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Simon J Davies

Publications and source records attributed to Simon J Davies.

At least 19 recordsLinked to original sources
PubMed2006

Exploring new evidence of the clinical benefits of icodextrin solutions.

BACKGROUND: Use of icodextrin has the potential of several clinical benefits, including reduced systemic and peritoneal glucose exposure and improvement in fluid status as a result of better ultrafiltration. This article explores the recent evidence for such benefits. METHODS: Systematic literature review to include all randomized controlled trials and longitudinal observational cohort studies of peritoneal dialysis patients treated with icodextrin. Secondary, comparative analysis of the relationship between increased ultrafiltration and preservation of residual urine volume. RESULTS: Several studies provide support for clinically relevant improvements in biocompatibility. In particular, improved glucose control in diabetics and hyperinsulinaemia and gastric emptying in non-diabetics indicate systemic benefits. Evidence for improved lipid profiles of blood pressure control is less compelling. The increases in net ultrafiltration, especially in high transport patients, in whom glucose solutions are associated with fluid reabsorption in the long dwell, are associated with sustained reductions in the extra-cellular fluid volume. For a given increase in ultrafiltration, residual urine volume is relatively well-preserved with icodextrin, but severe volume depletion puts residual renal function at risk. Considerable variability in achieved ultrafiltration is observed. CONCLUSION: The potential clinical benefits of icodextrin are increasingly supported by observational and randomized studies. Further research is required in order to understand the between-patient variability in the efficacy of ultrafiltration achieved with icodextrin, which might in part be explained by differences in metabolism.

Glucans↗
PubMed2006

Peritoneal dialysis after a failed transplant.

Failed transplantation is an increasingly common cause for starting dialysis treatment. As with all patients approaching dialysis there is a need for adequate physical and psychological preparation and yet whilst by definition these individuals are known to health professionals this is not always achieved. It is likely that given adequate information, a significant proportion of these patients would prefer PD on lifestyle grounds. There is increasingly strong evidence that patients commencing PD after transplant failure enjoy overall survival and technique survival that is no different to those new to dialysis, even when other risk factors such as age, comorbidity, race, gender and membrane function are taken into account. The risk of peritonitis is also not different. These patients tend to lose residual renal function more rapidly but this does not translate into worse outcomes. The role and benefit in modulating immune suppressive drugs before and after commencing PD is not clear.

Humans↗
PubMed2005

A detailed analysis of sodium removal by peritoneal dialysis: comparison with predictions from the three-pore model of membrane function.

BACKGROUND: The development of fluid and salt retention is a potential problem for all peritoneal dialysis (PD) patients. Sodium removal by the peritoneum is predominantly determined by convective fluid loss but influenced by diffusion and sieving due to free water transport as predicted by the three-pore model (TPM). The aim of the study was to establish the effect of transport status, dwell length and glucose concentration on observed ultrafiltration (UF), dialysate sodium concentration ([Na(+)](D)) and removal, and compare this with that predicted by a computer program based on the principles of the TPM. METHODS: This was a cross-sectional study of UF and [Na(+)](D) collected prospectively from dwells classified by length, glucose concentration and membrane transport characteristics. Solute transport, converted to area parameter and UF capacity, was measured on each occasion by the peritoneal equilibration test. These parameters, along with plasma [Na(+)], were entered into the computer model. Fixed values for other parameters, e.g. hydraulic conductance and lymphatic absorption and sump volume, were used. RESULTS: A total of 1853 dwells from 182 patients [10% were on automated PD (APD)] were analysed. There was a high degree of correlation (r = 0.83-95, P<0.001) between the observed and predicted values for UF, [Na(+)](D) and sodium removal across the full range of dwell categories. The model overpredicted UF as the net volume increased with increasing glucose concentration, independently of solute transport. This bias was not fully explained by the preferential use of hypertonic dialysate by patients with reduced UF capacity. The prediction of [Na(+)](D) described sodium sieving, which was overestimated in a small number of patients with UF failure. There were no discrepancies between continous ambulatory PD (CAPD) and APD patients. CONCLUSION: This analysis endorses the TPM as a description of membrane function, particularly in relation to sodium sieving and removal. The relationship between dialysate glucose concentration and achieved UF appears to be more complex; even accounting for extended time on treatment and reduction in the osmotic conductance in patients preferentially using hypertonic exchanges, further adjustments may be needed to account for the tendency to overestimate UF.

