Vancomycin and daptomycin stability in heparin or sodium citrate lock solutions.

BACKGROUND: We investigated physical and chemical stability of daptomycin and vancomycin in heparin or sodium citrate lock solutions. The aim of this study was to find the optimal combination of antimicrobials and additives for lock solutions, which maximized patient safety. METHODS: Vancomycin and daptomycin were diluted with heparin or sodium citrate to achieve final concentrations of vancomycin-heparin 2.5 mg/mL-833.33 U/mL, vancomycin-citrate 2.5-33.3 mg/mL, daptomycin-heparin 5 mg/mL-800 U/mL, and daptomycin-citrate 5-32 mg/mL and they were stored at room temperature (+25°C), 4°C, -20°C, and 37°C. Physical and chemical stability were analyzed for each antibiotic-anticoagulant combination in all conditions immediately after preparation, at 24, 48, 72 h and at different time points until unstable concentrations were obtained. Daptomycin-sodium citrate microbiological activity was also studied by evaluating two Staphylococcus aureus cultures in a calcium enriched medium with a daptomycin E test, with and without sodium citrate. RESULTS: After incubation at 37°C vancomycin and daptomycin combined with heparin retained at least 90% of the initial concentration over 48 h. Vancomycin-sodium citrate solution stored at 37°C reduced more than 10% of the initial concentration at 24 h. On the other hand, daptomycin-sodium citrate preparation was stable at 37°C for 72 h but the microbiological activity of daptomycin was lower in the presence of sodium citrate. CONCLUSIONS: The purpose is to prepare vancomycin and daptomycin lock solutions combined with heparin. They should be changed at 48 h and its stability is over 3 days at 25°C and 7 days at 4°C, which allow Hospital Pharmacy Services to manage their stocks. Daptomycin-sodium citrate combination is more stable for extended periods but its bioactivity has not been demonstrated.

Subclinical Hypothyroidism in Advanced Chronic Kidney Disease Patients: Prevalence and Associated Factors.

Introduction: Renal function and thyroid metabolism are tightly related. However, evidence about subclinical hypothyroidism prevalence in patients with chronic kidney disease and its related factors is scarce. Objectives: Our aim is to analyze subclinical hypothyroidism prevalence and its related factors in patients with advanced chronic kidney disease. Materials and methods. Nondialysis-dependent patients with chronic kidney disease at stages 3 to 5 were included. Other inclusion criteria were age above 18 years and clinical stability. Patients with diagnosed thyroid illnesses were excluded. Subclinical hypothyroidism was defined as thyroid stimulating hormone (TSH) > 5.3 mU/L, with free thyroxine 4 (FT4) between 0.54 and 1.24 ng/dl. Filiation data, comorbidities, and routine blood and urine test results were registered. Results: A total of 299 patients were included. Of them, 184 (61.5%) were men. The mean age was 71 ± 13 years old. The mean glomerular filtration rate (CKD-EPI) was 22 ± 9 ml/min/1.73 m2. According to chronic kidney disease stages, global distribution of patients was as follows: Stage 3, 67 patients (22.4%); Stage 4, 155 patients (51.8%); and Stage 5, 77 patients (25.8%). We found subclinical hypothyroidism in 54 (18.1%) patients. According to chronic kidney disease stages, distribution of affected patients was as follows: Stage 3, 9 patients (13%); Stage 4, 25 patients (16.1%); and Stage 5, 20 patients (26%). Differences among stages were statistically significant. By univariate analysis, factors related with subclinical hypothyroidism were as follows: age RR 1.048 (95% CI 1.019-1.078; p=0.001), hypertension RR 2.705 (95% CI 1.026-7.130; p=0.04), glomerular filtration rate RR 0.962 (95% CI 0.929-0.996; p=0.03), and proteinuria higher than 1 gram/day RR 2.387 (95% CI 1.303-4.374; p=0.005). By multivariate analysis adjusted by age, hypertension, glomerular filtration rate, proteinuria, diabetes, and cardiovascular disease history, only age RR 1.016 (95% CI 1.009-1.028; p=0.04) and glomerular filtration rate RR 0.963 (95% CI 0.930-0.997; p=0.03) preserved their independent association with subclinical hypothyroidism. Conclusions: Subclinical hypothyroidism prevalence in patients with chronic kidney disease is high and increases with renal disease severity. Factors independently related to subclinical hypothyroidism are age and glomerular filtration rate.

