Are Medium Cut-off Membranes the Future, or the Promising Reality for Chronic Hemodialysis Patients?

ABSTRACT The development of hemodialysis (HD) membranes has substantially advanced in the last decade. This has resulted in the manufacturing of medium cut-off membranes (MCO) whose internal architecture is based on greater pore size and a smaller diameter, thus promoting the clearance of particles of greater size as well as retrofiltration. Multiple studies have proven their efficacy in the clearance of uremic mid-sized molecules such as β2-microglobulin, free light chains, and some interleukins; this clearance is far superior with MCO membranes when compared with high-flux HD, and similar to that obtained with online hemodiafiltration. This review summarizes the results of the most relevant clinical studies of this membrane in terms of uremic toxin clearance, as well as the features of some clinical outcomes such as quality of life and hospitalizations.

Are medium cut-off membranes the future, or the promising reality for chronic hemodialysis patients?

The development of hemodialysis (HD) membranes has substantially advanced in the last decade. This has resulted in the manufacturing of medium cut-off membranes (MCO) whose internal architecture is based on greater pore size and a smaller diameter, thus promoting the clearance of particles of greater size as well as retrofiltration. Multiple studies have proven their efficacy in the clearance of uremic mid-sized molecules such as ß2-microglobulin, free light chains, and some interleukins; this clearance is far superior with MCO membranes when compared with high-flux HD, and similar to that obtained with online hemodiafiltration. This review summarizes the results of the most relevant clinical studies of this membrane in terms of uremic toxin clearance, as well as the features of some clinical outcomes such as quality of life and hospitalizations.

Evaluation of hemodialysis vascular access. Perspective from Mexico.

Chronic kidney disease (CKD) has become a global health problem. In 2019, it was related to 2.53% of general global mortality (2.35-2.66%); in the same year, in Latin America, mortality related to CKD reached 5.25% (4.92-5.49%), with an annual increase of 3.37%, proving increased mortality of 102% between 1990 and 2017. A nephrology specialty in Mexico recently fulfilled its first 50 years. Despite being relatively young, nephrologists are interested in "new" sub-specialties of nephrology and learning novel techniques and problem-solving skills. Our group is the first in our country to focus solely and exclusively on comprehensive VA care and we want to position ourselves as the first Mexican interdisciplinary group focused on vascular access (GIMEXAV).

Improved ß2-Microglobulin and Phosphorous Removal with Expanded Hemodialysis and Online Hemodiafiltration versus High-Flux Hemodialysis: A Cross-Over Randomized Clinical Trial.

INTRODUCTION: Expanded hemodialysis (HDx) is expected to provide enhanced permeability of medium-sized molecules, selective solute retention, and better internal retrofiltration. The primary objective of this study was to compare the efficiency for removal of ß2-microglobulin with 3 different extracorporeal therapies (ETs): high-flux hemodialysis (HF), online hemodiafiltration (OL-HDF), and HDx. The secondary objective was to evaluate the efficiency of removal of other uremic toxins, including urea, phosphate, CRP, IL-6, IL-10, TNF-⍺, indoxyl sulfate, and p-cresol. METHODS: This single-center, randomized, and cross-over study was performed. Patients were randomized to determine the initial modality of treatment, each period lasted 4 weeks and between one modality and another, there was a washout period of 1 week. Reduction ratios (RRs) of different-size molecules and albumin were calculated for the different ET. RESULTS: Twenty-two patients were included, ß2-microglobulin RR was greater during both OL-HDF and HDx as compared to HF (RR 62% vs. 73% vs. 27%, respectively, p = <0.0001), and there was no significant difference between HDx and OL-HDF (p = 0.09). A decrease in serum phosphate levels was observed in the HDx and OL-HDF periods, contrary to an increase in HF (-0.79 mg/dL vs. -1.02 mg/dL vs. + 0.11 mg/dL, respectively, p = <0.0001). There was no difference in RRs of other molecules (BUN, CRP, IL-6, IL-10, TNF-⍺, indoxyl sulfate, and p-Cresol). There was no decrease in serum albumin in any ET. CONCLUSION: HDx provides enhanced removal of ß2-microglobulin and phosphate as compared to HF, and similar efficacy as with OL-HDF. HDx should be considered an alternative to chronic convective therapies.

