Urinary chemokine C-X-C motif ligand 16 and endostatin as predictors of tubulointerstitial fibrosis in patients with advanced diabetic kidney disease.

BACKGROUND: Interstitial fibrosis and tubular atrophy (IFTA) is a well-recognized risk factor for poor renal outcome in patients with diabetic kidney disease (DKD). However, a noninvasive biomarker for IFTA is currently lacking. The purpose of this study was to identify urinary markers of IFTA and to determine their clinical relevance as predictors of renal prognosis. METHODS: Seventy patients with biopsy-proven isolated DKD were enrolled in this study. We measured multiple urinary inflammatory cytokines and chemokines by multiplex enzyme-linked immunosorbent assay in these patients and evaluated their association with various pathologic features and renal outcomes. RESULTS: Patients enrolled in this study exhibited advanced DKD at the time of renal biopsy, characterized by moderate to severe renal dysfunction [mean estimated glomerular filtration rate (eGFR) 36.1 mL/min/1.73 m2] and heavy proteinuria (mean urinary protein:creatinine ratio 7.8 g/g creatinine). Clinicopathologic analysis revealed that higher IFTA scores were associated with worse baseline eGFR (P < 0.001) and poor renal outcome (P = 0.002), whereas glomerular injury scores were not. Among measured urinary inflammatory markers, C-X-C motif ligand 16 (CXCL16) and endostatin showed strong correlations with IFTA scores (P = 0.001 and P < 0.001, respectively), and patients with higher levels of urinary CXCL16 and/or endostatin experienced significantly rapid renal progression compared with other patients (P < 0.001). Finally, increased urinary CXCL16 and endostatin were independent risk factors for poor renal outcome after multivariate adjustments (95% confidence interval 1.070-3.455, P = 0.029). CONCLUSIONS: Urinary CXCL16 and endostatin could reflect the degree of IFTA and serve as biomarkers of renal outcome in patients with advanced DKD.

Effects of early detection of peritoneal catheter migration on clinical outcomes: 15-years experiences from a single centre.

AIM: Catheter migration is an important cause of catheter malfunction in peritoneal dialysis (PD). The purpose of this study was to investigate the effect of early detection of catheter migration on clinical outcomes. METHODS: A retrospective review of 135 consecutive patients initiating PD immediately following catheter insertion from 2002 to 2017 was undertaken. In order to detect catheter migration without malfunction early, serial abdominal-pelvic radiographic examinations were performed according to a predefined protocol. Conservative management with rigorous catharsis was undertaken to correct catheter migration. A Kaplan-Meier method was used to calculate survival rate. RESULTS: Mean follow-up period was 42.8 ± 34.9 months. Catheter migration occurred in 62.4%. Among them, 85.9% occurred within the first 2 weeks after catheter insertion. There were no significant associations between catheter migration and variables such as gender, obesity, DM and type of catheter. Success rate of conservative management with rigorous catharsis was 91.1%. Catheter survival at 1 and 5 years were 91.5% and 64.6% in the migration group and 81.2% and 69.9% in the non-migration group, respectively (Log-rank test, P = 0.915). Patient survival at 1 and 5 years were 96.8% and 85.8% in the migration group and 91.9% and 82.3% in the non-migration group, respectively (P = 0.792). CONCLUSION: Early detection of PD catheter migration allowed the migrated tip to be easily corrected with conservative management. Once the migrated catheter tip was restored, catheter migration itself did not affect catheter survival. These findings suggest that early detection and correction of catheter migration is important for improving clinical outcomes.

New oral spherical carbon adsorbent effectively reduces serum indoxyl sulfate levels in moderate to advanced chronic kidney disease patients: a multicenter, prospective, open-label study.

