Impact of different COVID-19 waves on kidney replacement therapy epidemiology and mortality: REMER 2020.

BACKGROUND: Kidney replacement therapy (KRT) confers the highest risk of death from coronavirus disease 2019 (COVID-19). However, most data refer to the early pandemic waves. Whole-year analysis compared with prior secular trends are scarce. METHODS: We present the 2020 REMER Madrid KRT registry, corresponding to the Spanish Region hardest hit by COVID-19. RESULTS: In 2020, KRT incidence decreased 12% versus 2019, while KRT prevalence decreased by 1.75% for the first time since records began and the number of kidney transplants (KTs) decreased by 16%. Mortality on KRT was 10.2% (34% higher than the mean for 2008-2019). The 2019-2020 increase in mortality was larger for KTs (+68%) than for haemodialysis (+24%) or peritoneal dialysis (+38%). The most common cause of death was infection [n = 419 (48% of deaths)], followed by cardiovascular [n = 200 (23%)]. Deaths from infection increased by 167% year over year and accounted for 95% of excess deaths in 2020 over 2019. COVID-19 was the most common cause of death (68% of infection deaths, 33% of total deaths). The bulk of COVID-19 deaths [209/285 (73%)] occurred during the first COVID-19 wave, which roughly accounted for the increased mortality in 2020. Being a KT recipient was an independent risk factor for COVID-19 death. CONCLUSIONS: COVID-19 negatively impacted the incidence and prevalence of KRT, but the increase in KRT deaths was localized to the first wave of the pandemic. The increased annual mortality argues against COVID-19 accelerating the death of patients with short life expectancy and the temporal pattern of COVID-19 mortality suggests that appropriate healthcare may improve outcomes.

Characterization of hypersensitivity reactions to polysulfone hemodialysis membranes.

BACKGROUND: In recent years, cases have been reported in which unexpected systemic hypersensitivity reactions occurred in patients dialyzed with polysulfone- or polyethersulfone-biocompatible membranes in the absence of other risk factors. The pathomechanisms involved in these reactions are largely unknown. OBJECTIVE: To characterize hypersensitivity reactions to polysulfone hemodialysis using clinical and laboratory data and to identify biomarkers suitable for endotype identification and diagnosis. METHODS: We prospectively collected data from 29 patients with suspected hypersensitivity reactions to polysulfone hemodialysis membranes. Clinical laboratory parameters such as tryptase, blood cell counts, and complement levels were recorded. Acute samples were obtained from 18 cases for the ex vivo assessment of basophil activation by flow cytometry analysis of CD63, CD203, and FcεRI cell membrane expression. Serum cytokines and anaphylatoxin concentrations were evaluated in 16 cases by Luminex and cytometric bead array analysis. RESULTS: Tryptase was elevated during the acute reaction in 4 cases. Evidence of basophil activation was obtained in 10 patients. Complement activation was found in only 2 cases. However, C5a serum levels tended to increase during the acute reaction in those patients with hypoxemia. Significantly higher serum levels of interleukin-6 were observed during the acute reactions to polysulfone hemodialysis (P = .0103). CONCLUSION: Based on biomarker analysis, various endotypes were identified, including type I-like (with the involvement of mast cells or basophils), complement, and cytokine (interleukin-6) release-related reactions, with some patients showing mixed reactions. Further research is needed to unravel the exact mechanisms involved in the activation of these cellular and molecular pathways.

Markers of endothelial damage in patients with chronic kidney disease on hemodialysis.

Patients with Stage 5 chronic kidney disease who are on hemodialysis (HD) remain in a chronic inflammatory state, characterized by the accumulation of uremic toxins that induce endothelial damage and cardiovascular disease (CVD). Our aim was to examine microvesicles (MVs), monocyte subpopulations, and angiopoietins (Ang) to identify prognostic markers in HD patients with or without diabetes mellitus (DM). A total of 160 prevalent HD patients from 10 centers across Spain were obtained from the Biobank of the Nephrology Renal Network (Madrid, Spain): 80 patients with DM and 80 patients without DM who were matched for clinical and demographic criteria. MVs from plasma and several monocyte subpopulations (CD142+/CD16+, CD14+/CD162+) were analyzed by flow cytometry, and the plasma concentrations of Ang1 and Ang2 were quantified by ELISA. Data on CVD were gathered over the 5.5 yr after these samples were obtained. MV level, monocyte subpopulations (CD14+/CD162+ and CD142+/CD16+), and Ang2-to-Ang1 ratios increased in HD patients with DM compared with non-DM patients. Moreover, MV level above the median (264 MVs/µl) was associated independently with greater mortality. MVs, monocyte subpopulations, and Ang2-to-Ang1 ratio can be used as predictors for CVD. In addition, MV level has a potential predictive value in the prevention of CVD in HD patients. These parameters undergo more extensive changes in patients with DM.

