascular smooth muscle cells (VSMCs) is related to VC. Sirtuin-1 (Sirt1) deacetylase encompasses a broad range of transcription factors that are linked to an extended lifespan. Sirt1 enhances endothelial NO synthase and upregulates FoxOs to activate its antioxidant properties and delay cell senescence. Sirt1 reverses osteogenic phenotypic transdifferentiation by influencing RUNX2 expression in VSMCs. Low Sirt1 hardly prevents acetylation by p300 and phosphorylation of ß-catenin that, following the facilitation of ß-catenin translocation, drives osteogenic phenotypic transdifferentiation. Hyperphosphatemia induces VC by osteogenic conversion, apoptosis, and senescence of VSMCs through the Pit-1 cotransporter, which can be retarded by the sirt1 activator resveratrol. Proinflammatory adipocytokines released from dysfunctional perivascular adipose tissue (PVAT) mediate medial calcification and arterial stiffness. Sirt1 ameliorates release of PVAT adipokines and increases adiponectin secretion, which interact with FoxO 1 against oxidative stress and inflammatory arterial insult. Conclusively, Sirt1 decelerates VC by means of influencing endothelial NO bioavailability, senescence of ECs and VSMCs, osteogenic phenotypic transdifferentiation, apoptosis of VSMCs, ECM deposition, and the inflammatory response of PVAT. Factors that aggravate VC include vitamin D deficiency-related macrophage recruitment and further inflammation responses. Supplementation with vitamin D to adequate levels is beneficial in improving PVAT macrophage infiltration and local inflammation, which further prevents VC.

Association of psychiatric and physical illnesses with suicide in older adults in Taiwan.

OBJECTIVE: This study aimed to investigate the association of psychiatric and physical illnesses with suicide in older adults in Taiwan. METHODS: A nationwide database in Taiwan was used for this matched case-control study. Elderly participants with and without intentional self-harm from 2010 to 2012 were matched by propensity score by calendar year, gender, age, and area of residence. Psychiatric and physical illnesses were identified by tracing back 1 year from the date of death in suicide and from July 1 of the previous year to June 30 of the observational year in the controls. Associations between illnesses and the risk of suicide was assessed by conditional logistic regression analysis. RESULTS: 2,528 older adults who died by suicide were studied, and the crude suicide mortality rate was 33.7 per 100,000. The risk of suicide in older adults with depression (AOR = 9.06, 95% CI = 6.07-13.52), cancer (AOR = 8.51, 95% CI = 5.39-13.45) and schizophrenia (AOR = 7.34, 95% CI = 2.65-20.33), were significantly higher than control group. Other illnesses, such as bipolar disorder, chronic obstructive pulmonary disease, stroke, chronic kidney disease, hypertension, and diabetes mellitus (AOR = 3.63, 2.41, 1.94, 1.73, 1.68, 1.45, respectively), showed lower risk but still significantly higher in older adults with suicide. CONCLUSIONS: Psychiatric and physical illnesses, especially depression, cancer, and schizophrenia, were found to be independently associated with suicide in older adults. The result of this study can help clinicians to identify older adults at risk of suicide and open avenues for prevention.

The effects of cement fixation on survival in elderly patients with hip hemiarthroplasty: a nationwide cohort study.

BACKGROUND: Hip hemiarthroplasty (HHA) is a common treatment for hip fractures in the elderly population. Because of the fatal effects of bone cement implantation syndrome, the safety of cement utilization to enhance implant firmness in the femur is controversial. The aim of this study was to investigate the postoperative survival of elderly patients receiving HHA with and without cement fixation. METHODS: Claim data from the National Health Insurance Database and the National Register of Deaths Database were used for analysis in this retrospective cohort study. From 2008 to 2014, 25,862 patients aged 80 years or older treated with hip hemiarthroplasty were included in the analysis. A Cox proportional risk model was used to analyse the effects of cement utilization on postoperative mortality. RESULTS: The cemented group had a significantly higher mortality risk than the non-cemented group within 7, 30, 180 days and 1 year after the operation. The effect of bone cement on postoperative mortality was significantly stronger within 7 days than within 30, 180 days and 1 year. In addition, the male gender, age > 85 years and higher score on the Charlson Comorbidity Index were also risk factors for mortality (p < 0.05). Patients who received HHA in lower-volume hospitals had higher mortality rates within 180 days and 1 year than those in higher-volume hospitals. Compared with patients who were operated on by high-volume surgeons, those who received surgery performed by lower-volume surgeons were more likely to die within 30 days (aHR = 1.22), 180 days (aHR = 1.16) and 1 year (aHR = 1.19), respectively. CONCLUSIONS: The postoperative mortality rate of elderly patients undergoing HHA was significantly higher in the cemented group than in the non-cemented group.

