Gonzalo Ramírez-Guerrero

Introduction: Fluid overload in critically ill patients with acute kidney injury (AKI) is independently associated with increased mortality, prolonged mechanical ventilation and impaired renal recovery. Net ultrafiltration (UF ^NET ) during continuous renal replacement therapy (CRRT) is a cornerstone de-resuscitation strategy; however, tolerance to fluid removal is highly variable and difficult to predict. Ultrafiltration intolerance, encompassing haemodynamic instability, peripheral perfusion deterioration and tissue hypoperfusion during UF ^NET , lacks a standardised definition and has not been prospectively evaluated using a comprehensive multiparametric monitoring strategy. The Volume removal Intolerance during Net ultrafiltration in acute Kidney injury patients, an Observational study (VINKO) aims to identify clinical, haemodynamic, ultrasound-based, perfusion-related and biochemical factors associated with the development of ultrafiltration intolerance in critically ill patients with AKI undergoing CRRT. Methods and analysis: VINKO is a prospective, multicentre, observational analytical case–control study enrolling adult intensive care unit patients with AKI requiring CRRT with prescribed UF ^NET . Cases are defined as patients who develop ultrafiltration intolerance during the 24-hour observation period, whereas controls are patients who tolerate UF ^NET without meeting intolerance criteria. Serial assessments include macrohaemodynamic variables, dynamic functional tests (passive leg raising and sitting manoeuvre), focused echocardiography, venous congestion assessment using the Venous Excess Ultrasound protocol, peripheral perfusion markers (capillary refill time, mottling score and peripheral perfusion index) and biochemical markers including lactate, albumin, ionised calcium and B-type natriuretic peptide/N-terminal pro-B-type natriuretic peptide when available. Measurements are obtained at predefined time points from UF ^NET initiation through 24 hours, with additional off-schedule assessments triggered by intolerance events. The primary objective is to identify independent predictors of ultrafiltration intolerance. A total of 128 patients (64 cases and 64 controls) will be enrolled based on a predefined sample size calculation. Ethics and dissemination: The study has been approved by the Scientific Ethics Committee of the Talcahuano Health Service (Act No. 15, 14 April 2026) and will be conducted in accordance with the Declaration of Helsinki, Council for International Organizations of Medical Sciences (CIOMS) guidelines and current Chilean regulations. Results will be disseminated through presentations at scientific meetings and publication in peer-reviewed journals. Trial registration number: NCT07643597 .

Uremic toxicity extends beyond small solutes to include middle molecules and protein-bound uremic toxins (PBUTs), which are inadequately removed by conventional dialysis. These limitations arise from membrane-dependent transport mechanisms and the high-affinity binding of PBUTs to albumin, restricting their effective clearance. Hemoadsorption, when coupled with hemodialysis (HAHD), provides a complementary approach by enabling direct physicochemical interactions between circulating solutes and sorbent materials, thereby overcoming constraints related to molecular size and protein binding. The concept of residual uremic toxicity highlights the persistence of biologically active solutes despite optimized dialysis delivery. In this context, patient selection should follow a phenotype-based, toxin-domain approach. Four main phenotypes are proposed: inflammatory, PBUT-driven symptom, middle-molecule burden, and neurocognitive. Each phenotype reflects a dominant toxin profile and provides a rationale for targeted extracorporeal strategies beyond conventional adequacy metrics. HAHD should be considered in patients with persistent symptoms, inflammation, or biochemical abnormalities despite optimized therapy. Treatment prescription must be individualized, integrating frequency, duration, and blood flow to reduce cumulative toxin burden over time. Emerging evidence suggests that HAHD may improve inflammatory markers, patient-centered outcomes, and potentially survival. Overall, HAHD represents a phenotype-driven strategy to better align extracorporeal therapies with the complex biology of uremia.