Mechanisms Involved in Hypersensitivity Reactions to Polysulfone Hemodialysis Membranes.

Several cases of patients with anaphylactic or systemic hypersensitivity reactions to polysulfone (PS) hemodialysis (HD) membranes and tolerance to cellulose triacetate (CTA) membranes have recently been reported. To investigate the mechanisms involved in PS hypersensitivity, basophil, T cell, and complement activation were analyzed in acute-phase samples from two patients with systemic reactions to PS-based membranes. Basophil and T cell activation, as well as higher serum tryptase levels were detected in acute-phase samples compared with basal levels. Complement levels (C3 and C4) were decreased in acute-phase samples from PS-allergic patients to a higher extent than in samples from control donors taken at the same time points, indicating complement activation during the acute reactions. An experimental external circuit was established on pediatric membranes after rinsing with low or high priming volumes of saline solution, to analyze basophils, T cells, and complement activation in blood samples from 10 PS-allergic and 8 nonallergic HD patients upon contact with PS-based or CTA membranes. Predialysis and postdialysis samples were collected. Basophils from PS-allergic patients exhibited increased degranulation, and T cells showed significantly increased activation after contact with PS-based membranes primed with low volumes of saline. No activation was detected in leukocytes from nonallergic patients under the same experimental conditions. Membrane priming with high volumes of saline abrogated activation of basophils and T cells. However, basophils from allergic donors showed significantly higher responses to Fcεc stimulation after contact with PS membranes. Basophil degranulation and elevated serum tryptase levels in allergic patients during acute reactions support the systemic activation of mast cells and basophils during hypersensitivity reactions to PS-based membranes. A leachable component of the membranes might be responsible for cell activation in some patients.

Etiopathogenesis of chronic kidney disease-associated pruritus: putting the pieces of the puzzle together.

Defined as the unpleasant sensation that causes the desire to scratch, pruritus is the most common skin symptom associated with uremia and appears in almost half of patients with advanced chronic kidney disease (CKD). Beyond its direct impact on quality of life, CKD-associated pruritus (CKD-aP) is an independent predictor of mortality that also has a synergistic effect with other quality of life-related symptoms, such as insomnia, depression, and anxiety. Although different mechanisms have been proposed to explain the origin of Pa-ERC, its etiopathogenesis is still not fully understood. Since new therapeutic targets have been identified and several clinical trials have recently shown promising results, our current understanding of the interrelationships has expanded significantly and the pathophysiological mechanisms underlying CKD-aP are now considered to be multifactorial. The potential triggers of pruritus in patients with CKD are discussed in this review, including hypotheses about skin xerosis, accumulation of uremic toxins, dysregulation of the immune system and systemic inflammation, uremic neuropathy, and imbalances in the endogenous opioid system. Other non-uremic causes of pruritus are also discussed, with the aim of guiding the physicians to apply an adequate aetiopathogenic approach to CKD-aP in their day-to-day clinical practice.

Perception of Spanish nephrologists on an old unsolved problem: Pruritus associated with chronic kidney disease (CKD-aP).

