Toxicokinetics of Protein-bound Uremic Toxins in ESRD Patients

NCT05755503 | Recruiting DMC

• 1 other identifier: JYLJ202218
• Study Type: observational
• Target: 100
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Uremic; Toxemia; Pharmacokinetics; Renal Dialysis

Keywords

Renal Dialysis; Uremic; Toxemia; Pharmacokinetics

Outcome Measures

Primary Outcomes (3)

• The blood concentration of IS

  The concentration of the free and protein-bound IS

  From the beginning of dialysis to 48 hours after dialysis

• The dialysate concentration of IS

  The concentration of the free and protein-bound IS

  Four hours of dialysis

• The urine concentration of IS

  The concentration of the free and protein-bound IS

  Four hours of dialysis

Secondary Outcomes (1)

• Dialytic clearance

  Four hours of dialysis

Study Arms (1)

IS modeling and validation group

Uremia patients receiving hemodialysis.This group was used to establish the IS three-compartment model and verify the accuracy and predictive value of the model

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Uremia patients with maintenance hemodialysis in Shanghai ninth people's hospital

You may qualify if:

• Patients with maintenance hemodialysis were less than 85 years old and more than 18 years old, both male and female;
• Regular hemodialysis for more than 3 months, using arteriovenous fistula hemodialysis;
• Receiving high-throughput dialysis, HDF, and HP according to the conventional treatment regimen;
• Adequate dialysis (Kt/V\>1.2 within one month);
• 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;
• Understand and sign the informed consent

You may not qualify if:

• Patients with systemic or local severe infection;
• Patients with severe anemia: Hb\<60g/L;
• Patients with hypoproteinemia: Alb\<30g/L;
• Patients with insufficient daily protein intake: nPCR\>1.0g/kg/d;
• Patients with malignant tumors;
• 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;
• Patients with severe hematopoietic system diseases, such as aplastic anemia, globin aplastic anemia, thrombocytopenic purpura, etc.;
• 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;
• Pregnant women;
• Participating in other clinical trials within one month or currently;
• Researchers consider it inappropriate.

Sponsors & Collaborators

• Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University: lead

Study Sites (1)

Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University

Shanghai, Shanghai Municipality, 200011, China

RECRUITING

Related Publications (4)

• 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.

  PMID: 28871178 BACKGROUND

• 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.

  PMID: 17251385 BACKGROUND

• 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.

  PMID: 27182679 BACKGROUND

• 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.

  PMID: 24469432 BACKGROUND

Biospecimen

Retention: SAMPLES WITHOUT DNA

blood samples;urine samples;dialysate samples

MeSH Terms

Conditions

Toxemia

Condition Hierarchy (Ancestors)

Infections

Study Officials

• Ding Feng, PhD

  Division of Nephrology,Shanghai Ninth People's Hospital

  STUDY DIRECTOR

Central Study Contacts

Ding Feng, PhD

CONTACT

86-21-53315165; dingfeng@sjtu.edu.cn

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: professor

Study Record Dates

• First Submitted: March 2, 2023
• First Posted: March 6, 2023
• Study Start: February 21, 2023
• Primary Completion: June 30, 2025
• Study Completion: December 30, 2025
• Last Updated: April 17, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)