Importance of Confirmatory Tests for Sars-Cov-2 Infection in Hemodialysis Patients: A Multicenter Mexican Registry

Abstract Background: Since the beginning of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, patients with chronic kidney disease vulnerable to suffering more severe COVID-19 disease and worse outcomes have been identified Objectives: Our study's aim was to determine the incidence, characteristics, and outcomes of SARS-CoV-2 infection in patients of hemodialysis (HD) units in Mexico and to describe the availability of confirmatory testing Methods: This study was multicentric study of 19 HD units, conducted between March 2020 and March 2021 Results: From a total of 5779 patients, 955 (16.5%) cases of suspicious COVID-19 were detected; a SARS-CoV-2 reverse transcription polymerase chain reaction test was done in only 50.6% of patients. Forty-five percentages were hospitalized and 6% required invasive mechanical ventilation (IMV). There was no significant difference in mortality between confirmed (131/483) and suspicious (124/472) cases (p = 0.74). The percentage of patients in need of hospitalization, IMV, and deceased was greater than in the rest of the study population Conclusions: The study revealed that 49.4% of the cases were not confirmed, a worrisome observation given that this is a highly vulnerable population (higher probability of contagion and worse outcomes), in which 100% of patients should have a confirmatory test

What Did We Learn about Coronavirus Disease-19-Associated Acute Kidney Injury During the Pandemic?

ABSTRACT Initial reports suggested that kidney involvement after coronavirus disease 19 (COVID-19) infection was uncommon, but this premise appears to be incorrect. Acute kidney injury can occur through various mechanisms and complicate the course of up to 25% of patients with COVID-19 hospitalized in our Institution, and of over 50% of those on invasive mechanical ventilation. Mechanisms of injury include direct kidney injury and predominantly tubular, although glomerular injury has been reported, and resulting from severe hypoxic respiratory failure, secondary infection, and exposure to nephrotoxic drugs. The mainstay of treatment remains the prevention of progressive kidney damage and, in some cases, the use of renal replacement therapy. Although the use of blood purification techniques has been proposed as a potential treatment, results to date have not been conclusive. In this manuscript, the mechanisms of kidney injury by COVID-19, risk factors, and the mainstays of treatment are reviewed.

What did we learn about coronavirus disease-19-associated acute kidney injury during the pandemic?

Initial reports suggested that kidney involvement after coronavirus disease 19 (COVID-19) infection was uncommon, but this premise appears to be incorrect. Acute kidney injury can occur through various mechanisms and complicate the course of up to 25% of patients with COVID-19 hospitalized in our Institution, and of over 50% of those on invasive mechanical ventilation. Mechanisms of injury include direct kidney injury and predominantly tubular, although glomerular injury has been reported, and resulting from severe hypoxic respiratory failure, secondary infection, and exposure to nephrotoxic drugs. The mainstay of treatment remains the prevention of progressive kidney damage and, in some cases, the use of renal replacement therapy. Although the use of blood purification techniques has been proposed as a potential treatment, results to date have not been conclusive. In this manuscript, the mechanisms of kidney injury by COVID-19, risk factors, and the mainstays of treatment are reviewed.

Importance of Confirmatory Tests for Sars-Cov-2 Infection in Hemodialysis Patients: A Multicenter Mexican Registry.

Background: Since the beginning of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, patients with chronic kidney disease vulnerable to suffering more severe COVID-19 disease and worse outcomes have been identified. Objectives: Our study's aim was to determine the incidence, characteristics, and outcomes of SARS-CoV-2 infection in patients of hemodialysis (HD) units in Mexico and to describe the availability of confirmatory testing. Methods: This study was multicentric study of 19 HD units, conducted between March 2020 and March 2021. Results: From a total of 5779 patients, 955 (16.5%) cases of suspicious COVID-19 were detected; a SARS-CoV-2 reverse transcription polymerase chain reaction test was done in only 50.6% of patients. Forty-five percentages were hospitalized and 6% required invasive mechanical ventilation (IMV). There was no significant difference in mortality between confirmed (131/483) and suspicious (124/472) cases (p = 0.74). The percentage of patients in need of hospitalization, IMV, and deceased was greater than in the rest of the study population. Conclusions: The study revealed that 49.4% of the cases were not confirmed, a worrisome observation given that this is a highly vulnerable population (higher probability of contagion and worse outcomes), in which 100% of patients should have a confirmatory test.

Community- and Hospital-Acquired Acute Kidney Injury in COVID-19: Different Phenotypes and Dismal Prognosis.

