Søren Ladefoged

Kappa-opioid system in uremic pruritus: multicenter, randomized, double-blind, placebo-controlled clinical studies.

Uremic pruritus is a very common and frustrating condition for both patients and clinicians because no treatment has been demonstrated to be effective in relieving the itch. In this report, nalfurafine, a new kappa-opioid receptor agonist, was used to treat uremic pruritus in patients who were undergoing routine hemodialysis. Two multicenter, randomized, double-blind, placebo-controlled studies enrolled 144 patients with uremic pruritus to postdialysis intravenous treatment with either nalfurafine or placebo for 2 to 4 wk. A meta-analysis approach was used to assess the efficacy of nalfurafine. Statistically significant reductions in worst itching (P = 0.0212), itching intensity (P = 0.0410), and sleep disturbances (P = 0.0003) were noted in the nalfurafine group as compared with placebo. Improvements in itching (P = 0.0025) and excoriations (P = 0.0060) were noted for the nalfurafine-treated patients. Nalfurafine showed similar types and incidences of drug-related adverse events as did placebo. Nalfurafine was shown to be an effective and safe compound for use in this severely ill patient population.

Determination of urea, glucose, and phosphate in dialysate with Fourier transform infrared spectroscopy

Individual control and quantification of phosphate removal is desirable in dialysis treatment. Currently, no on-line method exists to quantify phosphate removal. We demonstrate that a multivariate calibration model based on infrared transmission spectra is capable of predicting phosphate, urea, and glucose concentrations at clinically relevant levels. The on-line monitoring of these components by infrared spectroscopy is therefore feasible.

Disinfection of Pseudomonas aeruginosa biofilm contaminated tube lumens with ultraviolet C light emitting diodes

Bacterial biofilms on long-term catheters are a major source of infection. Exposure to ultraviolet C (UVC – 265 nm) light was shown in an earlier study to reduce the number of bacteria substantially on ex vivo treated urinary patient catheters. Very large doses (long treatment times) should, however, be applied to obtain 99.9% disinfection rates. The major reason was that besides cells the mature biofilm contained absorbing and scattering particulates, which made the biofilm opaque. The potential of UVC light emitting diodes (LED) for disinfection purposes in catheter-like tubes contaminated with biofilm was investigated. It was shown that UVC light propagation was possible through both Teflon and catheter tubes (silicone). The disinfection efficiency of the diodes was demonstrated on tubes contaminated artificially with a Pseudomonas aeruginosa biofilm. The tubes were connected to a flow system and biofilms were produced during a 3 day period. Tubes in lengths of 10 (Teflon, silicone) and 20 cm (Teflon) were contaminated. Tubes for control and for UVC treatment were contaminated in parallel. Biofilms were sampled from the total inner surface of the tubes. Colony counts on the control samples were in the range of 5 × 105–1.3 × 109 CFU ml−1, with disinfection rates in the range 96–100%. The applied UVC doses corresponded to treatment times between 15 and 300 min. Disinfection (100%) was obtained in 10 cm Teflon tubes exposed for 30 min (detection limit <5 CFU ml−1). The same result was obtained for a 20 cm Teflon tube exposed for 300 min. The disinfection rate was 96% for the 20 cm tube if the dose was reduced to 30 min. A disinfection rate of 99.99% was observed for a 10 cm peritoneal dialysis catheter tube (silicone) exposed for 300 min. Differences between the tubes were dependent on the differences in length and the type of the material. The UVC light was transmitted six times more efficiently in Teflon than in silicone tubes of equal length (10 cm). The germicidal effect to obtain a 99.99% killing rate for the biofilm (∼78 J m−2) is comparable to that for the planktonic bacterium. It is concluded that there is potential for LED UVC light sources if they are used for disinfection of thin biofilms.

Dose requirements for UVC disinfection of catheter biofilms

Bacterial biofilms on permanent catheters are the major sources of infection. Exposure to ultraviolet-C (UVC) light has been proposed as a method for disinfecting the inner surface of catheters. Specification of a UVC-based device for in vivo disinfection is based on the knowledge of the required doses to kill catheter biofilm. Given these doses and the power of available UVC light sources, calculation of the necessary treatment times is then possible. To determine the required doses, contaminated urinary catheters were used as test samples and UVC treated in vitro. Patient catheters (n = 67) were collected and cut into segments of equal size and treated with various UVC doses. After treatment, the biofilm was removed by scraping and quantified by counting colony forming units. Percentage killing rates were determined by calculating ratios between UVC-treated samples and controls (no UVC treatment). Mean killing rates were 89.6% (0.5 min), 98% (2 min), and 99% (60 min). Approximately 99% killing was obtained with a UVC dose of 15 kJ m−2. This dose, which is about 100 to 1000 times greater than the lethal dose for planktonic cells, is expected to be the maximum dose required to maintain newly inserted catheters free of contamination. The combination of high doses required to kill mature biofilm and the limited effect of current UVC light sources result in a relative long treatment time (∼60 min). If a UVC-based method is to be of practical use for disinfection of catheters in the clinic, repeated preventive treatments should be carried out on newly inserted catheters.

