Hereditary Tubulointerstitial Nephritis (NTIH)

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.

Study Overview

• Status: Completed
• Conditions: Gout; Nephritis, Interstitial; Chronic Renal Failure; Renal Cysts
• Intervention / Treatment: Other: Blood and urine sample collections

Detailed Description

• 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).

• Study Type: Interventional
• Enrollment (Actual): 225
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Paris, France, 75015
    • Hopital Necker Enfants Malades

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Screening
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: HTIN	Other: Blood and urine sample collections; phenotype and genotype analysis, biological analysis; Other Names: phenotype and genotype analysis, biological analysis

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Genotype of HTIN	Number of patients/families with mutations in known genes responsible for HTIN	after 18 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Uromodulin dosage in urine	at 18 months

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Collaborators: Institut National de la Santé Et de la Recherche Médicale, France; URC-CIC Paris Descartes Necker Cochin
• Investigators: Principal Investigator: Bertrand Knebelmann, MD, PhD, Assistance Publique - Hopitaux de Paris

Publications and helpful links

General Publications

• Saei H, Moriniere V, Heidet L, Gribouval O, Lebbah S, Tores F, Mautret-Godefroy M, Knebelmann B, Burtey S, Vuiblet V, Antignac C, Nitschke P, Dorval G. VNtyper enables accurate alignment-free genotyping of MUC1 coding VNTR using short-read sequencing data in autosomal dominant tubulointerstitial kidney disease. iScience. 2023 Jun 17;26(7):107171. doi: 10.1016/j.isci.2023.107171. eCollection 2023 Jul 21.

Study record dates

Study Major Dates

• Study Start: November 1, 2010
• Primary Completion (Actual): February 1, 2014
• Study Completion (Actual): July 1, 2016

Study Registration Dates

• First Submitted: February 22, 2011
• First Submitted That Met QC Criteria: March 9, 2011
• First Posted (Estimated): March 11, 2011

Study Record Updates

• Last Update Posted (Estimated): December 1, 2025
• Last Update Submitted That Met QC Criteria: November 24, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: Tubulointerstitial renal diseases; Hereditary renal diseases; Uromodulin; Renin gene
• Additional Relevant MeSH Terms: Crystal Arthropathies; Urogenital Diseases; Musculoskeletal Diseases; Pathologic Processes; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Chronic Disease; Disease Attributes; Arthritis; Joint Diseases; Rheumatic Diseases; Purine-Pyrimidine Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Metabolic Diseases; Renal Insufficiency; Renal Insufficiency, Chronic; Nephritis; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases; Gout; Kidney Failure, Chronic; Nephritis, Interstitial; Investigative Techniques; Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Genetic Phenomena; Blood Specimen Collection; Genotype; Phenotype
• Other Study ID Numbers: P081258