INTRODUCTION: Acute kidney injury (AKI) is common in coronavirus disease 2019 (COVID-19). It is unknown if hospital-acquired AKI (HA-AKI) and community-acquired AKI (CA-AKI) convey a distinct prognosis. METHODS: The study aim was to evaluate the incidence and risk factors associated with both CA-AKI and HA-AKI. Consecutive patients hospitalized at a reference center for COVID-19 were included in this prospective cohort study. RESULTS: We registered 349 (30%) AKI episodes in 1,170 hospitalized patients, 224 (19%) corresponded to CA-AKI, and 125 (11%) to HA-AKI. Compared to patients with HA-AKI, subjects with CA-AKI were older (61 years [IQR 49-70] vs. 50 years [IQR 43-61]), had more comorbidities (hypertension [44 vs. 26%], CKD [10 vs. 3%]), higher Charlson Comorbidity Index (2 points [IQR 1-4] vs. 1 point [IQR 0-2]), and presented to the emergency department with more severe disease. Mortality rates were not different between CA-AKI and HA-AKI (119 [53%] vs. 63 [50%], p = 0.66). In multivariate analysis, CA-AKI was strongly associated to a history of CKD (OR 4.17, 95% CI 1.53-11.3), hypertension (OR 1.55, 95% CI 1.01-2.36), Charlson Comorbidity Index (OR 1.16, 95% CI 1.02-1.32), and SOFA score (OR 2.19, 95% CI 1.87-2.57). HA-AKI was associated with the requirement for mechanical ventilation (OR 68.2, 95% CI 37.1-126), elevated troponin I (OR 1.95, 95% CI 1.01-3.83), and glucose levels at admission (OR 1.05, 95% CI 1.02-1.08). DISCUSSION/CONCLUSIONS: CA-AKI and HA-AKI portend an adverse prognosis in CO-VID-19. Nevertheless, CA-AKI was associated with a higher comorbidity burden (including CKD and hypertension), while HA-AKI occurred in younger patients by the time severe multiorgan disease developed.

Prolonged Intermittent Renal Replacement Therapy for Acute Kidney Injury in COVID-19 Patients with Acute Respiratory Distress Syndrome.

INTRODUCTION: Patients with acute respiratory distress syndrome (ARDS) secondary to COVID-19 frequently develop severe acute kidney injury (AKI). Although continuous renal replacement therapy is the standard of care for critically ill patients, prolonged intermittent renal replacement therapy (PIRRT) may be a feasible option. We aimed to describe the tolerability and security of PIRRT treatments in COVID-19 patients with ARDS who required mechanical ventilation and developed severe AKI. METHODS: We prospectively analyzed patients who underwent PIRRT treatments at a COVID-19 reference hospital in Mexico City. Intradialytic hypotension was defined as a systolic blood pressure decrease of ≥20 mm Hg or an increase of 100% in vasopressor dose. RESULTS: We identified 136 AKI cases (60.7%) in 224 patients admitted to the intensive care unit. Among them, 21 (15%) underwent PIRRT (130 sessions) due to stage 3 AKI. The median age of the cohort was 49 (range 36-73) years, 17 (81%) were male, 7 (33%) had diabetes, and the median time between symptoms onset and PIRRT initiation was 12 (interquartile range [IQR] 7-14) days. The median of PIRRT procedures for each patient was 5 (IQR 4-9) sessions. In 108 (83%) PIRRT sessions, the total ultrafiltration goal was achieved. In 84 (65%) PIRRT procedures, there was a median increase in norepinephrine dose of +0.031 mcg/kg/min during PIRRT (IQR 0.00 to +0.07). Intradialytic hypotensive events occurred in 56 (43%) procedures. Fifteen (12%) PIRRT treatments were discontinued due to severe hypotension. Vasopressor treatment at PIRRT session onset (OR 6.2, 95% CI 1.4-28.0, p: 0.02) and a pre-PIRRT lactate ≥3.0 mmol/L (OR 4.63, 95% CI 1.3-12.8, p: 0.003) were independently and significantly associated with the risk of hypotension during PIRRT. During follow-up, 11 patients (52%) recovered from AKI and respiratory failure and 9 (43%) died. Several adaptations to our PIRRT protocol during the COVID-19 outbreak are presented. CONCLUSIONS: PIRRT was feasible in the majority of COVID-19 patients with ARDS and severe AKI, despite frequent transitory intradialytic hypotensive episodes. PIRRT may represent an acceptable alternative of renal replacement therapy during the COVID-19 outbreak.

Prevención y control de la infección por coronavirus SARS-CoV-2 (Covid-19) en unidades de hemodiálisis / Prevention and control of SARS-CoV-2 (Covid-19) coronavirus infection in hemodialysis units

Resumen: La pandemia del SARS-CoV-2 representa un riesgo especial para los pacientes en hemodiálisis crónica por su estado de inmunosupresión, edad avanzada y coexistencia de comorbilidades importantes, en particular patología cardiovascular, diabetes mellitus y otras. Adicionalmente, esta población constituye un conglomerado cerrado ya que los pacientes acuden a tratamiento con regularidad y permanecen horas en los lugares de tratamiento, expuestos a una posible adquisición de la infección. El hecho de acudir necesaria y regularmente a su tratamiento impide que permanezcan en aislamiento domiciliario y con exposición potencial en el traslado. Las presentes recomendaciones resumen las intervenciones propuestas por tres organizaciones internacionales, a las que se agregan algunas sugeridas por expertos nacionales, con el objetivo de identificar precozmente a los pacientes y personal de la salud en riesgo para disminuir el riesgo de infección.

