Toxicokinetics of Protein-bound Uremic Toxins in ESRD Patients

Pharmacokinetics Clinical Trial

Official title:

Toxicokinetics of Protein-bound Uremic Toxins in ESRD Patients

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05755503
• Other study ID #: JYLJ202218
• Status: Recruiting
• Start date: February 21, 2023
• Est. completion date: December 30, 2025

Study information

• Verified date: April 2024
• Source: Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University
• Contact: Ding Feng, PhD
• Phone: 86-21-53315165
• Email: dingfeng[@]sjtu.edu.cn
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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.

Description:

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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: December 30, 2025
• Est. primary completion date: June 30, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 85 Years

Eligibility

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.

Related Conditions & MeSH terms

• Pharmacokinetics
• Renal Dialysis
• Sepsis
• Toxemia
• Uremic; Toxemia

Locations

Country	Name	City	State
China	Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University	Shanghai	Shanghai

Sponsors (1)

Lead Sponsor	Collaborator
Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University

Country where clinical trial is conducted

China, 

References & Publications (4)

Devine E, Krieter DH, Ruth M, Jankovski J, Lemke HD. Binding affinity and capacity for the uremic toxin indoxyl sulfate. Toxins (Basel). 2014 Jan 24;6(2):416-29. doi: 10.3390/toxins6020416. — View Citation

Esquivias-Motta E, Martin-Malo A, Buendia P, Alvarez-Lara MA, Soriano S, Crespo R, Carracedo J, Ramirez R, Aljama P. Hemodiafiltration With Endogenous Reinfusion Improved Microinflammation and Endothelial Damage Compared With Online-Hemodiafiltration: A Hypothesis Generating Study. Artif Organs. 2017 Jan;41(1):88-98. doi: 10.1111/aor.12704. Epub 2016 May 16. — View Citation

Maheshwari V, Thijssen S, Tao X, Fuertinger D, Kappel F, Kotanko P. A novel mathematical model of protein-bound uremic toxin kinetics during hemodialysis. Sci Rep. 2017 Sep 4;7(1):10371. doi: 10.1038/s41598-017-10981-z. — View Citation

Meyer TW, Peattie JW, Miller JD, Dinh DC, Recht NS, Walther JL, Hostetter TH. Increasing the clearance of protein-bound solutes by addition of a sorbent to the dialysate. J Am Soc Nephrol. 2007 Mar;18(3):868-74. doi: 10.1681/ASN.2006080863. Epub 2007 Jan 24. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The blood concentration of IS	The concentration of the free and protein-bound IS	From the beginning of dialysis to 48 hours after dialysis
Primary	The dialysate concentration of IS	The concentration of the free and protein-bound IS	Four hours of dialysis
Primary	The urine concentration of IS	The concentration of the free and protein-bound IS	Four hours of dialysis
Secondary	Dialytic clearance	The total IS amount removed by dialysis	Four hours of dialysis