The project is to explore in humans the hypothesis of the link between the alteration of tubulo-interstitial metabolism and the rate of deterioration of renal function by comparing various nephropathies.
Patients with ANCA vasculitis with rapidly progressive glomerulonephritis with "crescent" will be compared to six other groups made up of patients with another nephropathy 1/extramembranous glomerulonephritis and 2/ nephropathy with minimal glomerular lesion (LGM) characterized by the absence of significant tubulointerstitial fibrosis lesions and slow evolution towards end-stage chronic renal failure ). Other groups of patients will 3/have interstitial nephropathy, 4/IgA mesangial glomerulopathy , 5/diabetic nephropathy, or 6/collapsing focal segmental hyalinosis.
Study Type
OBSERVATIONAL
Enrollment
146
Georges-Pompidou European Hospital, AP-HP
Paris, France
Spatial lipidomics for measuring tubular dysmetabolism
Measured either through biospy at baseline or from blood and urine samples taken at baseline, after 15 days, 2 months, 6 months and then every 6 months until the last patients completed 1 year follow-up. Their contribution for classifying ANCA vasculitis and other nephropathies will be evaluated.
Time frame: Through study completion up to end of study, when the last patients completed 1 year follow-up.
Co-staining for measuring tubular segments markers
Measured either through biospy at baseline or from blood and urine samples taken at baseline, after 15 days, 2 months, 6 months and then every 6 months until the last patients completed 1 year follow-up. Their contribution for classifying ANCA vasculitis and other nephropathies will be evaluated.
Time frame: Through study completion up to end of study, when the last patients completed 1 year follow-up
Immunofluorescence (at the protein level) for measuring peroxisome Proliferator-Activated Receptor-Gamma (PPAR-gamma)
Measured either through biospy at baseline or from blood and urine samples taken at baseline, after 15 days, 2 months, 6 months and then every 6 months until the last patients completed 1 year follow-up. Its contribution for classifying ANCA vasculitis and other nephropathies will be evaluated.
Time frame: Through study completion up to end of study, when the last patients completed 1 year follow-up
Spatial transcriptomics (at the mRNA level) for measuring peroxisome Proliferator-Activated Receptor-Gamma (PPAR-gamma)
Measured either through biospy at baseline or from blood and urine samples taken at baseline, after 15 days, 2 months, 6 months and then every 6 months until the last patients completed 1 year follow-up. Its contribution for classifying ANCA vasculitis and other nephropathies will be evaluated.
Time frame: Through study completion up to end of study, when the last patients completed 1 year follow-up
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Glomerular filtration rate evolution
CKDepi (Chronic Kidney Disease - EPIdemiology, a method for estimating glomerular filtration rate) decline. It is calculated with a patient's age, sexe and color of their skin as well as serum creatinine rates found in urine and blood samples. Measured at baseline, after 15 days, 2 months, 6 months and then every 6 months until the last patients completed 1 year follow-up. It will be used to study the differences of glomerular filtration rate evolution between patients with ANCA vasculitis and those with other nephropathies.
Time frame: Through study completion up to end of study, when the last patients completed 1 year follow-up.
Urinary protein/creatinine ratio evolution
Measured in urinary morning sample taken at baseline, after 2 months, 6 months and then every 6 months until the last patients completed 1 year follow-up. It will be used to : * group patients with similar characteristics in homogeneous groups. * study the differences in the evolution between patients with ANCA vasculitis and those with other nephropathies. * identify similaritites in patients trajectories according to which nephropathy they were diagnosed with.
Time frame: Through study completion up to end of study, when the last patients completed 1 year follow-up.
Urinary albumin/creatinine evolution ratio
Measured in urinary morning sample taken at baseline, after 2 months, 6 months and then every 6 months until the last patients completed 1 year follow-up. It will be used to : * group patients with similar characteristics in homogeneous groups. * study the differences in the evolution between patients with ANCA vasculitis and those with other nephropathies. * identify similaritites in patients trajectories according to which nephropathy they were diagnosed with.
Time frame: Through study completion up to end of study, when the last patients completed 1 year follow-up.
Lipidomic analysis
Measured in urinary morning sample taken at baseline, after 15 days, 2 months, 6 months and one year. More specifically there will be an anatomopathological analysis of lipid content (oil red o, Luxol blue, Nile red staining). It will be used to group patients with similar characteristics in homogeneous groups and identify similaritites in patients trajectories according to which nephropathy they were diagnosed with.
