Chronic Kidney FailurePhase 1NCT05105009
Furosemide and Creatinine Tubular Stress Test in Order to Measure Proximal Tubule Residual Function
A Phase 1 study testing Furosemide Injection, Creatinine Powder and Iohexol in people with Chronic Kidney Failure, run by Instituto Nacional de Cardiologia Ignacio Chavez at 1 site in Mexico.
Trial summary
This is a two phase study. The first part will take place at the National Institute of Cardiology in Mexico, the second phase will be made in collaboration with the University of California San Diego and University of Minnesota. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Chronic Kidney Failure
- What is being tested?
- Furosemide Injection, Creatinine Powder and Iohexol
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 1 siteMexico
- Study dates
- 3 Mar 2020to 27 Aug 2024
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Patients older than 18 years old.
- Patients with CKD that attends to the outpatient clinic.
- Residual uresis of 500 mL
Who cannot join
- Patients younger than 18 years old.
- Increase of Cr in a rate of 0.5 mg/dL, or loss of more than 30% of previous GFR.
- Patients with cardiorrenal syndrome type 1.
- Patients with dilated miocardiopathy.
- Volume overload or incomplete voiding
Trial locations and contacts
1 site in 1 country.
Mexico1 site
Instituto Nacional de Cardiologia Ignacio Chávez
Mexico City, Mexico City, 14080
About this study
Official title: Furosemide and Creatinine Tubular Stress Test in Order to Measure Proximal Tubule Residual Function: is It Better Than GFR?
This is a two phase study. The first part will take place at the National Institute of Cardiology in Mexico, the second phase will be made in collaboration with the University of California San Diego and University of Minnesota.
This is a non blind experimental study, 72 patients with different stages of CKD from the outpatient unit of the institute will be included. Each patient will receive a furosemide stress test of 1 mg/kg in non diuretic users and 1.5 mg/kg in diuretic users, in addition of 5 grams of creatinine oral intake, as well as Iohexol 5ml IV to measure GFR. After the intervention, blood and urine samples will be drawn at baseline, 60 minutes, 180 minutes, and 240 min. Urine output will be maintained during the study by the intravenous administration of Hartman's solution 1 -2 ml/kg body weight every hour, in addition to the volume of urine output in the preceding hour plus oral water ingestion as tolerated.
Read more
Blood and urine will be analized to measure creatinine (blood and urine), then samples will be processed for measurement of furosemide (HPLC-Uv vis), indoxyl sulphate, p-cresol, hippurate, and iohexol (mass spectometry).
The aim of this stiudy is to asses the differences between GFR and proximal tubule function.
Read the detailed description
Residual kidney function (RKF) its a critical tool in the CKD evolution and prognosis. It's well known that preserving RKF increases survival in patients with CKD.
Traditionally Glomerular Filtration Rate (GFR), and proteinuria have been the variables used to asses RKF, wich are glomerular residual function (GRF) variables. This glomerulocentric assestment of RKF has been challenged recently. It is knows that urea is not the principal uremic toxine, the protein boud uremic toxins are particullary important because it's elimination depends of the proximal tubular organic anionic transporters (OAT), and the organic cationic transporters (OCT). The functional integrity of this transporters are lost in advanced CKD stages, and it´s accumulation increases cardiovascular and renal damage because they activate proinflammatory citokines, increasing mortality, this was shown specially with the accumulation and clearance of hippurate and p-cresol independently of GFR.
The purpose of this study is to asses the functional capacity of two AOT (hOAT1, and hOAT3, that can be blocked by furosemide), and one OCT (OCT2 blocked by creatinine) using an stress test. The stress test will be performed in healthy subjects as well as in CKD from different stages. Protein bound uremic toxins such as indoxyl sulphate, p-cresol, and hippurate will be measured.
In the stress the typical furosemide stress test described previously by Mehta will be implemented, in addition to an oral load of 5 grams of creatinine oral load. This levels should be efficient enough to assess the functionality of the OCT2. A comparison between the tubular creatinine secretine to filtrated creatinine measuring GFR using Iohexol will be performed.
In conclusion this is a pilot study aimed to establish a practical methodology for the assesment of proximal tubular function.
- Conditions
- Chronic Kidney Failure
- Being tested
- Furosemide Injection, Creatinine Powder, Iohexol
- Medical subject headings
- Kidney Failure, Chronic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Furosemide InjectionDrug
Also called Furosemide
- Furosemide Stress Test ( 1mg/kg in non diuretic users and 1.5 mg/kg in diuretic users).