Computer Simulation↗
PubMed2005

Longitudinal membrane function in functionally anuric patients treated with APD: data from EAPOS on the effects of glucose and icodextrin prescription.

BACKGROUND: Peritoneal dialysis is associated with changes in membrane function that can lead eventually to ultrafiltration (UF) failure. Factors driving these changes are thought to include hypertonic glucose exposure, but previously reported associations are confounded by the presence of residual renal function. METHODS: Longitudinal membrane function (solute transport and UF capacity) were measured annually in a prospective cohort of 177 functionally anuric patients as part of the European Automated Peritoneal Dialysis Outcomes Study (EAPOS). Subgroup analysis was performed according to glucose exposure and icodextrin use at baseline. RESULTS: The whole cohort experienced an increase in solute transport and reduction in UF capacity at 12 and 24 months that could not be explained by informative censoring. These changes were accelerated and more severe in patients using either 2.27% or 3.86% glucose, or those not using icodextrin at baseline. These differences could not be explained by age, comorbidity score, previous time spent on renal replacement, differential dropout from the study, peritonitis rates, or, by definition, residual renal function. Patients using icodextrin at baseline had worse membrane function and were more likely to be diabetic. There was an association between membrane function changes and achieved 24-hour ultrafiltration over the 2-year study period. CONCLUSION: Anuric automated peritoneal dialysis (APD) patients experience significant detrimental changes in membrane function over a relatively short time period. Glucose appears to enhance these changes independent of residual renal function. Icodextrin use in these circumstances is associated with less deterioration in membrane function.

Anuria↗
PubMed2004

Influence of convection on the diffusive transport and sieving of water and small solutes across the peritoneal membrane.

The three-pore model of peritoneal membrane physiology predicts sieving of small solutes as a result of the presence of a water-exclusive pathway. The purpose of this study was to measure the diffusive and convective components of small solute transport, including water, under differing convection. Triplicate studies were performed in eight stable individuals using 2-L exchanges of bicarbonate buffered 1.36 or 3.86% glucose and icodextrin. Diffusion of water was estimated by establishing an artificial gradient of deuterated water (HDO) between blood/body water and the dialysate. (125)RISA (radio-iodinated serum albumin) was used as an intraperitoneal volume marker to determine the net ultrafiltration and reabsorption of fluid. The mass transfer area coefficient (MTAC) for HDO and solutes was estimated using the Garred and Waniewski equations. The MTAC of HDO calculated for 1.36% glucose and icodextrin were similar (36.8 versus 39.7 ml/min; P = 0.3), whereas for other solutes, values obtained using icodextrin were consistently higher (P < 0.05). A significant increase in the MTAC of HDO was demonstrated with an increase in the convective flow of water when using 3.86% glucose (mean value, 49.5 ml/min; P < 0.05). MTAC for urea was also increased with 3.86% glucose. The identical MTAC for water using 1.36% glucose and icodextrin indicates that diffusion is predominantly through small pores, whereas the difference in MTAC for the remaining solutes is a reflection of their sieving. The increase in the MTAC of water and urea associated with an increase in convection is most likely due to increased mixing within the interstitium.

Biological Transport↗
PubMed2004

Longitudinal relationship between solute transport and ultrafiltration capacity in peritoneal dialysis patients.

