AST-120 improved uremic pruritus by lowering indoxyl sulfate and inflammatory cytokines in hemodialysis patients.

BACKGROUND AND HYPOTHESIS: Pruritus is a common and distressing symptom that affects patients with chronic kidney disease. The concentration of protein bounded uremic toxin was associated with the uremic pruritus. The aim is to assess the efficacy of AST-120 for uremic pruritus in hemodialysis patients. MATERIALS AND METHODS: The participants were enrolled and then divided into the AST-120 treatment group and control group with a ratio of 2:1. All participants underwent pre-observation screenings two weeks before the study with three visits. In the treatment phase (week 1 to week 4), the treatment group added 6g/day of AST-120 along with routine anti-pruritic treatment. Visual analog scale (VAS) and biochemical parameters were measured. RESULTS: The VAS score began to be lower in the AST-120 treatment group after the 5th visiting (p < 0.05). The reduction in indoxyl sulfate (IS) at 5th week along with TNF-alpha. The reduction ratio of indoxyl sulfate correlated with reduction of parathyroid hormone. CONCLUSION: This study has demonstrated that the four-week treatment of AST-120 decreased the severity of uremic pruritus in patients with ESRD. The concentration of IS and TNF-alpha decreased in the AST-120 treatment group. The reduction of iPTH correlated with the reduction of IS in the AST-120 treatment.

Human Poisoning with Chlorpyrifos and Cypermethrin Pesticide Mixture: Assessment of Clinical Outcome of Cases Admitted in a Tertiary Care Hospital in Taiwan.

Background and Purpose: There is an overall paucity of data regarding the human toxicity of chlorpyrifos and cypermethrin pesticide mixture. Both organophosphate and pyrethroid insecticides are metabolized by carboxylesterases. Thus, its pesticide combination, organophosphates may boost the toxicity of pyrethroids via inhibited its detoxification by carboxylesterases. This study examined the clinical course, laboratory tests, and outcomes of patients with chlorpyrifos, cypermethrin or their pesticide mixture poisoning, and to determine what association, if any, might exist between these findings. Patients and Methods: Between 2000 and 2021, 121 patients poisoned with chlorpyrifos, cypermethrin, or their pesticide mixture were treated at Chang Gung Memorial Hospital. Patients were categorized as chlorpyrifos (n=82), cypermethrin (n=27) or chlorpyrifos and cypermethrin (n=12) groups. Demographic, clinical, laboratory and mortality data were collected for analysis. Results: The patients experienced a broad range of clinical symptoms, including aspiration pneumonia (44.6%), salivation (42.5%), acute respiratory failure (41.3%), acute kidney injury (13.9%), seizures (7.5%), hypotension (2.6%), etc. Leukocytosis (12,700±6600 /uL) and elevated serum C-reactive protein level (36.8±50.4 mg/L) were common. The acute respiratory failure rate was 41.3%, comprising 48.8% in chlorpyrifos, 11.1% in cypermethrin as well as 58.3% in chlorpyrifos and cypermethrin poisoning. Patients with chlorpyrifos and cypermethrin pesticide mixture poisoning suffered higher rates of acute respiratory failure (P=0.001) and salivation (P=0.001), but lower Glasgow Coma Scale score (P=0.011) and serum cholinesterase level (P<0.001) than other groups. A total of 17 (14.0%) patients expired. The mortality rate was 14.0%, including 17.1% in chlorpyrifos, 3.7% in cypermethrin as well as 16.7% in chlorpyrifos and cypermethrin poisoning. No significant differences in mortality rate were noted (P=0.214). Conclusion: Chlorpyrifos pesticide accounted for the major toxicity of the pesticide mixture. While the data show a higher rate of respiratory failure in the chlorpyrifos and cypermethrin pesticide mixture group than others, other measures of toxicity such as mortality and length of stay were not increased.

Hungry bone syndrome in peritoneal dialysis patients after parathyroid surgery.

