In the course of over four decades, I have worked with an R&D team on 12 major R&D projects, all with the goal of making hemodialysis simple, safe, effective, and suitable for use in the home. Our team has worked within a University and in private companies and has collaborated with major healthcare drug and device companies. As a practicing nephrologist, my definition of success is when I see the device or drug we helped to develop in widespread clinical use. By this measure, two of the projects were highly successful, but seven failed. Most failures were due to decisions made by various corporations, governmental agencies, and venture capital groups, out of the hands or control of the R&D company. Three projects are still ongoing. There is no shortage of creativity or new ideas in nephrology and in dialysis. The major challenge is in the commercialization of the products.

Long-Term Survival for Hemodialysis Patients Differ in Japan Versus Europe and the USA. What Might the Reasons Be?

Introduction Chronic central venous catheters (CVC) for dialysis lose patency and deliver lower blood flow over time, often due to fibrous sheathing that covers the lumen tips. The CentrosFLO central venous catheter has a shape that directs the arterial and venous tips away from the walls of the vena cava and right atrium, making sheathing of the tips less likely. Methods A prospective, multicenter, single arm, non-controlled, observational study was conducted at eight sites in the United States. All consenting dialysis patients receiving CentrosFLO catheters through the right or left internal jugular veins were accepted in the study, as long as the catheter was expected to be used for 45 days and was not an over-the-wire replacement for a previous CVC. Data were automatically collected on initial and average dialysis blood flow rate and initial arterial and venous pressures, for up to 26 weeks of dialysis therapy. Findings 75 patients were enrolled. Kaplan-Meier analysis indicated that 87% of patients maintained blood flow rate over 300 mL/min throughout 26 weeks of follow-up. There was no decline in average dialysis blood flow rate and no significant change in hydraulic resistance of the arterial or venous lumens of the catheters during the study. Discussion The CentrosFLO catheter demonstrates long term patency with good flow rates on dialysis, which, by comparison with previous studies, shows a clinically significant improvement in blood flow rate vs. other catheters. Stable hydraulic resistance of the catheter lumens showed no evidence of tip encroachment by fibrous sheaths.

Peritoneal dialysis is a very effective therapy in ESRD patients, especially when combined with some residual renal function. Peritonitis is the most common reason for transfer from peritoneal dialysis to other therapies, but catheter failure is the next most common cause. The success of peritoneal dialysis catheters is dependent upon the method of placement and the catheter design chosen but more dependent upon the skill and experience of the physician placing the catheter. This chapter reviews the types of catheters available currently and recently, proper location of catheter components, preoperative evaluation of the patient including ultrasound of the abdominal wall and peritoneum, overview of methods of placement, embedding of PD catheters and exteriorization, catheter repositioning, repair of pericatheter leaks and hernias, and catheter removal.

A 75-year-old man on chronic peritoneal dialysis had unrecognized stenosis of the superior vena cava (SVC) due to pacemaker wires placed 5 years earlier. The patient was placed on hemodialysis after hernia surgery. When a tunneled central venous catheter for dialysis was placed from the right internal jugular (IJ) vein, the venous lumen extended through the stenotic area but not the arterial lumen. Probably due to a subsequent clot at the arterial lumen port the patient developed SVC syndrome and when the catheter was run in the reversed flow direction he developed hypovolemic shock. The stenosis and SVC syndrome resolved with angioplasty of the SVC stenosis, removal of the IJ catheter and use of a femoral vein catheter. The patient eventually returned to peritoneal dialysis and the femoral catheter was removed.

Catheter-related bloodstream infection is the greatest threat to the safety of patients on hemodialysis. Catheter lock solutions containing heparin have been linked to an increased risk of hemorrhage and thrombocytopenia. To ascertain the safety and efficacy for prevention of catheter-related bloodstream infection and catheter loss from patency failure of a novel catheter lock solution with antimicrobial and antithrombotic activity containing 0.24 M (7.0%) sodium citrate, 0.15% methylene blue, 0.15% methylparaben, and 0.015% propylparaben (C-MB-P), compared with heparin. Multicenter, prospective, randomized, open-label trial with patients studied for up to 6 months. An independent clinical evaluation committee assessing trial outcomes was blinded to patients' treatment assignments. Twenty-five outpatient hemodialysis units. Patients with end-stage renal disease receiving maintenance hemodialysis through a percutaneous cuffed and tunneled internal jugular hemodialysis catheters. Participants' catheters were locked between hemodialysis sessions with the C-MB-P lock solution or sterile saline containing 5000 units of unfractionated heparin (control). We recorded and evaluated catheter-related bloodstream infections, catheter loss attributable to luminal thrombosis, and adverse events. A total of 407 patients participated in the trial (49,565 catheter days), 201 in the C-MB-P group and 206 in the heparin group. Patients in the two lock solution groups were comparable for risk factors predisposing to catheter-related bloodstream infection. Catheters locked with C-MB-P were significantly less likely to cause catheter-related bloodstream infection (0.24 vs. 0.82 per 1000 catheter days; relative risk, 0.29; 95% confidence interval, 0.12-0.70; p = .005) and were less likely to be lost because of patency failure (0 vs. 4; log rank, p = .04). The novel C-MB-P lock solution is well tolerated, significantly reduces the risk of catheter-related bloodstream infection, and provides protection comparable to heparin against patency failure.

