Uraemic brainstem encephalopathy mimicking ocular myasthenia: a case report.

BACKGROUND: Uraemia causes a generalised encephalopathy as its most common neurological complication. Isolated brainstem uraemic encephalopathy is rare. We report a case of fatigable ptosis and complex ophthalmoplegia in brainstem uraemic encephalopathy. CASE PRESENTATION: A 22-year-old Sri Lankan man with end stage renal failure presented with acute onset diplopia and drooping of eyelids progressively worsening over one week. The patient had not complied with the prescribed renal replacement therapy which was planned to be initiated 5 months previously. On examination, his Glasgow coma scale score was 15/15, He had a fatigable asymmetrical bilateral ptosis. The ice-pack test was negative. There was a complex ophthalmoplegia with bilateral abduction failure and elevation failure of the right eye. The diplopia did not worsen with prolonged stare. The rest of the neurological examination was normal. Serum creatinine on admission was 21.81 mg/dl. The repetitive nerve stimulation did not show a decremental pattern. Magnetic resonance imaging (MRI) of the brain demonstrated diffuse midbrain and pontine oedema with T2 weighted/FLAIR hyperintensities. The patient was haemodialyzed on alternate days and his neurological deficits completely resolved by the end of the second week of dialysis. The follow up brain MRI done two weeks later demonstrated marked improvement of the brainstem oedema with residual T2 weighted/FLAIR hyperintensities in the midbrain. CONCLUSIONS: Uraemia may rarely cause an isolated brainstem encephalopathy mimicking ocular myasthenia, which resolves with correction of the uraemia.

Prevention of dialysis disequilibrium syndrome in children with advanced uremia with a structured hemodialysis protocol: A quality improvement initiative study.

BACKGROUND: Dialysis disequilibrium syndrome (DDS) is a rare but significant concern in adult and pediatric patients undergoing dialysis initiation with advanced uremia or if done after an interval. It is imperative to gain insights into the epidemiological patterns, pathophysiological mechanisms, and preventive strategies aimed at averting the onset of this ailment. DESIGN: Prospective observational quality improvement initiative cohort study. SETTING AND PARTICIPANTS: A prospective single-center study involving 50 pediatric patients under 18 years recently diagnosed with chronic kidney disease stage V with blood urea ≥200 mg/dL, admitted to our tertiary care center for dialysis initiation from January 2017 to October 2023. QUALITY IMPROVEMENT PLAN: A standardized protocol was developed and followed for hemodialysis in pediatric patients with advanced uremia. This protocol included measures such as lower urea reduction ratios (targeted at 20%-30%) with shorter dialysis sessions and linear dialysate sodium profiling. Prophylactic administration of mannitol and 25% dextrose was also done to prevent the incidence of dialysis disequilibrium syndrome. MEASURES: Incidence of dialysis disequilibrium syndrome and severe dialysis disequilibrium syndrome, mortality, urea reduction ratios (URRs), neurological outcome at discharge, and development of complications such as infection and hypotension. Long-term outcomes were assessed at the 1-year follow-up including adherence to dialysis, renal transplantation, death, and loss to follow-up. RESULTS: The median serum creatinine and urea levels at presentation were 7.93 and 224 mg/dL, respectively. A total of 20% of patients had neurological symptoms attributable to advanced uremia at the time of presentation. The incidence of dialysis disequilibrium syndrome was 4% (n = 2) with severe dialysis disequilibrium syndrome only 2% (n = 1). Overall mortality was 8% (n = 4) but none of the deaths were attributed to dialysis disequilibrium syndrome. The mean urea reduction ratios for the first, second, and third dialysis sessions were 23.45%, 34.56%, and 33.50%, respectively. The patients with dialysis disequilibrium syndrome were discharged with normal neurological status. Long-term outcomes showed 88% adherence to dialysis and 38% renal transplantation. LIMITATIONS: This study is characterized by a single-center design, nonrandomized approach, and limited sample size. CONCLUSIONS: Our structured protocol served as a framework for standardizing procedures contributing to low incidence rates of dialysis disequilibrium syndrome.