Secondary hyperparathyroidism (SHPT) is a common complication of end-stage kidney disease (ESKD). Hungry bone syndrome (HBS) occurs frequently in patients on maintenance dialysis receiving parathyroidectomy for refractory SHPT. However, there is scanty study investigating the clinical risk factors that predict postoperative HBS, and its outcome in peritoneal dialysis (PD) patients. We conducted a single-center retrospective study to analyze 66 PD patients who had undergone parathyroidectomy for secondary hyperparathyroidism at Chang Gung Memorial Hospital between 2009 and 2019. The patients were stratified into two groups based on the presence (n=47) or absence (n=19) of HBS after parathyroidectomy. Subtotal parathyroidectomy was the most common surgery performed (74.2%), followed by total parathyroidectomy with autoimplantation (25.8%). Pathological examination of all surgical specimens revealed parathyroid hyperplasia (100%). Patients with HBS had lower levels of postoperative nadir corrected calcium, higher alkaline phosphate (ALP), and higher potassium levels compared with patients without HBS (all P<0.05). A multivariate logistic regression model confirmed that lower preoperative serum calcium level (OR 0.354, 95% CI 0.133-0.940, P=0.037), higher ALP (OR 1.026, 95% CI 1.008-1.044, P=0.004), and higher potassium level (OR 6.894, 95% CI 1.806-26.317, P=0.005) were associated with HBS after parathyroidectomy. Patients were followed for 58.2±30.8 months after the surgery. There was no significant difference between HBS and non-HBS groups in persistence (P=0.496) or recurrence (P=1.000) of hyperparathyroidism. The overall mortality rate was 10.6% with no significant difference found between both groups (P=0.099). We concluded that HBS is a common complication (71.2%) of parathyroidectomy for SHPT and should be managed appropriately.

Clinical Benefits of Laparoscopic Adhesiolysis during Peritoneal Dialysis Catheter Insertion: A Single-Center Experience.

Background and Objectives: In peritoneal dialysis (PD) therapy, intra-abdominal adhesions (IAAs) can cause catheter insertion failure, poor dialysis function, and decreased PD adequacy. Unfortunately, IAAs are not readily visible to currently available imaging methods. The laparoscopic approach for inserting PD catheters enables direct visualization of IAAs and simultaneously performs adhesiolysis. However, a limited number of studies have investigated the benefit/risk profile of laparoscopic adhesiolysis in patients receiving PD catheter placement. This retrospective study aimed to address this issue. Materials and Methods: This study enrolled 440 patients who received laparoscopic PD catheter insertion at our hospital between January 2013 and May 2020. Adhesiolysis was performed in all cases with IAA identified via laparoscopy. We retrospectively reviewed data, including clinical characteristics, operative details, and PD-related clinical outcomes. Results: These patients were classified into the adhesiolysis group (n = 47) and the non-IAA group (n = 393). The clinical characteristics and operative details had no remarkable between-group differences, except the percentage of prior abdominal operation history was higher and the median operative time was longer in the adhesiolysis group. PD-related clinical outcomes, including incidence rate of mechanical obstruction, PD adequacy (Kt/V urea and weekly creatinine clearance), and overall catheter survival, were all comparable between the adhesiolysis and non-IAA groups. None of the patients in the adhesiolysis group suffered adhesiolysis-related complications. Conclusions: Laparoscopic adhesiolysis in patients with IAA confers clinical benefits in achieving PD-related outcomes comparable to those without IAA. It is a safe and reasonable approach. Our findings provide new evidence to support the benefits of this laparoscopic approach, especially in patients with a risk of IAAs.

Human Poisoning with Methomyl and Cypermethrin Pesticide Mixture.

There is limited literature analyzing the outcome of human poisoning with methomyl and cypermethrin pesticide mixture. Between 2002 and 2018, a total of 63 patients intoxicated with methomyl, cypermethrin, or their pesticide mixture were treated at Chang Gung Memorial Hospital. The patients were categorized into three groups based on the type of pesticide, as methomyl (n = 10), cypermethrin (n = 31), or methomyl and cypermethrin (n = 22). Demographic, clinical, laboratory, and mortality data were obtained for analysis. The patients were aged 54.9 ± 18.9 years. Following ingestion, the patients experienced a wide range of clinical symptoms, including aspiration pneumonia (50.8%), acute respiratory failure (41.3%), acute kidney injury (33.3%), multiple organ failure (19.0%), emesis (19.0%), acute hepatitis (12.7%), diarrhea (7.9%), seizures (4.8%), lacrimation (4.8%), etc. After analysis, it was found that patients with methomyl and cypermethrin poisoning suffered higher incidences of acute respiratory failure (p < 0.001), aspiration pneumonia (p = 0.004), acute kidney injury (p = 0.011), and multiple organ failure (p < 0.001) than the other groups. Laboratory analyses revealed that patients with methomyl and cypermethrin poisoning had a higher creatinine level (p = 0.011), white blood cell count (p < 0.001), and neutrophil count (p = 0.019) than the other groups. A total of seven (11.1%) patients died. The average duration of hospitalization was 9.8 ± 10.0 days. In a multivariate logistic regression model, it was revealed that methomyl pesticide (p = 0.045) or methomyl and cypermethrin pesticide mixture (p = 0.013) were significant risk factors for acute respiratory failure. Nevertheless, no mortality risk factor could be identified. Therefore, the analytical results suggest that methomyl pesticide is the major contributor to the toxicity of methomyl and cypermethrin pesticide mixture poisoning. More research is needed.