- Oral creatinine load using 5 grams of creatinine
Creatinine PowderDrug
Also called Creatinine
5g of creatinine (Sigma) in 250 ml of water was taken orally
IohexolDrug
5 ml iohexol (Omnipaque) intravenously
| Study group | Role | What they receive |
|---|---|---|
| All KDIGO stages and healthy volunteers | Experimental | 15 healthy volunteers and 35 through all KDIGO stages. Receives: Drug: Furosemide Injection; Drug: Creatinine Powder; Drug: Iohexol |
What is being measured
The primary outcome is the main question the study is designed to answer.
Tubular Residual Kidney Function
To assess the functionallity of the hOAT1 and 3, and hOCT2 by stress test using furosemide and creatinine loads.
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Nov 2021
- Study start3 Mar 2020
- Primary completion21 Oct 2023
- Study completion27 Aug 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (28)Papers the sponsor has linked to this study.
- Other trials for Chronic Kidney FailureStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- all KDIGO stages and healthy volunteers (Kidney donors)
- Masking
- None (open label)
- Enrolment
- 50 participants (actual)
Sponsor and investigators
- Lead sponsor
- Instituto Nacional de Cardiologia Ignacio Chavez
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Magdalena Madero, Instituto Nacional de Cardiologia Ignacio Chavez
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05105009
- Sponsor's protocol ID
- 19-1131
- Status last verified
- Dec 2024
- First submitted
- 11 Mar 2020
- Last updated
- 17 Dec 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Bullen AL, Fregoso A, Ascher SB, Shlipak MG, Ix JH, Rifkin DE. Markers of Kidney Tubule Dysfunction and Major Adverse Kidney Events. Nephron. 2023;147(12):713-716. doi: 10.1159/000531946. Epub 2023 Jul 31.
PubMed 37524063Liu BC, Tang TT, Lv LL, Lan HY. Renal tubule injury: a driving force toward chronic kidney disease. Kidney Int. 2018 Mar;93(3):568-579. doi: 10.1016/j.kint.2017.09.033. Epub 2018 Jan 17.
PubMed 29361307Armenta A, Madero M, Rodriguez-Iturbe B. Functional Reserve of the Kidney. Clin J Am Soc Nephrol. 2022 Mar;17(3):458-466. doi: 10.2215/CJN.11070821. Epub 2021 Nov 10.
PubMed 34759007Lowenstein J, Grantham JJ. Residual renal function: a paradigm shift. Kidney Int. 2017 Mar;91(3):561-565. doi: 10.1016/j.kint.2016.09.052.
PubMed 28202171Toth-Manikowski SM, Sirich TL, Meyer TW, Hostetter TH, Hwang S, Plummer NS, Hai X, Coresh J, Powe NR, Shafi T. Contribution of 'clinically negligible' residual kidney function to clearance of uremic solutes. Nephrol Dial Transplant. 2020 May 1;35(5):846-853. doi: 10.1093/ndt/gfz042.
PubMed 30879076Mair RD, Lee S, Plummer NS, Sirich TL, Meyer TW. Impaired Tubular Secretion of Organic Solutes in Advanced Chronic Kidney Disease. J Am Soc Nephrol. 2021 Nov;32(11):2877-2884. doi: 10.1681/ASN.2021030336. Epub 2021 Aug 18.
PubMed 34408065Koepsell H. Organic Cation Transporters in Health and Disease. Pharmacol Rev. 2020 Jan;72(1):253-319. doi: 10.1124/pr.118.015578.
PubMed 31852803Emami Riedmaier A, Nies AT, Schaeffeler E, Schwab M. Organic anion transporters and their implications in pharmacotherapy. Pharmacol Rev. 2012 Jul;64(3):421-49. doi: 10.1124/pr.111.004614. Epub 2012 Mar 28.
PubMed 22457399Rehberg PB. Studies on Kidney Function: The Rate of Filtration and Reabsorption in the Human Kidney. Biochem J. 1926;20(3):447-60. doi: 10.1042/bj0200447. No abstract available.
PubMed 16743679Rodriguez-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.
PubMed 11231365Shannon JA. THE RENAL EXCRETION OF CREATININE IN MAN. J Clin Invest. 1935 Jul;14(4):403-10. doi: 10.1172/JCI100691. No abstract available.
PubMed 16694314Koyner JL, Davison DL, Brasha-Mitchell E, Chalikonda DM, Arthur JM, Shaw AD, Tumlin JA, Trevino SA, Bennett MR, Kimmel PL, Seneff MG, Chawla LS. Furosemide Stress Test and Biomarkers for the Prediction of AKI Severity. J Am Soc Nephrol. 2015 Aug;26(8):2023-31. doi: 10.1681/ASN.2014060535. Epub 2015 Feb 5.
PubMed 25655065Rivero J, Rodriguez F, Soto V, Macedo E, Chawla LS, Mehta RL, Vaingankar S, Garimella PS, Garza C, Madero M. Furosemide stress test and interstitial fibrosis in kidney biopsies in chronic kidney disease. BMC Nephrol. 2020 Mar 6;21(1):87. doi: 10.1186/s12882-020-01721-z.
