Cystinuria, Renal Lithiasis, Glomerulonephritis, Interstitial Nephritis
Conditions
Keywords
Mass spectrometry, Cystinuria, Inflammation, Nephrolithiasis
Brief summary
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.
Interventions
DIETARY_SUPPLEMENTPotassium citrate
Sponsors
Institut National de la Santé Et de la Recherche Médicale, France
Sponsor Name Pending
European Georges Pompidou Hospital
Study design
Observational model
CASE_CONTROL
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change from baseline urine inflammatory profile after 3 months of alkalizing treatment using mass spectrometry in patients with cystinuria. | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Assessment of urine inflammatory profile in controls groups using mass spectrometry. | 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. |
| Study of crystalluria (presence of crystals in urine) to assess nephrolithiasis activity. | 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. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Presence of stones in the renal cavities or in the urinary tract using ultrasonograhy. | 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. |
| Blood CRP concentrations to assess systemic inflammation | 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) |
Countries
France
Outcome results
None listed