Tuberculous peritonitis in patients on peritoneal dialysis: a 35-year experience from a large medical center in Northern Taiwan.

INTRODUCTION: Tuberculous peritonitis (TBP) is a rare but fatal complication in patients on peritoneal dialysis (PD). In this study, we aimed to determine the demographic features, clinical features, laboratory parameters, and clinical outcomes of PD patients with TBP and to clarify possible risk factors for mortality. MATERIALS AND METHODS: We retrospectively reviewed 2084 PD patients from January 1985 to December 2019. The diagnosis of TBP was established by positive peritoneal fluid culture for Mycobacterium tuberculosis. RESULTS: 18 patients were diagnosed with TBP. The incidence was 2.029 episodes per 1000 patient-years. The most common symptom was fever (94.4%), followed by cloudy effluent (83.3%) and abdominal pain (83.3%). The average peritoneal dialysis effluent (PDE) white blood cell (WBC) count was 172.7 cells/µL. Nine patients (50%) had WBC counts lower than 100 cells/µL and 13 patients (72.2%) had neutrophilic predominant WBC counts. Acid fast stain (AFS) was positive in 7 patients (38.9%). Only 2 patients (11.1%) continued with PD after TB infection, while 10 patients (55.6%) changed to hemodialysis. Seven patients (38.9%) died within 1 year. Significant differences were observed in sex (p = 0.040), the presence of diabetes mellitus (p = 0.024), and PD catheter removal (p < 0.001) between TBP patients with and without mortality. However, none of them was a significant factor for 1-year mortality in multivariate Cox regression model. CONCLUSION: Physicians should pay attention to the unusual presentations of peritonitis, especially if symptoms include fever or an initial low PDE WBC count. Catheter removal is not mandatory if early diagnosis and appropriate therapy are available.

Family Caregivers' Experiences of Preventing Harm to Older People during Hospitalization: A Phenomenographic Study.

Hospital admission is associated with a high risk of harm, particularly for older people, and family members play a critical role in providing care. The aim of this study was to explore family caregivers' experiences in preventing harm to older people during hospitalization. The phenomenographic approach was applied. Thirty family caregivers were asked to describe their experiences of preventing harm to older people. Semi-structured interviews were audiotaped and transcribed. Participants described preventing harm as "essential care", "an important step toward recovery", "a load off the mind", "outcomes of collaboration among caregivers and health professionals", and "improvement in the quality of life after discharge". The core theme was to achieve the goal of integrated care for older people. The results can help improve caregiving processes and prevent harm to older people during hospitalizations. They can assist in developing strategies for the delivery of safe care for older people.

Ultrafiltration in patients on automated peritoneal dialysis with Homechoice Claria connected to Sharesource: A pilot study.

INTRODUCTION: Fluid overload is an unavoidable problem in patients on peritoneal dialysis (PD) and is associated with poor outcomes. The aim of our study was to estimate ultrafiltration (UF) under different dextrose concentrations (DCs) and four peritoneal transport levels. MATERIALS AND METHODS: 70 patients, with a total of 1,848 daily treatment records and 8,266 single dwells on automated PD (APD) through Homechoice Claria with Sharesource were followed in October 2020 and categorized into two groups according to the DC (D1.5% and D2.5% groups). Baseline characteristics, peritoneal membrane characteristics, and daily PD treatment records from Sharesource were obtained. We compared UF under the different conditions. RESULTS: The mean night UF per cycle, the mean night UF corrected by fill volume (FV) per cycle, and the mean night UF corrected by FV and dwelling time (DT) per cycle were all significantly higher in the D2.5% group than in the D1.5% group (95.8 vs. 220.3 mL, 5.5 vs. 12.0%, and 5.0 vs. 11.6 0/000/minutes, all p < 0.001). However, there was no significant difference among the four transport categories in any group. CONCLUSION: This retrospective study presents precise UF measurements with two solutions at different DCs and four peritoneal transport levels. With a 2-L indwell (DT ranging from ~ 1 to 3 hours), the mean net UF rate was 1.0 mL/min in the D1.5% group and 2.3 mL/min in the D2.5% group.