INTRODUCTION: Pruritus associated with chronic kidney disease is defined as the sensation of itching, in people with chronic kidney disease, in a one area or all over the body that causes the need to scratch, after having ruled out other dermatological or systemic causes. It is an old and known problem whose prevalence has been able to decrease with the improvement of dialytic techniques but which still persists and is underdiagnosed. OBJECTIVES: The objective of this study was to analyse the current perception of nephrologists about this problem that influences the quality of life of people with chronic kidney disease through a survey. RESULTS: 135 nephrologists, most of them engaged in haemodialysis, participated. 86% considered that pruritus associated with chronic kidney disease is still a problem today that affects the quality of life. Most nephrologists believe that the main pathophysiological cause is uremic toxins (60%) and only 16% believe that it is due to the dysregulation of the opioid system/endorphins-dynorphins. Only 16% comment that the prevalence of pruritus in their centre is greater than 20%. 40% believe that the diagnosis is made because it is manifested by the patient and only 27% because it is asked by the doctor. Moreover, it is not usual to use scales to measure it or the codification in the medical records. The main treatment used is antihistamines (96%), followed by moisturizers/anaesthetics (93%) and modification of the dialysis regimen (70%). CONCLUSIONS: Pruritus associated with chronic kidney disease is still a current problem, it is underdiagnosed, not codified and with a lack of indicated, effective and safe treatments. Nephrologists do not know its real prevalence and the different pathophysiological mechanisms involved in its development. Many therapeutic options are used with very variable results, ignoring their efficacy and applicability at the present time. The new emerging kappa-opioid-receptor agonist agents offer us an opportunity to reevaluate this age-old problem and improve the quality of life for our patients with chronic kidney disease.

Chronic Kidney Disease-Associated Pruritus and Quality of Life: Learning from Our Patients.

Chronic kidney disease-associated pruritus is itching directly related to kidney disease that cannot be explained by any other condition. Despite technological advances in the different aspects of dialysis sessions and the best treatment for chronic kidney disease patients, it is still a common problem in our patients. The many complex physiological mechanisms involved, the different hypotheses made over the years on the aetiology of the condition, and the great clinical variability may partially explain the limited knowledge about this problem and the difficulties in treating it. The presence of all these factors leads to the persistence of unpleasant symptoms, which must affect the disease burden and quality of life of kidney patients. Through the presentation of an illustrative clinical case, the aim of this review article is to highlight the need for adequate diagnosis and an improved approach to all aspects of chronic kidney disease-associated pruritus, in view of the heavy burden of the disease and the huge impact on the patient's quality of life.

Pruritus in dialysis patients. Review and new perspectives.

Uremic pruritus (UP) is one of the most uncomfortable symptoms for patients in dialysis. UP has a great impact on dialysis patients' quality of life and has a great prevalence between those (28-70%). Physiopathology of UP is unknown and usually is unnoticed for most nephrologists (in more than 65% of centers is underdiagnosed). This lack of awareness drives to the unsuccessful treatment of this symptom. Moreover, the fact that most studies have been carried out on small populations and the difficulty assessing UP complicates a correct therapeutical approach. For this reason, we have designed treatment algorithms based on the efficacy of the drugs but also its safeness to avoid adverse effects.

Alternative activation of macrophages in human peritoneum: implications for peritoneal fibrosis.

BACKGROUND: Depending on the cytokine microenvironment, macrophages (Mϕ) can adopt a proinflammatory (M1) or a profibrotic (M2) phenotype characterized by the expression of cell surface proteins such as CD206 and CD163 and soluble factors such as CC chemokine ligand 18 (CCL18). A key role for Mϕ in fibrosis has been observed in diverse organ settings. We studied the Mϕ population in a human model of peritoneal dialysis in which continuous stress due to dialysis fluids and recurrent peritonitis represent a risk for peritoneal membrane dysfunction reflected as ultrafiltration failure (UFF) and peritoneal fibrosis. METHODS: We used flow cytometry and quantitative reverse transcription-polymerase chain reaction to analyse the phenotype of peritoneal effluent Mϕ and tested their ability to stimulate the proliferation of human fibroblasts. Mϕ from non-infected patients were compared with those from patients with active peritonitis. Cytokine production was evaluated by enzyme-linked immunosorbent assay (ELISA) in spent dialysates and cell culture supernatants. RESULTS: CD206(+) and CD163(+) M2 were found within peritoneal effluents by flow cytometry analysis, with increased frequencies of CD163(+) cells during peritonitis (P = 0.003). TGFB1, MMP9 and CCL18 messenger RNA (mRNA) levels in peritoneal macrophages (pMϕ) were similar to those found in M2 cells differentiated in vitro. The ability of pMϕ to stimulate fibroblast proliferation correlated with CCL18 mRNA levels (r = 0.924, P = 0.016). CCL18 production by pMϕ was confirmed by immunostaining of cytospin samples and ELISA. Moreover, CCL18 effluent concentrations correlated with decreased peritoneal function, which was evaluated as dialysate to plasma ratio of creatinine (r = 0.724, P < 0.0001), and were significantly higher in patients with UFF (P = 0.0025) and in those who later developed sclerosing peritonitis (P = 0.024). CONCLUSIONS: M2 may participate in human peritoneal fibrosis through the stimulation of fibroblast cell growth and CCL18 production as high concentrations of CCL18 are associated with functional deficiency and fibrosis of the peritoneal membrane.