BACKGROUND: Time on treatment is associated with a greater risk of impaired ultrafiltration (UF) in peritoneal dialysis (PD) patients. In addition to increasing solute transport, a potentially treatable cause of impaired ultrafiltration, cross-sectional studies suggest that there is also reduced osmotic conductance of the membrane. If this were the case then it would be expected that the UF capacity for a given rate of solute transport would change with time. The purpose of this analysis was to establish how solute transport and UF capacity change relative to one another with time on therapy. METHODS: Membrane function, using a standard peritoneal equilibration test, was measured at least annually in a well-characterized, single-center observational cohort of PD patients between 1990 and 2003. Demography included age, gender, original cause of renal failure, body surface area (BSA), validated comorbidity score, residual urine volume and urea clearances, peritoneal urea clearances, and plasma albumin. RESULTS: Data from 574 new PD patients were available for analysis. Independent demographic factors associated with higher solute transport at baseline were male gender and higher residual urine volume. Throughout time on therapy there was a negative relationship between solute transport and UF capacity and a significant increase and decrease in these parameters, respectively. During the first 12 months of treatment, the increase in solute transport was not associated with the expected fall in UF capacity, a phenomenon that was not explained by informative censoring, but was associated with an increased, albeit weak, correlation with BSA. In contrast, later in treatment there was a disproportionate fall in UF capacity, more accelerated in patients developing UF failure. Early exposure to higher intraperitoneal glucose concentrations, in the context of more comorbidity and relative lack of residual renal function, was associated with more rapid deterioration in membrane function. CONCLUSION: Despite a causal link between solute transport and UF capacity of the membrane, due to the effect of the former on the osmotic gradient, there is evidence of their longitudinal dissociation. This implies a change in the structure-function relationship with time on treatment that can, to some extent, be predicted from clinical factors present within the first year of treatment. Dialysis-induced membrane injury must involve at least two processes, for example, increased vascular surface area contact with dialysate combined with changes in hydraulic conductance due to scarring of the vessels and interstitium.

Adult↗
PubMed2003

Measuring transport of water across the peritoneal membrane.

INTRODUCTION: Mechanisms of water flow across the peritoneal membrane include diffusion, convection, and reabsorption. OBJECTIVES: To understand these processes more clearly we have developed a method to measure transport of water across the peritoneal membrane. METHODS: An artificial gradient of deuterated water (HDO) between blood and dialysate compartments was created in five subjects who took 0.3g per kg of body weight of D2O, which was allowed to equilibrate with total body water. During a test dwell (2 L, bicarbonate:lactate buffer, 1.36% glucose to minimize convection), frequent dialysate samples were drawn to determine the abundance of deuterium and other solutes and to calculate their time constants. Dialysate deuterium abundance was measured using flowing afterglow mass spectrometry (FA-MS). The method was combined with 125iodine-labeled albumin (RISA) to enable simultaneous estimates of intraperitoneal volume and thus calculation of the mass transfer area coefficient (MTAC) for small solutes using the Garred equation. RESULTS: The appearance of HDO in dialysate in four subjects is described by a single exponential fit with residuals of <1%, similar to method precision. In a fifth subject, the resolution of this method demonstrated that the best fit was a double exponential. When compared to other solutes, the time constant for water was as predicted by its molecular weight, with a MTAC of 38.7 +/- 4.4 mL/min. Total body water could also be estimated from the equilibrated dialysate deuterium abundance, with repeat estimates within 0.5%. CONCLUSION: Transport of water across the peritoneum can be measured with remarkable accuracy and when combined with an intraperitoneal volume estimation can be used to determine mass transfer. In conditions of low convection, the relative rate of deuterium appearance and mass transfer compared to other solutes suggests that water diffuses predominantly through the intercellular small pores.

Biological Transport↗
PubMed2003

Icodextrin improves the fluid status of peritoneal dialysis patients: results of a double-blind randomized controlled trial.

Worsening fluid balance results in reduced technique and patient survival in peritoneal dialysis. Under these conditions, the glucose polymer icodextrin is known to enhance ultrafiltration in the long dwell. A multicenter, randomized, double-blind, controlled trial was undertaken to compare icodextrin versus 2.27% glucose to establish whether icodextrin improves fluid status. Fifty patients with urine output <750 ml/d, high solute transport, and either treated hypertension or untreated BP >140/90 mmHg, or a requirement for the equivalent of all 2.27% glucose exchanges, were randomized 1:1 and evaluated at 1, 3, and 6 mo. Members of the icodextrin group lost weight, whereas the control group gained weight. Similar differences in total body water were observed, largely explained by reduced extracellular fluid volume in those receiving icodextrin, who also achieved better ultrafiltration and total sodium losses at 3 mo (P < 0.05) and had better maintenance of urine volume at 6 mo (P = 0.039). In patients fulfilling the study's inclusion criteria, the use of icodextrin, when compared with 2.27% glucose, in the long exchange improves fluid removal and status in peritoneal dialysis. This effect is apparent within 1 mo of commencement and was sustained for 6 mo without harmful effects on residual renal function.