Time frame: Through study from baseline until one year visit.
Metabolomic analysis
Measured in urinary morning sample taken at baseline, after 15 days, 2 months, 6 months and one year. It will be used to group patients with similar characteristics in homogeneous groups and identify similaritites in patients trajectories according to which nephropathy they were diagnosed with.
Time frame: Through study from baseline until one year visit.
Proportion of fibrotic tissues
Measured in % with biopsy at the beginning of study. It will be used to study the impact of interstitial fibrosis in the relation between tubular dysmetabolism and ANCA vasculitis against other nephropathies.
Time frame: At baseline.
Capillary density
Measured with biopsy at the beginning of study. It will be used to study the impact of interstitial fibrosis in the relation between tubular dysmetabolism and ANCA vasculitis against other nephropathies
Time frame: At baseline.
Markers of podocytes, renal epithelial cells and specific leukocyte populations
Measured with biopsy at the beginning of study. It will be used to study the impact of interstitial fibrosis in the relation between tubular dysmetabolism and ANCA vasculitis against other nephropathies
Time frame: At baseline.
Quantification of fibrosis
Measured with biopsy at the beginning of the study, by Sirius Red staining. It will be used to study the impact of interstitial fibrosis in the relation between tubular dysmetabolism and ANCA vasculitis against other nephropathies
Time frame: At baseline.
IMC (imaging mass cytometry)
Tubular cell labeling with dedifferentiation at the beginning of study. It will be used to study the impact of interstitial fibrosis in the relation between tubular dysmetabolism and ANCA vasculitis against other nephropathies.
Time frame: At baseline.
Transcriptomic analysis
Measured with biopsy at the beginning of study and blood sample taken at baseline, after 2 months, 6 months and then every 6 months until the last patients completed 1 year follow-up. More specifically an anatomopathological analysis with single cell transcriptomic analyses along a study of gene expression (epigenetic deregulation) will be carried out. It will be used to group patients with similar characteristics in homogeneous groups and identify similaritites in patients trajectories according to which nephropathy they were diagnosed with.
Time frame: Through study completion up to end of study, when the last patients completed 1 year follow-up.
Diastole
Measured in mmHg (average of 3 measures) at baseline, after 2 months, 6 months and then every 6 months until the last patients completed 1 year follow-up. It will be used to group patients with similar characteristics in homogeneous groups and identify similaritites in patients trajectories according to which nephropathy they were diagnosed with.
Time frame: Through study completion up to end of study, when the last patients completed 1 year follow-up.
Systole
Measured in mmHg (average of 3 measures) at baseline, after 2 months, 6 months and then every 6 months until the last patients completed 1 year follow-up. It will be used to group patients with similar characteristics in homogeneous groups and identify similaritites in patients trajectories according to which nephropathy they were diagnosed with.
Time frame: Through study completion up to end of study, when the last patients completed 1 year follow-up.
Heart rate
Measured in beat per minute (average of 3 measures) at baseline, after 2 months, 6 months and then every 6 months until the last patients completed 1 year follow-up. It will be used to group patients with similar characteristics in homogeneous groups and identify similaritites in patients trajectories according to which nephropathy they were diagnosed with.
Time frame: Through study completion up to end of study, when the last patients completed 1 year follow-up.
Blood count analysis
Measures on leukocytes, red blood cells and platelets with blood samples taken at baseline, after 2 months, 6 months and then every 6 months until the last patients completed 1 year follow-up. It will be used to group patients with similar characteristics in homogeneous groups and identify similaritites in patients trajectories according to which nephropathy they were diagnosed with.
Time frame: Through study completion up to end of study, when the last patients completed 1 year follow-up.
Leukocytes evolution
Measured in several ways : * by blood count with blood samples taken at baseline, after 2 months, 6 months and then every 6 months until the last patients completed 1 year follow-up * through anatomopathological analysis by IMC with the biopsy core taken at the beginning of the study * specific leukocytes population will be studied for interstitial fibrosis assessment Measured at baseline, after 15 days, 2 months, 6 months and then every 6 months until the last patients completed 1 year follow-up. They will be used to : * study the differences in the evolution between patients with ANCA vasculitis and those with other nephropathies. * identify similaritites in patients trajectories according to which nephropathy they were diagnosed with. * study the impact of interstitial fibrosis in the relation between tubular dysmetabolism and ANCA vasculitis against other nephropathies.
Time frame: Through study completion up to end of study, when the last patients completed 1 year follow-up.