PubMed 32143585Wu W, Bush KT, Nigam SK. Key Role for the Organic Anion Transporters, OAT1 and OAT3, in the in vivo Handling of Uremic Toxins and Solutes. Sci Rep. 2017 Jul 10;7(1):4939. doi: 10.1038/s41598-017-04949-2.
PubMed 28694431Lim YJ, Sidor NA, Tonial NC, Che A, Urquhart BL. Uremic Toxins in the Progression of Chronic Kidney Disease and Cardiovascular Disease: Mechanisms and Therapeutic Targets. Toxins (Basel). 2021 Feb 13;13(2):142. doi: 10.3390/toxins13020142.
PubMed 33668632
Study at a glance
From the registry record, last updated by the sponsor on 17 Dec 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Furosemide and Creatinine Tubular Stress Test in Order to Measure Proximal Tubule Residual Function: is It Better Than GFR?
- ClinicalTrials.gov ID
- NCT05105009
- Acronym / sponsor ID
- 19-1131
- Conditions
- Chronic Kidney Failure
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 50 participants (actual)
- Lead sponsor
- Instituto Nacional de Cardiologia Ignacio ChavezUniversity, hospital or other
- Study start
- 3 Mar 2020 (actual)
- Primary completion
- 21 Oct 2023 (actual)
- Study completion
- 27 Aug 2024 (actual)
- First posted
- 3 Nov 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a two phase study. The first part will take place at the National Institute of Cardiology in Mexico, the second phase will be made in collaboration with the University of California San Diego and University of Minnesota.
This is a non blind experimental study, 72 patients with different stages of CKD from the outpatient unit of the institute will be included. Each patient will receive a furosemide stress test of 1 mg/kg in non diuretic users and 1.5 mg/kg in diuretic users, in addition of 5 grams of creatinine oral intake, as well as Iohexol 5ml IV to measure GFR. After the intervention, blood and urine samples will be drawn at baseline, 60 minutes, 180 minutes, and 240 min. Urine output will be maintained during the study by the intravenous administration of Hartman's solution 1 -2 ml/kg body weight every hour, in addition to the volume of urine output in the preceding hour plus oral water ingestion as tolerated.
Blood and urine will be analized to measure creatinine (blood and urine), then samples will be processed for measurement of furosemide (HPLC-Uv vis), indoxyl sulphate, p-cresol, hippurate, and iohexol (mass spectometry).
The aim of this stiudy is to asses the differences between GFR and proximal tubule function.
Detailed description
Residual kidney function (RKF) its a critical tool in the CKD evolution and prognosis. It's well known that preserving RKF increases survival in patients with CKD.
Traditionally Glomerular Filtration Rate (GFR), and proteinuria have been the variables used to asses RKF, wich are glomerular residual function (GRF) variables. This glomerulocentric assestment of RKF has been challenged recently. It is knows that urea is not the principal uremic toxine, the protein boud uremic toxins are particullary important because it's elimination depends of the proximal tubular organic anionic transporters (OAT), and the organic cationic transporters (OCT). The functional integrity of this transporters are lost in advanced CKD stages, and it´s accumulation increases cardiovascular and renal damage because they activate proinflammatory citokines, increasing mortality, this was shown specially with the accumulation and clearance of hippurate and p-cresol independently of GFR.
The purpose of this study is to asses the functional capacity of two AOT (hOAT1, and hOAT3, that can be blocked by furosemide), and one OCT (OCT2 blocked by creatinine) using an stress test. The stress test will be performed in healthy subjects as well as in CKD from different stages. Protein bound uremic toxins such as indoxyl sulphate, p-cresol, and hippurate will be measured.
In the stress the typical furosemide stress test described previously by Mehta will be implemented, in addition to an oral load of 5 grams of creatinine oral load. This levels should be efficient enough to assess the functionality of the OCT2. A comparison between the tubular creatinine secretine to filtrated creatinine measuring GFR using Iohexol will be performed.
In conclusion this is a pilot study aimed to establish a practical methodology for the assesment of proximal tubular function.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- all KDIGO stages and healthy volunteers (Kidney donors)
| Arm | Type | Receives |
|---|---|---|
| All KDIGO stages and healthy volunteers | Experimental | Drug: Furosemide Injection, Drug: Creatinine Powder, Drug: Iohexol15 healthy volunteers and 35 through all KDIGO stages. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Patients older than 18 years old.
- Patients with CKD that attends to the outpatient clinic.
- Residual uresis of 500 mL
Key exclusion criteria (5 listed)
- Patients younger than 18 years old.
