Citrate Dialysate with and without Magnesium Supplementation in Hemodiafiltration: A Comparative Study Versus Acetate.

The choice of dialysate buffer in hemodialysis is crucial, with acetate being widely used despite complications. Citrate has emerged as an alternative because of its favorable effects, yet concerns persist about its impact on calcium and magnesium levels. This study investigates the influence of citrate dialysates (CDs) with and without additional magnesium supplementation on CKD-MBD biomarkers and assesses their ability to chelate divalent metals compared to acetate dialysates (ADs). A prospective crossover study was conducted in a single center, involving patients on thrice-weekly online hemodiafiltration (HDF). The following four dialysates were compared: two acetate-based and two citrate-based. Calcium, magnesium, iPTH, iron, selenium, cadmium, copper, zinc, BUN, albumin, creatinine, bicarbonate, and pH were monitored before and after each dialysis session. Seventy-two HDF sessions were performed on eighteen patients. The CDs showed stability in iPTH levels and reduced post-dialysis total calcium, with no significant increase in adverse events. Magnesium supplementation with CDs prevented hypomagnesemia. However, no significant differences among dialysates were observed in the chelation of other divalent metals. CDs, particularly with higher magnesium concentrations, offer promising benefits, including prevention of hypomagnesemia and stabilization of CKD-MBD parameters, suggesting citrate as a viable alternative to acetate. Further studies are warranted to elucidate long-term outcomes and optimize dialysate formulations. Until then, given our results, we recommend that when a CD is used, it should be used with a 0.75 mmol/L Mg concentration rather than a 0.5 mmol/L one.

Notification of biochemistry critical results and its clinical impact on outpatient care: experience in a Spanish tertiary hospital.

OBJECTIVES: The communication of critical results (CR) is considered an essential role in clinical laboratories to ensure patient safety. This is especially relevant to outpatients, who are non-hospitalized and more difficult to locate. In our laboratory, there is a specific protocol for CR management that sets up the communication pathway to adequately provide these results to clinicians. The aim of this study is to evaluate the impact of CR reporting on outpatient care. METHODS: This is a retrospective study focused on CR for biochemistry parameters in a clinical laboratory of a Spanish tertiary hospital during 2019. A total of 156 CR were determined and properly provided to clinicians. We collected CR, age, gender, and the requesting department. We also collected the medical action data resulting from the communication of the CR. RESULTS: Seventy-six outpatients (49%) were properly treated because of effective CR communication. Hypoglycemia was the most frequent event (33%), however, the greatest clinical impact was observed for patients with hyponatremia (100%), hyperkalemia (62%), hypokalemia (60%), and hypercalcemia (57%). Based on these findings, we evaluated new glucose alert thresholds depending on whether or not the outpatient was diabetic (1.7 and 2.2 mmol/L, respectively). Based on these new thresholds, we established a CR reporting protocol with 69% effectiveness in outpatients. CONCLUSIONS: We demonstrate that CR communication in outpatients has a significant clinical impact. To increase the effectiveness of the CR reporting protocol, we propose to adjust alert thresholds according to pathology, department, and patient population.

Vancomycin hemodialysis: Clearance differences between high-flux hemodialysis and on-line hemodiafiltration.

The aim of this study was to analyze the differences between vancomycin clearance (Kd) with high-flux hemodialysis (HFHD) and on-line hemodiafiltration (OL-HDF). The OL-HDF therapy combined the diffusion and convective transport of solutes. To compare the Kd, a vancomycin loading dose of 1 g was administered intravenously post-dialysis to 11 chronic and anuric (<100 mL/24 h) hemodialysis patients, undergoing HFHD and post-dilutional OL-HDF in consecutive therapies. Additional doses of 0.5 g were administered after 45 minutes at the end of each dialysis therapy during antibiotic treatment. Blood samples were drawn from arterial and venous lines at the start of hemodialysis sessions and at the first, second, third, and fourth hours. Additional samples were drawn at 15, 30, and 45 minutes after the end of dialysis therapy. Vancomycin plasma concentration, blood urea nitrogen (BUN), creatinine, and ß2 -microglobulin were measured. The patients' hydration status was evaluated by bioimpedance analysis. The mean of vancomycin dialyzer clearance (Kddc ) calculated was 110.8 ± 15 mL/min with HFHD and 146.8 ± 13.8 mL/min with OL-HDF (P = 0.025). Significant differences were also obtained for ß2 -microglobulin clearance, Kddc 72.6 ± 15.4 mL/min with HFHD and 113.4 ± 24.2 mL/min with OL-HDF (P = 0.012), whereas no differences were found for BUN or creatinine. Additionally, to analyze differences between HFHD and OL-HDF, a variable volume dual pool mathematical model was developed to estimate the body clearance (Kdbc ), extraction mass (Me ), and inter-compartment mass-transfer coefficient (K12 ) of each molecule. A higher vancomycin Kddc with OL-HDF produced by convection improved removal of antibiotic; this can compromise achieving a therapeutic concentration target. We recommended evaluating increased loading doses of vancomycin and avoiding administration during OL-HDF to assure adequate treatment.