Low-GDP peritoneal dialysis fluid ('balance') has less impact in vitro and ex vivo on epithelial-to-mesenchymal transition (EMT) of mesothelial cells than a standard fluid.

BACKGROUND: Peritoneal membrane deterioration during peritoneal dialysis (PD) is associated with epithelial-to-mesenchymal transition (EMT) of mesothelial cells (MC), which is believed to be mainly due to glucose degradation products (GDPs) present in PD solutions. Here we investigate the impact of GDPs in PD solutions on the EMT of MC in vitro and ex vivo. METHODS: For in vitro studies, omentum-derived MC were incubated with standard PD fluid or low-GDP solution diluted 1:1 with culture medium. For ex vivo studies, 33 patients, who were distributed at random to either the 'standard' or the 'low GDP' groups, were followed over 24 months. Effluents were collected every 6 months to determine EMT markers in effluent MC. RESULTS: Exposure of MC to standard fluid in vitro resulted in morphological change into a non-epitheloid shape, down-regulation of E-cadherin, indicative of EMT, and in a strong induction of vascular endothelial growth factor (VEGF) expression. In contrast, in vitro exposure of MC to low-GDP solution did not lead to these phenotype changes. This could be confirmed ex vivo, as the prevalence of non-epitheloid phenotype of MC in the standard group was significantly higher with increasing PD duration and MC isolated from this group showed significantly higher levels of EMT-associated molecules including fibronectin, collagen I, VEGF, IL-8 and TGF-ß levels when compared with the low-GDP group. Over time, the expression of E-cadherin also decreased in the standard but increased in the low-GDP group. In addition, the levels of EMT-associated molecules (fibronectin, VEGF and IL-8) increased in the standard but decreased in the low-GDP group. A similar trend was also observed for collagen I and for TGF-ß (for the first year), but did not reach global statistical significance. Accordingly, effluent MC with non-epitheloid morphology showed significantly lower levels of E-cadherin and greater levels of fibronectin, collagen I, VEGF and IL 8 when compared with MC with epitheloid phenotype. The incidence of peritonitis did not significantly influence these results. Drop-out due to technique failure was less in the 'balance' group. The functional, renal and peritoneal evaluation of patients being treated with either standard or 'balance' fluid did not show any significant difference over time. CONCLUSIONS: MC from PD effluent of patients treated with a PD fluid containing low GDP levels show fewer signs of EMT and the respective molecules than MC from patients treated with standard fluid, indicating a better preservation of the peritoneal membrane structure and a favourable outcome in patients using low-GDP fluid. It also confirms the hypothesis that the protection of EMT by GDP-reduced fluids is also present in vivo.

COVID-19 incidence and outcomes in a home dialysis unit in Madrid (Spain) at the height of the pandemic.

