Hereditary Tubulointerstitial Nephritis

Phenotypical and Genetic Characterization of Adult Hereditary Chronic Tubulointerstitial Renal Diseases

The aim of this study is to identify families with hereditary chronic tubulointerstitial renal diseases , characterize the phenotype and screen for mutations in known genesis (UMOD, REN, TCF2, NPHP1). Genome wide analysis will be performed in families without mutations identified.

• Inclusion of affected subjects with familial history of chronic renal failure, early gout ,renal cysts in several hospital in France
• Characterization of the phenotype; dosage of the urinary uromodulin in all subjects
• Collect DNA samples
• Screen for UMO mutations first
• Then for REN or TCF2 depending on the phenotype
• Validate the use of the dosage of urinary uromodulin for the diagnosis of UMOD associated disease.
• Identify new genes responsible for hereditary HTIN (Hereditary Tubulointerstitial Nephritis).

Inclusion Criteria:

• Age ≥ 18 years.
• HTIN of unknown cause
• Chronic renal failure defined by a eGFR (estimated Glomerular Filtration Rate) estimated according to MDRD (Modification of the Diet in Renal Disease) < 60ml / min / 1,73m2.
• At least two siblings affected by gout before 40 years or by chronic renal failure.
• Affiliated or benefiting from a national insurance
• Signature of the enlightened consent.

Exclusion Criteria:

• Endstage renal failure before the age of 18 years in all affected subjects of the family.
• Microscopic or macroscopic persistent hematuria, or proteinuria > 1gramme / 24hours.
• Other potential cause of TIN (Tubulointerstitial Nephritis): pyelonephritis, drug toxicity.
• High blood pressure known for more than 10 years before the discovery of the renal disease.
• Major cardiovascular before the discovery of the renal disease.
• Chronic auto-immune or infectious disease.
• Polycystic kidney disease with increased of the size of the kidneys