Urine Ethyl Glucuronide Unraveling the Reality of Abstinence Monitoring in a Routine Outpatient Setting: A Cross-Sectional Comparison with Ethanol, Self Report and Clinical Judgment.

AIMS: To test the screening performance of urinary ethyl glucuronide (EtG) under routine clinical conditions in a sample of alcohol-dependent outpatients, comparing it against urinary ethanol, self reports and clinical judgment. METHODS: A cross-sectional study under routine conditions was conducted in February 2015, where 613 consecutive urinary samples, provided by 188 outpatients with alcohol use disorders, were analyzed for ethanol and EtG (cut-off level = 500 ng/ml). Clinical variables such as the presence of aversive medication, comorbidities and clinician judgment were also collected. The discrepancy between the number of alcohol and EtG positives was recorded. A logistic regression analysis including clinical variables was conducted to assess for predictors of EtG positivity. RESULTS: Urinary alcohol yielded 9 positives (1.5% of all urine samples) belonging to 8 patients. EtG yielded 136 positives (22% of all urine samples) belonging to 74 patients. Of these, 93.4% (127 of 136) were negative for alcohol. All urinary alcohol positives resulted in EtG positives. The clinician judged 48 samples from 26 patients as belonging to not abstinent patients and 550 samples from 178 patients as belonging to abstinent patients. She was unsure in 15 samples from 15 patients. When comparing it against EtG as the gold standard, the area under the curve was 0.592. Self reports were extremely unreliable in this study, with only 5 patients reporting drinking in a total of 6 urine samples. In the logistic regression model, only aversive medications (OR 2.1, 95% CI 1.3-3.3) and clinician judgment (OR 2, 95% CI 1.4-2.9) resulted in significant effects. CONCLUSIONS: EtG performed largely better than ethanol for urine screening in alcohol outpatients, detecting an extra 20.4% (125 out of 613) of positives. It means that for each alcohol-positive sample, there were 15 EtG-positive samples. Although better than ethanol, clinician judgment was also not performed efficiently. If routinely implemented in the screening of alcohol outpatients, EtG might bring relevant changes that merit further research.

Correlation of plasmatic sodium determined by the laboratory and that determined by the dialysis machine.

INTRODUCTION: Changes in plasma sodium concentration (pNa, expressed in mEq/L) are common in hemodialysis (HD) patients. Hemodialysis monitors can estimate pNa by using an internal algorithm based on ion dialysance measurements. The present study studies the accuracy of the correlation between the pNa estimated by the dialysis monitor and that measured by the biochemistry laboratory at our center. MATERIAL AND METHODS: A single-centre prospective observational study in patients on a chronic HD program with the 6008 CAREsystem monitor and standard sodium (138mmol/L) and bicarbonate (32mmol/L) prescriptions. Venous blood samples were drawn from each patient before and after each HD session to ensure inter- and intra-individual validity. The pNa was measured in the biochemistry laboratory using indirect potentiometry and simultaneously the estimated pNa by the HD monitor was recorded at the beginning and at the end of the HD session. For statistical analysis, a scatterplot was made, and Spearman's correlation quotient was calculated. In addition, the differences between both methods were represented as Bland-Altman diagrams. RESULTS: The pre-dialysis pNa measured in the laboratory was 137.49±3.3, and that of the monitor, 137.96±2.91, with a correlation with R2 value of 0.683 (p<0.001). The post-dialysis pNa measured in the laboratory was 137.08±2.23, and that of the monitor was 138.87±1.88, with an R2 of 0.442 (p<0.001). On the Bland-Altman plots, the pre-dialysis pNa has a systematic error of 0.49, in favor of the monitor-estimated pNa, with a 95% confidence interval (CI) of (-3.24 to a 4.22). In the post-dialysis pNa, a systematic error of 1.79 with a 95% CI of (-1.64 to 5.22) was obtained. CONCLUSION: The correlation between the pNa estimated by Fresnius 6008 CAREsystem HD monitor and that measured by the laboratory is good, especially pre-dialysis measurements. Further studies should verify the external validity of these results.

