Controversy on the CONVINCE study findings: the PRO take / Controvérsia sobre os achados do estudo CONVINCE: a perspectiva PRO

ABSTRACT The CONVINCE study, recently published in the New England Journal of Medicine, reveals a groundbreaking 23% reduction in the relative risk of all-cause mortality among end-stage kidney patients undergoing high convective volume hemodiafiltration. This significant finding challenges the conventional use of high-flux hemodialysis and offers hope for improving outcomes in chronic kidney disease patients. While some controversies surround the study's findings, including concerns about generalizability and the causes of death, it is essential to acknowledge the study's design and its main outcomes. The CONVINCE study, part of the HORIZON 2020 project, enrolled 1360 patients and demonstrated the superiority of hemodiafiltration in reducing all-cause mortality overall, as well as in specific patient subgroups (elderly, short vintage, non-diabetic, and those without cardiac issues). Interestingly, it was shown that hemodiafiltration had a protective effect against infection, including COVID-19. Future research will address sustainability, dose scaling effects, identification of subgroups especially likely to benefit and cost-effectiveness. However, for now, the findings strongly support a broader adoption of hemodiafiltration in renal replacement therapy, marking a significant advancement in the field.

RESUMO O estudo CONVINCE, publicado recentemente no New England Journal of Medicine, revela uma redução inovadora de 23% no risco relativo de mortalidade por todas as causas entre pacientes renais em estágio terminal submetidos à hemodiafiltração de alto volume de convecção. Esse achado significativo desafia o uso convencional da hemodiálise de alto fluxo e oferece esperança de melhoria dos desfechos em pacientes com doença renal crônica. Embora algumas controvérsias cerquem os achados do estudo, incluindo preocupações sobre a generalização e as causas de óbito, é essencial reconhecer o desenho do estudo e seus principais desfechos. O estudo CONVINCE, parte do projeto HORIZON 2020, inscreveu 1.360 pacientes e demonstrou a superioridade da hemodiafiltração na redução da mortalidade por todas as causas em geral, bem como em subgrupos específicos de pacientes (idosos, HD de curta duração, não diabéticos e aqueles sem problemas cardíacos). Curiosamente, demonstrou-se que a hemodiafiltração teve um efeito protetor contra infecções, incluindo a COVID-19. Pesquisas futuras abordarão sustentabilidade, efeitos de escalonamento da dose, identificação de subgrupos especialmente propensos a se beneficiar e a relação custo-benefício. No entanto, por ora, os achados apoiam fortemente uma adoção mais ampla da hemodiafiltração na terapia renal substitutiva, marcando um avanço significativo na área.

Hemodiafiltration: a synergy yet to be convincing / Hemodiafiltração: uma sinergia ainda não convincente

ABSTRACT The desperate attempt to improve mortality, morbidity, quality of life and patient-reported outcomes in patients on hemodialysis has led to multiple attempts to improve the different modes, frequencies, and durations of dialysis sessions in the last few decades. Nothing has been more appealing than the combination of diffusion and convection in the form of hemodiafiltration. Despite the concrete evidence of better clearance of middle weight molecules and better hemodynamic stability, tangible evidence to support the universal adoption is still at a distance. Survival benefits seen in selected groups who are likely to tolerate hemodiafiltration with better vascular access and with lower comorbid burden, need to be extended to real life dialysis patients who are older than the population studied and have significantly higher comorbid burden. Technical demands of initiation hemodiafiltration, the associated costs, and the incremental benefits targeted, along with patient-reported outcomes, need to be explored further before recommending hemodiafiltration as the mode of choice.

RESUMO A tentativa desesperada de melhorar a mortalidade, morbidade, qualidade de vida e desfechos relatados pelos pacientes em indivíduos em hemodiálise levou a diversas tentativas de aprimorar os diferentes modos, frequências e durações das sessões de diálise nas últimas décadas. Nada foi mais atrativo do que a combinação de difusão e convecção na forma de hemodiafiltração. Apesar das evidências concretas de melhor depuração de moléculas de peso médio e melhor estabilidade hemodinâmica, evidências tangíveis para apoiar a adoção universal ainda estão distantes. Os benefícios de sobrevida observados em grupos selecionados que provavelmente toleram a hemodiafiltração com melhor acesso vascular e com menor carga de comorbidades precisam ser estendidos aos pacientes reais em diálise, que são mais velhos do que a população estudada e apresentam uma carga de comorbidades significativamente maior. As exigências técnicas do início da hemodiafiltração, os custos associados e os benefícios incrementais almejados, juntamente com os desfechos relatados pelos pacientes, precisam ser melhor explorados antes de se recomendar a hemodiafiltração como o modo de escolha.

