Physician, PhD student
Jeff Granhøj
Department of Clinical Genetics, Vejle Hospital
| Projekt styring | ||
| Projekt status | Open | |
| Data indsamlingsdatoer | ||
| Start | 14.02.2025 | |
| Slut | 14.02.2035 | |
Danish National Registry of Autosomal Dominant Tubulointerstitial Kidney Disease (ADTKD)
Short summary
ADTKD is a group of hereditary kidney disorders eventually leading to kidney failure with no targeted treatment options. However, genetic screening accelerates diagnosis and enables selection of familial kidney donors. The prevalence of ADTKD is largely unknown, but recent findings suggest that ADTKD is relatively common in Denmark. A national ADTKD registry will support research efforts to advance genetic screening and patient recruitment for future clinical trials.
Rationale
Chronic kidney disease (CKD) constitutes a significant health burden globally. Within the spectrum of CKD, autosomal dominant tubulointerstitial kidney diseases (ADKTD) represent a distinct group of hereditary kidney disorders characterized by a progressive decline in kidney function, a strong family history of CKD, and otherwise unspecific diagnostic features. Despite the serious implications of the disease, there is currently no approved targeted treatments for any subtype of ADTKD. ADTKD is genetically heterogeneous, with five known genes associated with ADTKD (UMOD, MUC1, HNF1B, REN, and SEC61A1). The classification of ADTKD subtypes are based on the specific genetic variant involved, such as ADTKD-MUC1. However, cases in which no genetic causes are identified are classified as ADTKD-NOS (Not Otherwise Specified). Recent studies have highlighted that ADTKD contribute significantly to the burden of CKD, although ADTKD may be underdiagnosed, particularly given the challenges associated with genetic analysis of certain genes like MUC1. Notably, the prevalence of ADTKD-MUC1 is recently found to be considerably higher in Danish patients with unexplained kidney failure by 50 years compared to other European cohorts. Further research into ADTKD is essential not only for improving diagnostic accuracy but also for improving patient care and developing targeted therapies. A recent breakthrough demonstrated that the toxic accumulation of misfolded MUC1 protein, a hallmark of ADTKD-MUC1, can be rescued in patient-derived kidney organoids and animal models using a novel treatment. These findings underscore the urgent need for a national ADTKD registry in Denmark to facilitate research, improve genetic screening, and support patient recruitment for clinical trials. Aims: The primary aim of this study is to establish a national registry of Danish patients with ADTKD. This registry will serve several key purposes: 1. Research. The registry will act as a valuable resource for clinicians and researchers, enabling collaborative studies, data sharing, and the identification of new genetic mutations associated with ADTKD-MUC1. 2. Genetic screening. By including patients with both genetically confirmed ADTKD and those meeting clinical criteria (ADTKD-MUC1), the registry will facilitate ongoing genetic screening research projects, especially as new ADTKD-related genes are discovered. 3. Patient recruitment for clinical trials. The registry will support the recruitment of patients for future research studies, including clinical trials of potential new therapies for ADTKD. The establishment of this registry is expected to significantly advance our understanding of ADTKD, improve patient care, and potentially lead to the development of effective treatments for this, currently untreatable group of diseases.
Description of the cohort
The perspective is construct a national registry cohort of patients from Danish families with either genetically or clinically diagnosed ADTKD. Participating departments report data to the registry when diagnosing a patients with ADTKD after obtaining the patient's informed consent.
Data and biological material
Questionnaire data on patient demographics, clinical information, and results of genetic analyses