Hospital and Patient Characteristics Regarding the Place of Death of Hospitalized Impending Death Patients: A Multilevel Analysis.

Objectives: To explore the influence of hospital and patient characteristics on deaths at home among inpatients facing impending death. Method: In this historical cohort study, 95,626 inpatients facing impending death from 362 hospitals in 2011 were recruited. The dependent variable was the place of death. The independent variables were the characteristics of the hospitals and the patients. A two-level hierarchical generalized linear model was used. Results: In total, 41.06% of subjects died at home. The hospital characteristics contributed to 29.25% of the total variation of the place of death. Private hospitals (odds ratio [OR] = 1.32, 95% confidence interval [CI] = 1.00-1.75), patients >65 years old (OR = 1.48, 95% CI. = 1.42-1.54), married (OR = 3.15, 95% CI. = 2.93-3.40) or widowed (OR = 3.39, 95% CI. = 3.12-3.67), from near-poor households (OR = 5.16, 95% CI. = 4.57-5.84), having diabetes mellitus (OR = 1.79, 95% CI. = 1.65-1.94), and living in a subcounty (OR = 2.27, 95% CI. = 2.16-2.38) were all risk factors for a death at home. Conclusion: Both hospital and patient characteristics have an effect of deaths at home among inpatients facing impending death. The value of the inpatient mortality rate as a major index of hospital accreditation should be interpreted intrinsically with the rate of deaths at home.

Mental Disabilities Increase the Risk of Respiratory Infection-related Healthcare Utilization.

Patients with chronic mental illness are highly vulnerable to chronic respiratory problems. We examined the influence of mental disability on respiratory infection-related utilization risk in individuals with and without mental disabilities. A population-based, retrospective cohort design and two-part model were used to analyze respiratory infection-related utilization in individuals with MDs (MD group) and a matched reference group. The respiratory infection-related utilization rate in one year was lower in the MD group (53.8%) than in the reference group (56.6%). The odds ratios (ORs) were significantly higher among individuals with profound MDs (aOR = 1.10; 95% CI 1.07-1.14) and those with a history of dental cavities (aOR = 1.16; 95% CI: 1.13-1.19) or periodontal disease (aOR = 1.22; 95% CI: 1.19-1.26) after controlling for covariables. The average number of visits was higher in the MD group (5.3) than in the reference group (4.0). The respiratory infection-related utilization rate and average number of visits were significantly higher in the mild, moderate and severe disabled groups with a history of periodontal disease, respectively, than that of the reference group. In conclusion, healthcare authorities must develop an incentive program to prevent respiratory infections among individuals with MDs.

A practical thrice weekly ertapenem in hemodialysis patients.

Change of ertapenem dosage from 500 mg daily to thrice weekly after each hemodialysis session can maintain the plasma concentration above 2 mg/L, and be practical in hemodialysis patients.

Association between continuity of care and emergency department visits and hospitalization in senior adults with asthma-COPD overlap.