[Neurological Complications Associated with Kidney Disease].

The kidneys filter the blood to excrete waste products and excess salt from the body as urine, while reabsorbing what the body needs and keeping it in the body. For this reason, when the function of the kidneys deteriorates, urine cannot be produced, and homeostasis of electrolytes and acid-bases cannot be maintained. As a result, waste products accumulate in the body, resulting in uremia and the need for dialysis induction or kidney transplant. This paper provides an overview of the neurological complications that appear in kidney disease and their treatment.

Clinical Efficacy and Long-term Prognosis of High Flux Hemodialysis Combined with Different Frequency Hemodiafiltration in the Treatment of Middle-Aged and Elderly Patients with Uremia.

INTRODUCTION: To analyze the clinical efficacy and long-term prognosis of high flux hemodialysis (HFHD) combined with different frequency hemodiafiltration (HDF) in uremic patients. METHODS: 86 middle-aged and elderly patients with uremia were divided into the HF group (HFHD combined with high-frequency HDF) and the LF group (HFHD combined with low-frequency HDF). The changes between the two groups in various indicators after 12 months of dialysis and the survival rate at 5 years of follow-up were compared. We used SPSS 25.0 software for data analysis. RESULTS: The differences of the levels of serum albumin, hemoglobin and transferrin in HF Group was significantly higher than LF Group before and after treatment (P < .05). The differences of the levels and clearance rate of calcium, phosphorus, parathyroid hormone, ß2-microglobulin and cysteine protease inhibitor C in the patients' blood after dialysis were significantly higher in HF Group than in LF Group (P < .05). The all-cause mortality rate, new cardiovascular event rate, new cerebrovascular event rate, and new infection event rate of HF Group were significantly lower than those of LFHD group, respectively (P < .05). The LF Group had a significantly higher risk of all-cause mortality events, new cardiovascular cerebrovascular and infectious events than the HF Group (P < .05). CONCLUSION: 1 week/time HDF combined with HFHD can more effectively eliminate the vascular related toxins in middle-aged and elderly patients with uremia, improve their nutritional status, treatment effect, and long-term prognosis.  DOI: 10.52547/ijkd.7864.

Effect of Membrane Permeance and System Parameters on the Removal of Protein-Bound Uremic Toxins in Hemodialysis.

Inadequate clearance of protein-bound uremic toxins (PBUTs) during dialysis is associated with morbidities in chronic kidney disease patients. The development of high-permeance membranes made from materials such as graphene raises the question whether they could enable the design of dialyzers with improved PBUT clearance. Here, we develop device-level and multi-compartment (body) system-level models that account for PBUT-albumin binding (specifically indoxyl sulfate and p-cresyl sulfate) and diffusive and convective transport of toxins to investigate how the overall membrane permeance (or area) and system parameters including flow rates and ultrafiltration affect PBUT clearance in hemodialysis. Our simulation results indicate that, in contrast to urea clearance, PBUT clearance in current dialyzers is mass-transfer limited: Assuming that the membrane resistance is dominant, raising PBUT permeance from 3 × 10-6 to 10-5 m s-1 (or equivalently, 3.3 × increase in membrane area from ~ 2 to ~ 6 m2) increases PBUT removal by 48% (from 22 to 33%, i.e., ~ 0.15 to ~ 0.22 g per session), whereas increasing dialysate flow rates or adding adsorptive species have no substantial impact on PBUT removal unless permeance is above ~ 10-5 m s-1. Our results guide the future development of membranes, dialyzers, and operational parameters that could enhance PBUT clearance and improve patient outcomes.

Clinical value of ultrasound in adult Wilms' tumor patient with uremia: A case report and literature review.