Adult↗
PubMed2003

Survival of functionally anuric patients on automated peritoneal dialysis: the European APD Outcome Study.

The European APD Outcome Study (EAPOS) is a 2-yr, prospective, multicenter study of the feasibility and clinical outcomes of automated peritoneal dialysis (APD) in anuric patients. A total of 177 patients were enrolled with a median age of 54 yr (range, 21 to 91 yr). Previous median total time on dialysis was 38 mo (range, 1.6 to 259 mo), and 36% of patients had previously been on hemodialysis for >90 d. Diabetes and cardiovascular disease were present in 17% and 46% of patients, respectively. The APD prescription was adjusted at physician discretion to aim for creatinine clearance (Ccrea) >/=60 L/wk per 1.73 m(2) and ultrafiltration (UF) >/=750 ml/24 h during the first 6 mo. Baseline solute transport status (D/P) was determined by peritoneal equilibration test. At 1 yr, 78% and 74% achieved Ccrea and UF targets, respectively; median drained dialysate volume was 16.2 L/24 h with 50% of patients using icodextrin. Baseline D/P was not related to UF achieved at 1 yr. At 2 yr, patient survival was 78% and technique survival was 62%. Baseline predictors of poor survival were age (>65 yr; P = 0.006), nutritional status (Subjective Global Assessment grade C; P = 0.009), diabetic status (P = 0.008), and UF (<750 ml/24 h; P = 0.047). Time-averaged analyses showed that age, Subjective Global Assessment grade C and diabetic status predicted patient survival with UF the next most significant variable (risk ratio, 0.5/L per d; P = 0.097). Baseline Ccrea, time-averaged Ccrea, and baseline D/P had no effect on patient or technique survival. This study shows that anuric patients can successfully use APD. Baseline UF, not Ccrea or membrane permeability, is associated with patient survival.

Adult↗
PubMed2003

Perceptual completion and object-based representations in short-term visual memory.

Object-based representations in visual short-term memory (VSTM) were examined using a change detection memory task. A display comprising two rows of four differently colored elements was followed by a probe display in which only one of the rows reappeared. On same trials, the probed row was identical to the corresponding row in the memory display. On different trials, two of the elements in the probed row had their colors exchanged. In each memory display, a task-irrelevant visual element appeared between the two rows, with the potential to function as an occluder. Performance was enhanced when perceptual completion meant that four, rather than eight, objects were perceived in the memory display and when the probe display revealed that the occluded elements continued behind the occluder. It appears that several forms of representation can co-occur to support VSTM, one of which is object based.

Feedback↗
PubMed2002

Comparative measurements of total body water in healthy volunteers by online breath deuterium measurement and other near-subject methods.

BACKGROUND: We developed a new near-subject approach, using flowing afterglow-mass spectrometry (FA-MS) and deuterium dilution, which enables the immediate measurement of total body water (TBW) from single exhalations. OBJECTIVES: The objectives were to show the efficacy of the new FA-MS method in measuring TBW in healthy subjects and to compare these measurements with values derived from multifrequency bioelectrical impedance analysis, skinfold-thickness (SFT) measurements, and both recent and historical published regression equations. DESIGN: After baseline measurement of breath deuterium abundance, 24 healthy subjects ingested 0.3 g D(2)O/kg body wt. A second breath sample was taken after 3 h to measure the increase in deuterium, from which TBW was calculated. Bioelectrical impedance analysis was carried out with a multifrequency analyzer, and SFT was measured by a single trained observer. Methods were compared with the use of Pearson's correlation coefficient and Bland-Altman analyses. RESULTS: TBW measures obtained by all methods were highly correlated (r = 0.95-0.98, P < 0.001), especially those between FA-MS, SFT measurement, and recent regression equations. The mean values obtained were within 2% of those published for age-matched control subjects and varied by 1-6% when all methods were compared. Systematic bias was greatest when FA-MS was compared with bioelectrical impedance analysis, which tended to underestimate TBW in smaller, female subjects. No bias related to subject size was observed in a comparison of FA-MS with SFT measurement or with more recent regression equations. CONCLUSIONS: FA-MS is a simple and effective new approach to TBW measurement in healthy subjects. The difficulty of using population-derived equations to estimate TBW in individual subjects is emphasized.