Comparative Effects of Acetate- and Citrate-Based Dialysates on Dialysis Dose and Protein-Bound Uremic Toxins in Hemodiafiltration Patients: Exploring the Impact of Calcium and Magnesium Concentrations.

Modern hemodialysis employs weak acids as buffers to prevent bicarbonate precipitation with calcium or magnesium. Acetate, the most used acid, is linked to chronic inflammation and poor dialysis tolerance. Citrate has emerged as a potential alternative, though its effect on dialysis efficiency is not clear. This study aims to compare the efficacy of acetate- and citrate-based dialysates, focusing on protein-bound uremic toxins and dialysis doses. This single-center prospective crossover study includes prevalent patients participating in a thrice-weekly online hemodiafiltration program. Four dialysates were tested: two acetate-based (1.25 and 1.5 mmol/L calcium) and two citrate-based (1.5 mmol/L calcium with 0.5 and 0.75 mmol/L magnesium). Pre- and post-dialysis blood samples of eighteen patients were analyzed for urea, creatinine, p-cresyl sulfate, indoxyl sulfate, and albumin. Statistical significance was assessed using paired t-tests and repeated measures of ANOVA. There were no significant differences in dialysis dose (Kt), urea, creatinine, or indoxyl sulfate reduction ratios between acetate- and citrate-based dialysates. However, a significant decrease in the reduction ratio of p-cresyl sulfate was observed with the acetate dialysate containing 1.25 mmol/L calcium and the citrate dialysate with 0.5 mmol/L magnesium compared to the acetate dialysate containing 1.5 mmol/L calcium and the citrate dialysate with 0.75 mmol/L magnesium (51.56 ± 4.75 and 53.02 ± 4.52 vs. 65.25 ± 3.38 and 58.66 ± 4.16, p 0.007). No differences in dialysis dose were found between acetate- and citrate-based dialysates. However, citrate dialysates with lower calcium and magnesium concentrations may reduce the albumin displacement of p-cresyl sulfate. Further studies are needed to understand the observed differences and optimize the dialysate composition for the better clearance of protein-bound uremic toxins.

Prevalence, risk factors and the impact of tenofovir treatment in SARS-CoV-2 infection and COVID-19 disease among people living with HIV. A cross-sectional population-based study.

The prevalence and risk factors of SARS-CoV-2 infection among unvaccinated people living with HIV (PWH) are not well understood, and the protective role of tenofovir remains controversial. This study aimed to assess the SARS-CoV-2 prevalence and associated risk factors among unvaccinated PWH, and to evaluate the impact of tenofovir. We conducted as a cross-sectional study between November 2020 and May 2021. Plasma samples from 4,400 of 5,476 PWH were tested for total antibodies, IgG, IgM, and IgA. Among the participants (median age 48 years, 84% male), 92% had undetectable HIV viral loads and 5% had syphilis. The prevalence of SARS-CoV-2 infection was 18% (95% CI 17-19), with 1,180 individuals showing antibodies (IgG 13%, IgA 10%, IgM 11%). Of those seropositive for SARS-CoV-2, 67.5% were asymptomatic, 29% had mild disease, and 3.5% had severe/critical conditions. Risk factors included younger age, being female, men who have sex with men (MSM) status, non-European origin, and a history of syphilis. Neither antiretrovirals nor tenofovir provided protection against SARS-CoV-2 infection or COVID-19 disease. Ongoing surveillance and tailored interventions are crucial for at-risk PWH amid evolving SARS-CoV-2 variants.

Tailoring the dialysate bicarbonate eliminates pre-dialysis acidosis and post-dialysis alkalosis.