Abstract The SARS-CoV-2 pandemic is of hich risk for patients on chronic hemodialysis due to their immunosuppressed state, advanced age, and the coexistence of significant comorbidities, in particular cardiovascular disease, diabetes mellitus, and others. Additionally, they constitute a closed conglomerate since they come to treatment regularly, spending hours in the treatment places, exposed to a possible acquisition of the infection. Finally, going to their treatment regularly prevents them from remaining in home isolation and with potential exposure. These recommendations summarize the interventions proposed by three international organizations and add some suggested by national experts, with the aim to early identify the patients and health personnel at risk and reducing the risk of infection.

[Prevention and control of SARS-CoV-2 (Covid-19) coronavirus infection in hemodialysis units.] / Prevención y control de la infección por coronavirus SARS-CoV-2 (Covid-19) en unidades de hemodiálisis.

The SARS-CoV-2 pandemic is of hich risk for patients on chronic hemodialysis due to their immunosuppressed state, advanced age, and the coexistence of significant comorbidities, in particular cardiovascular disease, diabetes mellitus, and others. Additionally, they constitute a closed conglomerate since they come to treatment regularly, spending hours in the treatment places, exposed to a possible acquisition of the infection. Finally, going to their treatment regularly prevents them from remaining in home isolation and with potential exposure. These recommendations summarize the interventions proposed by three international organizations and add some suggested by national experts, with the aim to early identify the patients and health personnel at risk and reducing the risk of infection.

La pandemia del SARS-CoV-2 representa un riesgo especial para los pacientes en hemodiálisis crónica por su estado de inmunosupresión, edad avanzada y coexistencia de comorbilidades importantes, en particular patología cardiovascular, diabetes mellitus y otras. Adicionalmente, esta población constituye un conglomerado cerrado ya que los pacientes acuden a tratamiento con regularidad y permanecen horas en los lugares de tratamiento, expuestos a una posible adquisición de la infección. El hecho de acudir necesaria y regularmente a su tratamiento impide que permanezcan en aislamiento domiciliario y con exposición potencial en el traslado. Las presentes recomendaciones resumen las intervenciones propuestas por tres organizaciones internacionales, a las que se agregan algunas sugeridas por expertos nacionales, con el objetivo de identificar precozmente a los pacientes y personal de la salud en riesgo para disminuir el riesgo de infección.

Cholecalciferol supplementation increases FGF23 in peritoneal dialysis patients with hypovitaminosis D: a randomized clinical trial.

BACKGROUND: Vitamin D deficiency is common in peritoneal dialysis (PD) patients, so its supplementation has been advocated as potentially beneficial. METHODS: Double-blind, placebo-controlled, randomized clinical trial. Subjects on PD treated with high calcium peritoneal dialysate (Ca 3.5 mEq/l) and serum levels of 25-hydroxi vitamin D (25D) < 20 ng/ml were randomized to receive cholecalciferol (4800 IU/daily) or placebo for 16 weeks. The outcome measures were the effects on the osteogenic biomarkers osteoprotegerin (primary endpoint), intact fibroblast growth factor-23 (iFGF23), osteocalcin, osteopontin, iPTH, 1,25-dyhydroxivitamin D (1,25D), and interleukin-6. RESULTS: Fifty-eight subjects were randomly assigned. Baseline characteristics were similar in both groups. Cholecalciferol supplemented subjects had a significant increase in serum 25D (from 11.4 ± 5.0 to 28.3 ± 10.3 ng/ml), 1,25D and iFGF23 compared with placebo group. iFGF23 levels increased an average of 10,875 pg/ml per month (95% CI 11,778-88,414) in the cholecalciferol group and was unchanged in the placebo group (2829 pg/ml, 95% CI - 2181 to 14,972). Extremely high iFGF23 levels (> 30,000 pg/ml) were observed in 74% of subjects receiving cholecalciferol although iFGF23 returned to baseline values after 32 weeks of withdrawal. The observed changes in iFGF23 correlated with 1,25D levels and were not modified by other variables. No difference was observed between groups in osteoprotegerin or other osteogenic biomarkers levels. CONCLUSIONS: Cholecalciferol supplementation increases serum 25D levels in subjects on PD exposed to high calcium dialysate, yet it induces an exponential increase of iFGF23 in most patients, which disappear after withdrawal of supplementation and may be a major concern for this maneuver.