BACKGROUND: Elevated levels of serum indoxyl sulfate (IS) have been linked to cardiovascular complications in patients with chronic kidney disease (CKD). Oral sorbent therapy using spherical carbons selectively attenuates IS accumulation in CKD patients. This study aimed to investigate whether oral administration of a new oral spherical carbon adsorbent (OSCA), reduces serum IS levels in moderate to severe CKD patients. METHODS: This prospective, multicenter, open-label study enrolled patients with CKD stages 3-5. Patients were prescribed OSCA for 8 weeks (6 g daily in 3 doses) in addition to standard management. Serum IS levels were measured at baseline and 4 and 8 weeks of treatment with OSCA. RESULTS: A total of 118 patients were enrolled and 87 eligible patients completed 8 weeks of study. The mean age of the study subjects was 62.8 ± 13.7 years, and 80.5% were male. Baseline levels of serum IS were negatively correlated with estimated glomerular filtration rate (eGFR) (r = - 0.406, P < 0.001) and increased with increasing CKD stages (stage 3, 0.21 ± 0.21 mg/dL; stage 4, 0.54 ± 0.52 mg/dL; stage 5, 1.15 ± 054 mg/dL; P for trend = 0.001). The patients showed significant reduction in serum total IS levels as early as 4 weeks after OSCA treatment (22.5 ± 13.9% reduction from baseline, P < 0.001) and up to 8 weeks (31.9 ± 33.7% reduction from baseline, P < 0.001). This reduction effect was noted regardless of age, kidney function, or diabetes. No severe adverse effects were reported. Gastrointestinal symptoms were the most commonly reported adverse effects. In total, 21 patients withdrew from the study, with dyspepsia due to heavy pill burden as the most common reason. The medication compliance rate was 84.7 ± 21.2% (min 9%, max 101%) for 8 weeks among those who completed the study. CONCLUSIONS: OSCA effectively reduced serum IS levels in moderate to severe CKD patients. Gastrointestinal symptoms were the most commonly reported complications, but no treatment-related severe adverse effects were reported. TRIAL REGISTRATION: Clinical Research Information Service ( KCT0001875 . 14 December 2015.).

Perceptions of resilience in patients undergoing peritoneal dialysis: A Q-methodology study.

Resilience is a potential human psycho-social ability that can reduce negative emotion and promote adaptation to adversity. Most previous studies on resilience have highlighted positive factors for patients with chronic illnesses; however, very few focus on the resilience of patients undergoing peritoneal dialysis (PD) using a qualitative approach. Using Q-methodology, we identified the perceptions of resilience of patients undergoing PD. We recruited 33 Korean participants undergoing PD in a university hospital, and classified 37 Q-samples into a 9-point normal distribution grid. Collected data were analyzed using the PC-QUANL program. The perceived subjectivity of the resilience of Korean patients undergoing PD was categorized as three factors: "support-based acceptance," "gloomy isolation," and "active life-oriented." The three factors explained 47.4% of the total variance. The eigenvalues were 9.99, 3.40, and 2.26, respectively. These findings suggest that a differentiated approach is needed for interventions to enhance the resilience of patients undergoing PD. This study highlights that clinical nurses and health professionals should understand the perceptions of resilience of patients undergoing PD, and consider their viewpoints in the caring and treatment process.

Phosphate supplementation for hypophosphatemia during continuous renal replacement therapy in adults.

BACKGROUND: Hypophosphatemia is common during continuous renal replacement therapy (CRRT) in critically ill patients and can cause generalized muscle weakness, prolonged respiratory failure, and myocardial dysfunction. This study aimed to investigate the efficacy and safety of adding phosphate to the dialysate and replacement solutions to treat hypophosphatemia occurring in intensive CRRT in critically ill patients. METHODS: We retrospectively analyzed 73 patients treated with intensive CRRT (effluent flow ≥35 ml/kg/hr) in the intensive care unit. The control group (group 1, n = 22) received no phosphate supplementation. The treatment groups received dialysate and replacement solution phosphate supplementation at 2.0 mmol/L (group 2, n = 26) or 3.0 mmol/L (group 3, n = 25). RESULTS: The CRRT-induced hypophosphatemia incidence was 59.0%. Correction of hypophosphatemia with phosphate supplementation changed the mean serum phosphorus levels to 1.24 ± 0.37 and 1.44 ± 0.31 mmol/L in groups 2 and 3, respectively (p = .02). The time required for correction was 1.65 ± 0.80 and 1.39 ± 1.43 days for groups 2 and 3, respectively and was significantly longer in group 2 (p = .02). After supplementation, hypophosphatemia, and hyperphosphatemia both occurred in 7% of group 2. Group 3 developed no hypophosphatemia, but 20% developed hyperphosphatemia. The serum phosphate levels in hyperphosphatemia cases returned to normal within 2.0 days (group 2) and 1.0 day (group 3) after stopping phosphate supplementation. CONCLUSION: Phosphate supplementation effectively corrected CRRT-induced hypophosphatemia in critically ill patients with an acute kidney injury. The use of 2 mmol/L phosphate is appropriate in patients with CRRT-induced hypophosphatemia, but a different concentration could be required to prevent hypophosphatemia at the start of CRRT.