Hemodialysis Treatment for Patients with Lithium Poisoning.

BACKGROUND: Hemodialysis is often recommended to treat severe lithium poisoning. Nevertheless, the application rate of hemodialysis in patients with lithium poisoning is varied across different groups and the effect of hemodialysis is still undetermined. Therefore, this study aimed to analyze the hemodialysis rate of patients with lithium poisoning and to explore the clinical features of lithium-poisoned-patients treated or untreated with hemodialysis. METHODS: Between 2001 and 2019, 36 patients treated at the Chang Gung Memorial Hospital for the management of lithium poisoning were stratified according to whether they were treated with hemodialysis (n = 7) or not (n = 29). RESULTS: The patients were aged 50.7 ± 18.1 years. The poisoning patterns were acute on chronic (61.1%), chronic (25.0%) and acute (13.9%). The precipitating factors of dehydration and infection were noted in 36.1% and 25.0% of patients, respectively. Bipolar disorder (72.2%), depressive disorder (27.8%) and psychotic disorder (11.1%) were the top three psychiatric comorbidities. The hemodialysis group not only had a lower Glasgow Coma Scale (GCS) score (p = 0.001) but also had a higher respiratory failure rate (p = 0.033), aspiration pneumonia rate (p = 0.033) and acute kidney injury network (AKIN) score (p = 0.002) than the non-hemodialysis group. Although none of the patients died of lithium poisoning, the hemodialysis group required more endotracheal intubation (p = 0.033), more intensive care unit admission (p = 0.033) and longer hospitalization (p = 0.007) than the non-hemodialysis group. CONCLUSION: The analytical results revealed zero mortality rate and low hemodialysis rate (1.9%). Compared with patients without hemodialysis, patients receiving hemodialysis suffered severer lithium-associated complications and needed a more intensive care unit admission and longer hospital stay.

Intelligent and thermo-responsive Au-pluronic® F127 nanocapsules for Raman-enhancing detection of biomolecules.

Thermo-responsive Raman-enhanced nanocapsules were successfully fabricated by Pluronic® F127 (F127) decorated with gold nanoparticles (AuNPs) for surface-enhanced Raman scattering (SERS) detection of biomolecules. F127 nanocapsules changes from hydrophilicity (swelling) to hydrophobicity (de-swelling) when the temperature increases from 15 °C to 37 °C, owing to the lower critical solution temperature (LCST) of F127 is about 26.5 °C. The size of nanocapsules would be enormous shrinking from 160 nm to 20 nm, resulting in a significant decrease in the distance between AuNPs to enhance hot spot effect, which increases the sensitivity of SERS detection. Based on the thermo-sensitive behavior, the ratio of AuNPs and F127 would be manipulated to find the optimal SERS enhancement effect. SERS nanocapsules can rapidly detect biomolecules (adenine and R6G) with limit of detection (LOD) lower than 10-6 M. In addition, the relatively difficult to detect clinical samples, carboxyl-terminal parathyroid hormone fragments (C-PTH), can also be measured by the thermo-responsive SERS nanocapsules developed in this work. It is expected the biomolecules can be adsorbed at low temperature (15 °C), as well as collected and concentrated at high temperature (37 °C) for SERS detection, to increase the sensitivity and stability of SERS detection.

Blood Aluminum Levels in Patients with Hemodialysis and Peritoneal Dialysis.