RATIONALE: Wilms' tumor (WT) is the most common pediatric kidney malignancy and is rarely found in adults. Nonspecific clinical symptoms and imaging features often lead to delayed diagnosis or misdiagnosis of adult WT, resulting in poor clinical outcomes. Ultrasound (US), as an efficient and noninvasive examination method, has been widely used in clinical diagnosis and treatment. Therefore, various US evidence is meaningful to improve understanding of adult WT characteristics in ultrasound. PATIENT CONCERNS: A 45-year-old female patient with uremia (regular hemodialysis for 13 years) with painless gross hematuria was diagnosed with a right kidney tumor penetrating to the lung. Preoperatively, B-mode ultrasonography showed an ill-defined hyperechoic mass in the right kidney, which revealed an unclear border, uneven internal echoes, and calcification. Besides, the internal blood flow signal of the tumor was detected. Contrast-enhanced ultrasound (CEUS) showed an uneven hyper-enhancement in the tumor ("fast in and slow out"). Contrast-enhanced computed tomography of the kidney indicated a similar result as the CEUS. Moreover, the chest CT identified multiple pulmonary metastatic nodules. DIAGNOSES: An ultrasound-guided percutaneous core needle biopsy of the tumor proceeded to make a definite diagnosis of adult WT (epithelial type). INTERVENTIONS: The patient was treated with tislelizumab. OUTCOMES: No progress was found to date. LESSONS: We report the first case in which CEUS was performed in an adult WT patient with uremia and multiple pulmonary metastases. The features obtained by the US can help in the diagnosis of adult WT and direct further diagnostic procedures.

Protective effect of activated charcoal against progression of chronic kidney disease: A randomized clinical study.

Chronic kidney disease (CKD) is a non-reversible and progressive disease affecting the kidneys, significantly impacting global public health. One of the complications of chronic kidney disease is impaired intestinal barrier function, which may allow harmful products such as urea to enter the bloodstream and cause systemic inflammation. This study aimed to investigate whether supplementation with activated charcoal could reduce uremic toxins in patients with end-stage renal disease (ESRD). The study was a randomized clinical trial conducted at the Dialysis Center of al Diwaniyah Medical Hospital in the Diwaniyah Governorate. Eighty-two patients with ESRD on regular hemodialysis were enrolled, with 15 patients receiving oral supplementation with activated charcoal in addition to standard care and 13 patients receiving only standard care. Blood samples were collected at baseline and after eight weeks, and several biomarkers were measured, including estimated glomerular filtration rate (eGFR), creatinine, urea, phosphorus, albumin, and indoxyl sulfate. The results showed a significant reduction in both serum urea and serum phosphorus levels after eight weeks of oral-activated charcoal treatment. However, the other biomarkers were not affected by the treatment. In conclusion, the use of oral-activated charcoal for eight weeks in Iraqi patients undergoing maintenance hemodialysis improved urea and phosphorus levels.

Effects of Increased Blood Flow Rate and Oral Activated Charcoal on the Severity of Uremic Pruritus: A Randomized Crossover Clinical Trial.

The aim of this study was to compare the effect of increased blood flow rate and the administration of an activated charcoal suspension on the severity of uremic pruritus in hemodialysis patients in a crossover clinical trial. Each group (n = 20) received three 2-week interventions, including increased pumping speed, daily administration of a charcoal suspension (6 g), and the concurrent use of increased pumping speed and oral administration of the charcoal suspension. After each intervention, they had a 2-week washout period. The severity and quality of pruritus were measured using the Yosipovitch's pruritus questionnaire. The results showed that the mean severity, highest pruritus score, and lowest pruritus score decreased after all three interventions, but the highest decrease was related to the third intervention. Considering the results of this study, simultaneous use of increased pumping speed and oral administration of a charcoal suspension is recommended to reduce uremic pruritus in hemodialysis patients.