Comparative efficacy and safety of gemigliptin versus linagliptin in type 2 diabetes patients with renal impairment: A 40-week extension of the GUARD randomized study.

AIMS: The long-term safety and efficacy of gemigliptin was evaluated in the present extension study after a 12-week study during a 40-week follow-up period. METHODS: The main study was a randomized, placebo-controlled, double-blinded, phase IIIb study in which 50 mg of gemigliptin (N = 66) or placebo (N = 66) was administered to patients with type 2 diabetes mellitus (T2DM) and moderate or severe renal impairment over a 12-week period. Patients with a glycated haemoglobin (HbA1c) level of 7% to 11% and an estimated glomerular filtration rate (eGFR) of 15 to 59 mL/min/1.73 m2 were enrolled in the main study. After 12 weeks, patients in the gemigliptin group continued to receive gemigliptin (N = 50), whereas patients in the placebo group were transitioned from placebo to linagliptin (N = 52). Each group received the indicated treatment over the subsequent 40-week period. A total of 102 patients consented to participate in the extension study, and 79 patients ultimately completed the study. RESULTS: The HbA1c levels of both groups were significantly reduced at week 52 compared with baseline. Specifically, the adjusted mean change ± standard error in HbA1c level in the gemigliptin and placebo/linagliptin groups was 1.00% ± 0.21% and 0.65% ± 0.22% lower at week 52 than at baseline (P < .001 and P = .003), respectively. No significant difference in the change in HbA1c level was found between the 2 groups (P = .148). Trends in fasting plasma glucose, fructosamine and glycated albumin levels in the 2 groups were similar to trends in HbA1c levels. The eGFR of both groups was also significantly lower at week 52 than at baseline, and no significant difference in change in eGFR was found between the 2 groups. In contrast, both drugs had little effect on urinary albumin excretion, although both drugs significantly reduced the urinary type IV collagen level. The overall rates of adverse events were similar between the 2 groups. CONCLUSIONS: Gemigliptin and linagliptin did not differ with respect to safety and efficacy in patients with T2DM and renal impairment. The 2 drugs had similar glucose-lowering effects, and the changes in eGFR and albuminuria were also similar. Additionally, the risk of side effects, including hypoglycaemia, was similar between the 2 groups.

CRISPR/Cas9 system as an innovative genetic engineering tool: Enhancements in sequence specificity and delivery methods.

While human gene therapy has gained significant attention for its therapeutic promise, CRISPR/Cas9 technology has made a breakthrough as an efficient genome editing tool by emulating prokaryotic immune defense mechanisms. Although many studies have found that CRISPR/Cas9 technology is more efficient, specific and manipulable than previous generations of gene editing tools, it can be further improved by elevating its overall efficiency in a higher frequency of genome modifications and reducing its off-target effects. Here, we review the development of CRISPR/Cas9 technology, focusing on enhancement of its sequence specificity, reduction of off-target effects and delivery systems. Moreover, we describe recent successful applications of CRISPR/Cas9 technology in laboratory and clinical studies.

Recent developments and clinical studies utilizing engineered zinc finger nuclease technology.