High volume online hemodiafiltration: a global perspective and the Brazilian experience / Hemodiafiltração on-line de alto volume: uma perspectiva global e a experiência brasileira

ABSTRACT Online hemodiafiltration (HDF) is a rapidly growing dialysis modality worldwide. In Brazil, the number of patients with private health insurance undergoing HDF has exceeded the number of patients on peritoneal dialysis. The achievement of a high convection volume was associated with better clinical imprand patient - reported outcomes confirming the benefits of HDF. The HDFit trial provided relevant practical information on the implementation of online HDF in dialysis centers in Brazil. This article aims to disseminate technical information to improve the quality and safety of this new dialysis modality.

RESUMO A hemodiafiltração (HDF) on-line é uma modalidade dialítica em rápido crescimento no mundo. No Brasil, o número de pacientes com planos de saúde privados tratados por HDF já ultrapassa aquele de pacientes em diálise peritoneal. O alcance de um alto volume convectivo associado à redução de desfechos clínicos e do risco de morte confirmam os benefícios da HDF. Dados nacionais do estudo HDFit forneceram informações práticas relevantes sobre a implementação da HDF on-line em clínicas de diálise no Brasil. O objetivo desta publicação é a disseminação de informações técnicas que possam auxiliar na utilização, com qualidade e segurança, dessa nova modalidade dialítica.

Hemodiafiltration versus Hemodialysis in End-Stage Kidney Disease: A Systematic Review and Meta-Analysis.

Rationale & Objective: The use of hemodiafiltration (HDF) as a kidney replacement therapy (KRT) in patients with end-stage kidney disease (ESKD) has sparked a debate regarding its advantages over conventional hemodialysis (HD). The present study aims to shed light on this controversy by comparing mortality rates and cause-specific deaths between ESKD patients receiving HDF and those undergoing HD. Study Design: Systematic review and meta-analysis of randomized controlled trials (RCTs). The search was conducted using PubMed, EMBASE, and Cochrane Central on July 1, 2023. Setting & Participants: Adult patients with ESKD on regular KRT. Exposure: Studies with participants undergoing HDF. Outcomes: Primary outcomes were all-cause mortality, cardiovascular (CV) mortality, deaths related to infections, and kidney transplant. We also evaluated the endpoints for deaths related to malignancy, myocardial infarction, stroke, arrhythmias, and sudden death. Analytical Approach: We included RCTs evaluating HDF versus HD. Crossover trials and studies with overlapping populations were excluded. Two authors independently extracted the data following predefined search criteria and quality assessment. The risk of bias was assessed with Cochrane's RoB2 tool. Results: We included 5 RCTs with 4,143 patients, of which 2,078 (50.1%) underwent HDF, whereas 2,065 (49.8%) were receiving HD. Overall, HDF was associated with a lower risk of all-cause mortality (risk ratio [RR], 0.81; 95% confidence interval [CI], 0.73-0.91; P < 0.001; I2 = 7%) and a lower risk of CV-related deaths (RR, 0.75; 95% CI, 0.61-0.92; P = 0.007; I2 = 0%). The incidence of infection-related deaths was also significantly different between therapies (RR, 0.69; 95% CI, 0.50-0.95; P = 0.02; I2 = 26%). Limitations: In individual studies, the HDF groups achieved varying levels of convection volume. Conclusions: Compared with those undergoing HD, patients receiving HDF experienced a reduction in all-cause mortality, CV mortality, and infection-related mortality. These results provide compelling evidence supporting the use of HDF as a beneficial intervention in ESKD patients undergoing KRT. Registration: Registered at PROSPERO: CRD42023438362.

Hemodiafiltration with endogenous reinfusion for uremic toxin removal in patients undergoing maintenance hemodialysis: a pilot study.

