Sánchez-Ospina Didier, Romero-Cote Maria, Criado-Bellido Lucia, Saez-Calero Maria Isabel, Hijazi-Prieto Badawi, Delgado-Cuesta Sandra, Herrera-Gómez Francisco, Mujika-Marticorena Maddalen, Gonzalez-Parra Emilio, Izquierdo-Ortiz Maria Jesus, Mas-Fontao Sebastián
Servicio Análisis Clínicos, Hospital Universitario de Burgos, Burgos, Spain.
Laboratory of Renal pathology and diabetes, IIS-Fundación Jiménez Díaz, Autonoma University, Madrid, Spain.
Clin Kidney J. 2025 Jun 14;18(7):sfaf195. doi: 10.1093/ckj/sfaf195. eCollection 2025 Jul.
In chronic kidney disease, the accumulation of protein-bound uremic toxins (PBUTs), such as hippuric acid (HA), p-cresyl sulfate (PCS) and indoxyl sulfate (IS), contributes to systemic toxicity and organ dysfunction. These toxins bind to plasma proteins, primarily albumin, rendering them resistant to clearance by conventional dialysis. This study hypothesizes that loop diuretics, particularly torasemide and furosemide, can displace PBUTs from their albumin-binding sites, increasing their free fraction and enhancing their removal during hemodialysis.
This pilot multicenter crossover study included 17 anuric hemodialysis patients recruited from two hospitals. Participants underwent sequential treatment with furosemide and torasemide, each phase separated by a 1-week washout period. Plasma concentrations of HA, PCS and IS were measured pre- and post-dialysis during baseline (no diuretics) and diuretic treatment phases using high-performance liquid chromatography coupled with tandem mass spectrometry. Changes in pre- and post-dialysis toxin levels were evaluated across treatment phases. Repeated measures analysis of variance assessed the effect of each diuretic treatment on toxin levels and clearance rates.
Both loop diuretics increased the free fraction and clearance of PBUTs compared with baseline. Torasemide demonstrated higher efficacy in enhancing the clearance of HA (76.8%) compared with furosemide (63.2%) and baseline (57.3%). For PCS, furosemide achieved greater reductions (66.3%) than torasemide (61.8%) and baseline (24%). Indoxyl sulfate clearance increased significantly with both diuretics (59.1% for furosemide and 58.8% for torasemide) compared with baseline (26.2%).
This study demonstrates that loop diuretics, especially torasemide, can enhance the clearance of PBUTs during hemodialysis. Their use mobilizes PBUTs from tissue stores and increases their dialyzability. These findings warrant further investigation in larger, long-term studies to validate the efficacy and clinical benefits of this approach.
在慢性肾脏病中，蛋白质结合型尿毒症毒素（PBUTs）如马尿酸（HA）、对甲酚硫酸盐（PCS）和硫酸吲哚酚（IS）的蓄积会导致全身毒性和器官功能障碍。这些毒素与血浆蛋白（主要是白蛋白）结合，使其难以通过传统透析清除。本研究假设袢利尿剂，尤其是托拉塞米和呋塞米，可将PBUTs从其白蛋白结合位点置换出来，增加其游离分数，并在血液透析期间增强其清除。
这项初步的多中心交叉研究纳入了从两家医院招募的17名无尿血液透析患者。参与者先后接受呋塞米和托拉塞米治疗，每个阶段间隔1周的洗脱期。在基线期（未使用利尿剂）和利尿剂治疗阶段，使用高效液相色谱-串联质谱法在透析前和透析后测量HA、PCS和IS的血浆浓度。评估各治疗阶段透析前后毒素水平的变化。重复测量方差分析评估每种利尿剂治疗对毒素水平和清除率的影响。
与基线相比，两种袢利尿剂均增加了PBUTs的游离分数和清除率。与呋塞米（63.2%）和基线（57.3%）相比，托拉塞米在增强HA清除率方面显示出更高的疗效（76.8%）。对于PCS，呋塞米的降低幅度（66.3%）大于托拉塞米（61.8%）和基线（24%）。与基线（26.2%）相比，两种利尿剂均可显著提高硫酸吲哚酚的清除率（呋塞米为59.1%，托拉塞米为58.8%）。
本研究表明，袢利尿剂，尤其是托拉塞米，可在血液透析期间增强PBUTs 的清除。它们的使用可使PBUTs从组织储存中释放出来，并增加其透析性
。这些发现值得在更大规模、长期研究中进一步探究，以验证这种方法疗效和临床益处。