Efficient methods for creating targeted genetic modifications have long been sought for the investigation of gene function and the development of therapeutic modalities for various diseases, including genetic disorders. Although such modifications are possible using homologous recombination, the efficiency is extremely low. Zinc finger nucleases (ZFNs) are custom-designed artificial nucleases that make double-strand breaks at specific sequences, enabling efficient targeted genetic modifications such as corrections, additions, gene knockouts and structural variations. ZFNs are composed of two domains: (i) a DNA-binding domain comprised of zinc finger modules and (ii) the FokI nuclease domain that cleaves the DNA strand. Over 17 years after ZFNs were initially developed, a number of improvements have been made. Here, we will review the developments and future perspectives of ZFN technology. For example, ZFN activity and specificity have been significantly enhanced by modifying the DNA-binding domain and FokI cleavage domain. Advances in culture methods, such as the application of a cold shock and the use of small molecules that affect ZFN stability, have also increased ZFN activity. Furthermore, ZFN-induced mutant cells can be enriched using episomal surrogate reporters. Additionally, we discuss several ongoing clinical studies that are based on ZFN-mediated genome editing in humans. These breakthroughs have substantially facilitated the use of ZFNs in research, medicine and biotechnology.

Immediate-start peritoneal dialysis without break-in-period: an 18-year retrospective cohort study on patient survival.

Background: Immediate-start peritoneal dialysis (ISPD) is an effective renal replacement therapy that can prevent central venous catheterization due to its immediate initiation of peritoneal dialysis (PD) after catheter insertion without a break-in period. This study aimed to investigate the effect of ISPD on long-term patient survival. Methods: In this retrospective single-center cohort study, 178 consecutive patients who started PD from August 2005 to March 2023 were enrolled, from whom 144 patients with ISPD were analyzed. PD was initiated without a break-in period within 24 hours of catheter insertion using percutaneous needle-guidewire technique. The primary outcome was patient survival, estimated using the Kaplan-Meier method. A Cox proportional hazard regression model was used to identify factors independently associated with patient survival. Results: The median follow-up period was 4.00 years (interquartile range, 1.23‒5.75 years). The mean age of patients was 61.6 ± 13.6 years; 58 patients (40.3%) were male and 93 patients (64.6%) were diabetic. Overall patient survival rates at 1, 3, 5, and 10 years were 98.5%, 93.5%, 92.1%, and 65.6%, respectively. The technique survival rates at 1, 3, 5, and 10 years were 88.1%, 74.9%, 63.2%, and 40.2%, respectively. The peritonitis-free survival rates at 1, 3, 5, and 10 years were 92.3%, 76.0%, 59.4%, and 28.0%, respectively. In the multivariate analysis, diabetes was the only factor associated with patient survival and technique survival. Conclusion: Our study demonstrated that patient survival and technique survival rates were relatively high in ISPD patients who were catheterized using percutaneous needle-guidewire technique.

Correction: Kim et al. The Medium Cut-Off Membrane Does Not Lower Protein-Bound Uremic Toxins. Toxins 2022, 14, 779.

In the original publication [...].

Immunogenicity of recombinant human erythropoietin in Korea: a two-year cross-sectional study.

Immunogenicity of erythropoietin (EPO) is related with pure red cell aplasia (PRCA). We sought to determine the prevalence of antibody (Ab)-mediated PRCA in Korea and threshold diagnostic criteria by dual parameters: Ab titer and neutralizing activity. This study was a multi-center, cross-sectional study for two years. In the first year study (1 YS), 209 samples suspected to be EPO resistance were collected. In the second year study (2 YS), all the patients who consented to participate (N = 946) were enrolled. In 1 YS, we found three and six serum samples that were positive and borderline for anti-EPO Abs, respectively. The first three patients had neutralizing activity (NT) and were diagnosed as PRCA. In 2 YS, seven patients were anti-EPO positives and six had borderline levels. Among them, one patient with NT was diagnosed as PRCA and one with NT as aplastic anemia. The prevalence of PRCA was 0.106%. The correlation analysis of the 22 patients who had anti-EPO Ab showed that dual crossed cut-off lines (anti-EPO Ab titer ≥ 40 ng/ml, % NT ≥ 25%) were able to clearly isolate red cell aplasia. We suggest novel diagnostic criteria for diagnosis and prediction of Ab-mediated PRCA with data from both Ab titer assays and NT bioassays.

Why should we focus on high-volume hemodiafiltration?