Expanded Hemodialysis ameliorates uremia-induced impairment of vasculoprotective KLF2 and concomitant proinflammatory priming of endothelial cells through an ERK/AP1/cFOS-dependent mechanism.

Aims: Expanded hemodialysis (HDx) therapy with improved molecular cut-off dialyzers exerts beneficial effects on lowering uremia-associated chronic systemic microinflammation, a driver of endothelial dysfunction and cardiovascular disease (CVD) in hemodialysis (HD) patients with end-stage renal disease (ESRD). However, studies on the underlying molecular mechanisms are still at an early stage. Here, we identify the (endothelial) transcription factor Krüppel-like factor 2 (KLF2) and its associated molecular signalling pathways as key targets and regulators of uremia-induced endothelial micro-inflammation in the HD/ESRD setting, which is crucial for vascular homeostasis and controlling detrimental vascular inflammation. Methods and results: First, we found that human microvascular endothelial cells (HMECs) and other typical endothelial and kidney model cell lines (e.g. HUVECs, HREC, and HEK) exposed to uremic serum from patients treated with two different hemodialysis regimens in the Permeability Enhancement to Reduce Chronic Inflammation II (PERCI-II) crossover clinical trial - comparing High-Flux (HF) and Medium Cut-Off (MCO) membranes - exhibited strongly reduced expression of vasculoprotective KLF2 with HF dialyzers, while dialysis with MCO dialyzers led to the maintenance and restoration of physiological KLF2 levels in HMECs. Mechanistic follow-up revealed that the strong downmodulation of KLF2 in HMECs exposed to uremic serum was mediated by a dominant engagement of detrimental ERK instead of beneficial AKT signalling, with subsequent AP1-/c-FOS binding in the KLF2 promoter region, followed by the detrimental triggering of pleiotropic inflammatory mediators, while the introduction of a KLF2 overexpression plasmid could restore physiological KLF2 levels and downmodulate the detrimental vascular inflammation in a mechanistic rescue approach. Conclusion: Uremia downmodulates vasculoprotective KLF2 in endothelium, leading to detrimental vascular inflammation, while MCO dialysis with the novel improved HDx therapy approach can maintain physiological levels of vasculoprotective KLF2.

Knowledge, attitude, and practice of patients receiving maintenance hemodialysis regarding hemodialysis and its complications: a single-center, cross-sectional study in Nanjing.

BACKGROUND: Good knowledge of and attitudes toward hemodialysis and its complications might be expected to promote good practices and improve adherence. This study investigated, the knowledge, attitude, and practice of patients receiving hemodialysis regarding hemodialysis and its complications. METHODS: This cross-sectional study enrolled patients with uremia who were receiving hemodialysis at the Second Affiliated Hospital of Nanjing Medical University (China) between January 9, 2023, and January 16, 2023. A questionnaire was designed that included the following dimensions: demographic/clinical information, knowledge, attitude, and practice. Correlations between knowledge, attitude, and practice scores were evaluated by Pearson correlation analysis. RESULTS: The analysis included 493 patients (305 males, 61.87%). The average knowledge, attitude, and practice score was 19.33 ± 7.07 (possible range, 0-31), 28.77 ± 3.58 (possible range, 8-40), and 43.57 ± 6.53 (possible range, 11-55) points, respectively. A higher knowledge score was associated with younger age (P < 0.001), a higher education level (P < 0.001), and not living alone (P < 0.001), while a higher practice score was associated with a shorter history of hemodialysis (P < 0.001). There were positive correlations between the knowledge and practice scores (r = 0.220, P < 0.001) and between the attitude and practice scores (r = 0.453, P < 0.001), although the knowledge and attitude scores were not significantly correlated. CONCLUSIONS: The results provide important insights into the knowledge, attitudes, and practices of patients with uremia in Nanjing (China) regarding hemodialysis and its complications. These findings may facilitate education programs to improve self-care practices in patients receiving maintenance hemodialysis in Nanjing (China).