INTRODUCTION: The 2019 coronavirus (COVID-19) is a viral infection caused by a new coronavirus that is affecting the entire world. There have been studies of patients on in-center hemodialysis (HD), but home dialysis population data are scarce. Our objective is to study the incidence and course of COVID-19 in a home dialysis unit (HDU) at the height of the pandemic. METHODS: an observational, retrospective study enrolling all patients diagnosed with COVID-19 from the HDU of Hospital Universitario La Paz [La Paz University Hospital] (Madrid, Spain) between March 10 and May 15, 2020. We collected clinical data from the HDU (57 patients on peritoneal dialysis [PD] and 22 patients on home hemodialysis [HHD]) and compared the clinical characteristics and course of patients with and without COVID-19 infection. RESULTS: twelve patients were diagnosed with COVID-19 (9 PD; 3 HHD). There were no statistically significant differences in terms of clinical characteristics between patients with COVID-19 and the rest of the unit. The mean age was 62 ± 18.5 years; most were men (75%). All patients but one required hospitalization. Ten patients (83%) were discharged following a mean of 16.4 ± 9.7 days of hospitalization. Two patients were diagnosed while hospitalised for other conditions, and these were the only patients who died. Those who died were older than those who survived. CONCLUSION: The incidence of COVID-19 in our HDU in Madrid at the height of the pandemic was high, especially in patients on PD. No potential benefit for preventing the infection in patients on home dialysis was observed. Advanced age and nosocomial transmission were the main factors linked to a worse prognosis.

[COVID-19 incidence and outcomes in a home dialysis unit in Madrid (Spain) at the height of the pandemic]. / Incidencia y resultados de la COVID-19 en una unidad de diálisis domiciliaria en Madrid (España) durante el pico de la pandemia.

INTRODUCTION: The 2019 coronavirus (COVID-19) is a viral infection caused by a new coronavirus that is affecting the entire world. There have been studies of patients on in-center hemodialysis, but home dialysis population data are scarce. Our objective is to study the incidence and course of COVID-19 in a home dialysis unit (HDU) at the height of the pandemic. METHODS: An observational, retrospective study enrolling all patients diagnosed with COVID-19 from the HDU of Hospital Universitario La Paz (La Paz University Hospital) (Madrid, Spain) between March 10 and May 15, 2020. We collected clinical data from the HDU (57 patients on peritoneal dialysis and 22 patients on home hemodialysis) and compared the clinical characteristics and course of patients with and without COVID-19 infection. RESULTS: Twelve patients were diagnosed with COVID-19 (9 peritoneal dialysis; 3 home hemodialysis). There were no statistically significant differences in terms of clinical characteristics between patients with COVID-19 and the rest of the unit. The mean age was 62±18.5 years; most were men (75%). All patients but one required hospitalization. Ten patients (83%) were discharged following a mean of 16.4±9.7 days of hospitalization. Two patients were diagnosed while hospitalized for other conditions, and these were the only patients who died. Those who died were older than those who survived. CONCLUSION: The incidence of COVID-19 in our HDU in Madrid at the height of the pandemic was high, especially in patients on peritoneal dialysis. No potential benefit for preventing the infection in patients on home dialysis was observed. Advanced age and nosocomial transmission were the main factors linked to a worse prognosis.

Pruritus in dialysis patients. Review and new perspectives. / Prurito en pacientes en diálisis. Revisión de la literatura y nuevas perspectivas.

Uremic pruritus (UP) is one of the most uncomfortable symptoms for patients in dialysis. UP has a great impact on dialysis patients' quality of life and has a great prevalence between those (28-70%). Physiopathology of UP is unknown and usually is unnoticed for most nephrologists (in more than 65% of centers is underdiagnosed). This lack of awareness drives to the unsuccessful treatment of this symptom. Moreover, the fact that most studies have been carried out on small populations and the difficulty assessing UP complicates a correct therapeutical approach. For this reason, we have designed treatment algorithms based on the efficacy of the drugs but also its safeness to avoid adverse effects.

Multidisciplinary nutritional consensus on assessment and nutritional dietary treatment in patients with chronic kidney disease and SARS-CoV-2 infection.

The presence of malnutrition in patients with Chronic Kidney Disease (CKD) is high, it can be made worse by SARS-CoV2 infection. The nutritional assessment should be adapted to minimize the infection, recommending monitoring: weight loss percentage, body mass index (BMI), loss of appetite, analytical parameters and functional capacity using the dynamometer. As well as the sarcopenia assessment using the SCARF scale, and the possibility of using the GLIM criteria in those patients who have been tested positive by MUST. It is important to adapt the nutritional recommendations in the caloric and protein intake, to the CKD stage and to the SARS-CoV2 infection stage. In patients with hypercatabolism, to prioritize preserving the nutritional status (35 kcal/kg weight/day, proteins up to 1.5 g/kg/day). The rest of the nutrients will be adapted to CKD stage and the analytical values. In the post-infection stage, a complete nutritional assessment is recommended, including sarcopenia. The energy and protein requirements in this phase will be adapted to the nutritional status, with special attention to the loss of muscle mass. Dietary recommendations need to be tailored to side effects of SARS-CoV-2 infection: anorexia, dysphagia, dysgeusia, and diarrhea. Anorexia and hypercatabolism makes it difficult to meet the requirements through diet, therefore the use of oral nutritional supplements is recommended as well as the enteral or parenteral nutrition in severe phases.