Background. This retrospective observational study attempted to examine the prevalence of abnormal blood aluminum levels in dialysis patients, and to explore the association of pathogenic factors, such as demographic, clinical, laboratory as well as the use of phosphate binding drugs, drugs for secondary hyperparathyroidism and erythropoiesis-stimulating drugs with the blood aluminum levels. Methods. The study included 1175 patients (874 hemodialysis and 301 peritoneal dialysis), recruited from Chang Gung Memorial Hospital in November 2020. Patients were stratified into two groups by their blood aluminum levels, as normal (<2 µg/dL, n = 1150) or abnormal (≥2 µg/dL, n = 25). Results. The patients aged 60.4 ± 13.2 years and were dialyzed for 8.6 ± 8.1 years. The average blood aluminum level was 1.0 ± 0.4 µg/dL. Patients with abnormal blood aluminum levels received more sevelamer than patients with normal blood aluminum level (p = 0.014). Patients with abnormal blood aluminum levels had higher platelet count (p = 0.001), triglyceride (p < 0.001) and total iron binding capacity (p = 0.003) than patients with normal blood aluminum levels. Moreover, the cardiothoracic ratio was higher in patients with abnormal blood aluminum levels than patients with normal blood aluminum levels (p = 0.003). Conclusions. The prevalence of abnormal blood aluminum levels was low at 2.2%. Nevertheless, the linking of cardiothoracic ratio of more than 0.5 as well as elevated blood platelet count and triglyceride level with blood aluminum levels are interesting, and warranted more researches in this area.

Interleukin-17A induces renal fibrosis through the ERK and Smad signaling pathways.

Interleukin (IL)-17A is upregulated in several renal diseases and plays a crucial role in renal inflammation. However, it remains unclear how IL-17A contributes to renal fibrosis. Our result demonstrated that IL-17A expression was upregulated in the obstructed kidney of unilateral ureter obstruction (UUO) mice when compared to the contralateral control kidney. Inhibition of IL-17A functions by the intravenous administration of an anti-IL-17A receptor antibody (100 µg) 2 h prior to UUO and on post-UUO day 1 and 3 significantly reduced fibronectin expression in the UUO kidney. The addition of IL-17A (25-100 µg) to human renal proximal tubular cells or renal fibroblasts caused an increase in fibronectin production and extracellular signal-regulated kinase (ERK)1/2 activation, which were reduced upon pretreatment with the ERK inhibitor U0126. The level of phosphorylated (p)-ERK1/2 was increased in the UUO kidney, but reduced by the administration of the anti-IL-17A receptor antibody, verifying the importance of the ERK pathway in vivo. TGF-ß1 mRNA expression and protein were increased in the UUO kidney and in IL-17A-stimulated cultured cells. The administration of an anti-TGF-ß1 neutralizing antibody or TGF-ß1 receptor I inhibitor (SB431542) to cells abrogated the IL-17A-mediated increase of fibronectin production. IL-17A induced an increase in p-Smad2 and p-Smad3 expression at 7.5 min and 24 h and pretreatment with the anti-TGF-ß1 neutralizing antibody, and SB431542 reduced the IL-17A-stimulated increase of p-Smad2. Knockdown of Smad2 or Smad3 expression inhibited the IL-17A-enhanced production of fibronectin. These results suggest an essential role for the TGF-ß/Smad pathway in the IL-17A-mediated increase of fibronectin production. This study demonstrates that IL-17A contributes to the production of extracellular matrix, and targeting its associated signaling pathways could provide a therapeutic target for preventing renal fibrosis.

High anti-neutrophil cytoplasmic antibody titers are associated with the requirement of permanent dialysis in patients with myeloperoxidase-ANCA-associated vasculitis.

BACKGROUND/PURPOSE: A reliable noninvasive prognostic factor of ANCA-associated vasculitis (AAV) is still lacking, but little research has focused on the value of MPO-ANCA titers in patients with active vasculitis. This study explored the prognostic significance of MPO-ANCA titer in active AAV patients. METHODS: Ninety-seven inpatients diagnosed with MPO-ANCA associated vasculitis at Linkou Chang Gung Memorial hospital and Keelung Chang Gung Memorial hospital from January 2005 to December 2016 were enrolled. Serum ANCA titers and basic characteristics of these patients at diagnosis were collected completely Medical records since AAV diagnosis were reviewed to evaluate two years renal and patient outcome. RESULTS: The patients were divided into the two groups according to the median ANCA titers, the more than four times of the normal cut-off value group (high titer group) and the less ANCA titer group (low titer group). The high titer group had significant poor initial renal function (eGFR 16.7 vs 40.7 mL/min/1.73 m2, P = 0.006), and significantly lower two-year renal survival (Log rank P < 0.001). Whereas patient survival (Log rank P = 0.894) was not different The Cox regression models revealed that baseline Birmingham Vasculitis Activity Score, eGFR and a 4-fold increase in ANCA titer were associated with the requirement of permanent dialysis. In the subgroup analysis, the ANCA titer was still an important risk factor for renal outcomes (P = 0.036) in patients with better initial renal function (eGFR≧15 mL/min). CONCLUSION: This study demonstrated that higher MPO-ANCA titers at diagnosis was associated with poor initial renal function and 2-year renal outcomes.

