Introduction

Indoxyl sulfate which a protein-bound uremic toxins are excreted by the kidneys via proximal tubular secreti[1], Consequently, they accumulate in the blood of patients with impaired renal function [1,2] and affect endothelial barrier function, endothelial cell proliferation and wound repair also [3], the levels correlated with aortic calcification, and in addition also with vascular stiffness [4,5]. increasingly evidences suggests that protein-bound uremic toxins play an important role in complications, especially in cardiovascular disease [6,7]. Notably, protein-bound uremic toxins have emerged as focus targets of therapeutic removal [6]. Moreover, they cannot be efficiently removed by conventional haemodialysis and hemodiafiltration [8], due to their high binding affinity for albumin [1,2,9], which are poorly eliminated by the commonly used dialysis techniques; Studies had shown that protein binding uremic toxins can absorb in intestine by oral adsorbents and hemodialysis combine adsorbents in order to clear it out from blood.Therefore, we are eager to know the variation of the clearance rates of water-soluble and protein bound uremic toxins by different blood purification methods, including High Flux Dialysis (HD), Hemodiafiltration (HDF), High Flux Dialysis Combine With Hemoperfusion (HD+HP).

Materials and Methods

Five volunteers (4 male and 1female) from Tangshan Likang Hospital received hemodialysis three times a week more than three years, body weight 80.9 ± 2.3Kg.All patients were sampled 10ml of blood, at 0 and 2 and 4 hrs during hemodialysis or hemodiafiltration or hemodialysis combined with perfusion, then immediately centrifuge at 3000rpm for 15min, and freeze the serum at -70℃. Until detected for BUN, creatinine, phosphorus, β 2-Microglobulin and indoxyl sulfate; All serum sample were assayed by Mindray 85-820M full-automatic biochemical analyzer (Mindray Medical International Co., Ltd, Shenzhen, China). And the Indoxyl sulfate was measured by HPLC using an Agilent 1100 Series system (Agilent Technologies Co. Ltd., Palo Alto, CA, USA). The results are expressed in Mean ± SD, and this study has been approved by the Medical Ethics Committee of Tangshan Likang Hospital (No. 2022112301), all patient’s age are more than 18 years old and informed consent. The patient’s treatment schedule is High flux Dialysis (HD) 290ml/min, HD+HP 240ml/min, Hemodiafiltration (post-dilution) 290ml/min, HD+HP 290ml/min. (The prescription was shown as Table 1).

Table 1: The blood purification prescription for volunteers:Dialysate/exchange solution compound: Na 140meq/L, Ca 1.5mmol/L, Dextrose 5.5mmol/L(100mg/dl), temperature 36℃, dialysate flow rate 500ml/min, treatment for 4 hours. OCI-160 used as perfusion device which containing 160 ml resin (OCI Medical Devices Co., Ltd, Chengdu, China) and all patients were used OCI-HF200 dialyzer (OCI Medical Devices Co., Ltd, Chengdu, China).

Result

All volunteers were followed the doctor’s instructions to control a weight gain of 3-4 kilograms (less than 5% BW) during the dialysis interval, their pre dialysis blood pressure was 130-150/80-90mmHg; and after dialysis 120~140/80mmHg; The clearance of water-soluble uremic toxins (BUN, Creatinine, Phosphorus β2-microglobulin) is HDF>HD and HD is equivalent to HD+HP; the clearance rate of indoxyl sulfate is HD+HP>HDF>HD. The clearance rate at 4 hours in all groups is greater than that at 2 hours. The clearance rate of uremic toxins by different blood purification methods are detailed in Table 2.

Table 2: The clearance rate of uremic toxins by different blood purification methods.

Discussion

Indoxyl Sulfate (IS) which a protein bound uremic toxin is derived from tryptophan and metabolized by bacteria in the gastrointestinal tract [10-13], More than 90% of IS in the blood binds to albumin. When kidney function is normal, Blood circulation of IS passes through the kidneys then excreted into urine [13-14]. Indoxyl sulfate is also widely recognized as an endoheliotoxin. The serum levels elevate in advanced stage of Chronic Kidney Disease (CKD) and related to the degree of reduction in glomerular filtration rate. Therefore, accumulate in the serum of patients with CKD, they may have different clinical impacts in terms of cardiovascular disease and other complication [1,15]. Due to they can induce endothelial dysfunction and cardiovascular disease in CKD patients [11,16,17]. And there were plenty of evidences had pointed out indoxyl sulfate is an independent risk of the cardiovascular disease are correlated with cardiovascular mortality in the patients with renal insufficiency or dialysis patients [18,19]. The serum levels of indoxyl sulfate are approximately 54 times and cardiovascular death in dialysis patients is 10-20 times more than in healthy individuals [15].Therefore, how to eliminate protein bound toxins is a new issue in the dialysis community, The current clinical direction is try to reduce the intestinal generation and absorption, and increasing elimination by kidney in order to reduce the serum level and attenuate the progression of cardiovascular disease [20,21]. The principle of well- known oral adsorbents (AST-120, KREMEZIN), protein bound toxins is absorbed by adsorbents and excreted in the feces before into the bloodstream, thereby reducing the accumulation of IS in CKD patients [11]. However, since the oral binders only affect the intestinal duct, it cannot remove that had taken into the circulation. To eliminate the absorbed protein bound uremic toxins remains a thorny issue.Based on the protein bound uremic toxins are hydrophobic can be adsorbed by hydrophobic adsorbers and most hydrophobic uremic toxins are anionic. They have high binding affinity for albumin and cannot be efficiently removed by conventional haemodialysis and hemodiafiltration [8,22], new strategies for remove hydrophobic uremic toxins are needed. Therefore, use cationic adsorbents to remove protein bound hydrophobic uremic toxins is a new choice [8].