Though noticeable technological advances related to hemodialysis (HD) have been made, unfortunately, the survival rate of dialysis patients has yet to improve significantly. However, recent research findings reveal that online hemodiafiltration (HDF) significantly improves patient survival in comparison to conventional HD. Accordingly, the number of patients receiving online HDF is increasing. Although the mechanism driving the benefit has not yet been fully elucidated, survival advantages are mainly related to the lowering of cardiovascular mortality. High cardiovascular mortality among HD patients is seemingly attributable to the cardiovascular changes that occur in response to renal dysfunction and the HD-induced myocardial stress and injury, and online HDF appears to improve such secondary cardiovascular changes. Interestingly, patient survival improves only if the convection volume is supplied sufficiently over a certain level during online HDF treatment. In other words, survival improvement from online HDF is related to convection volume. Therefore, there is a growing interest in high-volume HDF in terms of improving the survival rate. The survival improvement will require a minimum convection volume of 23 L or more per 4-hour session for postdilution HDF. To obtain an optimal high convection volume in online HDF, several factors, such as the treatment time, blood flow rate, filtration fraction, and dialyzer, need to be considered. High-volume HDF can be performed easily and safely in routine clinical practice. Therefore, when the required equipment is available, performing high-volume HDF will help to improve the survival rate of dialysis patients.

The Medium Cut-Off Membrane Does Not Lower Protein-Bound Uremic Toxins.

The accumulation of protein-bound uremic toxins (PBUT) is associated with increased cardiovascular outcomes in patients on dialysis. However, the efficacy of PBUT removal for a medium-cutoff (MCO) membrane has not been clarified. This study was designed to assess the efficacy of PBUT clearance according to dialysis modalities. In this prospective and cross-over study, we enrolled 22 patients who received maintenance hemodiafiltration (HDF) thrice weekly from three dialysis centers. The dialysis removal of uremic toxins, including urea, beta 2-microglobulin (B2MG), lambda free light chain (λ-FLC), indoxyl sulfate (IS), and p-cresyl sulfate (pCS), was measured in the 22 patients on high-flux HD (HF-HD), post-dilution online HDF (post-OL-HDF), and MCO-HD over 3 weeks. The average convection volume in post-OL-HDF was 21.4 ± 1.8 L per session. The reduction rate (RR) of B2MG was higher in post-OL-HDF than in MCO-HD and HF-HD. The RR of λ-FLC was the highest in MCO-HD, followed by post-OL-HDF and HF-HD. The dialysate albumin was highest in MCO-HD, followed by post-OL-HDF and HF-HD. Post-dialysis plasma levels of IS and pCS were not statistically different across dialysis modalities. The total solute removal and dialytic clearance of IS and pCS were not significantly different. The clearance of IS and pCS did not differ between the HF-HD, post-OL-HDF, and MCO-HD groups.

Helicobacter pylori eradication with a 7-day low-dose triple therapy in hemodialysis patients.

BACKGROUND: The optimal therapeutic regimen for Helicobacter pylori (H. pylori) infection has not been established in end-stage renal disease (ESRD) patients receiving hemodialysis. We investigated the efficacy and safety of a 7-day omeprazole-based triple therapy with low doses of amoxicillin and clarithromycin (OAC) for eradication of H. pylori infection in ESRD patients receiving hemodialysis. METHODS: Thirty-three hemodialysis patients and 55 patients with normal renal function underwent upper gastrointestinal endoscopy. For eradication of H. pylori infection, a 7-day triple therapy with low-dose OAC (omeprazole 40 mg daily, amoxicillin 500 mg daily, and clarithromycin 500 mg daily) regimen was used. Four weeks after the completion of the OAC regimen, the success of the H. pylori eradication therapy was determined by histological examination and rapid urease test. RESULTS: The prevalence of H. pylori infection was 36.4% in hemodialysis patients and 65.5% in non-uremic patients (p = 0.0150). The mean duration of hemodialysis in H. pylori-positive and -negative patients was 56.8 ± 26.9 versus 66.4 ± 26.1 months, respectively (p = 0.3196). Eradication was successful in 83.4% of hemodialysis patients and 81.0% of non-uremic patients (p = 1.000). All patients completed the eradication therapy without any serious adverse effects. CONCLUSION: A 7-day triple therapy with a low-dose OAC regimen was effective and safe for eradication of H. pylori infection in hemodialysis patients.