OBJECTIVE: To investigate associations between continuity of care (COC) and emergency department (ED) visits and hospitalization for chronic obstructive pulmonary disease (COPD) or asthma among elderly adults with asthma-COPD overlap (ACO). METHODS: A retrospective cohort study was performed using the Taiwan National Health Insurance research database. A total of 1141 ACO patients aged ≥65 years during 2005-2011 were observed and followed for 2 years. The Bice and Boxerman COC index (COCI) was used to evaluate COC by considering ambulatory care visits duo to COPD or asthma in the first year; ED visits and hospitalization for COPD or asthma were identified in the subsequent year, respectively. The COCI was divided into three levels (COCI < 0.3= low, 0.3 ≤ COCI<1=medium, COCI = 1=high). The Cox model was used to estimate the hazard ratio (HR) for ED visits and hospital admissions due to COPD or asthma. RESULTS: The average COCI was 0.55. 21.3% patients received outpatient care from a single physician. Compared to patients with high COC, those with low and medium COC had a higher risk of ED visits (aHR = 2.80 and 2.69, P < .01) and admissions (aHR = 1.80 and 1.72, P < .05). CONCLUSION: Increasing COC is beneficial for elderly patients with ACO in disease management. Policymakers could create effective pay-for-performance programs for the elderly ACO population to enhance COC and improve care outcomes.

Risk of suicide according to the level of psychiatric contact in the older people: Analysis of national health insurance databases in Taiwan.

PURPOSE: Suicide in the older people is a serious problem worldwide; however the effect of psychiatric contact on the risk of suicide has not been fully explored. The aim of this study was to investigate the relationship between psychiatric contact and suicide in the older people in Taiwan. METHODS: A population-based database was used in this national case-control study. Propensity score matching was used to match older people who did and did not commit suicide from 2010 to 2012 by calendar year, gender, age, and area of residence. The level of psychiatric contact in the preceding year was classified as "no psychiatric contact," "only outpatient psychiatric contact," "psychiatric emergency room contact," or "psychiatric hospital admission". Conditional logistic regression analysis was used to assess associations between variables and the risk of suicide. RESULTS: A total of 2528 older people committed suicide from 2010 to 2012, with a crude suicide mortality rate of 3.37/10,000. Compared to those who had no psychiatric contact in the preceding year, the adjusted odds ratios of suicide were 10.15 (95% CI=5.8-17.7) for those who had psychiatric emergency room contact, 6.57 (95% CI=3.7-11.6) for those who had psychiatric hospital admissions, and 3.64 (95% CI=3.0-4.4) for those with only outpatient psychiatric contact. The risk of suicide was higher in those who had depression (OR=3.49, 95% CI=2.2-5.4) and bipolar disorder (OR=1.98, 95% CI=1.1-3.6). Patients with cancer were associated with suicide (OR=8.96, 95% CI=5.6-14.4). CONCLUSIONS: The positive association with suicide and the level of psychiatric contact in the preceding year in older people indicated that the health personnel need to do a better job in determining possible risk for older people who had psychiatric contact, especially in emergency visit or psychiatric admission. A systematic approach to quality improvement in these settings is both available and necessary. Careful discharge planning and safe transitions of care to outpatient services are required for suicide prevention of high-risk patients after discharge.

TGF-ß/Smad3 signalling regulates the transition of bone marrow-derived macrophages into myofibroblasts during tissue fibrosis.

Myofibroblasts are a main cell-type of collagen-producing cells during tissue fibrosis, but their origins remains controversial. While bone marrow-derived myofibroblasts in renal fibrosis has been reported, the cell origin and mechanisms regulating their transition into myofibroblasts remain undefined. In the present study, cell lineage tracing studies by adoptive transfer of GFP+ or dye-labelled macrophages identified that monocyte/macrophages from bone marrow can give rise to myofibroblasts via the process of macrophage-myofibroblast transition (MMT) in a mouse model of unilateral ureteric obstruction. The MMT cells were a major source of collagen-producing fibroblasts in the fibrosing kidney, accounting for more than 60% of α-SMA+ myofibroblasts. The MMT process occurred predominantly within M2-type macrophages and was regulated by TGF-ß/Smad3 signalling as deletion of Smad3 in the bone marrow compartment of GFP+ chimeric mice prevented the M2 macrophage transition into the MMT cells and progressive renal fibrosis. In vitro studies in Smad3 null bone marrow macrophages also showed that Smad3 was required for TGF-ß1-induced MMT and collagen production. In conclusion, we have demonstrated that bone marrow-derived fibroblasts originate from the monocyte/macrophage population via a process of MMT. This process contributes to progressive renal tissue fibrosis and is regulated by TGF-ß/Smad3 signalling.