Background: Both metabolic acidosis and alkalosis increase hospitalizations, haemodynamic instability and mortality in haemodialysis patients. Unfortunately, current practices opt for a one-size-fits-all approach, leaving many patients either acidotic before or alkalotic after dialysis sessions. Therefore an individualized adjustment of these patients' dialysate bicarbonate prescriptions could reduce these acid-base imbalances. Methods: This is a prospective single-cohort study of patients on a chronic haemodiafiltration programme. The dialysate bicarbonate prescription was modified according to the pre- and post-dialysis total carbon dioxide (TCO2) values of 19-25 mEq/L and ≤29 mEq/L, respectively, with an adjustment formula calculated with the data obtained from previously published work by our group. In addition, we analysed this adjustment's effect on plasma sodium, potassium, phosphorus, parathyroid hormone (PTH) and calcium. Results: At baseline, only 67.9% of patients were within the desired pre- and post-dialysis TCO2 target range. As of the first month, every followed patient met the TCO2 target range objective in pre-dialysis measurements and ˃95% met the post-dialysis TCO2 target. At the end of the study, 75% of the patients were on dialysate bicarbonate of 32-34 mEq/L. There were no clinically significant changes in calcium, phosphate, PTH, sodium or potassium levels. Also, we did not notice any increase in intradialytic adverse events. Conclusions: We suggest an individualized adjustment of the dialysate bicarbonate concentration according to the pre- and post-dialysis TCO2 values. With it, nearly every patient in our cohort reached the established range, potentially reducing their mortality risk.

Quality Assurance in Lactation: Reliability of OM-6050 Station System to Test Mother's Milk Osmolality.

BACKGROUND: Mother's own milk does not provide enough nutrients to feed a preterm baby born before 32 weeks' gestation; therefore, human milk fortifiers are needed. However, human milk fortifiers increase the osmolality, and enteral administration of high osmolality fluids has been associated with gastrointestinal symptoms. For this reason, it is necessary for laboratories to have a validated system in order to measure human milk osmolality. RESEARCH AIM: The aim of this study was to validate the OM-6050 Station System for measuring the osmolality of fortified mother's milk samples. METHODS: Osmolality was measured using the osmometer OM-6050 Station System. Milk samples from healthy mothers (N = 3) unfortified and with two fortifiers (Almirón Fortifier® or NAN FM85®), as well as a nutritional supplement (Duocal MCT®) were used in the validation study through precision and linearity analysis. RESULTS: In the precision study the mean intra-assay coefficient of variation was 1.2% and 1.7% for mother's milk and fortified mother's milk, respectively. The mean inter-assay coefficient of variation was ≤ 1% in both cases. In the linearity study the regression analysis had a linear response to fortified mother's milk osmolality between 294 mOsm/kg and 539 mOsm/kg. CONCLUSION: The osmometer OM-6050 Station was reliable for determining the osmolality of fortified and unfortified mother's milk. It may be useful in the clinical practices within Neonatal Intensive Care Units.

Optimization of dialysate bicarbonate in patients treated with online haemodiafiltration.

BACKGROUND: Metabolic acidosis is a common problem in haemodialysis patients, but acidosis overcorrection has been associated with higher mortality. There is no clear definition of the optimal serum bicarbonate target or dialysate bicarbonate. This study analysed the impact of reducing dialysate bicarbonate from 35 to 32 mEq/L on plasma bicarbonate levels in a cohort of patients treated with online haemodiafiltration (OL-HDF). METHODS: We performed a prospective cohort study with patients in a stable chronic OL-HDF programme for at least 12 months in the Hospital Clinic of Barcelona. We analysed pre- and post-dialysis total carbon dioxide(TCO2) before and after dialysate bicarbonate reduction from 35 to 32 mEq/L, as well as the number of patients with a pre- and post-dialysis TCO2 within 19-25 and ≤29 mEq/L, respectively, after the bicarbonate modification. Changes in serum sodium, potassium, calcium, phosphorous and parathyroid hormone (PTH) were also assessed. RESULTS: We included 84 patients with a 6-month follow-up. At 6 months, pre- and post-dialysis TCO2 significantly decreased (26.78 ± 1.26 at baseline to 23.69 ± 1.92 mEq/L and 31.91 ± 0.91 to 27.58 ± 1.36 mEq/L, respectively). The number of patients with a pre-dialysis TCO2 >25 mEq/L was significantly reduced from 80 (90.5%) to 17 (20.2%) and for post-dialysis TCO2 >29 mEq/L this number was reduced from 83 (98.8%) to 9 (10.7%). PTH significantly decreased from 226.09 (range 172-296) to 182.50 (125-239) pg/mL at 6 months (P < 0.05) and post-dialysis potassium decreased from 3.16 ± 0.30 to 2.95 ± 0.48 mEq/L at 6 months (P < 0.05). Sodium, pre-dialysis potassium, calcium and phosphorous did not change significantly. CONCLUSIONS: Reducing dialysate bicarbonate concentration by 3 mEq/L significantly and safely decreased pre- and post-dialysis TCO2, avoiding acidosis overcorrection and improving secondary hyperparathyroidism control. An individualized bicarbonate prescription (a key factor in the adequate control of acidosis) according to pre-dialysis TCO2 is suggested based on these results.