Rationale for Adsorption in Extracorporeal Blood Purification.

A strong rationale supports the development of adsorption-based extracorporeal blood purification in conditions such as sepsis, acute kidney disease, uremia, and acute liver failure. The retention of compounds as a consequence of acute or chronic organ dysfunction might have detrimental effects. When a causative effect of an accumulated compound in a pathogenic condition is demonstrated, a rationale for the removal of this solute is also established. Adsorption is a mass transfer mechanism in which a solute chemically interacts with the surface of a solid structure (sorbent) and is removed from its solvent (i.e., blood or plasma). Traditional extracorporeal blood purification techniques utilize semipermeable membranes and depend mainly on diffusion and convection as mechanisms of mass transfer. Protein-bound solutes and water-soluble compounds with molecular weight above 25 kDa are scantly removed by either diffusive or convective clearances. In contrast, recently developed resins have demonstrated safety aligned with notable adsorptive capability, which enables the extraction of endotoxins, inflammatory mediators, and uremic toxins. The understanding of the kinetics of these elements and the improvement in patient selection are key factors to propel exploratory and confirmatory trials that ultimately will lead to the expected changes in clinical practice.

Etiopathogenesis of chronic kidney disease-associated pruritus: putting the pieces of the puzzle together.

Defined as the unpleasant sensation that causes the desire to scratch, pruritus is the most common skin symptom associated with uremia and appears in almost half of patients with advanced chronic kidney disease (CKD). Beyond its direct impact on quality of life, CKD-associated pruritus (CKD-aP) is an independent predictor of mortality that also has a synergistic effect with other quality of life-related symptoms, such as insomnia, depression, and anxiety. Although different mechanisms have been proposed to explain the origin of Pa-ERC, its etiopathogenesis is still not fully understood. Since new therapeutic targets have been identified and several clinical trials have recently shown promising results, our current understanding of the interrelationships has expanded significantly and the pathophysiological mechanisms underlying CKD-aP are now considered to be multifactorial. The potential triggers of pruritus in patients with CKD are discussed in this review, including hypotheses about skin xerosis, accumulation of uremic toxins, dysregulation of the immune system and systemic inflammation, uremic neuropathy, and imbalances in the endogenous opioid system. Other non-uremic causes of pruritus are also discussed, with the aim of guiding the physicians to apply an adequate aetiopathogenic approach to CKD-aP in their day-to-day clinical practice.

Implications of uremic cardiomyopathy for the practicing clinician: an educational review.

Studies over recent years have redeveloped our understanding of uremic cardiomyopathy, defined as left ventricular hypertrophy, congestive heart failure, and associated cardiac hypertrophy plus other abnormalities that result from chronic kidney disease and are often the cause of death in affected patients. Definitions of uremic cardiomyopathy have conflicted and overlapped over the decades, complicating the body of published evidence, and making comparison difficult. New and continuing research into potential risk factors, including uremic toxins, anemia, hypervolemia, oxidative stress, inflammation, and insulin resistance, indicates the increasing interest in illuminating the pathways that lead to UC and thereby identifying potential targets for intervention. Indeed, our developing understanding of the mechanisms of UC has opened new frontiers in research, promising novel approaches to diagnosis, prognosis, treatment, and management. This educational review highlights advances in the field of uremic cardiomyopathy and how they may become applicable in practice by clinicians. Pathways to optimal treatment with current modalities (with hemodialysis and angiotensin-converting enzyme inhibitors) will be described, along with proposed steps to be taken in research to allow evidence-based integration of developing investigational therapies.

Blood-brain barrier perturbations by uremic toxins: Key contributors in chronic kidney disease-induced neurological disorders?