OBJECTIVE: To delineate the efficacy and safety profile of hemodiafiltration with endogenous reinfusion (HFR) for uremic toxin removal in patients undergoing maintenance hemodialysis (MHD). METHODS: Patients who have been on MHD for a period of at least 3 months were enrolled. Each subject underwent one HFR and one hemodiafiltration (HDF) treatment. Blood samples were collected before and after a single HFR or HDF treatment to test uremic toxin levels and to calculate clearance rate. The primary efficacy endpoint was to compare uremic toxin levels of indoxyl sulfate (IS), λ-free light chains (λFLC), and ß2-microglobulin (ß2-MG) before and after HFR treatment. Secondary efficacy endpoints was to compare the levels of urea, interleukin-6 (IL-6), P-cresol, chitinase-3-like protein 1 (YKL-40), leptin (LEP), hippuric acid (HPA), trimethylamine N-oxide (TMAO), asymmetric dimethylarginine (ADMA), tumor necrosis factor-α (TNF-α), fibroblast growth factor 23 (FGF23) before and after HFR treatment. The study also undertook a comparative analysis of uremic toxin clearance between a single HFR and HDF treatment. Meanwhile, the lever of serum albumin and branched-chain amino acids before and after a single HFR or HDF treatment were compared. In terms of safety, the study was meticulous in recording vital signs and the incidence of adverse events throughout its duration. RESULTS: The study enrolled 20 patients. After a single HFR treatment, levels of IS, λFLC, ß2-MG, IL-6, P-cresol, YKL-40, LEP, HPA, TMAO, ADMA, TNF-α, and FGF23 significantly decreased (p < 0.001 for all). The clearance rates of λFLC, ß2-MG, IL-6, LEP, and TNF-α were significantly higher in HFR compared to HDF (p values: 0.036, 0.042, 0.041, 0.019, and 0.036, respectively). Compared with pre-HFR and post-HFR treatment, levels of serum albumin, valine, and isoleucine showed no significant difference (p > 0.05), while post-HDF, levels of serum albumin significantly decreased (p = 0.000). CONCLUSION: HFR treatment effectively eliminates uremic toxins from the bloodstream of patients undergoing MHD, especially protein-bound toxins and large middle-molecule toxins. Additionally, it retains essential physiological compounds like albumin and branched-chain amino acids, underscoring its commendable safety profile.

Dosing lutetium Lu 177-dotatate for a hemodialysis patient.

Lu177-dotatate (Lutathera™) is a radioactive drug approved for the treatment of adults with gastro-entero-pancreatic neuroendocrine tumors and is predominantly renally excreted. Currently all patients receive 7400 MBq (200 mCi), and there are no guidelines for treating hemodialysis patients. We measured radioactivity prior to and post administration of two cycles of Lu177-dotatate in a hemodialysis patient, and radiation exposure to staff. We reduced the standard 7400 MBq by 33% for the first cycle and patient radioactivity fell by 40% following postdilution hemodiafiltration started 6 h post dosing, and by 45% for the second cycle and radioactivity fell by 47% with postdilution hemodiafiltration started 5 h post administration. By reducing the initial administered radioactivity, coupled with early dialysis, and choosing postdilution hemodiafiltration we were able to achieve radioactivity retention curves similar to those from patients with normal renal function receiving the standard administration of 7400 MBq.

A case of acute liver failure caused by Budd-Chiari syndrome salvaged by brain-dead donor liver transplantation.

A 24-year-old man was admitted to our hospital with abdominal distension. He was found to have acute liver failure and diagnosed with Budd-Chiari syndrome based on angiography and liver biopsy. Liver transplantation was deemed necessary when angiography showed extensive thrombotic occlusion of the hepatic veins and liver biopsy revealed submassive hepatic necrosis. The patient was found to have the JAK2V617F mutation, indicating a myeloproliferative neoplasm as the background disease. He developed hepatic encephalopathy but remained conscious on on-line hemodiafiltration. Brain-dead donor liver transplantation was performed on hospital day 30. Since then, the patient has remained well.

Unveiling the Clinical Benefits of High-Volume Hemodiafiltration: Optimizing the Removal of Medium-Weight Uremic Toxins and Beyond.