[Multidisciplinary nutritional consensus on assessment and nutritional dietary treatment in patients with chronic kidney disease and SARS-CoV-2 infection]. / Consenso multidisciplinar sobre la valoración y el tratamiento nutricional y dietético en pacientes con enfermedad renal crónica e infección por SARS-CoV-2. Consenso de nutrición en enfermedad renal crónica e infección por SARS-CoV-2.

The presence of malnutrition in patients with chronic kidney disease (CKD) is high, it can be made worse by SARS-CoV-2 infection.The nutritional assessment should be adapted to minimize the infection, recommending monitoring: weight loss percentage, body mass index (BMI), loss of appetite, analytical parameters and functional capacity using the dynamometer. As well as the sarcopenia assessment using the SCARF scale, and the possibility of using the GLIM criteria in those patients who have been tested positive by MUST.It is important to adapt the nutritional recommendations in the caloric and protein intake, to the CKD stage and to the SARS-CoV-2 infection stage. In patients with hypercatabolism, to prioritize preserving the nutritional status (35 kcal/kg weight/day, proteins up to 1.5 g/kg/day). The rest of the nutrients will be adapted to CKD stage and the analytical values.In the post-infection stage, a complete nutritional assessment is recommended, including sarcopenia. The energy and protein requirements in this phase will be adapted to the nutritional status, with special attention to the loss of muscle mass.Dietary recommendations need to be tailored to side effects of SARS-CoV-2 infection: anorexia, dysphagia, dysgeusia, and diarrhea.Anorexia and hypercatabolism makes it difficult to meet the requirements through diet, therefore the use of oral nutritional supplements is recommended as well as the enteral or parenteral nutrition in severe phases.

High stable serum adiponectin levels are associated with a better outcome in prevalent dialysis patients.

AIMS: Our aim was to evaluate the prognostic value of 2 measurements of serum adiponectin levels for all-cause mortality and cardiovascular (CV) mortality in uremic patients. METHODS: We analyzed 184 patients (19-86 years) undergoing peritoneal dialysis (n = 86) or hemodialysis (n = 98). All patients had 2 measurements of serum adiponectin levels (at baseline and after 1 year). Relationships between adiponectin and mortality were studied by means of survival analysis and Cox regression analysis. RESULTS: During a median follow-up time of 31.2 months, 67 patients (36.4%) died, 26 (14.1%) as a result of CV disease. Mean survival time for CV mortality in patients with 1-year adiponectin values in the upper tertile was significantly higher than that found in patients in the middle and lower tertiles. Hazard ratios (HR) for all-cause mortality per SD change were 0.70 (95% CI, 0.50-0.98; p < 0.05) for baseline adiponectin levels and 0.68 (0.49-0.95; p < 0.05) for mean baseline and 1-year adiponectin levels. Mean adiponectin levels were also negatively related with CV mortality [HR 0.43 (0.21-0.86); p < 0.05] and CV events [HR 0.74 (0.55-0.99); p < 0.05]. CONCLUSIONS: In this population of dialysis patients, adiponectin seems to behave as a CV protective factor. Patients with high mean adiponectin levels had a better survival rate.

Higher daily peritoneal protein clearance when initiating peritoneal dialysis is independently associated with peripheral arterial disease (PAD): a possible new marker of systemic endothelial dysfunction?