Blood purification in patients on maintenance dialysis has evolved far beyond the historical paradigm of urea removal, reflecting a deeper understanding of the biological complexity of uremia. Despite technological advances in conventional hemodialysis (HD), persistent cardiovascular mortality, accelerated loss of residual kidney function, and sustained symptom burden underscore the limitations of diffusion-dominant therapy. Uremic toxins, including middle-to-large molecules and protein-bound toxins, contribute to systemic inflammation, vascular injury, and multiorgan dysfunction, necessitating broader clearance strategies. Hemodiafiltration (HDF), expanded hemodialysis (HDx), and hemoadsorption combined with HD represent a triad of emerging approaches designed to address these unmet clinical needs. High-volume HDF has demonstrated a dose-dependent survival advantage, reinforcing the clinical relevance of convective intensity. HDx offers enhanced middle-molecule clearance within a simplified operational framework, using back-filtration as its core mechanism to achieve broader molecule clearance through medium-cut-off membranes. Adsorptive techniques further expand the therapeutic spectrum by targeting protein-bound and inflammatory solutes using sorbent materials inserted in a cartridge configuration in line with the HD circuit. Differences in clearance profiles across modalities translate into signals for survival, preservation of residual kidney function, and improvements in patient-reported outcomes. Together, these strategies redefine dialysis as a mechanism-driven, individualized intervention aimed at improving patient care.

Introduction: Sepsis is a life-threatening condition driven by a dysregulated immune response to infection, often leading to multi-organ failure and high mortality. Beyond oxygen transport, red blood cells (RBCs) may contribute to sepsis pathophysiology through eryptosis, a form of programmed RBC death characterized by cell shrinkage, membrane changes, and phosphatidylserine exposure. This study explored the association between bacterial exposure and eryptosis, assessing its potential as a biomarker for sepsis progression. Methods: Three in vitro experiments were conducted using RBCs from healthy donors. First, baseline eryptosis was evaluated over time in the absence of bacterial exposure. Second, RBCs were exposed to different concentrations of Staphylococcus aureus and Escherichia coli to assess the relationship between bacterial load and eryptosis. Finally, both bacterial species were tested at equal concentrations to compare their pro-eryptotic effects. Eryptosis was assessed by flow cytometry using Annexin V-FITC staining. Results: Eryptosis increased over time under control conditions, although activation remained low at 72 h. Exposure to bacteria resulted in a time- and concentration-dependent increase in eryptosis. In the experiment using different bacterial concentrations, S. aureus induced greater eryptosis than E. coli at the tested doses. However, when both bacteria were evaluated at equal concentrations, E. coli induced higher eryptosis levels than S. aureus. Conclusion: Eryptosis may serve as a biomarker of sepsis severity, sensitive to bacterial type and concentration. Gram-negative bacteria, particularly E. coli, caused greater RBC injury at comparable bacterial loads. These findings warrant further investigation into eryptosis as a potential diagnostic tool and therapeutic target in sepsis.

Clinical outcomes in patients on maintenance dialysis are still unsatisfactory. Despite delivery of adequate dialysis, residual symptoms and signs of uremic intoxication are often present, such as pruritus and xeroderma, restless leg syndrome, sleep disorders, cognitive impairment, anxiety and depression, cramps, fatigue, and muscular weakness, mineral and bone disorders, cardiovascular complications, chronic inflammation, and accelerated atherosclerosis. These have been correlated with retention of inflammatory chemical mediators, protein-bound uremic toxins, and middle to large molecular weight toxins that are insufficiently cleared by current dialysis techniques. A new extracorporeal technique combining hemoadsorption with hemodialysis (HAHD) has been utilized with promising results but enormous variability of procedures, resulting in limited evidence. Previous experience in incorporating innovative approaches has demonstrated that, after several years of pioneering work, a common pathway is necessary to generate sufficient evidence, spanning from case reports, expert debates, retrospective and observational studies, registries, and underpowered trials to multicenter international randomized clinical trials and meta-analyses. Thus, the widespread adoption of HAHD requires the application of implementation science techniques supported by healthcare policies. The scope of this conference is to conduct an objective appraisal of current knowledge and to propose a standardized application modality, enabling the design of comparable clinical trials and the acquisition of homogeneous datasets suitable for evaluation and discussion.