Adult↗
PubMed2002

Quantifying comorbidity in peritoneal dialysis patients and its relationship to other predictors of survival.

BACKGROUND: Comorbidity is the single most important determinant of outcome in patients on renal replacement therapy. The aims of this study were to evaluate a semi-quantitative approach to comorbidity scoring in predicting survival of patients commencing peritoneal dialysis (PD), and to establish the interaction between this and other known predictors of patient outcome, in particular membrane function, residual renal function (RRF) and plasma albumin. METHODS: Comorbidity was recorded in a prospective, single centre cohort study of 303 patients commencing on PD. Using seven disease domains, chosen to reflect the dominance of cardiovascular morbidity in the end-stage renal failure population, comorbidity was graded as '0' when absent, '1' when one or two, and '2' when three or more conditions were present. The Wright comorbidity index, which includes age within the scoring method, was also evaluated. RRF, plasma albumin and peritoneal solute transport were measured every 6 months. Patients were censored at death. RESULTS: Median survival according to grade of comorbidity was 105, 42 and 29 months, respectively (P<0.0001), with good separation of the actuarial survival curves. Using Cox regression, the addition of age and the grade of comorbidity to Kt/V(urea), solute transport and plasma albumin increased the predictive power of the model. All were independent predictors of outcome with the exception of albumin. The Wright comorbidity index also enhanced the Cox model, although was not as powerful as when age and comorbidity were considered independently. At baseline, RRF was not different according to comorbidity unless diabetes was considered separately. Diabetics started with higher RRF, but after 6 months on PD this was the same as non-diabetic patients. Otherwise, initial rate of decline of RRF was similar across the comorbid grades, although the impact of higher drop-out due to earlier loss in patients with more comorbidity may have disguised earlier loss in these patients. Peritoneal solute transport tended to be higher in patients with increased comorbidity at baseline, chi(2) 13.8, P=0.032, and this was sustained with time on treatment. CONCLUSION: Comorbidity has a quantitative effect on survival that is independent of age, RRF and membrane function in PD patients. Comorbidity also appears to be associated with increased solute transport at the start of treatment, which is sustained. With the exception of diabetes, grade of comorbidity does not have a profound effect on loss of RRF.

Analysis of Variance↗
PubMed2001

Peritoneal glucose exposure and changes in membrane solute transport with time on peritoneal dialysis.

Peritoneal solute transport increases with time on treatment in a proportion of peritoneal dialysis (PD) patients, contributing to ultrafiltration failure. Continuous exposure of the peritoneum to hypertonic glucose solutions results in morphologic damage that may have a causative role in changes in peritoneal function. The purpose of this analysis was to establish whether increased exposure to glucose preceded changes in solute transport in a selected group of long-term PD patients. Peritoneal solute transport, residual renal function, peritonitis rate, and peritoneal exposure to glucose were recorded prospectively in a cohort of 303 patients at a single dialysis center. A subgroup of individuals, treated continuously for 5 yr, were identified and defined retrospectively as having either stable or increasing transport status. Of the 22 patients who were treated continuously for 5 yr, 13 had stable solute transport (solute transport at start, 0.67 [+/-0.1]; at 5 yr, 0.67 [+/-0.1]), whereas 9 had a sustained increase (solute transport at start, 0.56 [+/-0.08]; at 5 yr, 0.77 [+/-0.09]). Compared with the stable patients, those with increasing transport had earlier loss in residual renal function and were exposed to significantly more hypertonic glucose during the first 2 yr of treatment that preceded the increase in solute transport. This was associated with greater achieved ultrafiltration compensating for the reduced urinary volumes in these patients. Further increases in glucose exposure were observed as solute transport continued to rise. Peritonitis, including severity of infection and causative organism, was similar in both groups. In this selected group of long-term survivors on PD, an increase in solute transport with time was preceded by increased peritoneal exposure to hypertonic glucose. This is supportive evidence that hypertonic glucose may play a causative role in alterations in peritoneal membrane function.

Adult↗
PubMedDate not supplied

A novel treatment of postherpetic neuralgia using peppermint oil.

