Study to Examine the Effect of the Diuretic Furosemide on the Plasma Levels of Toxins and the Removal of Toxins from the Blood in Patients with Chronic Kidney Disease

NCT06750575 | Recruiting

• 2 other identifiers: NL81338.041.2323-239/G
• Study Type: observational
• Target: 34
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this observational study is to examine the interaction between the diuretic furosemide and certain toxins called protein-bound uremic toxins (PBUTs) in patients with chronic kidney disease (CKD). The main question it aims to answer is: what is the effect of furosemide on plasma levels of PBUTs in patients with CKD? Besides, the investigators will also look at the effect of furosemide on the excretion of PBUTs via the urine. Participants will be included in the study once they will be prescribed furosemide as part of routine patient care. Before they start with the furosemide treatment, patients will undergo the following:

• Blood pressure measurement
• Blood sample withdrawal
• Urine sample collection
• 12-hour urine collection Then, one to four weeks after starting with furosemide treatment, patients will undergo the following:
• Blood pressure measurement
• Blood sample prior to furosemide intake (Tmin)
• Blood sample withdrawal 90 minutes after furosemide intake (Tmax: time at which the highest furosemide plasma level is expected)
• Urine sample collection 60-120 minutes after furosemide intake
• 12-hour urine collection The investigators expect furosemide to increase plasma levels of PBUTs by decreasing the renal excretion of the toxins.

Conditions

Chronic Kidney Diseases; Renal Failure Chronic

Keywords

Furosemide; Drug-toxin interactions; Protein-bound uremic toxins; P-cresyl sulfate; Indoxyl sulfate

Outcome Measures

Primary Outcomes (7)

• Plasma levels of the PBUT indoxyl sulfate

  Indoxyl sulfate plasma levels (in ng/mL) will be determined before and after start of furosemide treatment.

  This will be assessed three times during the study participation period (between 1-4 weeks).

• Plasma levels of the PBUT p-cresyl sulfate

  P-cresyl sulfate plasma levels (in ng/mL) will be determined before and after start of furosemide treatment.

  This will be assessed three time during the study participation period (between 1-4 weeks).

• Plasma levels of the PBUT indole-3-acetic acid

  Indole-3-acetic acid plasma levels (in ng/mL) will be determined before and after start of furosemide treatment.

  This will be assessed three times during the study participation period (between 1-4 weeks).

• Plasma levels of the PBUT kynurenic acid

  Kynurenic acid plasma levels (in ng/mL) will be determined before and after start of furosemide treatment.

  This will be assessed three times during the study participation period (between 1-4 weeks).

• Plasma levels of the PBUT L-kynurenine

  L-kynurenine plasma levels (in ng/mL) will be determined before and after start of furosemide treatment.

  This will be assessed three times during the study participation period (between 1-4 weeks).

• Plasma levels of the PBUT hippuric acid

  Hippuric acid plasma levels (in ng/mL) will be determined before and after start of furosemide treatment.

  This will be assessed three times during the study participation period (between 1-4 weeks).

• Plasma levels of the PBUT p-cresyl glucuronide

  P-cresyl glucuronide plasma levels (in ng/mL) will be determined before and after start of furosemide treatment.

  This will be assessed three times during the study participation period (between 1-4 weeks).

Secondary Outcomes (6)

• Surrogate for PBUT clearance

  This will be assessed three times during the study participation period (between 1-4 weeks).

• Fractional PBUT excretion

  This will be assessed three times during the study participation period (between 1-4 weeks).

• PBUT protein binding

  This will be assessed three times during the study participation period (between 1-4 weeks).

• Ratio of the surrogate PBUT clearance / CKD-EPI creatinine equation

  This will be assessed three times during the study participation period (between 1-4 weeks).

• Ratio of the surrogate PBUT clearance / CKD-EPI cystatin C equation

  This will be assessed three times during the study participation period (between 1-4 weeks).