Evaluation of care quality for disabled older patients living at home and in institutions.

AIMS AND OBJECTIVES: This study aimed to evaluate the level of care quality received by disabled older patients residing at home vs. those residing in institutions. BACKGROUND: Taiwan has an aging society and faces issues of caring for disabled older patients, including increasing needs, insufficient resources and a higher economic burden of care. DESIGN: Retrospective study extracting patient data from Taiwan's National Health Insurance database. METHODS: We enrolled 76,672 disabled older patients aged 65 years and older who resided at home or institutions and had submitted claims for coverage of National Health Insurance for home care received for the first time between 2004-2006. Propensity score matching was applied to create a home-care group and an institutional-care group with 27,894 patients each. Indicators of care quality (emergency services use, hospitalisation, infection, pressure ulcers, death) within the first year were observed. RESULTS: The home care group had significantly higher emergency services use, fewer hospital admissions and fewer infections, but had significantly higher occurrence of pressure ulcers. The institutional-care group had significantly lower time intervals between emergencies, fewer deaths, lower risk of emergencies and lower pressure ulcer risk. Males had significantly higher emergency services use than females, and higher risk of hospital admission and death. CONCLUSIONS: Care quality indicators for elder care are significantly different between home care and institutional care. The quality of home care is associated with higher emergency services use and pressure ulcer development, and institutional care is associated with number of infections and hospitalisations. RELEVANCE TO CLINICAL PRACTICE: Care quality indicators were significantly different between home-care and institutional-care groups and were closely associated with the characteristics of individual patients' in the specific settings. Nursing capabilities must be directed towards reducing unnecessary care quality-related events among high-risk disabled older patients.

Characteristics and 3-year mortality and infection rates among incident hemodialysis patients with a permanent catheter undergoing a first vascular access conversion.

BACKGROUND: Although vascular access conversions to arteriovenous fistula (AVF)/arteriovenous graft (AVG) in incident and maintenance hemodialysis (HD) patients are reported to be associated with lower mortality and infection risk, it is unclear whether these effects are limited to the first year. The aims of this historical cohort study were to investigate patient characteristics of vascular access conversion and the impact of vascular access conversion on 1- and 3-year mortality and infection rates in incident HD patients with a permanent catheter to initiate HD. METHODS: Our study included 868 incident patients who underwent HD for at least 3 months and who, between January 1, 2004 and December 31, 2006, received a permanent catheter within 3 days of starting HD. The effects of vascular access conversion on rates of infection and mortality during the subsequent 3 years were assessed using claims data from the National Health Insurance Program in Taiwan. RESULTS: Factors associated with lower 1- and 3-year mortality and infection rates were a first vascular access converted to AVF or AVG, female gender, age <65 years, and the presence of a lower Romano-Charlson comorbidity index score (P < 0.05). Patients who received an AVF/AVG at hospitals which perform a high number of vascular access procedures annually had lower 3-year infection rates. CONCLUSION: The lower mortality and infection rates also extended throughout the 3-year period in incident patients starting HD with a permanent catheter to receiving vascular access conversion to AVF (Hazard ratio [HR] 0.47, 95 % CI 0.32-0.67, P < 0.0001) and AVG (HR 0.51, 95 % CI 0.27-0.99, P < 0.05).

Progression in comorbidity before hemodialysis initiation is a valuable predictor of survival in incident patients.