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.

Candida auris Invasive Infection after Kidney Transplantation.

INTRODUCTION: C. auris has been associated not only with a variety of invasive fungal infections, including candidemia, sometimes related to central venous catheter, but also with pericarditis and respiratory tract and urinary tract infections. MATERIALS AND METHODS: We describe the case of a patient with persistent fever despite antibiotics, who presented with Candida isolation in blood cultures, typified as Candida auris species. RESULTS: A 57-year-old male receiving peritoneal dialysis underwent kidney transplantation which was complicated by primary nonfunction due to arterial thrombosis necessitating graft nephrectomy. During the postoperative period, he presented with Pseudomonas aeruginosa pneumonia that was treated with levofloxacin and catheter-related Enterococcus faecalis bacteremia treated with linezolid. After hospital discharge, he then presented with herpes zoster infection treated with valacyclovir. Ten days later, he developed peritonitis and exit site infection with multidrug-resistant Pseudomonas aeruginosa treated with intraperitoneal aztreonam and peritoneal dialysis catheter removal. Despite broad-spectrum antibiotic therapy, the patient remained febrile. All microbiology laboratory tests were negative, so it was decided to stop antibiotic therapy for 48 hours and repeat cultures in order to avoid possible false negatives. In new blood cultures performed after suspension of antibiotic therapy, candidemia was observed, later typified as Candida auris species. After completing antifungal treatment (three weeks with intravenous amphotericin B 100 mg qd and two weeks of intravenous anidulafungin 100 mg qd), microbiological cultures remained negative and the patient made uneventful recovery. CONCLUSION: Candida auris invasive infection has been mainly described in patients with severe underlying comorbidities and immunocompromise. Multidrug-resistant clusters of Candida auris are increasingly emerging.

Characteristics and technical survival of home hemodialysis in the Valencian Community (1976-2020).

INTRODUCTION: Home hemodialysis (HDD) is implemented in the Valencian Community with a higher prevalence than to the rest of the national territory, with a prevalence of 13.4 patients pmp in December 2018. We carried out an assessment of the patients characteristics and the overall and technical survival in HDD depending on the historical moment of onset and its origin. MATERIAL AND METHODS: We conducted a retrospective and descriptive study including patients of the Valencian Registry of Renal Patients from the beginning of data reported until December 2020. We calculated overall survival (combined event death-technical failure, censoring transplantation) and technical survival (event technical failure, censoring exitus and transplantation). Comparing technical survival according to the starting era: ancient (1976-2000) vs modern (2001-2020) and according to the modality of origin. We performed univariate and multivariate Cox regression in the total series for both overall and technical survival. RESULTS: 236 patients on HDD (611.4 patient-years of follow-up), mean age 49.7±16.3 years; median time of prior renal replacement therapy 0.2 years. The ratio of transplantation, death, and technical failure were 13.2, 4.4, and 7 events per 100 patient-years, respectively. In the comparison by ancient (n=57) vs modern (n=179) eras, age (37.5 vs 53.5 years), DM (3.5 vs 13.4%) and chronic tubuleinterstitial nephropathy (24.6 vs 8.9%) as a cause of chronic kidney disease were statistically significant. The probability of coming from outpatient consultation (33.3 vs 48.6%) and peritoneal dialysis (1.8 vs 12.8%) were higher in modern era with statistical significance. In the ancient era a single hospital centralized 57.9% of the patients, and in the modern era between two hospitals centralized 55.8% of the patients. Overall survival in the ancient era was 83.7% at 1year, 77.4% at 2 years, and 61% at 5 years; and in the modern era 87.3% per year, 83% 2 years and 47.8% 5 years (Log Rank 0.521). Technical survival in the ancient era was 85.4% at 1year, 79% 2 years, and 64.1% 5 years; and in the modern era 91.4% per year, 88.5% 2 years and 74.5% 5 years (Log Rank 0.195). There were no statistical differences in the comparison based on technical of provenance. In the Cox regression it was statistically significant for overall survival: the age and being diagnosed with heart disease, vascular disease or active neoplasia and for technical survival liver disease or social problem, both in univariate and multivariate. CONCLUSIONS: In the modern era there is a considerable increase in HDD patients in the Valencian Community. There was a center effect in the development of HDD programs, most of the patients depended on few healthcare centers. The patients were older and had greater comorbidity in the modern era, despite this without affecting the technical and overall survival of the HDD.