Prevalence and risk factors of mild chronic renal failure in HIV-infected patients: influence of female gender and antiretroviral therapy.

BACKGROUND: In people living with HIV, much is known about chronic kidney disease, defined as a glomerular filtration rate under 60mL/min. However, there is scarce data about prevalence and risk factors for milder impairment (60-89mL/min). OBJECTIVE: The present study aims to assess the influence of sex, antiretroviral therapy, and classical risk factors on the occurrence of mild decreased renal function in a large Spanish cohort of HIV-infected patients. METHODS: Cross-sectional, single center study, including all adult HIV-1-infected patients under antiretroviral treatment with at least two serum creatinine measures during 2014, describing the occurrence of and the risk factors for mildly decreased renal function (eGFR by CKD-EPI creatinine equation of 60-89mL/min). RESULTS: Among the 4337 patients included, the prevalence rate of mildly reduced renal function was 25%. Independent risk factors for this outcome were age older than 50 years (OR 3.03, 95% CI 2.58-3.55), female sex (OR 1.23, 95% CI 1.02-1.48), baseline hypertension (OR 1.57, 95% CI 1.25-1.97) or dyslipidemia (OR 1.48, 95% CI 1.17-1.87), virologic suppression (OR 1.88, 95% CI 1.39-2.53), and exposure to tenofovir disoproxil-fumarate (OR 1.67, 95% CI 1.33-2.08) or ritonavir-boosted protease-inhibitors (OR 1.19, 95% CI 1.03-1.39). CONCLUSIONS: Females and patients over 50 seem to be more vulnerable to renal impairment. Potentially modifiable risk factors and exposure to tenofovir disoproxil-fumarate or ritonavir-boosted protease-inhibitors are present even in earlier stages of chronic kidney dysfunction. It remains to be determined whether early interventions including antiretroviral therapy changes (tenofovir alafenamide, cobicistat) or improving comorbidities management will improve the course of chronic kidney disease.

Prevalence and risk factors of mild chronic renal failure in HIV-infected patients: influence of female gender and antiretroviral therapy

ABSTRACT Background In people living with HIV, much is known about chronic kidney disease, defined as a glomerular filtration rate under 60 mL/min. However, there is scarce data about prevalence and risk factors for milder impairment (60-89 mL/min). Objective The present study aims to assess the influence of sex, antiretroviral therapy, and classical risk factors on the occurrence of mild decreased renal function in a large Spanish cohort of HIV-infected patients. Methods Cross-sectional, single center study, including all adult HIV-1-infected patients under antiretroviral treatment with at least two serum creatinine measures during 2014, describing the occurrence of and the risk factors for mildly decreased renal function (eGFR by CKD-EPI creatinine equation of 60-89 mL/min). Results Among the 4337 patients included, the prevalence rate of mildly reduced renal function was 25%. Independent risk factors for this outcome were age older than 50 years (OR 3.03, 95% CI 2.58-3.55), female sex (OR 1.23, 95% CI 1.02-1.48), baseline hypertension (OR 1.57, 95% CI 1.25-1.97) or dyslipidemia (OR 1.48, 95% CI 1.17-1.87), virologic suppression (OR 1.88, 95% CI 1.39-2.53), and exposure to tenofovir disoproxil-fumarate (OR 1.67, 95% CI 1.33-2.08) or ritonavir-boosted protease-inhibitors (OR 1.19, 95% CI 1.03-1.39). Conclusions Females and patients over 50 seem to be more vulnerable to renal impairment. Potentially modifiable risk factors and exposure to tenofovir disoproxil-fumarate or ritonavir-boosted protease-inhibitors are present even in earlier stages of chronic kidney dysfunction. It remains to be determined whether early interventions including antiretroviral therapy changes (tenofovir alafenamide, cobicistat) or improving comorbidities management will improve the course of chronic kidney disease.