Dialysis treatment has improved the survival of patients with kidney failure. However, the hospitalization and mortality rates remain alarmingly high, primarily due to incomplete uremic toxin elimination. High-volume hemodiafiltration (HDF) has emerged as a promising approach that significantly improves patient outcomes by effectively eliminating medium and large uremic toxins, which explains its increasing adoption, particularly in Europe and Japan. Interest in this therapy has grown following the findings of the recently published CONVINCE study, as well as the need to understand the mechanisms behind the benefits. This comprehensive review aims to enhance the scientific understanding by explaining the underlying physiological mechanisms that contribute to the positive effects of HDF in terms of short-term benefits, like hemodynamic tolerance and cardiovascular disease. Additionally, it explores the rationale behind the medium-term clinical benefits, including phosphorus removal, the modulation of inflammation and oxidative stress, anemia management, immune response modulation, nutritional effects, the mitigation of bone disorders, neuropathy relief, and amyloidosis reduction. This review also analyzes the impact of HDF on patient-reported outcomes and mortality. Considering the importance of applying personalized uremic toxin removal strategies tailored to the unique needs of each patient, high-volume HDF appears to be the most effective treatment to date for patients with renal failure. This justifies the need to prioritize its application in clinical practice, initially focusing on the groups with the greatest potential benefits and subsequently extending its use to a larger number of patients.

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.

Advances in hemodialysis therapy.

End-stage renal disease (ESRD) continues to be a disease process with a high rate of hospitalization and mortality. There has been little innovation in nephrology over the last few decades compared to revolutionary high-tech advancements in other areas like oncology and cardiovascular medicine. Kidney transplantation, the only available alternative to renal replacement therapy, is limited in its availability. It is essential to have advances in this field to improve the efficiency of currently available treatments and devise new therapies. The current description of renal replacement therapy is inappropriate as it only replaces the filtration function of the failed kidney without addressing its other vital metabolic, endocrinologic, and immunologic roles and portability. Hence, it is critical to have newer therapies focusing on total replacement and portability, not just clearance. This review will address the developments in hemodialysis therapy. Advances in hemodialysis therapy include hemodiafiltration, portable machines, wearable artificial kidneys, and bioartificial kidneys. Although promising, newer technologies in this direction are still far from clinical application. Several organizations and enterprises including the Kidney Health Initiative and Kidney X: The Kidney Innovation Accelerator, as well as The Advancing American Kidney Health Initiative, are working in tandem to develop new therapies that could customize the treatment of ESRD.

Dialysis-related Amyloidosis Presenting as a Fever of Unknown Origin: Symptoms and Management.

A 74-year-old woman with a 34-year history of hemodialysis presented with an intermittent fever, which later coincided with recurrent bilateral shoulder and hip joint pain. Imaging studies suggested amyloid arthropathy, which was histologically confirmed by a synovial biopsy. Increasing ß2-microglobulin clearance during dialysis alone attenuated the intermittent fever and joint pain, but the symptoms did not disappear until the administration of prednisolone 10 mg/day. Reported cases of dialysis-related amyloidosis with a fever imply that changing to blood purification methods with high ß2-microglobulin clearance is crucial for controlling the condition long-term, whereas concurrent use of anti-inflammatory agents promptly alleviates the symptoms.

A case of severe paraquat poisoning treated by continuous hemodiafiltration without sequelae.

Background: In a suicide attempt, a 49-year-old male ingested pesticides. He arrived at the hospital restless and vomiting blue liquid. Case Presentation: The patient was diagnosed with paraquat poisoning at a lethal dose and experienced renal dysfunction during treatment. He underwent continuous hemodiafiltration (CHDF). Hemodialysis was temporarily initiated and found to improve renal function. He was discharged on day 36 in good condition. He remains well with only mild renal impairment and no pulmonary fibrosis, 240 days after the incident. The fatality rate of paraquat poisoning is approximately 80%, regardless of the treatment. Early hemodialysis combined with CHDF within 4 h has been reported to be effective. In this case, CHDF was initiated approximately 3 h after paraquat administration and showed a successful outcome. Conclusion: CHDF should be performed as soon as possible to treat paraquat poisoning.

Clinical outcome of intraoperative hemodialysis using a hemoconcentrator during cardiopulmonary bypass for dialysis-dependent patients.