Characteristics and technical survival of home hemodialysis in the Valencian Community (1976-2020). / C aracterísticas y supervivencia técnica de la hemodiálisis domiciliaria en la Comunidad Valenciana (1976-2020).

INTRODUCTION: Home hemodialysis (HDD) is implemented in the Valencian Community with a higher prevalence than to the rest of the national territory, with a prevalence of 13.4 patients' pmp in December 2018. We carried out an assessment of the patients' characteristics and the overall and technical survival in HDD depending on the historical moment of onset and its origin. MATERIAL AND METHODS: We conducted a retrospective and descriptive study including patients of the Valencian Registry of Renal Patients from the beginning of data reported until December 2020. We calculated overall survival (combined event death-technical failure, censoring transplantation) and technical survival (event technical failure, censoring exitus and transplantation). Comparing technical survival according to the starting era: ancient (1976-2000) vs modern (2001-2020) and according to the modality of origin. We performed univariate and multivariate Cox regression in the total series for both overall and technical survivals. RESULTS: 236 patients on HDD (611.4 patient-years of follow-up), mean age 49.7±16.3 years; median time of prior renal replacement therapy 0.2 years. The ratio of transplantation, death, and technical failure were 13.2, 4.4, and 7 events per 100 patient-years, respectively. In the comparison by ancient (n=57) vs modern (n=179) eras, age (37.5 vs 53.5 years), DM (3.5 vs 13.4%) and chronic tubuleinterstitial nephropathy (24.6 vs 8.9%) as a cause of chronic kidney disease were statistically significant. The probability of coming from outpatient consultation (33.3 vs 48.6%) and peritoneal dialysis (1.8 vs 12.8%) were higher in modern era with statistical significance. In the ancient era a single hospital centralized 57.9% of the patients, and in the modern era between two hospitals centralized 55.8% of the patients. Overall survival in the ancient era was 83.7% at 1 year, 77.4% at 2 years, and 61% at 5 years; and in the modern era 87.3% per year, 83% 2 years and 47.8% 5 years (Log Rank 0.521). Technical survival in the ancient era was 85.4% at 1 year, 79% 2 years, and 64.1% 5 years; and in the modern era 91.4% per year, 88.5% 2 years and 74.5% 5 years (Log Rank 0.195). There were no statistical differences in the comparison based on technical of provenance. In the Cox regression it was statistically significant for overall survival: the age and being diagnosed with heart disease, vascular disease or active neoplasia and for technical survival liver disease or social problem, both in univariate and multivariate. CONCLUSION: In the modern era there is a considerable increase in HDD patients in the Valencian Community. There was a center effect in the development of HDD programs, most of the patients depended on few healthcare centers. The patients were older and had greater comorbidity in the modern era, despite this without affecting the technical and overall survival of the HDD.

Experience in Spain with the first patients in home hemodialysis treated with low-flow dialysate monitors. / Experiencia en España con los primeros pacientes en hemodiálisis domiciliaria tratados con monitores de bajo flujo de líquido de diálisis.

Home hemodialysis (HHD) with low-flow dialysate devices has gained popularity in recent years due to its simple design, portability, and ability to provide greater freedom of movement for our patients. However, there are doubts about the adequacy that this technology offers, since it uses monitors with low-flow bath and lactate. The aim of this study was to demonstrate the clinical benefits of low-flow HHD with the NxStage System One® recently introduced in Spain. We present the results of an observational, retrospective cohort study that included the first patients who started short daily HHD with this device in 12 Spanish centers. We analyzed the evolution of 86 patients at 0, 6 and 12 months, including data related to prescription, and evolution of biochemical parameters related to dialysis dose, anemia, mineral-bone metabolism; evolution of residual renal function, medication usage, and causes of withdrawal during the followup. We were able to demonstrate that this NxStage System One® monitor, in patients with HHD, have provided an adequate dialysis dose, with optimal ultrafiltration rate, with improvement of main biochemical markers of dialysis adequacy. The usage of this technique was associated to a decrease of antihypertensive drugs, phosphate binders and erythropoietin agents, with very good results both patient and technique survival. The simplicity of the technique, together with its good clinical outcomes, should facilitate the growth and utilization of HHD, both in incident and prevalent patients.

Expanded home hemodialysis: case reports.