- Increase of Cr in a rate of 0.5 mg/dL, or loss of more than 30% of previous GFR.
- Patients with cardiorrenal syndrome type 1.
- Patients with dilated miocardiopathy.
- Volume overload or incomplete voiding
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Furosemide InjectionAlso: Furosemide* Furosemide Stress Test ( 1mg/kg in non diuretic users and 1.5 mg/kg in diuretic users). * Oral creatinine load using 5 grams of creatinine | Drug | All KDIGO stages and healthy volunteers |
| Creatinine PowderAlso: Creatinine5g of creatinine (Sigma) in 250 ml of water was taken orally | Drug | All KDIGO stages and healthy volunteers |
| Iohexol5 ml iohexol (Omnipaque) intravenously | Drug | All KDIGO stages and healthy volunteers |
Primary outcome
Tubular Residual Kidney Function
Time frame: 1 year
To assess the functionallity of the hOAT1 and 3, and hOCT2 by stress test using furosemide and creatinine loads.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Dec 2024.
- Background: PubMed 37524063Bullen AL, Fregoso A, Ascher SB, Shlipak MG, Ix JH, Rifkin DE. Markers of Kidney Tubule Dysfunction and Major Adverse Kidney Events. Nephron. 2023;147(12):713-716. doi: 10.1159/000531946. Epub 2023 Jul 31.
- Background: PubMed 29361307Liu BC, Tang TT, Lv LL, Lan HY. Renal tubule injury: a driving force toward chronic kidney disease. Kidney Int. 2018 Mar;93(3):568-579. doi: 10.1016/j.kint.2017.09.033. Epub 2018 Jan 17.
- Background: PubMed 34759007Armenta A, Madero M, Rodriguez-Iturbe B. Functional Reserve of the Kidney. Clin J Am Soc Nephrol. 2022 Mar;17(3):458-466. doi: 10.2215/CJN.11070821. Epub 2021 Nov 10.
- Background: PubMed 28202171Lowenstein J, Grantham JJ. Residual renal function: a paradigm shift. Kidney Int. 2017 Mar;91(3):561-565. doi: 10.1016/j.kint.2016.09.052.
- Background: PubMed 30879076Toth-Manikowski SM, Sirich TL, Meyer TW, Hostetter TH, Hwang S, Plummer NS, Hai X, Coresh J, Powe NR, Shafi T. Contribution of 'clinically negligible' residual kidney function to clearance of uremic solutes. Nephrol Dial Transplant. 2020 May 1;35(5):846-853. doi: 10.1093/ndt/gfz042.
- Background: PubMed 34408065Mair RD, Lee S, Plummer NS, Sirich TL, Meyer TW. Impaired Tubular Secretion of Organic Solutes in Advanced Chronic Kidney Disease. J Am Soc Nephrol. 2021 Nov;32(11):2877-2884. doi: 10.1681/ASN.2021030336. Epub 2021 Aug 18.
- Background: PubMed 31852803Koepsell H. Organic Cation Transporters in Health and Disease. Pharmacol Rev. 2020 Jan;72(1):253-319. doi: 10.1124/pr.118.015578.
- Background: PubMed 22457399Emami Riedmaier A, Nies AT, Schaeffeler E, Schwab M. Organic anion transporters and their implications in pharmacotherapy. Pharmacol Rev. 2012 Jul;64(3):421-49. doi: 10.1124/pr.111.004614. Epub 2012 Mar 28.
- Background: PubMed 16743679Rehberg PB. Studies on Kidney Function: The Rate of Filtration and Reabsorption in the Human Kidney. Biochem J. 1926;20(3):447-60. doi: 10.1042/bj0200447. No abstract available.
- Background: PubMed 11231365Rodriguez-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.
- Background: PubMed 16694314Shannon JA. THE RENAL EXCRETION OF CREATININE IN MAN. J Clin Invest. 1935 Jul;14(4):403-10. doi: 10.1172/JCI100691. No abstract available.
- Background: PubMed 25655065Koyner JL, Davison DL, Brasha-Mitchell E, Chalikonda DM, Arthur JM, Shaw AD, Tumlin JA, Trevino SA, Bennett MR, Kimmel PL, Seneff MG, Chawla LS. Furosemide Stress Test and Biomarkers for the Prediction of AKI Severity. J Am Soc Nephrol. 2015 Aug;26(8):2023-31. doi: 10.1681/ASN.2014060535. Epub 2015 Feb 5.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Furosemide Injection, Creatinine Powder and Iohexol in people with Chronic Kidney Failure, run by Instituto Nacional de Cardiologia Ignacio Chavez at 1 site in Mexico.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 17 Dec 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Mexico. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Tubular Residual Kidney Function (time frame: 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05105009, which also lists 28 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Dec 2024.