OBJECTIVES: The basic materials and structure of a hemoconcentrator incorporated into cardiopulmonary bypass (CPB) circuits are similar to those of hemodialyzers. Gravity drainage hemodiafiltration (GHDF) is an easy-to-use intraoperative renal replacement therapy (RRT) that utilizes a hemoconcentrator. This study aimed to verify whether GHDF can correct electrolyte imbalance and remove uremic toxins in dialysis-dependent patients and to evaluate the clinical outcomes of GHDF by comparing it with a conventional method of dilutional ultrafiltration (DUF). METHODS: This study retrospectively compared perioperative clinical values of 41 dialysis-dependent patients (21 patients with GHDF and 20 patients with DUF) who underwent open-heart surgery. Changes in serum parameters before and after passing through the hemoconcentrator were also compared. RESULTS: Compared to DUF, GHDF significantly lowered potassium, blood urea nitrogen, and creatinine levels at the outflow of the hemoconcentrator. Less catecholamine was needed to wean CPB in GHDF than in DUF. The P/F ratio (arterial blood oxygen pressure/inhaled oxygen concentration) at the end of surgery was significantly higher in GHDF than in DUF (450.8 ± 149.7 vs. 279.3 ± 153.5; p < 0.001). Postoperative intubation time was shorter in GHDF than in DUF (8.3 ± 5.9 vs. 18.7 ± 16.1 h; p = 0.006). The major morbidity and mortality rates were comparable in both groups. CONCLUSIONS: GHDF removed both potassium and uremic toxins more efficiently than DUF in dialysis-dependent patients. Less catecholamine was needed to wean CPB using GHDF. It improved the immediate postoperative respiratory function and enabled earlier extubation. GHDF is a novel and effective option for intraoperative RRT in dialysis-dependent patients undergoing open-heart surgery.

Pharmacokinetic profile of acyclovir in a child receiving continuous kidney replacement therapy for acute liver failure.

BACKGROUND: Continuous venovenous hemodiafiltration (CVVHDF) is one of the treatments of critically ill children presenting severe acute liver failure. This affliction might be induced by HSV infection requiring a treatment by acyclovir. Continuous kidney replacement therapy (CKRT) can alter its pharmacokinetics, according to its physicochemical properties and CVVHDF settings. CASE-DIAGNOSIS/TREATMENT: The patient was a 21-month-old female presenting liver failure with hyperammonemia treated by acyclovir with presumed HSV infection. CKRT was initiated on day 1 with substantial replacement and dialysate flow rates (respectively 75 and 220 mL/kg/h). Acyclovir was intravenously administered every 8 h with a 1-h infusion of 500 mg/m2. Plasma and effluent concentrations were measured by liquid chromatography-tandem mass spectrometry assay to estimate the area under a curve (AUC) and CKRT clearance by 2 methods (one based on pre- and post-filter concentrations and the other one on dialysate flow rates). Clearance was estimated between 19.2 and 26.3 mL/min with the first method and between 27.6 and 44.3 mL/min with the second one. Concentrations were highly above the therapeutic index (peak concentration was measured at 28 mg/L), but AUC was appropriate. CONCLUSIONS: This case describes acyclovir pharmacokinetics during CKRT in a pediatric patient treated by acyclovir. The patient was treated with adapted exposure with the usual dosing, but lower dosing should be investigated with complementary studies. TRIAL REGISTRATION: ClinicalTrials.gov NCT02539407.

Anti-Inflammatory Approach in Chronic Dialysis Patients with SARS-CoV-2: ATA or PMMA Dialyzers?

INTRODUCTION: High-flux hemodialysis membranes may modulate the cytokine storm of SARS-CoV-2, but their impact on chronic hemodialysis (CHD) patients is unknown. The aim of the study was the evaluation of asymmetric cellulose triacetate (ATA) and polymethylmethacrylate (PMMA) dialyzers on inflammatory markers and clinical outcomes in CHD patients with SARS-CoV-2. METHODS: A prospective, observational study on CHD patients with SARS-CoV-2 was carried out. Patients were enrolled from March 2020 to May 2021. Pre- and postdialysis C-reactive protein (CRP), procalcitonin (PCT), and interleukin-6 (IL-6) were determined at each session. Patients who underwent on-line hemodiafiltration (OLHDF) with a PMMA dialyzer were compared with those treated with OLHDF with a ATA dialyzer. The primary endpoint was the differences in the reduction ratio per session (RR) of CRP, PCT, IL-6, and IL-6 RR >25%. RESULTS: We consecutively enrolled 74 CHD patients with COVID-19, 48 were treated with ATA membrane, and 26 with PMMA. Median IL-6 RR was higher in the ATA group compared to PMMA (17.08%, IQR -9.0 to 40.0 vs. 2.95%, IQR -34.63 to 27.32). Median CRP RR was 7.77% (IQR 2.47-13.77) in the ATA group versus 4.8% (IQR -2.65 to 11.38) in the PMMA group (p = 0.0017). Median PCT-RR% was 77.38% (IQR 70.92-82.97) in ATA group versus 54.59% (IQR 42.62-63.16) in the PMMA group (p < 0.0001). A multiple logistic regression analysis with IL-6 RR >25% as the outcome including the membrane employed, pre-dialysis IL-6, CRP, PCT, and ferritin showed that ATA led to a higher probability to reach the outcome (OR 1.891, 95% CI 1.273-2.840, p = 0.0018) while higher CRP favors the risk of lower IL-6 RR values (OR 0.910, 95% CI 0.868-0.949, p ≤ 0.0001). CONCLUSIONS: In SARS-CoV-2 CHD patients treated with OLHDF, ATA showed a better anti-inflammatory profile, regarding IL-6 RR, compared to PMMA.