Among the different hemodialysis (HD) strategies, the short daily hemodialysis performed at home (SDHHD) provides clinical benefits to the patient. Expanded hemodialysis (HDx) employs cutoff medium membranes that exhibit greater clearance capacity of uremic toxins of medium-high molecular weight. This case series study reported the results of seven patients who were transferred to expanded hemodialysis at home (HHDx), from December 2017 to March 2019, over a 12-month follow-up period. The AK-98 monitor and Theranova 400 membrane (Baxter International Inc., Deerfield, IL, USA) were used. The main outcome measures were blood analytical values and drug consumption. The blood levels of ß2-microglobulin were significantly reduced (p = 0.0082), while maintaining albumin levels with less use of phosphorus binders. Regarding the safety profile, technique-related adverse events were not reported. According to the results of the current study, HHDx was a safe technique, which additionally had the ability to provide benefits to patients due to its greater purification capacity. Further studies, especially multicenter ones, with a greater number of patients are needed to confirm these results.

Is Expanded Hemodialysis an Option to Online Hemodiafiltration for Small- and Middle-Sized Molecules Clearance?

BACKGROUND: Recent evidence suggests a better reduction rate of some uremic toxins with expanded hemodialysis (HDx). METHODS: Prospective study including 8 hemodialysis patients. We divided the study in 2 phases; within the first one, we assigned 4 patients (group 1) to undergo online hemodiafiltration with a PF 210H dialyzer, and the other 4 patients (group 2) to undergo HDx with the high retention onset Theranova 500 dialyzer during 24 sessions. Later, during the second phase and after a washout period, the same patients were switched to receive HDx (group 1) and HDF (group 2). RESULTS: No differences were found in the Urea and ß2-microglobulin reduction ratio. However, in the case of myoglobin, the reduction ratio with HDF was 35 vs. 60% with HDx (p < 0.001). Similarly, in the case of prolactin, the reduction ratio with HDF was 45 and 61% with HDx (p < 0.001). CONCLUSIONS: We conclude that HDx is not inferior to online hemodiafiltration in the clearance of small and middle molecules and could be superior in the clearance of larger middle molecules.

Experiencia en hemodiálisis domiciliaria en España / Spanish home hemodialysis experience

Resumen Antecedentes: existe actualmente un interés creciente, a nivel mundial, por las posibilidades que ofrece la hemodiálisis domiciliaria, la cual se encuentra más extendida en países del norte de Europa, Canadá, Reino Unido, Estados Unidos, Australia y Nueva Zelanda. En España, ha crecido de manera muy lenta, excepto en determinadas regiones como la provincia de Castellón, donde hemos puesto especial interés en la expansión de las técnicas dialíticas domiciliarias. Objetivo: describir la experiencia en el programa de hemodiálisis domiciliaria del Hospital General de Castellón. Metodología: estudio descriptivo de los pacientes incluidos en el programa de hemodiálisis domiciliaria del Hospital General de Castellón, desde su inicio en enero del 2008 hasta diciembre del 2017. Resultados: en su conjunto, entrenamos a 41 pacientes, de los que 36 llegaron a hemodializarse en casa (régimen corto-diario). La edad de los pacientes era 58,3±13,4 años; y el índice de Charlson, 4,1±1,6. 62 % de los pacientes eran hombres, 25,6 % padecían diabetes mellitus; 15,4 % tenían diagnóstico de insuficiencia cardíaca y 32 % eran portadores de fístula de hemodiálisis. El 38,5 % de los pacientes en edad laboral estaba activo. Obtuvimos una supervivencia técnica considerando el evento muerte+fallo técnico, censurando el trasplante, del 79,4 % al año, 75,2 % a los 2 años y 42,1 % a los 5 años. En el análisis univariante, resultaron determinantes la edad, la presencia de diabetes mellitus y la presencia de insuficiencia cardíaca. En el análisis multivariante, solo se mantuvo la insuficiencia cardíaca. Las reducciones semanales de fósforo y beta-2-microglobulina fueron significativamente mayores con hemodiálisis corta diaria, en comparación con la hemodiafiltración on-line. La hemodiafiltración on-line fue superior en la reducción semanal a partir de los 17 800 daltons para la mioglobina. Conclusiones: la hemodiálisis domiciliaria es una técnica posible que ofrece al paciente una adecuada reinserción sociolaboral, buenos niveles de reducción semanal de toxinas urémicas y una aceptable supervivencia técnica en el tiempo.