BACKGROUND: Most studies investigate the association between the baseline Romano-Charlson comorbidity index (CCI) and survival on hemodialysis (HD). Few consider the effect of progression in the CCI score (CCIp) on patient survival before HD initiation. That is CCIp = CCI-1 - CCI-3, where CCI(-1) is the CCI score in the first year before HD initiation, and CCI-3 is the CCI score in the third year before HD initiation. The present study investigated whether CCIp affects the survival of incident HD patients. METHODS: Using the National Health Insurance (NHI) Research Database of Taiwan, we recruited 7391 adult incident HD patients in the year 2006 for this historical cohort study. We followed the cohort until the end of 2007. Using the Romano-Charlson method, each comorbidity was assigned a score of 1, 2, 3 or 6. The scores were then summed to produce a total score (CCI), which predicts mortality. The log-rank test and a Cox regression model were used to analyze the association between CCIp and survival, and the risk markers of survival. RESULTS: Diabetes, ulcers, congestive heart failure, chronic pulmonary disease and cerebrovascular disease were the most common comorbid conditions. The median CCI-3 was 2 (interquartile range 0-3). The overall survival rate in 1 year was 82.8%. In incident patients with a CCI-3 score of <3, the rate was 85.1%, and in patients with a CCI-3 score of ≥ 3, the rate was 76.8%. Each increase of one point in the CCI-3 score (HR = 1.69, 95% CI 1.42-2.01) and the CCIp (HR = 1.22, 95% CI 1.17-1.27) affected survival in HD patients. CONCLUSIONS: The CCI-3 and CCIp before HD initiation are valuable predictors of survival in incident patients.

Impact of thyroid dysfunction on erythropoietin dosage in hemodialysis patients.

BACKGROUND: Although thyroid diseases exist in patients with renal failure, thyroid function tests are not routine tests in patients on chronic hemodialysis (HD). Therefore, the impact of thyroid diseases on erythropoietin (EPO) dosage in HD patients is not well defined. This study evaluated the relationship between the dose of EPO and the presence or absence of thyroid dysfunction in HD patients. METHODS: This study included 1013 adult patients on HD who did not have a malignancy, liver cirrhosis, thalassemia, iron deficiency, gastrointestinal bleeding, or a major operation within 6 months. Patients were characterized as being euthyroid, or having the sick euthyroid syndrome, primary hypothyroidism, subclinical hypothyroidism, hyperthyroidism, or subclinical hyperthyroidism based on thyroid function tests. Routine biochemistry profiles including an index of the efficiency of HD, along with clinical data over the previous 6-month period, were collected and analyzed. Multiple regression models were employed to assess the relationship between the dose of EPO and the presence or absence of thyroid status. RESULTS: The mean monthly EPO dosages were 77.7±37.0, 70.2±40.6, 90.8±68.4, 78.5±46.7, and 82.3±41.2 µg, respectively, in the sick euthyroid syndrome, euthyroid patients, hypothyroidism, subclinical hypothyroidism, and subclinical hyperthyroidism groups (p<0.05). After adjustment of all other variables in multiple regression, the mean monthly EPO dosage was 19.00±8.59 µg more in hypothyroid patients compared with euthyroid patients (p=0.027). Further, considering an interaction with the presence of diabetes, the mean monthly EPO dosage in patients with either hypothyroidism or subclinical hypothyroidism and diabetes was 54.66±17.12 µg (p=0.001) and 31.51±10.38 µg more than that of euthyroid patients, respectively (p=0.002). CONCLUSIONS: In HD patients, the EPO dosage required to maintain the target hemoglobin level is significantly higher in patients having both hypothyroidism or subclinical hypothyroidism and diabetes than in euthyroid patients.

Severe proteinuria secondary to amyloidosis requiring bilateral renal artery embolization.

In the case reported here, after prolonged medical therapy resistance, severe proteinuria subsided following bilateral renal artery embolization (RAE). Thereafter, respiratory distress, anasarca edema, muscle mass, and serum albumin level improved after regular hemodialysis. Although RAE is reported to be a safe and effective therapeutic procedure, it is rarely used for severe proteinuria with prolonged medical therapy resistance. The limited use of bilateral RAE for nephrological purposes may be partly related to its tendency to destroy renal function, which results in anuria and subsequent regular dialysis. However, delayed RAE could cause the patient to reach a life-threatening cachexic state and could increase the risk of morbidity and mortality due to severe proteinuria-induced hypoalbuminemia. Our case and selected previous reports reveal important information for physicians and patients while discussing prognoses and considering the pros and cons of bilateral RAE.

Conditioned mesenchymal stem cells attenuate progression of chronic kidney disease through inhibition of epithelial-to-mesenchymal transition and immune modulation.

