Effect of Urine Alkalinazation on Urinary Inflammatory Markers in Patients With Cystinuria

March 21, 2022 updated by: Marie Courbebaisse, European Georges Pompidou Hospital

Effect of Urine Alkalinazation on Urinary Inflammatory Markers Analyzed Using Mass Spectrometry in Patients With Cystinuria

It has recently been described the presence of a urinary inflammatory signature in patients with cystinuria, the most common cause of renal lithiasis of genetical origin. These data are very innovative in this pathology but deserve further studies to establish the specificity of this inflammatory signature in patients with cystinuria compared to other nephropathies and other renal lithiasis diseases. Moreover, the effect of the usual treatment of cystinuria (namely urine alkalanization) on urinary inflammatory biomarkers deserves to be tested.

The objectives of the present study are: i) To study the urinary inflammatory profile by mass spectrometry (a very efficient tool to detect and identify proteins) in patients with cystinuria and in patients with lithiasis of other origin and in patients with inflammatory renal disease ; ii) To study the potential effect of urine alkalinazation with potassium citrate (usual treatment according to European recommendations) on the inflammatory signature of patients with cystinuria. To this aim, urine of non treated cystinuric patients will be collected before treatement initiation and 3 months after the start of the alkalizing treatment.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Observational

Enrollment (Actual)

63

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
    • Ile-de-France
      • Paris, Ile-de-France, France, 75015
        • Eurpean Georges Pompidou Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

Patients with cystinuria, as well as patients with renal lithiasis not due to cystinuria and patients with an inflammatory renal pathology will be selected by the investigators of the study during their usual medical consultation.

At that time, patients will be given the information note and will be asked to sign the written informed consent.

Description

Inclusion Criteria:

  • age superior or equal to 18 years
  • patient able to understand the information note and to sign the informed consent
  • patient with an Health coverage
  • no current urinary tract infection (assessed by a cytobacteriological examination of the urine)
  • For the cystinuria group: patient with cystinuria not yet treated or for whom the alkalizing treatment or the cystein binding thiol agents have been discontinuated for at least 3 months AND with an estimated GFR (using the MDRD formula) greater than 60 ml/min/1.73m2.
  • For the control groups: patient presenting either a renal lithiasis not due to cystinuria, or an inflammatory renal pathology confirmed by an anterior renal biopsy (glomerulonephritis or interstitial nephritis) AND with an estimated GFR (using the MDRD formula) greater than 30 ml/ min/1.73m2.

Exclusion Criteria:

  • Cystinuric patient already treated (whatever the treatment)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Case-Control
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Cystinuria
10 patients with cystinuria. Experimental. Urine collected before treatment initiation and 3 months after. Treatment: Usual alkalizing treatment using oral potassium citrate. The initial dosage will be 4 g/day divided into 3 to 4 oral daily doses. If the objective of urinary pH is not reached after the first two weeks of treatment, the dose will be increased by 2 grams (6 grams total). If the urinary pH remains below 7.5 after 2 weeks with 6 grams of potassium citrate per day, the alkalizing treatment will then be supplemented with oral sodium bicarbonate in the form of Vichy water or officinal preparation. This treatment is the usual treatment recommended for cystinuria .
Dietary supplement: Potassium citrate
Other Names:
  • Sodium bicarbonate
Non cystinuria nephrolithiasis
20 patients with a nephrolithiasis not due to cystinuria. Control group. Urine collected once to study biomarkers of inflammation No intervention.
Inflammatory nephropathy

10 patients with an inflammatory nephropathy of glomerular or tubulo interstitial origin (confirmed by renal biopsy).

Control group. Urine collected once to study biomarkers of inflammation. No intervention.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change from baseline urine inflammatory profile after 3 months of alkalizing treatment using mass spectrometry in patients with cystinuria.
Time Frame: at inclusion and after three months of the usual alkalizing treatment for the patients with cystinuria
Study of urine inflammatory biomarkers profile using mass spectrometry to determine if the alkalizing treatment is susceptible to modify the urine inflammatory profile. Proteases inhibitors will be added to the urine sample immediately after urination. Urine will then be frozen at -80°C until mass spectrometry analysis. Mass spectrometry will determine the differential expression of all the proteins present the urine sample. For the purpose of the present study, the investigators will focus on the expression of inflammatory biomarkers among them MMP9 (matrix metallopeptidase), Myeloperoxydase, Proteinase 3, Neutrophil Elastase, Cathepsine G, LSP1 (lymphocyte specific protein), Fibrinogen beta and gamma chains. The aim of mass spectrometry is to detect the presence of proteins in the urine sample and to assess the differential levels of expression of the detected proteins but not to precisely measure the urine concentration of the detected proteins.
at inclusion and after three months of the usual alkalizing treatment for the patients with cystinuria

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Assessment of urine inflammatory profile in controls groups using mass spectrometry.
Time Frame: at inclusion for patients with a nephrolithiasis not due to cystinuria and in patients an inflammatory nephropathy of glomerular or tubulo interstitial origin
Study of urine inflammatory biomarkers with mass spectrometry in control groups to determine if the urine inflammatory profile is specific to cystinuria. Proteases inhibitors will be added to the urine sample immediately after urination. Urine will then be frozen at -80°C until analysis. Mass spectrometry will determine the differential expression of all the proteins present the urine sample. For the purpose of the present study, the investigators will focus on the expression of inflammatory biomarkers. The aim of mass spectrometry is to detect the presence of proteins in the urine sample and to assess the differential levels of expression of the detected proteins but not to precisely measure the urine concentration of these proteins. Moreover, urine analysis by mass spectrometry will detect all urinary proteins and the investgators do exclude to find unexpected proteins. For those reasons, urine analysis by mass spectrometry is a unique outcome.
at inclusion for patients with a nephrolithiasis not due to cystinuria and in patients an inflammatory nephropathy of glomerular or tubulo interstitial origin
Study of crystalluria (presence of crystals in urine) to assess nephrolithiasis activity.
Time Frame: at inclusion for these two groups and after three months of the usual alkalizing treatment for the patients with cystinuria
Assessment of the presence of crystals in the second morning urine sample in patients with cystinuria and in patients with a nephrolithiasis not due to cystinuria, to assess nephrolithiasis activity.
at inclusion for these two groups and after three months of the usual alkalizing treatment for the patients with cystinuria

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Presence of stones in the renal cavities or in the urinary tract using ultrasonograhy.
Time Frame: at inclusion for these two groups and after three months of the usual alkalizing treatment for the patients with cystinuria
assessment of the presence of urinary stones using ultrasonogrpahy in patients with cystinuria and in patients with a nephrolithiasis not due to cystinuria.
at inclusion for these two groups and after three months of the usual alkalizing treatment for the patients with cystinuria
Blood CRP concentrations to assess systemic inflammation
Time Frame: at inclusion for all groups and and after three months of the usual alkalizing treatment for the patients with cystinuria
Blood CRP concentration (mg/L)
at inclusion for all groups and and after three months of the usual alkalizing treatment for the patients with cystinuria

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

European Georges Pompidou Hospital

Collaborators

Institut National de la Santé Et de la Recherche Médicale, France
Sponsor Name Pending

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 2, 2015

Primary Completion (Actual)

January 31, 2020

Study Completion (Actual)

December 31, 2020

Study Registration Dates

First Submitted

January 21, 2019

First Submitted That Met QC Criteria

February 7, 2019

First Posted (Actual)

February 11, 2019

Study Record Updates

Last Update Posted (Actual)

March 22, 2022

Last Update Submitted That Met QC Criteria

March 21, 2022

Last Verified

March 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • EuropeanGPH

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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