Abstract Background: There is currently a growing interest, worldwide, for the possibilities offered by home hemodialysis, which is more widespread in northern European countries, Canada, the United Kingdom, the United States, Australia and New Zealand. In Spain, it has grown very slowly, except in certain regions such as the province of Castellón, where we have placed special interest in the expansion of home dialysis techniques. Objective: To describe the experience in the Home Hemodialysis program of the Hospital General de Castellón. Methodology: Descriptive study of the patients included in the home hemodialysis program of the Hospital General de Castellón, from its beginning in January 2008 to December 2017. Results: As a whole, we trained 41 patients, of whom 36 came to hemodialysis at home (short-day regimen). Age 58,3±13,4 years, Charlson index 4,1±1,6, 62 % men, 25,6 % with diabetes mellitus, 15,4 % with diagnosis of heart failure, 32 % with hemodialysis fistula, 38,5 % of working-age patients were active. We obtained a technical survival considering the event death+technical failure, censoring transplant of 79,4 % a year, 75,2 % at 2 years and 42,1 % at 5 years, resulting determinants of the event in the univariate analysis: age, presence of diabetes mellitus and presence of heart failure, and only heart failure in the multivariate. The weekly reductions of phosphorus and beta-2-microglobulin were significantly greater with daily short hemodialysis with respect to on-line haemodiafiltration. Being the on-line hemodiafiltration superior in the weekly reduction from the 17800 daltons of myoglobin. Conclusions: Home hemodialysis is a possible technique that offers the patient an adequate social-labor reintegration with good levels of weekly reduction of uraemic toxins and an acceptable technical survival over time.

Evaluation of coagulation and anti-Xa factor when using a heparin-coated AN69ST® dialyser.

BACKGROUND: Hemodialysis systems are potentially thrombogenic, so it is routinely used anticoagulation. Its prescription is with risks though which the recommendations regarding the scheduled dose are still based on very different criteria. METHODS: We performed a randomized, crossover pilot study. Six patients underwent six sessions of post-dilution hemodiafiltration with polysulfone HF80® dialyzer and standard anticoagulation with nadroparin, and six sessions with heparin-coated poliacrylonitrile AN69ST® membrane without using systemic anticoagulation. Dialyser and the extracorporeal circuit clotting grade was evaluated through visual scale every hour and coagulation parameters like anti-Xa factor. Our endpoint was to assess anti-Xa activity without differences in the rate of massive clotting between the two groups. RESULTS: No complete or grade 4 dialyzer clotting occurred in any of 36 sessions with each dialyzer. A partial lower 25% (grade 1-2) dialyzer clotting was in 32 (89.7%) AN69ST® sessions and 35 (97.2%) with the usual dialyzer and upper 25% (grade 3-4) in 4 (11.1%) AN69ST® sessions and 1 (2.8%) dialysis session with heparin. Arterial chamber blood coagulation was not greater than 25% (grade 3 and 4) in any of the studied sessions and the venous chamber in only 1 (2.8%) session with the usual dialyzer and 3 (8.4%) with no differences AN69ST® between the two dialyzers. The activated partial thromboplastin time at two hours showed differences between techniques related to administration of low molecular weight heparin (33.3 ± 2.7s with polysulfone and 27.5 ± 2.3s in AN69ST®; P < 0.05) which remained significant at the end of the session (29.8 ± 2.1s with polysulfone and 27.2 ± 1.8s with AN69ST®; P < 0.05). Anti-Xa factor activity was maximal two hours after administration of nadroparin, with differences between the two dialyzers (0.46 ± 0.13 IU / ml in dialysis with polysulfone and 0.04 ± 0.04 IU / ml with AN69ST®p<0.005) and went down after 4 hours (0.17 ± 0.12 IU / ml in dialysis with polysulfone and 0.02 ± 0.03 IU / ml in AN69ST®; p<0.05). One patient in dialysis AN69ST®; had an adverse reaction characterized by generalized pruritus and was excluded from the study, by withdrawing the consent in the first session. CONCLUSION: We demonstrate the low thrombogenicity of the AN69ST®; dialyzer that allows post-dilution hemodiafiltration sessions without systemic anticoagulation, and without increasing the frequency of severe clotting events compared to HF80®; dialyzer with nadroparin and with less risk of bleeding by not modifying the anti-Xa factor activity.