Clinical usefulness of bioimpedance analysis for assessing volume status in patients receiving maintenance dialysis.

Chronic volume overload is associated with left ventricular hypertrophy and high cardiovascular mortality in patients undergoing dialysis. Therefore, estimating body fluid status is important in these patients. However, most dry-weight assessments are still performed clinically, while attempts have been made to measure the volume status and dry weight of patients undergoing dialysis using bioimpedance analysis (BIA). BIA uses the electrical properties of the human body to alternate current flow and measures resistance values to estimate body water content and composition. BIA is divided into single-frequency BIA, multi-frequency BIA, and bioimpedance spectroscopy (BIS) according to the number of frequencies used, and into whole-body and segmental BIA according to whether or not the whole body is divided into segments. Extracellular water (ECW), intracellular water, and total body water (TBW) contents can be measured with BIA. Dry weight can be estimated by measuring the volume overload of the patient through the ECW/TBW and ECW-to-body weight ratios. Other estimation methods include the normovolemia/hypervolemia slope method, a resistance-reactance (RXc) graph, overhydration measurements using a body composition monitor, and calf BIS. In this review, we will examine the principles of BIA, introduce various volume status measurement methods, and identify the optimal method for patients undergoing dialysis.

Puromycin induces reversible proteinuric injury in transgenic mice expressing cyclooxygenase-2 in podocytes.

Previous studies from our own group and others have demonstrated that cyclooxygenase-2 (COX-2) inhibitors could reduce proteinuria in some experimental models of progressive renal disease. To investigate a possible role of COX-2 in podocytes during the course of self-limited glomerular injury, we administered puromycin nucleoside (PAN) on day 1 (15 mg/100 g BW) and day 3 (30 mg/100 g BW) to wild-type and transgenic mice with podocyte-specific COX-2 expression driven by a nephrin promoter. An additional group received both PAN and the COX-2-specific inhibitor, SC58236 (6 mg/l in drinking water). There was no significant difference in the albumin (microg)/creatinine (mg) ratio between wild-type (26.3 +/- 4.2, n = 8) and transgenic (28.9 +/- 2.3, n = 8) mice under baseline conditions. PAN induced significant albuminuria only in the transgenic mice with a peak at day 3: 72.1 +/- 8.9 microg/mg creatinine (n = 12, p < 0.05, compared with basal level), which remitted by day 10 (37.4 +/- 4.4 microg/mg, n = 7, p < 0.05, compared with day 3). Electron microscopy demonstrated that PAN caused 56.7 +/- 4.2% foot process effacement in transgenic mice compared with 38.8 +/- 4.1% in wild type at day 3. PAN increased immunoreactive COX-2 in glomeruli from transgenic mice (day 3: 1.47 +/- 0.08 fold; day 10: 1.25 +/- 0.16 fold, n = 5-9, p < 0.05 compared with basal level), which was restricted to podocytes. Real time PCR indicated that endogenous COX-2 mRNA increased (2.6 +/- 0.1 fold of wild-type control at day 3 and 2.2 +/- 0.2 at day 10, n = 4, p < 0.05), while the nephrin-driven COX-2 mRNA was unchanged. Nephrin mRNA and protein expression were decreased by PAN in the transgenic mice. The COX-2-specific inhibitor, SC58236, reduced foot process effacement in transgenic mice administered PAN to 21.7 +/- 5.2% and significantly reduced the albuminuria at day 3 (42.2 +/- 3.8, n = 13, p < 0.05 compared with untreated) without significantly altering COX-2 expression. In summary, in transgenic mice with podocyte COX-2 overexpression, PAN increased albuminuria and induced foot process fusion. Thus, increased COX-2 expression increased podocyte susceptibility to further injury.

Immediate initiation of CAPD following percutaneous catheter placement without break-in procedure.