Incremental value of a combination of cardiac troponin T, N-terminal pro-brain natriuretic peptide and C-reactive protein for prediction of mortality in end-stage renal disease

Abstract Objective. To determine the relative prognostic merits of C-reactive protein (CRP), cardiac troponin T (cTnT) and N-terminal pro-brain natriuretic peptide (NT-pro-BNP) for prediction of all-cause death in patients with end-stage renal disease (ESRD) receiving haemodialysis. Material and methods. This prospective, controlled cohort study included 109 patients. Biomarkers were sampled at inclusion and considered as categorical and continuous variables in Cox proportional hazard models. Results. Mean follow-up ± SD was 926 ± 385 days, during which 52 patients (48%) died. All three markers were predictive of death in univariate analysis. In multivariable analysis, elevated cTnT (> 0.01 μg/l) and CRP (> 1.0 mg/dl) remained significantly associated with mortality [hazard ratio (95% confidence interval), 3.2 (1.2–8.5), p = 0.017 for cTnT; 2.0 (1.0–3.8), p = 0.032 for CRP], while NT-pro-BNP lost independent prognostic power. Addition of cTnT and CRP to established risk factors significantly improved the global fit of the model (p < 0.001), increased the c statistic from 0.726 to 0.758 and significantly increased the integrated discrimination improvement (p < 0.001). Conclusion. The results suggest that cTnT and CRP can be used in combination for risk stratification in patients with ESRD and highlight the additive effect they confer in this regard.

Online monitoring of urea concentration in dialysate with dual-beam Fourier-transform near-infrared spectroscopy

The robustness of a dual-beam, optical null, Fourier-transform near-infrared (FTNIR) spectrometer was investigated by means of online, near-infrared measurements and predictions of urea concentrations in spent dialysate during hemodialysis treatment. Simple multivariate calibration using a few factors based on a small number of prepared samples provided stable and accurate predictions over a period of 1 month. The calibration was robust when faced with adjustment of reference cell intensity and did not require a daily measured reference spectrum. The root-mean-square error of prediction of urea was 0.4 mM based on a two-factor partial least-squares regression model.

UVC fluencies for preventative treatment of Pseudomonas aeruginosa contaminated polymer tubes

Exposing Pseudomonas aeruginosa biofilm grown on the inner surface of Teflon and silicone tubes to UVC light (265 nm) from light emitting diodes (LED) has previously been shown to substantially reduce biofilm growth. Smaller UVC fluencies were required to disinfect Teflon tubes compared to silicone tubes. Light propagation enhancement in tubes can be obtained if the refractive index of the intra-luminal saline solution is higher than that of the polymer. This condition is achieved by using Teflon tubes with a low refractive index (1.34) instead of the polymers with a high refractive index (1.40–1.50) normally used for tubing in catheter production. Determining whether or not UVC light exposure can disinfect and maintain the intra-luminal number of colony forming units (CFUs) at an exceedingly low level and thus avoid the growth and establishment of biofilm is of interest. The use of UVC diodes is demonstrated to be a preventative disinfection treatment on tubes made of Teflon, which enhances the UVC light propagation, and on tubes made of a softer material, ethylene vinyl acetate (EVA), which is suitable for catheters but much less suitable for UVC light propagation. Simulating an aseptic breach (∼103–104 CFU ml−1), the UVC disinfection set-up was demonstrated using tubes contaminated with planktonic P. aeruginosa. After the tubes (10–20 cm) were inoculated with the bacterial solution for 3 h, they were emptied and filled with saline solutions (0.9–20%). Next UVC fluencies (0–21 mJ cm−2) were applied to the tubes 3 h after inoculation. Colony counts were carried out on liquid samples drawn from the tubes the first day after UVC treatment and liquid and surface samples were collected and analyzed 3–4 days later. A fluence of approximately 1.0 mJ cm−2 was noted as being sufficient for no growth for a period of 3–4 days for the Teflon tubes. Determining the fluence threshold for the EVA tubes was not possible. Almost all of the UVC-treated EVA tubes were disinfected simply by filling the tubes with a saline solution. Direct UVC treatment of the contaminated EVA tubes revealed, however, that a fluence of 21 mJ cm−2 killed the bacteria present in the tubes and kept them disinfected for a period of 3–4 days.