The objective of this study was to evaluate the bactericidal activity of a new antiseptic in an in vitro model using reference bacterial strains and on abdominal and inguinal skin of healthy human subjects. ZuraPrep (C/MB/P/IPA) contains citrate, methylene blue, parabens and isopropyl alcohol 70%. In vitro and in vivo studies evaluate immediate and persistent activity of the tested solution using bovine rawhides inoculated with single strains of microorganisms and natural bacterial flora on skin of adult human subjects. Depending upon the anatomical site (abdominal or inguinal), several different configurations of test times were executed. Post-prep surface cultures were performed at 10 min and 6h after application of the test solution. Tested solution showed high efficiency in log reduction of viable microbes both in vitro and in vivo. Post-prep activity 10 min after application ranged from 2.5 to 3 log(10) reduction from baseline on abdominal sites and 3.5-4.5 on inguinal sites. Similar levels of reduction persisted 6h after application. The level of antisepsis provided by the tested solution is similar or greater than that obtained with other antiseptics currently in use, and further clinical testing of the new antiseptic is warranted.

Some antibiotic solutions increase bacterial resistance and may cause toxic side effects. Heparin, frequently used as an anticoagulant in catheter lock solutions, may cause bleeding and stimulate biofilm formation. The aim of this study was to investigate the effect of a new antibacterial/antithrombotic solution, citrate/Methylene Blue/parabens (C/MB/P), versus various heparin solutions on the viability and the structure of preformed mature biofilms of Staphylococcus aureus bacteria. The degree of eradication of both planktonic and sessile microorganisms was evaluated. The changes in the structure of biofilms after exposure to C/MB/P and several concentrations of heparin were analysed by means of confocal laser scanning microscopy. COMSTAT image analysis was utilized to compare biofilm biomass, average and maximum height, surface coverage and roughness coefficient. Viability studies were performed on both biofilms and supernatant solutions. C/MB/P, in contrast to heparin solutions, significantly reduced biofilm biomass and thickness and reduced viability by 5 log when compared with saline treatment. No viable planktonic bacteria were detected and the few remaining biofilm cells appeared to be lysed. In contrast, most heparin solutions only reduced viability up to 1.0 log and failed to eradicate planktonic bacteria. C/MB/P has a rapid bactericidal effect on the preformed, mature biofilm of S. aureus. The structural changes of biofilms treated with C/MB/P, together with the observed log reduction of viable biofilm cells, confirmed the high potential of this solution to eliminate sessile bacteria. Furthermore, the tested solution entirely eliminated planktonic bacteria detached from the biofilm.

Background. Microbial infections are the most serious complications associated with indwelling central venous catheters. A catheter lock solution that is both antibacterial and antithrombotic is needed. The goal of this study was to determine whether a new catheter lock solution containing citrate, methylene blue and parabens has antimicrobial properties against planktonic bacteria and against sessile bacteria within a biofilm. These effects were compared to the antimicrobial properties of heparin at 2500 units/ml.Methods. The tested solution (C/MB/P comprising 7% sodium citrate, 0.05% methylene blue and 0.165% parabens) and individual components were challenged against gram-positive and gram-negative organisms and fungi. Control solutions were heparin with preservatives. Studies included evaluation of eradication of planktonic bacteria and sessile organisms in a biofilm grown on polymeric and glass coupons. Biofilm samples were inspected by scanning electron microscopy, atomic force microscopy and vital stains.Results. The C/MB/P solution, contrary to heparin, kills most tested planktonic microorganisms within 1 h of incubation. All tested organisms have an MIC of 25% or less of the original concentration of a new catheter lock. Bacteria strains did not develop resistance over more than 40 passages of culture suspensions. The C/MB/P solution is able to kill nearly all sessile bacteria in biofilm growth on plastic or glass discs in 1 h. Microscopic methods demonstrated extensive physical elimination of biofilm deposits from treated coupons. In contrast, heparin had a minimal effect on planktonic or biofilm organisms.Conclusions. The new multicomponent lock solution has strong antimicrobial properties against both planktonic and sessile microorganisms. By comparison, heparin with preservative has weak antibacterial properties against planktonic and biofilm bacteria. The tested catheter lock may have usefulness in preventing bacterial colonization of haemodialysis catheters and diminishing the incidence of catheter-related bacteraemia.