George Wu

Glucose but not N-acetylglucosamine accelerates in vitro senescence of human peritoneal mesothelial cells

Background Preservation of the mesothelial cells (MCs) is crucial for longevity of the peritoneal dialysis membrane. Glucose accelerates aging of MC and we tested whether N-acetylglucosamine (NAG) has an identical effect. Methods Replicative aging of MCs was studied during 10 passages performed every three days in cells cultured in standard medium or in medium supplemented with Glucose 30 mmol/L or NAG 30 mmol/L. Changes in population doubling time and β-galactosidase activity were used as an index of aging and compared with other cellular parameters. Results Repeated passages of MC cause their aging, as reflected by prolongation of the population doubling time, increased β-galactosidase activity, oxidative stress and release of cytokines. Healing of injured mesothelial monolayer is impaired in senescent cells. Glucose accelerates in vitro aging of MC, whereas NAG does not cause this effect. Conclusions Replacement of glucose with NAG in the dialysis fluid can slow down aging of MC.

Fibroblast Growth Factor 23 Predicts Mortality and End-Stage Renal Disease in a Canadian Asian Population with Chronic Kidney Disease.

Background: Chronic kidney disease (CKD) is a leading cause of morbidity and mortality. Biomarkers that predict end-stage renal disease (ESRD) and/or mortality could usher in new therapeutics to halt this onslaught. While fibroblast growth factor (FGF)23 can predict both ESRD and mortality, it has not been studied in North American CKD patients of Asian ethnicity. Method: This is a prospective investigation about the role of FGF23 in 998 Canadian patients of Asian descent with CKD defined by an estimated glomerular filtration rate (eGFR) <60 mL/min/m2 and followed up for 3 years. Results: The mean age of patients was 68.9 years and 68.3% were males. The mean (range) eGFR, and median FGF23 were 40.2 (11.0-59.0) mL/min and 154.1 (7.0-7,823.0) RU/mL, respectively. Over the 3 years, higher values of FGF23 levels at baseline were associated with higher risk of ESRD (hazard ratio [HR] for log[Fgf23] = 2.16 [95% CI 1.20-3.89]). Despite the short follow-up, 42 patients died due to cardiovascular diseases (38.8%), cancer (14.9%), and infections (12.7%). Log-FGF23 levels were independently associated with death, HR 1.94, 95% CI 1.24-3.03. Mortality risk increased in FGF23 subgroups from <100 to >400 RU/mL. In a time-changing covariate analysis, serial log-FGF23 levels over the 3 years predicted mortality with a HR of 2.66 (95% CI 1. 79-3.95). Conclusion: In a Canadian Asian population with CKD, FGF23 levels obtained at 6-monthly intervals for 3 years predicted ESRD and mortality suggesting that it is also a risk marker in Asians.

Hemodialysis Infection Prevention using Polysporin Ointment with Shower Technique in Satellite Units (HIPPO-SAT) Pilot Study Design

Background: Hemodialysis patients are often advised not to shower if they have a central ve- nous catheter (catheter). We developed a shower technique catheter protocol for hemodialysis patients with healed catheter exit sites, designed to permit showering but not increase catheter- related infection risk. Research question: Is it feasible to conduct a randomized control trial comparing the rate of catheter related bacteremia in adult satellite hemodialysis patients using the shower technique protocol versus standard catheter care alone with 6 month follow up? Study Design: This pilot study is a multi-centre randomized control trial. Eligible participants will be randomized to shower technique protocol versus standard care after meeting predefined criteria to confirm healed tunneled catheter exit site. Primary Outcome: Feasibility will be determined by 5 outcome measures: 1) accuracy of the catheter related bacteremia rate documentation in the satellite hemodialysis centre setting, per- centage of patients 2) screened, 3) recruited, 4) educated successfully in the shower technique protocol (intervention arm), and 5) treatment contamination of study groups. Study Setting: In 2 academic and 3 community based satellite hemodialysis centres in south central Ontario, Canada. Patient Population: Adult satellite hemodialysis patients dialyzing via tunneled central venous catheters with healed catheter exit sites. Intervention: Shower technique protocol and standard catheter care or control (standard cath- eter care only). Analysis: Each measure of feasibility has its own statistical threshold for success. If the thresh- old is reached in 4 of the 5 measures, the full study will be deemed feasible. Discussion: A pilot feasibility study of the larger study is critical due to the potential challenges associated with recruitment, compliance and participant ascertainment bias.

Successful Use of CAPD in Refractory Heart Failure

Four patients with end-stage heart failure, massive ascites refractory to medical intervention, and a variable degree of renal failure were treated successfully with CAPD for 8 to 24 months. The New York Heart Association functional class improved in all four. In two patients, who presented initially with signs and symptoms mainly of right-sided heart failure, ejection fraction improved. Each day dialysis achieved a significant degree of ultrafiltration and a negative sodium balance. We propose that CAPD is an alternative therapeutic modality in patients with severe heart failure refractory to conventional medical treatment.