Introduction: Socioeconomic and developmental diversity across Latin America (LA) significantly affects the availability of extracorporeal blood purification (EBP) therapies to treat acute kidney injury (AKI) and the training of nephrology fellows in these technologies. This survey assessed the availability of EBP therapies and perceived training needs of nephrologists and intensivists in the region. Objective: The aim of this study was to evaluate the availability of EBP therapies to treat AKI and identify training needs among LA nephrologists and intensivists. Methods: Between March and December 2024, the AKI and extracorporeal organ support therapy committee of SLANH conducted an online survey targeting nephrologists and intensivists. The survey gathered data on the availability of EBP technologies in their institutions and perceived training needs. Results: A total of 505 responses were collected, with 93% submitted by nephrologists. Participants represented 20 LA countries, primarily from South America (58%), Mexico (23.6%), and the Caribbean (10.1%). Intermittent hemodialysis (IHD) was the most widely available therapy, accessible in 98% of centers. Peritoneal dialysis (PD) was available in 65% of hospitals, while continuous renal replacement therapy (CRRT) in 59% of centers but reported as unavailable in Haiti, Nicaragua, Paraguay, and Venezuela. Therapeutic plasma exchange (TPE) was available in 60% of hospitals, although accessibility varied significantly by country. Multi-organ support therapies showed limited regional availability, including liver support (11.9%), extracorporeal membrane oxygenation (ECMO, 16.7%), extracorporeal CO2 removal (ECCO2R, 7%), and hemoadsorption (20.6%). The greatest perceived training needs were identified for ECMO (54.2%), ECCO2R (51.3%), CRRT (48.7%), and TPE (46.8%), whereas demand for further training in IHD and PD was comparatively lower. These findings underscore substantial disparities in therapy access and highlight urgent regional priorities for advanced EBP training. Conclusion: This study highlights significant disparities in EBP therapy availability across LA, with advanced modalities such as CRRT and multi-organ support largely inaccessible in several countries. Additionally, there is a high perceived need for training in ECMO, ECCO2R, CRRT, and TPE. Addressing these gaps requires expanding access to EBP, implementing standardized training programs, establishing regional centers of excellence, and fostering international collaboration. Policy advocacy and increased resource allocation will be essential to improving access and optimizing patient outcomes across the region.

Background: Coupled plasma filtration and adsorption (CPFA) is a non-selective extracorporeal technique designed to modulate systemic inflammation through plasma filtration combined with resin-based adsorption. While preclinical data were promising, randomized trials in septic shock yielded conflicting results and raised safety concerns, leading to its discontinuation. Nonetheless, selected patients might benefit from CPFA when adequately delivered. Methods: We performed a retrospective, single-center observational study of 36 critically ill patients treated with CPFA between 2019 and 2022. A total of 56 CPFA sessions were analyzed, evaluating clinical indications, plasma-treated volume (VPT), hemodynamic changes, and clinical outcomes. Results: The main indication was sepsis (75%), followed by rhabdomyolysis and intoxications (8% each). Most patients received one to two sessions, with a mean duration of 9 ± 1 h and a VPT of 10,103 ± 4275 mL. Survival at 72 h and 28 days was 85% and 61%, respectively, with no early deaths. Patients achieving a VPT ⩾18% of estimated plasma volume had better 28-day survival (81% vs 42%, p = 0.03), although they had lower initial severity scores. A non-significant trend toward vasopressor reduction was observed. No major adverse events occurred. Conclusion: In this cohort, CPFA was feasible and safe, with possible hemodynamic and survival benefits when a sufficient plasma-treated volume was reached. Patient selection and optimized treatment delivery appear crucial. However, the retrospective design and lack of a control group limit definitive conclusions. Future research should focus on more effective and targeted extracorporeal strategies for immune modulation in critically ill patients.