OBJECTIVE: To evaluate the effect of a modified method of percutaneous catheter placement without a break-in procedure on the development of catheter-related complications in patients on continuous ambulatory peritoneal dialysis (CAPD). DESIGN: A prospective, observational clinical study. SETTING: Peritoneal dialysis (PD) units of two university-based hospitals. PATIENTS AND METHODS: This study included 51 consecutive patients on CAPD. A straight double-cuffed Tenckhoff catheter with a straight intraperitoneal segment was used, and all catheters were inserted using a modified percutaneous placement method under local anesthesia. The catheter was introduced directly into the deep pelvis through an intramuscular tract, which had been created by tapered dilators. Peritoneal dialysis was initiated immediately after catheter insertion without a break-in procedure. Catheter-related complications were surveyed during the 12 months after initiation of CAPD. RESULTS: Within the first month, only 1 pericatheter leakage (1.9%) was detected. There were no cases of visceral perforation or severe hemorrhage during catheter insertions. Catheter malfunction due to catheter tip migration, exit-site infection, and peritonitis developed in only 1.9%, 3.9%, and 3.9% of patients, respectively. After 1 month following catheter insertion, no further incidences of pericatheter leakage occurred during the follow-up period. All catheters, except one that was reinserted due to tip migration, survived throughout the study period. CONCLUSION: The rates of pericatheter leakage and other catheter-related complications are relatively low in CAPD patients using our percutaneous catheter placement method without a break-in procedure. This procedure is comparatively simple and less invasive than other catheter placement methods, and allows for immediate start of PD after catheter insertion, without a break-in procedure.

Risk factors for rhabdomyolysis following doxylamine overdose.

The objective of this prospective study was to identify risk factors for developing rhabdomyolysis in patients with doxylamine overdose. Patients who were admitted to a university teaching hospital between July 2000 and September 2005 due to doxylamine overdose were recruited. Demographic information, clinical variables, and laboratory data were investigated. Twenty-seven (M/F 12/15, age 33.2 +/-13.1 years) patients were enrolled. Sixteen (59%) of 27 patients developed rhabdomyolysis and three (19%) of 16 patients with rhabdomyolysis also developed acute renal failure. Patients who developed rhabdomyolysis differed from those who did not in the amount of doxylamine ingested, initial serum creatitnine and arterial pH. In multivariate regression analysis, the only reliable predictor of rhabdomyolysis was the amount of doxylamine ingested (P = 0.039). The amount of doxylamine ingested (>/= 20 mg/kg) predicted the development of rhabdomyolysis with a sensitivity of 81%, a specificity of 82%, a positive predictive value of 87%, and a negative predictive value of 75%.In conclusion, rhabdomyolysis following doxylamine overdose was common, occurring in 87% of patients who ingested more than 20 mg/kg. The amount of doxylamine ingested was the only reliable predictor for developing rhabdomyolysis following doxylamine overdose.

Intracellular Remodeling and Accumulation of Aberrant Lysosomes in Differentiation of Tonsil-Derived Mesenchymal Stem Cells into Parathyroid-Like Cells.

Differentiation of mesenchymal stem cells (MSC) into a variety of cell lineages such as adipocytes, osteocytes, and chondrocytes is often accompanied up-regulation of autophagy. In our study, we demonstrated that the expression of autophagy-associated proteins (p-Beclin 1, LC3A, LC3B, p-AMPK, p-mTOR and ATG3, ATG7, and ATG12-5) over a period of time was hardly distinguishable from control tonsil-derived MSC (TMSC). Despite the unnoticeable difference in autophagy activation between differentiated TMSC (dTMSC) and the control (cTMSC), we reported significant changes in intracellular compositions in differentiated TMSC into functional parathyroid-like cells secreting parathyroid hormone (PTH). By using transmission electron microscopy (TEM), we observed accumulation of multivesicular bodies (MVB) comprising small, degraded compartments densely accumulated as dark granular or amorphous clumps, multilamellar bodies and lipid droplets in dTMSC. However, no such structures were found in cTMSC. These results suggest that differentiation of TMSC into parathyroid-like cells producing PTH hormone is hardly dependent on autophagy activation in the beginning of our conditions. Furthermore, our results of intracellular remodeling and accumulated endo-lysosomal storage bodies in the later stages of TMSC differentiation present a possible role of the structures in PTH secretion.