Mesenchymal stem cells (MSCs) have been shown to improve the outcome of acute renal injury models; but whether MSCs can delay renal failure in chronic kidney disease (CKD) remains unclear. In the present study, the were cultured in media containing various concentrations of basic fibroblast growth factor, epidermal growth factor and ascorbic acid 2-phosphate to investigate whether hepatocyte growth factor (HGF) secretion could be increased by the stimulation of these growth factors. Then, TGF-ß1-treated renal interstitial fibroblast (NRK-49F), renal proximal tubular cells (NRK-52E) and podocytes were co-cultured with conditioned MSCs in the absence or presence of ascorbic acid 2-phosphate to quantify the protective effects of conditioned MSCs on renal cells. Moreover, male Sprague-Dawley rats were treated with 1 × 10(6) conditioned MSCs immediately after 5/6 nephrectomy and every other week through the tail vein for 14 weeks. It was found that basic fibroblast growth factor, epidermal growth factor and ascorbic acid 2-phosphate promoted HGF secretion in MSCs. Besides, conditioned MSCs were found to be protective against TGF-ß1 induced epithelial-to-mesenchymal transition of NRK-52E and activation of NRK-49F cells. Furthermore, conditioned MSCs protected podocytes from TGF-ß1-induced loss of synaptopodin, fibronectin induction, cell death and apoptosis. Rats transplanted with conditioned human MSCs had a significantly increase in creatinine clearance rate, decrease in glomerulosclerosis, interstitial fibrosis and increase in CD4(+)CD25(+)Foxp3(+) regulatory T cells counts in splenocytes. Together, our studies indicated that conditioned MSCs preserve renal function by their anti-fibrotic and anti-inflammatory effects. Transplantation of conditioned MSCs may be useful in treating CKD.

Peritoneal dialysis as compared with hemodialysis is associated with higher overhydration but non-inferior blood pressure control and heart function.

BACKGROUND/AIMS: Fluid overload is an important factor causing cardiovascular complications in dialysis patients. We compared fluid status, blood pressure (BP) and heart function between peritoneal dialysis (PD) patients and hemodialysis (HD) patients. METHODS: We recruited 94 PD and 75 HD patients in our hospital. Fluid status was assessed by bioimpedance spectroscopy. Home BP was recorded. Use of antihypertensives was retrieved by chart review. In each group, 39 patients received echocardiographic examinations. RESULTS: PD patients' fluid status was similar to that of predialysis HD patients. PD patients had lower systolic BP. E/E' and left ventricular mass index (LVMI) showed no significant intergroup difference. In multiple linear regression analyses, overhydration (OH)/extracellular water ratio >0.15 was associated with higher systolic BP, E/E' and LVMI. CONCLUSIONS: While PD was associated with higher OH but non-inferior BP control and heart function, OH was indeed related to poor BP control, diastolic dysfunction and left ventricular hypertrophy.

Essential trace element status and clinical outcomes in long-term dialysis patients: a two-year prospective observational cohort study.

BACKGROUND & AIMS: Essential trace elements are involved in many biological processes for normal cell function including immunological defense against oxidation and infection. Deficiency of these elements generally leads to illness or even death in the general population. Therefore, we investigated the predictive values of trace element status on clinical outcomes in dialysis patients, who are more prone to trace element deficiency. METHODS: We enrolled 111 prevalent patients on maintenance dialysis from a Taipei tertiary-care referral hospital and measured serum levels of selenium, copper, and zinc. Patients were followed for 2 years or until death or withdrawal. RESULTS: Multivariate Cox regression analysis indicated that patients with diabetes mellitus (HR, 2.162 [95% CI, 1.105-4.232], p=0.024), prior stroke (HR, 3.876 [95% CI, 1.136-13.221], p=0.030), and zinc deficiency (HR, 0.979 [95% CI, 0.966-0.992], p=0.002) were more likely to be hospitalized for infectious diseases. Furthermore, beyond traditional risk factors, such as old age and hypoalbuminemia, multivariate Cox regression also indicated that lower serum level of zinc independently predicts overall mortality (HR, 0.973 [95% CI, 0.948-0.999], p=0.046). CONCLUSIONS: In long-term dialysis patients, the serum level of zinc was an independent predictor of future hospitalization due to infectious diseases and of overall mortality.