RESUMO
A hallmark of chronic kidney disease is the retention of solutes that normally are eliminated by the kidneys. The current classification defines uremic toxins based on molecular weight and protein affinity. The retention of solutes is already detected in the early stages of the disease when patients are pauci-symptomatic or asymptomatic but the role of therapies to retard the loss of kidney function in patients with chronic kidney disease (e.g., modulators of the renin-angiotensin-aldosterone system, sodium-glucose cotransporter inhibitors) in reducing uremic toxins is poorly understood. Most of the research evaluating the impact of therapies to lower serum concentrations of those toxic compounds is carried out in patients with kidney failure already undergoing kidney replacement therapy. The removal of those molecules relies in physicochemical mass transfer phenomena, i.e., adsorption, diffusion, and convection. In the past 2 decades, the rise and broad adoption of blood purification strategies with enhanced convective properties, such as high-volume online hemodiafiltration and expanded hemodialysis, considerably amplified the ability to mechanically extract middle molecules (molecular weight >0.5 kDa) from the blood compartment. Nonetheless, the classification of uremic toxins has not evolved in parallel with dialysis advancements. Mounting evidence demonstrates the link between middle molecules with uremic symptoms, cardiovascular and mortality risks. An urgent need for updating the classification exists. Defining the causative relationship between specific solutes and specific clinical outcomes will promote the development of targeted therapies. In parallel, the inclusion of new pertinent dimensions to the classification like the influence of new dialysis membranes, sorbents, and intestinal chelators in the concentration of uremic toxins would improve the understanding of the pathogenesis of chronic kidney disease, setting the pace for future research in nephrology.
Assuntos
Hemodiafiltração , Falência Renal Crônica , Insuficiência Renal Crônica , Toxinas Biológicas , Uremia , Humanos , Diálise Renal/efeitos adversos , Toxinas Urêmicas , Insuficiência Renal Crônica/terapia , Insuficiência Renal Crônica/complicações , Hemodiafiltração/métodos , Falência Renal Crônica/terapia , Toxinas Biológicas/metabolismoRESUMO
Rationale & Objective: This study investigated the effects on patients' outcomes of using medium cutoff (MCO) versus high-flux (HF) dialysis membranes. Study Design: A retrospective, observational, multicenter, cohort study. Setting & Participants: Patients aged greater than 18 years receiving hemodialysis at the Baxter Renal Care Services dialysis network in Colombia. The inception of the cohort occurred from September 1, 2017, to November 30, 2017, with follow-up to November 30, 2019. Exposure: The patients were divided into 2 cohorts according to the dialyzer used at the inception: (1) MCO membrane or (2) HF membrane. Outcomes: Primary outcomes were the hospitalization rate from any cause and hospitalization days per patient-year. Secondary outcomes were acute cardiovascular events and mortality rates from any cause and secondary to cardiovascular causes. Laboratory parameters were assessed throughout the 2-year follow-up period. Analytical Approach: Descriptive statistics were used to report population characteristics. Inverse probability of treatment weighting was applied to each group before analysis. All categorical variables were compared using Pearson's χ2 test, and continuous variables were analyzed with the t test. Baseline differences between groups with a value of >10% were considered clinically meaningful. Laboratory variables were measured at 5 consecutive time points. A between-patient effect was analyzed using a split-plot factorial analysis of variance. Results: The analysis included 1,098 patients, of whom 564 (51.3%) were dialyzed with MCO membranes and 534 (48.7%) with HF membranes. Patients receiving hemodialysis with MCO membranes had a lower all-cause hospitalization incidence rate (IR) per patient-year (IR = 0.93; 95% CI, 0.82-1.03) than those receiving hemodialysis with HF membranes (IR = 1.13; 95% CI, 0.96-1.30), corresponding to a significant incident rate ratio (MCO/HF) of 0.82 (95% CI, 0.68-0.99; P = 0.04). The frequency of nonfatal cardiovascular events showed statistical significance, with a lower incidence in the MCO group (incident rate ratio = 0.66; 95% CI, 0.46-0.96; P = 0.03). No statistically significant differences in all-cause time until death were observed (P = 0.48). Albumin levels were similar between the 2 dialyzer cohorts. Limitations: Despite the robust statistical analysis, there remains the possibility that unmeasured variables may still generate residual imbalance and, therefore, skew the results. Conclusions: The incidences of hospitalization and cardiovascular events in patients receiving hemodialysis were lower when dialyzed with MCO membranes than HF membranes. A randomized controlled trial would be desirable to confirm these results. Trial Registration: Clinical Trials.gov, ISRCTN12403265.