Diuretic Testing in Chronic Kidney Disease (U-TUBE 2)

The goal of this clinical trial is to predict the progression of chronic kidney disease by diuretic testing in patients with chronic kidney disease. The main questions it aims to answer are:

Does a worse result of a diuretic test predict the progression of chronic kidney disease?

If there is a comparison group: Researchers will compare the diuretic test in patients with chronic kidney disease to healthy participants to see if the results are different in a healthy kidney.

Participants will undergo diuretic testing. This involves the administration of bumetanide and hydrochlorothiazide with subsequent blood and urine collections.

Study Overview

• Status: Recruiting
• Conditions: Kidney Disease, Chronic
• Intervention / Treatment: Diagnostic test: Diuretic Testing

• Study Type: Interventional
• Enrollment (Estimated): 86
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Sebastian B Beckmann, MD; Phone Number: +31 6 39022349; Email: s.beckmann@erasmusmc.nl

Study Locations

• Netherlands
  • South Holland
    • Rotterdam, South Holland, Netherlands, 3015GD
      • Recruiting
      • Erasmus MC
      • Contact: Sebastian B. Beckmann, MD; Phone Number: + 31 639022349; Email: s.beckmann@erasmusmc.nl
      • Contact: Madonna Salib, PhD, PharmD; Phone Number: +33 749172531; Email: m.salib@erasmusmc.nl
      • Principal Investigator: Ewout J. Hoorn, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria for CKD subjects:

• CKD stage G3 (creatinine-based eGFR 30-59 mL/min/1.73m2) during the last outpatient visit

Inclusion Criteria for Healthy subjects:

• eGFR within the expected range for age (a decline of 1 ml/min/1.73 m2 per year starting from age 40 is considered the normal age-related decline in kidney function

Exclusion Criteria:

• Known intolerance or allergy to the diuretics
• Current systemic chemotherapy for malignancy
• Kidney transplant recipient
• Use of calcineurin-inhibitors
• Life expectancy < 12 months
• Current immunosuppressive treatment for glomerulonephritis
• Incapacitated subjects or subjects who are deemed unfit to adequately adhere to instructions from the research team
• Hypokalemia or hyperkalemia (K+ < 3.0mmol/L or K+ > 5.5 mmol/L) at inclusion visit
• Hypo- or hypernatremia (Na+ < 130 mmol/L or Na+ > 150mmol/L) at inclusion visit
• Inherited tubulopathy as the cause of CKD
• Autosomal dominant polycystic or tubulointerstitial kidney disease causing CKD
• Clinically relevant heart failure (New York Heart Association class III or IV)
• Therapy-resistant hypertension, defined as systolic blood pressure > 180mmHg at the inclusion visit
• Current treatment with inhibitors of Organic anion transporters: probenecid, pravastatin, cimetidine, cephalosporins, acetazolamide [22]
• Active hepatitis during last outpatient visit
• Liver cirrhosis in advanced stage (Child-Pugh B or C)
• Active drug- or alcohol abuse
• Not being able to tolerate a 28-day washout of one of the drugs interfering with diuretic testing.
• Women who are pregnant, breastfeeding, or planning on becoming pregnant before the test day

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Diuretic Group; Administration of diuretics on the test day	Diagnostic test: Diuretic Testing; The administration of hydrochlorothiazide and bumetanide is used to stimulate and assess tubular function.
No Intervention: Time control group; No diuretics will be administered

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression of Chronic Kidney Disease	This composite outcome consists of the reduction of kidney function of 30% measured as creatinine-based estimated glomerular filtration rate (eGFR) using the chronic kidney disease epidemiology collaboration (CKD-EPI) 2021 formula or the initiation of kidney replacement therapy (dialysis or kidney transplantation)	3 years

Collaborators and Investigators

• Sponsor: Erasmus Medical Center
• Collaborators: European Research Council
• Investigators: Principal Investigator: Ewout J. Hoorn, MD, PhD, Erasmus Medical Center

Publications and helpful links

General Publications

• Rodriguez-Iturbe B, Herrera J, Marin C, Manalich R. Tubular stress test detects subclinical reduction in renal functioning mass. Kidney Int. 2001 Mar;59(3):1094-102. doi: 10.1046/j.1523-1755.2001.0590031094.x.
• Chawla LS, Davison DL, Brasha-Mitchell E, Koyner JL, Arthur JM, Shaw AD, Tumlin JA, Trevino SA, Kimmel PL, Seneff MG. Development and standardization of a furosemide stress test to predict the severity of acute kidney injury. Crit Care. 2013 Sep 20;17(5):R207. doi: 10.1186/cc13015.
• Colussi G, Bettinelli A, Tedeschi S, De Ferrari ME, Syren ML, Borsa N, Mattiello C, Casari G, Bianchetti MG. A thiazide test for the diagnosis of renal tubular hypokalemic disorders. Clin J Am Soc Nephrol. 2007 May;2(3):454-60. doi: 10.2215/CJN.02950906. Epub 2007 Mar 14.

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2025
• Primary Completion (Estimated): October 31, 2029
• Study Completion (Estimated): October 31, 2029

Study Registration Dates

• First Submitted: February 18, 2025
• First Submitted That Met QC Criteria: February 18, 2025
• First Posted (Actual): February 24, 2025

Study Record Updates

• Last Update Posted (Actual): August 7, 2025
• Last Update Submitted That Met QC Criteria: August 6, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Keywords: Chronic Kidney Disease; Disease Progression; Diuretic Testing; Kidney Tubular Function
• Additional Relevant MeSH Terms: Urogenital Diseases; Pathologic Processes; Male Urogenital Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Chronic Disease; Disease Attributes; Renal Insufficiency; Kidney Diseases; Renal Insufficiency, Chronic; Physiological Effects of Drugs; Natriuretic Agents; Diuretics
• Other Study ID Numbers: MEC-2024-0799; 101125504 (Other Grant/Funding Number: European Research Council); NL-005327 (Other Identifier: Onderzoeksportaal); NL87576.078.24 (Other Identifier: Toetsing Online)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No