BACKGROUND: Patients starting peritoneal dialysis (PD) with active cardiovascular disease (CVD) show higher protein and albumin levels in peritoneal effluent. Peripheral arterial disease (PAD) is increasingly recognized as an entity particularly associated with higher mortality. METHODS: To explore whether higher daily peritoneal protein clearance (PrC) on starting PD is a cardiovascular risk marker, we have formulated the hypothesis that PAD, as an expression of the highest CVD grade, is specifically related to the amount of PrC. RESULTS: The average of 24-h effluent peritoneal protein losses (PPL) was 6.88 +/- 3.31 g. The median of PrC was 94.43 ml/day and quartiles 1 and 4 were delimited by 56.25 and 114.18 ml/day, respectively. A significant positive correlation between PrC and peritoneal small solute transport was detected. Patients in the highest quintile of Cr-MTAC (>14.04 ml/min) demonstrated significantly greater PrC than the remainder. An inverse significant correlation with plasma albumin levels was also demonstrated (r = -0.52, P = 0.0001). Eighteen patients with PAD showed significantly higher PrC than patients with no PAD (130.62 +/- 74.89 versus 88.77 +/- 47.56 ml/day; P = 0.033). Other CVDs were not significantly associated with greater PrC. In the univariable logistic regression analysis, PAD was directly and significantly related to PrC, Charlson's index, gender, diabetes and age. Multivariable analysis confirmed that PAD was significantly related to PrC, independent of age (RR: 1.07, IC: 1.02-1.12, P = 0.006) and diabetes (RR: 11.29, IC: 2.9-42.60, P = 0.000). CONCLUSION: Our study shows that daily peritoneal PrC on initiating PD is significantly and independently related to the presence of PAD. Peritoneal PrC appears to be a possible new marker of systemic endothelial dysfunction.

Evaluating the optimal time for amikacin administration with respect to haemodialysis using an in vitro pharmacodynamic simulation against epidemic nosocomial OXA-48 producing Klebsiella pneumoniae ST405 strains.

OBJECTIVES: Bacterial viability and enrichment of resistance resulting from three different amikacin administration schedules with respect to haemodialysis (HD) were assessed against three OXA-48-producing Klebsiella pneumoniae isolated during an outbreak in a Spanish hospital. METHODS: A previously described two-compartment dynamic system was used. Three possible amikacin administration schedules were simulated: (i) haemodialysis immediately after amikacin infusion (pre-HD); (ii) infusion immediately after haemodialysis (post-HD); and (iii) infusion at 50% interdialytic period. Amikacin standard dose (SD) and double dose (DD) were simulated for each schedule. Values of Cmax/MIC, Cmax/MPC (mutant prevention concentration), AUC0-48h/MIC, AUC0-48h/MPC and %TMSW (percentage of time that the concentration was inside the mutant selection window) were determined with experimental data and were correlated with the area under the bacterial killing curve of the total population and the resistant subpopulation. RESULTS: Both with SD and DD, the pre-HD schedule resulted in increases at 48h in bacterial counts of the total population at the expense of enrichment of pre-existing resistant subpopulations from 12h onwards for all strains. The estimated %TMSW that prevented enrichment of resistant mutants was <61.5%. The AUC0-48h/MPC (with values of ≈40 being associated with countering of increases in resistant subpopulations) was better than the %TMSW as a predictive parameter. CONCLUSION: This study showed that the longest times concentrations were above the MPC (i.e. highest AUC0-48h/MPC, lowest %TMSW), the lowest enrichment of resistant subpopulations. This implies use of the highest possible amikacin dose (limited by toxicity) and post-HD as the best administration schedule.

Peritoneal dialysis in the comprehensive management of end-stage renal disease patients with liver cirrhosis and ascites: practical aspects and review of the literature.

The treatment of cirrhotic patients with ascites and end-stage renal disease is complex, due mainly to decreased effective arterial volume and hemodynamic instability. Peritoneal dialysis as a continuous therapy represents an alternative to hemodialysis-related intolerance. We report on our experience and that of others with cirrhotic patients with ascites treated by peritoneal dialysis. Hemodynamic tolerance was excellent in all patients and solute and water peritoneal transport increased to above the normal range in almost all cases. Morbidity and mortality were related principally to liver disease and other comorbidities. Peritoneal protein losses, initially high, decreased over time, maintaining serum albumin within the low normal range. The incidence of peritonitis was similar or slightly higher than usual in these patients, with peculiar etiology. The experiences with peritoneal dialysis suggest consideration of this treatment as the first choice for cirrhotic patients with ascites and that need to start dialysis.