Chronic kidney disease is multifactorial and estimated to affect more than 840 million people worldwide constituting a major global health crisis. The number of patients will continue to rise mostly because of the aging population and the increased prevalence of comorbidities such as diabetes and hypertension. Patients with advanced stages display a loss of kidney function leading to an accumulation of, a.o. protein-bound uremic toxins that are poorly eliminated by renal replacement therapies. This systemic retention of toxic metabolites, known as the uremic syndrome, affects other organs. Indeed, neurological complications such as cognitive impairment, uremic encephalopathy, and anxiety have been reported in chronic kidney disease patients. Several factors are involved, including hemodynamic disorders and blood-brain barrier (BBB) impairment. The BBB guarantees the exchange of solutes between the blood and the brain through a complex cellular organization and a diverse range of transport proteins. We hypothesize that the increased exposure of the brain to protein-bound uremic toxins is involved in BBB disruption and induces a perturbation in the activity of endothelial membrane transporters. This phenomenon could play a part in the evolution of neurological disorders driven by this kidney-brain crosstalk impairment. In this review, we present chronic kidney disease-induced neurological complications by focusing on the pathological relationship between the BBB and protein-bound uremic toxins. The importance of mechanistically delineating the impact of protein-bound uremic toxins on BBB integrity and membrane drug transporter expression and function in brain endothelial capillary cells is highlighted. Additionally, we put forward current knowledge gaps in the literature.

Early clinical observation of supra-hemodiafiltration with endogenous reinfusion in the treatment of uremic pruritus.

BACKGROUND: To evaluate the clinical efficacy of supra-hemodiafiltration with endogenous reinfusion (Supra-HFR) for pruritus in uremic maintenance hemodialysis (HD) patients and explore the possible mechanism. METHODS: This study prospectively included 60 patients with uremia who underwent maintenance hemodialysis and developed pruritus. Patients were randomly divided into a study group (30 cases) and a control group (30 cases). Patients in the study group underwent dialysis once a week with Supra-HFR and twice a week with HD. The group received HD dialysis 3 times a week. Visual analog scales (VAS) scores, 5-D itch scale scores, and 12-Item Pruritus Severity Scale (12-PSS) were used to evaluate the itching degree of patients. Quality of life was assessed using KDTA and SF-36 scores. Blood levels of hypersensitive C-reactive protein, calcium ion (Ca2+), phosphorus ion (P3+ ), free parathyroid hormone (iPTH), and ß2-microglobulin (ß2-MG) were compared between the two groups before treatment and at follow-up 24 weeks after treatment. RESULTS: Before treatment, there was no significant difference in VAS, 5-D itch scale, and 12-PSS score between the study group and the control group (all p > 0.05). After 24 weeks of treatment, the VAS score of the study group (2.82 ± 0.91) was significantly lower than that of the control group (7.47 ± 1.32, p < 0.001), the 5-D itch scale score of the study group (9.47 ± 2.34) was significantly lower than that of the control group (18.53 ± 4.02, p < 0.001), the 12-PSS score of the study group (11.20 ± 1.81) was significantly lower than that of the control group (16.47 ± 2.09, p < 0.001). KDTA of the study group (64.17 ± 8.07 vs. 47.83 ± 13.46, p < 0.001) and SF-36 scores (65.37 ± 6.28 vs. 55.90 ± 14.28, p = 0.002) were significantly higher than that in the control group. The levels of hs-CRP, P3+ , iPTH, and ß2-MG in the study group after treatment were lower than those before treatment, and lower than those in the control group after treatment (all p < 0.05). CONCLUSIONS: The Supra-HFR can effectively reduce the itching symptoms of uremia patients and improve their quality of life.

The Role of Uremic Retention Solutes in the MIA Syndrome in Hemodialysis Subjects.

