Toxicokinetics of Protein-bound Uremic Toxins in ESRD Patients

Toxicokinetics of Protein-bound Uremic Toxins in ESRD Patients

Protein-bound uremic toxins (PBUTs) are important uremic toxins, represented by indoxyl sulfate (IS), derived from the fermentation of dietary proteins by gut bacteria. The purpose of this study was to study the changes of IS in maintenance hemodialysis patients, and to construct a metabolic kinetics model of IS clearance. The model was then used to estimate the clearance rate of indoxyl sulfate by hemoperage, and to verify the application value of the model. This study intends to collect a series of serum, dialysate and urine samples from maintenance hemodialysis patients receiving high-throughput dialysis or hemodialysis filtration, so as to clarify the variation rule of IS during various blood purification treatments. Furthermore, a three-compartment model of dialysis IS metabolism kinetics was constructed according to the IS clearance of dialysis and residual kidney, and the above model was verified internally and externally. Finally, the model's fit and predictive value were validated in a group of MHD patients treated with HP without residual kidney.

The results of this study are helpful to clarify the rules of clearance and metabolism of PBUTs in hemodialysis patients, and lay a foundation for exploring effective means of blood purification and drugs to eliminate PBUTs, so as to reduce the incidence and mortality of complications in uremia patients.

Hemodialysis parameter setting: Blood flow 250ml/min, high throughput dialysis mode, dialysis process lasted for 4h

Samples collection time point:Blood samples: before hemodialysis, 1h, 2h, 4h after hemodialysis, 0.5h, 1h, 2h, 4h, 8h, 12h, 24h, 48h after hemodialysis.Dialysate samples: 1h, 1.5h, 2h, 3h, 4h after hemodialysis.Urine samples: 4h urine samples during hemodialysis.Hemoperfusion samples: before hemodialysis, 5min, 15min, 30min, 45min, 60min, 90min, 120min after hemodialysis.

The proposed model of IS toxicokinetics is a three-compartment model, in which the circulatory system is the central compartment, intertissue fluid is the fast equilibrium chamber, and cerebrospinal fluid, intracellular fluid, lymphatic fluid, etc. are the slow equilibrium chamber

Inclusion Criteria:

1. Patients with maintenance hemodialysis were less than 85 years old and more than 18 years old, both male and female;
2. Regular hemodialysis for more than 3 months, using arteriovenous fistula hemodialysis;
3. Receiving high-throughput dialysis, HDF, and HP according to the conventional treatment regimen;
4. Adequate dialysis (Kt/V>1.2 within one month);
5. Keep your diet steady. Generally in good condition, have self-awareness, have a good understanding of their own illness and physical condition, and can communicate well with others;
6. Understand and sign the informed consent

Exclusion Criteria:

1. Patients with systemic or local severe infection;
2. Patients with severe anemia: Hb<60g/L;
3. Patients with hypoproteinemia: Alb<30g/L;
4. Patients with insufficient daily protein intake: nPCR>1.0g/kg/d;
5. Patients with malignant tumors;
6. Patients with severe cardiovascular and cerebrovascular diseases, such as unstable angina pectoris, malignant hypertension, persistent atrial fibrillation, abnormal Q-wave of electrocardiogram, or patients with acute myocardial infarction, stroke, or coronary stent implantation within 3 months;
7. Patients with severe hematopoietic system diseases, such as aplastic anemia, globin aplastic anemia, thrombocytopenic purpura, etc.;
8. Patients with severe digestive diseases, such as dysphagia, liver insufficiency, active gastrointestinal bleeding, intestinal obstruction, intestinal perforation, or previous subtotal gastrectomy, and other diseases that may affect digestion and absorption;
9. Pregnant women;
10. Participating in other clinical trials within one month or currently;
11. Researchers consider it inappropriate.