In vitro analysis of factors affecting the continuous hemodiafiltration clearance of teicoplanin.

BACKGROUND: In the treatment of sepsis, continuous hemodiafiltration (CHDF) and the administration of antibiotics such as teicoplanin (TEIC) are frequently performed in parallel. We aimed to clarify the factors influencing the CHDF clearance (CLCHDF ) of TEIC using a polymethylmethacrylate (PMMA) membrane or a polyacrylonitrile and sodium methallyl sulfonate copolymer membrane coated with polyethylenimine (AN69ST). We also investigated whether the adsorption of TEIC onto the hemofilters inhibits the adsorption of interleukin (IL)-6 onto the membranes. METHODS: TEIC, human serum albumin (HSA), and IL-6 were incubated with pieces of hemofilter membranes and adsorption rates were calculated. The CLCHDF , diafiltration rate, and adsorption rate of TEIC were calculated using an in vitro CHDF circuit model. RESULTS: The adsorption rates of TEIC onto the pieces of PMMA and AN69ST membranes ranged from 15.0% to 100% and from -10% to 5%, respectively. The adsorption rate of IL-6 was similar with or without TEIC. The CLCHDF and adsorption rate of TEIC under PMMA-CHDF depended on HSA, but not on effluent flow rate (Qe). The CLCHDF under AN69ST-CHDF depended on HSA and Qe. The observed CLCHDF under AN69ST-CHDF was similar to the predicted value (the product of Qe and the plasma unbound fraction). The observed CLCHDF under PMMA-CHDF was 2.0-7.8 times greater than the predicted value. CONCLUSIONS: Adsorption mainly contributes to the CLCHDF of TEIC using PMMA membranes, whereas diafiltration mainly contributes to the CLCHDF of TEIC using AN69ST membranes. TEIC adsorption might not affect the adsorption of IL-6 onto PMMA membrane.

Residual Renal Phosphate Clearance in Patients Receiving Hemodialysis or Hemodiafiltration.

OBJECTIVES: Substantial levels of residual renal clearance and urine output may occur in patients treated with hemodialysis or hemodiafiltration. However, the relationships among residual renal urea, creatinine, and phosphate clearances, respectively, and between clearances and urine volume have not been well described. METHODS: We performed a prospective, cross-sectional study which enrolled hemodialysis and hemodiafiltration patients with a urine volume of >100 mL/day, in whom at least 2 residual renal clearances were obtained over a 6-month observation period. Urine was collected for 24 hours prior to the midweek treatment session and concentrations of urea, creatinine, and phosphate were measured. RESULTS: Thirty-eight patients (24 men, 14 women) with a mean age of 70.4 ± 12.4 (SD) years were included in this analysis. All patients were dialyzed 3 times per week with mean treatment duration of 243 ± 7.89 minutes. Twenty patients were undergoing hemodiafiltration and 18 patients high-flux hemodialysis. In total, 102 dialysis sessions, of which 52 were hemodiafiltration, and urine collections were analyzed. Mean urine volume was 457 ± 254 mL per 24 hours. Residual renal clearance rates of urea (Kr Urea), creatinine (Kr Cr), and phosphate (Kr Phos) were 1.60 ± 0.979, 4.69 ± 3.79, and 1.98 ± 1.36 mL/minute, respectively. Mean ratios of Kr Cr/Kr Urea, Kr Phos/Kr Urea, and Kr Phos/Kr Cr were 2.83 ± 1.21, 1.23 ± 0.387, and 0.477 ± 0.185, respectively. There was a modest correlation between Kr Phos and daily urine volume (r = 0.605, P = .001). CONCLUSIONS: In maintenance hemodialysis and hemodiafiltration patients, residual renal phosphate clearance is approximately 23% higher than residual renal urea clearance. Urine volume is a modestly accurate surrogate for estimating residual renal phosphate clearance, but only when urine volume is <300 mL/day.