Polyomavirus BK, BKV microRNA, and urinary neutrophil gelatinase-associated lipocalin can be used as potential biomarkers of lupus nephritis.

OBJECTIVE: Lupus nephritis (LN) frequently progresses to end-stage renal disease. Finding a biomarker for LN and a predictor for the development of chronic kidney disease (CKD) is important for patients with systemic lupus erythematosus (SLE). METHODS: Ninety patients with SLE were divided into biopsy-proven LN (n = 54) and no kidney involvement (non-LN) (n = 36) groups and followed up for 54 months. RESULTS: Of 36 patients with LN, 3 (5.6%) had class II disease, 3 (5.6%) had class III, 35 (64.8%) had class IV, 10 (18.5%) had class V, and 3 (5.6%) had class VI (advanced sclerosis). Compared to the non-LN group, patients in the LN group had higher autoimmunity evidenced by a higher proportion of low C3 and C4 levels, positive anti-double-stranded DNA antibody levels, and lower estimated glomerular filtration rates (eGFR). Urinary neutrophil gelatinase-associated lipocalin (uNGAL) levels were significantly higher in the LN group (LN vs non-LN, 670 vs 33 ng/mL, respectively). The patients with LN had a higher urinary polyomavirus BK (BKV) load (3.6 vs 3.0 log copies/mL) and a lower urinary BKV miRNA (miR-B1) 5p level (0.29 vs 0.55 log copies/mL, p = 0.025), while there was no significant difference in the level of miR-B1-3p. Urinary miR-B1-5p level but not urinary BKV load was negatively correlated with uNGAL level (r = -0.22, p = 0.004). At the cutoff value of 80 ng/mL, the receiver operating characteristic curve analysis showed that uNGAL level as a predictor of the presence of LN had a high sensitivity (98%) and specificity (100%) (area under the curve [AUC], 0.997; p < 0.001). During the 54-month follow-up period, 14 (7%) patients with LN and none of the non-LN patients developed CKD. Multivariate Cox regression analysis revealed that baseline uNGAL level was the only predictive factor for CKD development, while baseline serum creatinine level and eGFR were not. CONCLUSION: An elevated urinary BKV viral load with a decreased level of miR-B1 implies the presence of LN. In addition, an increased uNGAL level is a good biomarker not only in predicting the presence of LN but also for prediction of CKD development in patients with SLE.

The value of time-averaged serum high-sensitivity C-reactive protein in prediction of mortality and dropout in peritoneal dialysis patients.

PURPOSE: C-reactive protein (CRP) is a useful biomarker for prediction of long-term outcomes in patients undergoing chronic dialysis. This observational cohort study evaluated whether the time-averaged serum high-sensitivity CRP (HS-CRP) level was a better predictor of clinical outcomes than a single HS-CRP level in patients undergoing peritoneal dialysis (PD). PATIENTS AND METHODS: We classified 335 patients into three tertiles according to the time-averaged serum HS-CRP level and followed up regularly from January 2010 to December 2014. Clinical outcomes such as cardiovascular events, infection episodes, newly developed malignancy, encapsulating peritoneal sclerosis (EPS), dropout (death plus conversion to hemodialysis), and mortality were assessed. RESULTS: During a 5-year follow-up, 164 patients (49.0%) ceased PD; this included 52 patient deaths (15.5%), 100 patients (29.9%) who converted to hemodialysis, and 12 patients (3.6%) who received a kidney transplantation. The Kaplan-Meier survival analysis and log-rank test revealed a significantly worse survival accumulation in patients with high time-average HS-CRP levels. A multivariate Cox regression analysis revealed that a higher time-averaged serum HS-CRP level, older age, and the occurrence of cardiovascular events were independent mortality predictors. A higher time-averaged serum HS-CRP level, the occurrence of cardiovascular events, infection episodes, and EPS were important predictors of dropout. The receiver operating characteristic analysis verified that the value of the time-average HS-CRP level in predicting the 5-year mortality and dropout was superior to a single serum baseline HS-CRP level. CONCLUSION: This study shows that the time-averaged serum HS-CRP level is a better marker than a single baseline measurement in predicting the 5-year mortality and dropout in PD patients.