Other Outcomes (23)

• Baseline characteristics: age

  This will be collected once throughout the study participation period (between 1-4 weeks) during the first study visit.

• Baseline characteristics: sex

  This will be collected once throughout the study participation period (between 1-4 weeks) during the first study visit.

• Baseline characteristics: BMI

  This will be collected once throughout the study participation period (between 1-4 weeks) during the first study visit.

Study Arms (1)

Chronic kidney disease stage 3-5

Participants with an age of 18 years or older and with CKD stage 3-5 (an estimated glomerular filtration rate of 60 mL/min/1.73m\^2 or lower for at least three months). Participants need to have an indication to start with furosemide as part of routine patient care.

Diagnostic Test: Invasive measurements

Interventions

Invasive measurements DIAGNOSTIC_TEST

Blood and urine samples will be collected during the study.

Chronic kidney disease stage 3-5

Eligibility Criteria

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

Study Population

The study population will consist of patients with CKD stage 3-5 (eGFR \<60 mL/min/1.73m2) of 18 years and older with an indication for starting treatment with furosemide as part of routine patient care. Participants will be recruited at the Department of Nephrology in the University Medical Center Utrecht (UMCU, Utrecht, The Netherlands) who have not yet started furosemide treatment or any renal replacement therapy.

You may qualify if:

• An age of 18 years or older
• An eGFR \<60 mL/min/1.73m2 for at least three months (diagnosis of CKD stage 3-5)
• An indication for the start of treatment with furosemide as part of routine patient care
• Willingness to participate in the study and a signed informed consent

You may not qualify if:

• Patients who are already on furosemide treatment
• Patients with a liver disease with hyperbilirubinemia
• Patients who receive any type of renal replacement therapy (peritoneal dialysis, haemodialysis)
• Patients with end-stage renal failure without residual diuresis
• Patients who will start with medication simultaneously with start of furosemide treatment that might interfere with PBUT excretion or PBUT protein binding
• Patients who are incapacitated

Sponsors & Collaborators

• UMC Utrecht: lead
• Maastricht University, MERLN Institute for Technology-Inspired Regenerative Medicine: collaborator
• Utrecht Institute for Pharmaceutical Sciences: collaborator

Study Sites (1)

University Medical Center Utrecht (UMCU)

Utrecht, Utrecht, 3584 CX, Netherlands

RECRUITING

Related Publications (1)

• Mihaila SM, Faria J, Stefens MFJ, Stamatialis D, Verhaar MC, Gerritsen KGF, Masereeuw R. Drugs Commonly Applied to Kidney Patients May Compromise Renal Tubular Uremic Toxins Excretion. Toxins (Basel). 2020 Jun 12;12(6):391. doi: 10.3390/toxins12060391.

  PMID: 32545617 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

Serum and urine samples will be temporarily retained during this study for batch measurement. Afterwards, the samples will be retained until publication of the data.

MeSH Terms

Conditions

Renal Insufficiency, Chronic

Condition Hierarchy (Ancestors)

Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Karin GF Gerritsen, MD, PhD

  UMC Utrecht

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Dian P Bolhuis, MD, MSc

CONTACT

+31-887557375; d.p.bolhuis-3@umcutrecht.nl

Karin GF Gerritsen, MD, PhD

CONTACT

+31-887557375; k.g.f.gerritsen@umcutrecht.nl

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate professor, MD

Study Record Dates

• First Submitted: October 17, 2024
• First Posted: December 27, 2024
• Study Start: June 10, 2024
• Primary Completion: July 1, 2025
• Study Completion: July 1, 2025
• Last Updated: December 27, 2024

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: Our data will be shared with third parties after approval of the Principal Investigator. The criteria and time period will be determined on a case-by-case basis.
• Access Criteria: Our data will be shared with third parties after approval of the Principal Investigator. The criteria and time period will be determined on a case-by-case basis.

Locations

NL (1)