Comparison of four different cardiac troponin assays in patients with end-stage renal disease on chronic haemodialysis

Background: Several studies have documented the importance of troponin elevation as a prognostic marker in end-stage renal disease (ESRD). The reason for the elevated concentrations is not clarified. We do not know whether the different assays recognize the same patients within ESRD populations. The aim of this study was to compare concentrations of troponin measured by four different assays in a cohort of patients with ESRD, to investigate whether haemodialysis affects troponin concentrations, and to compare the prognostic potential of the different assays. Methods: We included 109 patients on chronic haemodialysis. Serum cardiac troponin T (cTnT) was measured pre- and postdialysis using Elecsys 2010 and troponin I (cTnI) using Access AccuTnI, Dimension R×L and AIA-600II. Results: The cTnT assay had the highest percentage of elevated concentrations for all chosen cut-offs with a reduction in percentage of patients with elevated concentrations during haemodialysis. Elecsys 2010 and AIA-600II demonstrated a significant increased mortality with raised concentrations of troponin. Conclusions: The diverging results in previous studies are most likely based on substantial differences in the analytical performance of the assays. The prognostic value of cTnT appears superior to cTnI, which amplifies the prognostic significance of this cardiovascular marker in patients with ESRD.

Presence and significance of TT virus in Danish patients on maintenance hemodialysis

OBJECTIVES To determine the prevalence of TT virus (TTV) in a population of Danish hemodialysis patients and evaluate possible relations between TTV infection and elevated levels of C-reactive protein (CRP) and hypo-response to treatment with erythropoietin (EPO). MATERIAL AND METHODS Patients on maintenance hemodialysis at a single center were invited to participate. Demographic and clinical data were registered. Blood samples for virological and routine biochemical tests were drawn simultaneously. TTV DNA was detected using polymerase chain reaction (PCR). TTV viral load was estimated by means of semi-quantitative PCR. All patients were tested for hepatitis B, hepatitis C and GB virus C. RESULTS Of 252 patients, 204 (80.9%) gave their written informed consent to participate in the study. The prevalence of TTV was 68% and 50% of TTV-positive patients had a high TTV viral load. TTV-positive patients were significantly older than TTV-negative patients (p = 0.011). No relations were found between TTV infection and elevated levels of alanine aminotransferase (ALT) or CRP or hypo-response to EPO treatment. The mean hemoglobin concentration was 11.24 +/- 1.48 g/dl. Patients with a high TTV viral load had a lower level of hemoglobin (10.86 +/- 1.47 g/dl) than the others (p = 0.01). This trend suggested a positive relation between TTV infection and the number of blood transfusions. A restriction fragment length polymorphism assay suggested that patients were infected with different TTV strains. CONCLUSIONS TTV is common in patients on maintenance hemodialysis. The presence of TTV is associated with increasing age. Patients with a high TTV viral load had lower levels of hemoglobin than the others. TTV infection is not related to elevated levels of ALT or CRP or to hypo-response to EPO treatment.

Potassium dynamics are attenuated in hyperkalemia and a determinant of QT adaptation in exercising hemodialysis patients

Disturbances in plasma potassium concentration (pK) are well known risk factors for the development of cardiac arrhythmia. The aims of the present study were to evaluate the effect of hemodialysis on exercise pK dynamics and QT hysteresis, and whether QT hysteresis is associated with the pK decrease following exercise. Twenty-two end-stage renal disease patients exercised on a cycle ergometer with incremental work load before and after hemodialysis. ECG was recorded and pK was measured during exercise and recovery. During exercise, pK increased from 5.1 ± 0.2 to 6.1 ± 0.2 mM (mean ± SE; P < 0.0001) before hemodialysis and from 3.8 ± 0.1 to 5.1 ± 0.1 mM (P < 0.0001) after hemodialysis. After 2 min of recovery, pK had decreased to 5.0 ± 0.2 mM and 4.1 ± 0.1 mM (P < 0.0001) before and after hemodialysis, respectively. pK increase during exercise was accentuated after hemodialysis. The pK increase was negatively linearly correlated with pK before exercise (β = -0.21, R(2) = 0.23, P = 0.001). QT hysteresis was negatively linearly correlated with the decrease in pK during recovery (β = -28 ms/mM, R(2) = 0.36, P = 0.006). Thus, during recovery, low pK was associated with relatively longer QT interval. In conclusion, new major findings are an accentuated increase in pK during exercise after hemodialysis, an attenuated increase in pK in hyperkalemia, and an association between pK and QT interval adaptation during recovery. The acute pK shift after exercise may modulate QT interval adaptation and trigger cardiac arrhythmias.