Family Aggregation and Heritability of ESRD in Taiwan: A Population-Based Study.

BACKGROUND: Aggregation of end-stage renal disease (ESRD) has been observed in families of European origin, as well as those of African origin. However, it is not well documented if this disease aggregates in Asian families. Furthermore, the contribution of genetic factors and shared environmental factors to family aggregation remains unclear. STUDY DESIGN: Population-based cross-sectional cohort study. SETTING & PARTICIPANTS: All 23,422,955 individuals registered in the Taiwan National Health Insurance Research Database in 2013. Among these, 47.45%, 57.45%, 47.29%, and 1.51% had a known parent, child, sibling, or twin, respectively. We identified 87,849 patients who had a diagnosis of ESRD. PREDICTOR: Family history of ESRD. OUTCOMES & MEASUREMENTS: ESRD and heritability defined as the proportion of phenotypic variance attributable to genetic factors. RESULTS: Having an affected first-degree relative with ESRD was associated with an adjusted relative risk of 2.46 (95% CI, 2.32-2.62). Relative risks were 96.38 (95% CI, 48.3-192.34) for twins of patients with ESRD, 2.15 (95% CI, 2.02-2.29) for parents, 2.78 (95% CI, 2.53-3.05) for offspring, 4.96 (95% CI, 4.19-5.88) for siblings, and 1.66 (95% CI, 1.54-1.78) for spouses without genetic similarities. Heritability in this study was 31.1% to 11.4% for shared environmental factors and 57.5% for nonshared environmental factors. LIMITATIONS: This was a registry database study and we did not have detailed information about clinical findings or the definite causes of ESRD. CONCLUSIONS: This whole population-based family study in Asia confirmed, in a Taiwanese population, that a family history of ESRD is a strong risk factor for this disease. Moderate heritability was noted and environmental factors were related to disease. Family history of ESRD is an important piece of clinical information.

Identification of a major epitope by anti-interferon-γ autoantibodies in patients with mycobacterial disease.

The binding of autoantibodies (autoAbs) to interferon (IFN)-γ in people with mycobacterial diseases has become an emerging medical concern. Many patients display specific human leukocyte antigen (HLA) class II haplotypes, which suggests that a common T cell-dependent and B cell-dependent mechanism might underlie the production of specific anti-IFN-γ autoAbs. We show here that these autoAbs target a major epitope (amino acids 121-131, designated position (P)121-131) in a region crucial for IFN-γ receptor (IFN-γR) activation to impair IFN-γ-mediated activities. The amino acid sequence of this epitope is highly homologous to a stretch in the Noc2 protein of Aspergillus spp., which was cross-reactive with autoAbs from patients. Rats immunized with Aspergillus Noc2 developed antibodies that reacted with human IFN-γ. We generated an epitope-erased variant of IFN-γ (EE-IFN-γ), in which the major neutralizing epitope region was altered. The binding affinity of anti-IFN-γ autoAbs for EE-IFN-γ was reduced by about 40%, as compared to that for IFN-γ1-131. Moreover, EE-IFN-γ activated the IFN-γR downstream signaling pathway ex vivo, irrespectively of anti-IFN-γ autoAbs. In conclusion, we identified a common, crucial B cell epitope that bound to anti-IFN-γ autoAbs in patients, and we propose a molecular-mimicry model for autoAb development. In addition, treatment with EE-IFN-γ might be worth investigating in patients producing anti-IFN-γ autoAbs.

Acute Kidney Injury Predicts Mortality after Charcoal Burning Suicide.

A paucity of literature exists on risk factors for mortality in charcoal burning suicide. In this observational study, we analyzed the data of 126 patients with charcoal burning suicide that seen between 2002 and 2013. Patients were grouped according to status of renal damage as acute kidney injury (N = 49) or non-acute kidney injury (N = 77). It was found that patients with acute kidney injury suffered severer complications such as respiratory failure (P = 0.002), myocardial injury (P = 0.049), hepatic injury (P < 0.001), rhabdomyolysis (P = 0.045) and out-of-hospital cardiac arrest (P = 0.028) than patients without acute kidney injury. Moreover, patients with acute kidney injury suffered longer hospitalization duration (16.9 ± 18.3 versus 10.7 ± 10.9, P = 0.002) and had higher mortality rate (8.2% versus 0%, P = 0.011) than patients without injury. In a multivariate Cox regression model, it was demonstrated that serum creatinine level (P = 0.019) and heart rate (P = 0.022) were significant risk factors for mortality. Finally, Kaplan-Meier analysis revealed that patients with acute kidney injury suffered lower cumulative survival than without injury (P = 0.016). In summary, the overall mortality rate of charcoal burning suicide population was 3.2%, and acute kidney injury was a powerful predictor of mortality. Further studies are warranted.

