Alport Syndrome
Conditions
Keywords
Alport Syndrome, Rare disease, European database, Quality of life, Kidney disease, Molecular diagnostics, Predictive biomarkers
Brief summary
Alport syndrome is a rare, inherited condition characterized by a combination of glomerular nephropathy progressing to kidney failure, deafness, and eye involvement. This disease is associated with mutations in the genes encoding one of the three IV collagen chains expressed in the glomerular basement membrane. Significant progress has been made in understanding the molecular mechanisms responsible for the disease, but relatively little in understanding the progression of renal failure and in the area of therapeutics. We have shown in a retrospective European study that blockers of the renin angiotensin system may slow disease progression, but no controlled studies have been performed. Finally, innovative therapies (anti-micro-RNA, stem cells) have recently shown their effectiveness in animal models of the disease, and industrials are planning to quickly carry out phase 1 trials to test molecules. Carrying out therapeutic trials in humans will require full knowledge of the natural history of the disease (isolated hematuria, microalbuminuria, macroalbuminuria, renal failure and its progression) and gathering a sufficient number of patients, especially in the early stages. These trials and the indications for treatments would be greatly facilitated by the discovery of biomarkers that make it possible to predict the progression to renal failure earlier than the onset of proteinuria. The study aims to: * Establish a European database on Alport syndrome to assess the natural history of the disease. * To investigate the impact of the disease on the educational and professional life of patients and their families, and on the adherence and tolerance to renin-angiotensin system blockers prescribed to proteinuric patients. * Investigate access to molecular diagnostics and genetic counseling, as well as identify biomarkers that can predict progression of kidney disease. This project will be carried out at a French level with the support and participation of the very active renal rare disease sector, in collaboration with various countries wishing to participate.
Interventions
None listed
Sponsors
Institut National de la Santé Et de la Recherche Médicale, France
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
Inclusion criteria
* Diagnosis of AS based on electron microscopic examination of the renal biopsy and/or molecular studies and/or abnormal expression of type IV collagen chains on skin and/or glomerular basement membranes. * Signed informed consent
Exclusion criteria
\- No
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Ocular symptoms (presence or not of lenticonus, cataract, retina and cornea impairment) | Through study completion, at 1 year, 2 year, 3 year |
| Renal function: eGFR, age at ESRD, requirement of Renal Replacement Therapy (RRT) and type of RRT | Through study completion, at 1 year, 2 year, 3 year |
| Urine bio-analysis results: Presence or not and quantification of hematuria, microalbuminuria and proteinuria | Through study completion, at 1 year, 2 year, 3 year |
| Presence or not of hypertension | Through study completion, at 1 year, 2 year, 3 year |
| Level of Hearing loss | Through study completion, at 1 year, 2 year, 3 year |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Adverse events for the long-term safety of RAAS blockers treatment | Through study completion, at 1 year, 2 year, 3 year | — |
| Quality of life questionnaires | Through study completion, at 1 year, 2 year, 3 year | Impact of disease on quality of life will be evaluated through scores of quality of life questionnaires SF36 for Adult et SF10 for paediatric patients |
| Compliance | Throughout the follow-up | Compliance will be evaluated using X. Girerd Compliance Questionnaire |
Other
| Measure | Time frame | Description |
|---|---|---|
| Disease stage | Throughout the follow-up | Stratification of patients according to their disease stage; patients' distribution analysis among countries |
| Urinal concentration of specific molecules | Through study completion, at 1 year, 2 year, 3 year | Correlation assessment between the urinal concentration of the five molecules recently described by Terzi's lab as predicting progression of CKD (or other putative biomarkers) with the rate of decline of the GFR (according of the estimated GFR) on a 3 year- period |
Countries
France
Contacts
Primary ContactLaurence Heidet, PHD
Backup ContactBertrand Knebelmann, PHD
Outcome results
None listed