ADTKD Subregistry
ADTKD-subregistry is a goal of the ADTKD-Net - a European platform for collaborative research in tubulointerstitial hereditary kidney disease.
General information
Autosomal dominant tubulointerstitial kidney disease (ADTKD) is a recently defined genetic progressive kidney disease characterised by tubular damage and interstitial fibrosis in the absence of glomerular lesions (bland sediment). Affected individuals develop chronic kidney disease (CKD) over the course of their lives, which can lead to kidney failure and the need for renal replacement therapy in adulthood. As an extrarenal manifestation, early onset gout, anemia, or hypotension can occur.
ADTKD is one of the most common monogenic kidney diseases after autosomal dominant polycystic kidney disease, accounting for ~5% of monogenic disorders causing CKD. ADTKD is caused by pathogenic variants in the two main genes UMOD and MUC1, and less commonly in at least another three genes REN, HNF1Band, SEC61A1 .
As a common pathomechanism, disease causing variants lead to the deposition of defective proteins (toxic-gain-of-function) in the renal tubule cells and impair their function. A reliable diagnosis is made by genetic testing, as clinical evidence alone is insufficient to determine a specific subtype. The diagnosis of ADTKD-MUC1 requires a specific genetic test, which is currently only available in specialised human genetics institutes.
There is currently no specific curative therapy for ADTKD. Treatment focuses on managing symptoms and slowing the progression of CKD. Maintaining kidney function, preventing urinary tract infections, and ensuring multidisciplinary care are crucial. Since ADTKD can also affect children and adolescents, collaboration between nephrology, urology, and pediatrics is essential, particularly for managing urinary tract infections or structural abnormalities.
Objectives
The primary objective of the ADTKD-subregistry is to establish retrospective and prospective data collection from a representative European cohort of patients with ADTKD. Our specific aims are to:
- i) capture the natural course in terms of kidney- and non-kidney-related clinical outcomes;
- ii) define genetic and environmental variables accounting for disease variability as well as gender differences in progression rates and disease manifestation;
- iii) identify patterns of prognostic biomarkers reflecting such variability and iv) pave the way for immediate recruitment into future therapeutic trials.
A dedicated pathology image repository (“OMERO”) will be used to collect images of biopsy slides.
Inclusion and Exclusion Criteria
Inclusion in the ADTKD subregistry requires the presence of a molecular genetic diagnosis of ADTKD.
Ethical aspects
Data entry in this subregistry is covered by the consent for ERKNet participation.
Data collection
Data from individuals in the ADTKD subregistry will come from three different sources:
- (i) from ADTKD patients already included in ERKReg (< 200 for structural AD disorders in total);
- (ii) from patient data currently stored in decentralised databases of ADTKD-Net participants (Berlin (DE), Erlangen (DE), Zurich-Brussels (CH/BE), Paris (FR), P5 Barcelona (SP), Dublin (IR), Cyprus (CYP), Prague (CZ) and Newcastle (UK));
- (iii) from data entry by all other ERKNet and non-ERKNet centres during the course of the project. Based on the activities of ADTKD-Net, we expect the total number of ADTKD patients to increase from 1,000 to approximately 1,500 within 3 years.
Basic data
General information collected for all patients in the ERKNet registry: sex, date of birth, ethnicity, date of first symptoms, date of first visit or date of diagnosis. For the ADTKD subregistry we will define additional disease-specific data, e.g. method used to establish the diagnosis of ADTKD, date of genetic testing, method of genetic testing, diagnostic genetic finding, family history of kidney disease (affected family members, parental consanguinity), information on stored biomaterials.
Medication data
Medication information includes current medications, medication changes, medications with potential impact on disease progression (e.g., ACE-I and SGLT2-I).
Visit data
Information collected at each patient visit includes:
- Clinical parameters: Date of visit, current renal status (e.g. G1-5 stage, A1-3 stage), current weight in kilograms
- Relevant symptoms: Gout (if yes - age/date of first episode; number of gout episodes, location), hypertension (if yes - how established, age at first diagnosis of hypertension, age at start of B/P medication)
- Additional clinical events: Anaemia, malignancies, cardiovascular events, hyperuricemia, episodes of kidney stones (if yes - location and type), episodes of AKI (if yes - aetiology).
- Additional relevant kidney examinations: MR-based renal imaging or renal biopsies, hospitalisations (if any - reason)
- Blood parameters: such as uric acid (UA), eGFR (CKD-EPI), serum creatinine, haemoglobin, UMOD.
- Renal replacement therapy information (if applicable): conservative or renal replacement therapy, i.e. dialysis or transplantation, time of disease recurrence after transplantation.
Additionally, information about lifestyle (e.g. occupation, diets, environmental exposure, infection, comorbidities) will be collected.
User manual
Coordination Structure / Scientific Committee
The subregistry is overseen by the following steering committee members:
Prof. Dr. med. Kai-Uwe Eckardt/ Prof. Dr. med. Jan Halbritter
Charité - Universitätsmedizin Berlin, Dept. of Nephrology and Medical Intensive Care
kai-uwe.eckardt@charite.de/jan.halbritter@charite.de
Prof. Dr. med. Michael Wiesener
Universitätsklinikum Erlangen, Dept. of Medicine 4 - Nephrology and Hypertension
michael.wiesener@uk-erlangen.de
Prof. MD . Olivier Devuyst
University of Zurich, Inst. of Physiology
Prof. Corinne Antignac, PhD
Institut Imagine, Laboratory of Hereditary Kidney Diseases
Dr. Roser Torra
Institut de Recerca de l’Hospital de la Santa Creu i Sant Pau / Nephrology Research Group C
Prof. MD Peter Conlon
Royal College of Surgeons in Ireland
Contact Person
For more information please contact:
Prof. Dr. med Jan Halbritter: jan.halbritter@charite.de