Oral Tori in Chronic Peritoneal Dialysis Patients.

BACKGROUND: The pathogenesis of oral tori has long been debated and is thought to be the product of both genetic and environmental factors, including occlusal forces. Another proposed mechanism for oral tori is the combination of biomechanical forces, particularly in the oral cavity, combined with cortical bone loss and trabecular expansion, as one might see in the early stages of primary hyperparathyroidism. This study investigated the epidemiology of torus palatinus (TP) and torus mandibularis (TM) in peritoneal dialysis patients, and analyzed the influences of hyperparathyroidism on the formation of oral tori. METHOD: In total, 134 peritoneal dialysis patients were recruited between July 1 and December 31, 2015 for dental examinations for this study. Patients were categorized into two subgroups based on the presence or absence of oral tori. Demographic, hematological, biochemical, and dialysis-related data were obtained for analysis. RESULTS: The prevalence of oral tori in our sample group was high at 42.5% (57 of 134), and most patients with oral tori were female (61.4%). The most common location of tori was TP (80.7%), followed by TP and TM (14.0%), then TM (5.3%). All 54 TP cases were at the midline, and most were <2 cm (59.3%), flat (53.7%), and located in the premolar region (40.7%). Of the 11 TM cases, all were bilateral and symmetric, mostly <2 cm (81.9%), lobular (45.4%), and located at premolar region (63.6%). Interestingly, patients with oral tori had slightly lower serum levels of intact parathyroid hormones than those without oral tori, but the difference was not statistically significant (317.3±292.0 versus 430.1±492.6 pg/mL, P = 0.126). In addition, patients with oral tori did not differ from patients without tori in inflammatory variables such as serum high sensitivity C-reactive protein levels (6.6±8.2 versus 10.3±20.2 mg/L, P = 0.147) or nutritional variables such as serum albumin levels (3.79±0.38 versus 3.77±0.45 g/dL, P = 0.790). Furthermore, there were no differences between patients with and without oral tori in dialysis adequacy (weekly Kt/Vurea, 2.14±0.39 versus 2.11±0.33, P = 0.533; weekly creatinine clearance rate, 59.31±17.58 versus 58.57±13.20 L/1.73 m2, P = 0.781), or peritoneal membrane transporter characteristics (P = 0.098). CONCLUSION: Secondary hyperparathyroidism does not contribute to the formation of tori in peritoneal dialysis patients. Further studies are warranted.

Conversion to mTOR-inhibitors with calcineurin inhibitor elimination or minimization reduces urinary polyomavirus BK load in kidney transplant recipients.

BACKGROUND/PURPOSE: Polyomavirus BK (BKV) reactivation causes allograft dysfunction in some kidney transplant recipients. The use of mammalian target of rapamycin (mTOR) inhibitor-based immunotherapy is associated with a lower incidence of polyomavirus-associated nephropathy compared with other immunosuppressants. This retrospective study assessed whether conversion to mTOR inhibitor-based immunotherapy directly reduced urinary BKV load. METHODS: A total of 63 kidney recipients were divided into mTOR inhibitor-conversion (21 patients) and nonconversion (42 patients) groups. Urinary BKV loads were determined before and at least 6 months after the conversion. RESULTS: The results demonstrated that urinary BKV titer was significantly reduced in the conversion group (3.94 ± 0.43 copies (log)/mL to 2.49 ± 0.19 copies (log)/mL) and remained unaltered in the nonconversion group (3.19 ± 0.20 copies (log)/mL to 2.90 ± 0.20 copies (log)/mL). In addition, the percentage of patients with reduced urinary BKV load was significantly higher in the conversion group (76.2% vs. 42.9%). The estimated glomerular filtration rate after 24 months mTOR inhibitor conversion was significantly increased compared with that in the nonconversion group. Conversion to mTOR-inhibitor-based immunotherapy was the only factor associated with an increase in estimated glomerular filtration rate. CONCLUSION: This study reveals an association of conversion to mTOR-inhibitor-based immunotherapy with the reduction of urinary BKV load.