INTRODUCTION: In chronic kidney disease (CKD), the high morbidity and mortality risk for cardiovascular disease (CVD) are not easily explained only on the basis of traditional factors. Among nontraditional ones involved in CKD, malnutrition, inflammation, and atherosclerosis/calcification have been described as the "MIA syndrome." METHODS: In this pilot study, we evaluated the association between the variation in serum levels of 27 uremic retention solutes plus 6 indexes related to the MIA syndrome processes in a population of dialysis patients. RESULTS: As expected, we found a direct correlation between serum albumin and both phosphate and total cholesterol (r = 0.54 and 0.37, respectively; p < 0.05). Moreover, total cholesterol and phosphate directly correlate (r = 0.40, p < 0.05). The relationship between malnutrition and inflammation is highlighted by the correlation of serum cholesterol levels with serum alpha-1 acid glycoprotein and IL-6 levels (r = -0.56, r = -0.39, respectively; p < 0.05). Moreover, the relation between inflammation and atherosclerosis/calcification is supported by the correlation of IL-6 with VEGF levels and vascular smooth muscle cell high-Pi in vitro calcification (r = 0.81, r = 0.66, respectively; p < 0.01). CONCLUSION: We found significant correlations between several uremic retention solutes and malnutrition, inflammation, and atherosclerosis/calcification. Our findings support the hypothesis of a central role of the uremic milieu in the MIA syndrome and ultimately in the pathogenesis of CKD-specific CVD risk factors.

Proposal for a New Classification of Solutes of Interest in Uremia and Hemodialysis.

Uremic toxins contribute to clinical manifestations of kidney dysfunction. These toxins include organic and inorganic elements or compounds. While the kidney typically clears uremic toxins, gut dysbiosis, and tissue inflammation could lead to increased production of substances that can further the clinical manifestations of uremia. The uremic toxins are quantitatively measurable in biological fluids and have an established relationship with azotemia signs and symptoms. Their elimination is associated with mitigated uremic manifestations, while their administration to the uremic levels leads to uremic signs in animal or human models or in vitro studies. Besides, the uremic toxins have an established and plausible pathophysiologic relationship with uremic manifestations. The previous classification of uremic toxins was mainly focused on the physicochemical characteristics of these substances to divide them into three categories, (1) free water-soluble low-molecular-weight (<500 Da) solutes, (2) protein-bound, water-soluble, low molecular weight (<500 Da), (3) middle molecular weight (>500 Da and <12,000 Da), and (4) high molecular weight (>12,000 Da). Unfortunately, the classification named above was not centered around patient outcomes and quality of life among those with severe kidney failure. Therefore, a panel of experts convened virtually to provide additional insights into the current state and propose a new uremic toxin classification. This article describes the group's consensus recommendations regarding the new classification of uremic toxins into more clinically oriented categories.

Critical Appraisal of Limitations in the Current Definition/Classification of Uremic Toxins.

Progress in the identification and characterization of uremic retention solutes has refined our understanding of the pathophysiology of the uremic syndrome. Furthermore, the evolution of dialysis and other techniques designed to remove uremic retention solutes offers opportunities to provide a more personalized and targeted treatment for patients with chronic kidney disease (CKD) with an aim to improve outcomes. Considering these developments, a consensus report was recently published that readdressed the 2003 definition and classification of uremic toxins and formulated recommendations for future research to enhance the understanding of uremic retention solutes. In the present work, the authors of a work group that contributed to the consensus report provide a more detailed rationale for the recommendations related to their theme "Critical appraisal of limitations in the current definition/classification of uremic toxins." In summary, the authors propose that the current definition of uremic toxins should remain organized on hemodialysis strategies, membranes, and removal patterns since hemodialysis is the most frequently applied therapeutic strategy to reduce their concentration in advanced CKD. Nevertheless, the work group also acknowledges that any classification based on cutoff values and/or molecular spatial configurations is arbitrary and will likely need to be changed with therapeutic advancements. Furthermore, the current physicochemical classification might be extended to reflect the degree of toxicity of a specific toxin that is likely to support more personalized and targeted dialysis prescriptions and improve the outcomes for patients with CKD.