BACKGROUND: Postherpetic neuralgia remains a difficult problem to treat. A number of therapies have been shown to be effective, but some patients have intractable pain. PATIENT: The case of a 76-year-old woman whose pain had been resistant to standard therapies is described. The pattern of quantitative sensory testing results for this patient led the authors to believe that she had an "irritable nociceptor" type of pathophysiology. INTERVENTION: The patient was instructed to apply neat peppermint oil (containing 10% menthol) to her skin, resulting in an almost immediate improvement in her pain. This pain relief persisted for 4-6 hours after application of the oil. RESULTS: The patient was successfully treated with topical peppermint oil. During 2 months of follow-up she has had only a minor side effect, with continuing analgesia. The authors believe this is the first evidence of peppermint oil (or menthol) having a strong analgesic effect on neuropathic pain. The possible mechanisms of action of peppermint oil are discussed.

Aged↗
PubMedDate not supplied

Selected growth factors in peritoneal dialysis: their relationship to markers of inflammation, dialysis adequacy, residual renal function, and peritoneal membrane transport.

OBJECTIVES: Markers of chronic inflammation, acute-phase reactants, and growth factors may be concomitantly involved in a number of pathologic processes in the general population and uremic patients. In addition, growth factors may influence peritoneal membrane transport characteristics. However, the association between plasma growth factors, markers of chronic inflammation, and peritoneal membrane transport remains largely unknown. The aim of this study was to evaluate the relationship between plasma levels of selected growth factors [basic fibroblast growth factor (bFGF), transforming growth factor beta1 (TGFbeta1), vascular endothelial growth factor (VEGF)] and markers of chronic inflammation [interleukin (IL)-6, C-reactive protein (CRP), and fibrinogen] in continuous ambulatory peritoneal dialysis (CAPD) patients. The potential link between the above substances and dialysis adequacy was also explored. DESIGN: Single-center, cross-sectional study. SETTING: Peritoneal Dialysis Unit, Medical Faculty, Jagiellonian University Hospital, Kraków, Poland. PATIENTS: 32 stable end-stage renal disease patients (13 M, 19 F; mean age 53.6 +/- 13.7 years) on CAPD for a median period of 19.5 months. Patients free from signs and symptoms of any inflammatory disease (including peritonitis) for at least 3 months were included into the study. All patients underwent measurements of dialysis dose [Kt/V, weekly creatinine clearance (wCCr)] and peritoneal solute transport using a standard peritoneal equilibration test (PET). METHODS: TGFbeta1, bFGF, VEGF, and IL-6 were measured with ELISA, CRP was assayed with immunonephelometry, and fibrinogen with Multifibren U reagent (Dade Behring Marburg GmbH, Marburg, Germany). Nephron 97 for Windows software was used to assess dialysis adequacy. RESULTS: Significant positive correlations between plasma bFGF and IL-6, as well as fibrinogen concentrations (R = 0.36, p < 0.05 and R = 0.39, p < 0.05, respectively), were found. VEGF correlated significantly with IL-6 and CRP (R = 0.65, p < 0.0001 and R = 0.51, p < 0.005, respectively). An association between VEGF and bFGF was also found (R = 0.59, p < 0.0005). Serum level of TGFbeta1 revealed no relationship with any marker of acute-phase activation, remaining growth factors, or dialysis adequacy. Positive correlation between TGFbeta1 concentration and dialysate-to-plasma ratio for creatinine in PET (R = 0.35, p < 0.05) was found. In addition, patients with lower solute transport (low/low-average transporters) had lower serum levels of both bFGF and TGFbeta1 compared to patients with higher solute transport. Patients with total wCCr > 60 L/ week/m2 were characterized by lower levels of bFGF and IL-6. Serum level of IL-6 and plasma levels of bFGF and VEGF were significantly lower among subjects with residual renal function (RRF) > 2.0 mL/minute. CONCLUSIONS: Our results indicate that systemic inflammation in peritoneal dialysis patients is associated with increased plasma VEGF and bFGF but not TGFbeta1. The negative correlation with RRF suggests that either the renal clearance of these cytokines and growth factors may contribute to their elimination, or cytokines and growth factors have a negative impact on RRF. We also suggest an association between serum levels of growth factors tested and peritoneal membrane function.

Adult↗