Suggested organism entry portal of necrotizing fasciitis with complete DNA from fascia, blood, and pharyngeal ulcers: A case report.

Introduction and importance: In approximately 50% of patients with necrotizing fasciitis, infection begins deep in the soft tissues. A history of trauma is often absent. The mechanism of spread has not been elucidated. We report a case of type II necrotizing fasciitis in which the streptococcal strain was identical to isolates from other locations in the same patient. Case presentation: A 42-year-old man presented with left leg pain. Two days prior, he had a non-penetrating injury to the left thigh while playing futsal. Workup revealed swelling of the left gastrocnemius. He was admitted to orthopaedics. On the third hospital day, he was referred to our department for hypotension, impending respiratory failure, and decreased sensorium, and subsequently admitted to the ICU. A biopsy was done on the left gastrocnemius fascia. He was diagnosed with necrotizing fasciitis. On the seventh hospital day, left hip amputation and extensive debridement of the trunk were done. Patient improved and eventually recovered. Clinical discussion: Group A streptococcus was isolated in from the fascia, blood, and pharyngeal ulcer. Pulsed field gel electrophoresis showed all isolates to be genetically identical. An oral route of infection was considered. Conclusions: This is the first report in which etiologic agent of necrotizing fasciitis is genetically identical with isolates from other parts in the absence of trauma.

[Three cases of hemodiafiltration for the treatment of CAR-T related grade 3 - 4 cytokine release syndrome after ineffective treatment with IL-6 receptor inhibitors].

Objective: To investigate the efficacy and safety of hemodiafiltration (HDF) in treating CAR-T related grade 3-4 cytokine release syndrome after ineffective treatment with IL-6 receptor inhibitors. Methods: Between July 2015 and July 2021, retrospective analysis of hemodiafiltration for the treatment of 3 patients, including 2 cases of acute B-lymphoblastic leukemia and 1 case of diffuse large B-cell lymphoma, with grade 3-4 CRS after CAR-T cell therapy and ineffective treatment with IL-6 receptor inhibitor was carried out. Results: The patient's clinical symptoms, including body temperature, blood pressure, and blood oxygen, were relieved within 12 hours of all treatments, and the cytokines (IL-6, IL-10, TNF-α, INF-γ) and C-reactive protein (CRP) levels decreased significantly. No adverse side effects were observed during the follow-up period of 3 months. Conclusion: HDF can be a safe and feasible method to treat CAR-T related grade 3- 4 CRS after ineffective treatment with IL-6 receptor inhibitors.

A case report of two siblings with hypertyrosinemia type 1 presenting with hepatic disease with different onset time and severity.

Hereditary tyrosinemia type 1 (HT1) is an autosomal recessive disorder caused by a defect in fumarylacetoacetate hydroxylase (FAH) encoded by the FAH gene. Patients with HT1 disorder present with increased blood tyrosine, succinyl acetoacetate, and succinyl acetone levels, and develop clinical manifestations including liver failure, kidney tubular dysfunction, growth failure, rickets, pseudo-porphyric crises, and hepatocellular carcinoma. We encountered two siblings with HT1. Among the siblings, the elder brother developed acute liver failure with coagulopathy at the age of 2 months and was rescued by liver transplantation (LT) following combination therapy with continuous hemodiafiltration and plasma exchange. The younger sister was followed up from the prenatal period for signs of HT1 due to prior history of the condition in her sibling. She was initially considered a carrier of HT1 owing to the lack of overt signs of the disease and negative urine screening for succinyl acetone (SA). She was eventually diagnosed with HT1 because of liver disorder at 9 months of age, associated with a positive urine SA result. Her disease state was controlled by treatment with nitisinone (NTBC). DNA analysis of both siblings identified heterozygous status for a previously reported FAH pathogenic allele (c.782C > T) and a novel likely pathogenic variant (c.688C.G). The siblings have stable lives with no developmental delay or impaired growth. NTBC treatment is effective in preventing the progression of liver and kidney diseases. However, even in cases treated without LT, clinicians should follow up the clinical outcomes over long term, as patients may require LT when developing complications, such as hepatocellular carcinoma.