International ADTKD SUMMIT 2026
A treatment for ADTKD - What is the current state of research and development?
12 April 2026 – In March, the Rare Kidney Disease Foundation (RKDF) held the 5th International ADTKD Summit. Over two days, experts from around the world reported on the current state of research into autosomal dominant tubulointerstitial kidney disease. The focus was on genetic diagnostics and therapeutic approaches currently under investigation. For ADTKD-UMOD, preclinical study data on the effect of calorie restriction on disease progression were presented.
How are rare kidney diseases diagnosed today?
Martina Živná – Charles University, Prague (Czech Republic)
In order for therapies to be developed at all, as many affected patients as possible must be identified worldwide. Genetic diagnosis forms the basis for better understanding the disease and developing targeted therapies. Furthermore, it serves as the foundation for genetic counselling, enables prenatal testing and is crucial for selecting suitable living kidney donors within affected families. The human geneticist described the diagnostic procedure.
Affected individuals and families are first identified on the basis of medical history and symptoms, followed by DNA analysis to identify the causative mutations. Mutations can lead to dysfunctional or toxic proteins. In ADTKD, the disease is caused by a dysfunction within specific tubular cells of the kidney.
Various genetic tests are available. Routine diagnostics utilise gene panels covering 200–300 kidney-related genes, or whole-exome sequencing, in which the coding regions of approximately 20,000 genes are analysed. In whole-genome sequencing, the entire DNA sequence is analysed.
The results of genetic tests can be divided into three categories:
- A positive result confirms a pathogenic variant and enables a definitive diagnosis.
- An ambiguous result identifies a ‘variant of unknown significance’ that requires further functional validation.
- A negative result indicates that no relevant variant has been detected.
It is worth noting, according to Živná, that in rare kidney diseases “the most common result from routine diagnostics is either inconclusive or negative”.
Using a case study, the expert reported on the discovery of a new genetic cause for ADTKD. After routine tests yielded negative results, whole-exome and genome sequencing identified variants in the APOA4 gene. Only a more detailed tissue analysis revealed amyloid deposits formed by the mutated protein. These deposits were located in regions of the kidney that are typically not biopsied.
As the expert reported, research teams are now able to resolve even difficult cases by sharing findings via international networks such as ERKNet . Despite these advances, the genetic cause remains unclear in a significant proportion of families – around 70 in the ADTKD registry.
What therapies for ADTKD are currently being researched?
Anna Greka - The Broad Institute of MIT & Harvard, Cambridge (USA)
Although there is no approved therapy yet, several promising strategies are emerging – ranging from orally administered small-molecule drugs to RNA-based therapies and gene editing.
- The most advanced approach involves small molecules that can be administered orally. Preclinical data in mouse models show that such agents can reduce tubular damage and the accumulation of mutated proteins. They cannot cure the disease, but they can modify its course and thus slow its progression.
- Another strategy involves antisense oligonucleotides (ASOs); these are administered via injection. These nucleic acid-based therapies degrade mutated mRNA, thereby preventing the production of misfolded proteins. In animal models, the concentration of mutated proteins was reduced by over 75% without any side effects. Greka described this as “another shot on goal”.
- In the more distant future, genome editing technologies such as CRISPR, base editing and prime editing offer the prospect of a true cure. The biggest challenge is delivery, as it is difficult to target kidney cells efficiently. Although there are proof-of-concept results for other organs, Greka emphasised that “the kidney is lagging behind” and that significant technical hurdles remain before this concept can be implemented clinically.
Greka also explained why drug development for rare diseases is particularly challenging. Only 13% of initial human trials ultimately achieve approval. Consequently, the path to a therapy requires perseverance and repeated adjustments. Funding constraints further hinder progress, as small patient groups can limit commercial incentives. Nevertheless, the “genetic clarity” in ADTKD offers advantages, particularly in terms of identifying patients and their willingness to participate in trials.
Greka estimates that within 3 to 5 years, at least one or two clinical trials – likely involving small molecules or ASOs – could be initiated. These could then become available in 5–10 years. Over a longer timeframe of 10 to 15 years, gene therapy could enable curative approaches. She emphasised, however, that these forecasts are not certain.
How does a therapy reach the market?
Aliza Thompson – U.S. Food and Drug Administration (FDA)
Thompson explained that the FDA’s mandate is to ensure that all therapies are safe and effective. She highlighted the role of the Centre for Drug Evaluation and Research (CDER) and its Office of New Drugs. These bodies oversee applications for authorisation and marketing of therapies for cardiovascular and renal diseases, including new treatment approaches for ADTKD.
Drug development itself proceeds in several phases, beginning with discovery and preclinical research, in which drug candidates are identified and tested in laboratory and animal models. This phase is followed by clinical trials, which are divided into three phases:
- Phase 1 focuses primarily on safety and pharmacological properties, often in healthy volunteers.
- In Phase 2, the therapy is introduced to patients to establish proof of concept and determine the appropriate dosage.
- Phase 3 provides definitive proof of efficacy and safety in larger patient groups.
Following successful trials, an application for regulatory approval can be submitted.
Using the example of ADTKD, she illustrated the challenges in researching rare diseases: small patient groups, delayed diagnoses and an incomplete understanding of the disease progression complicate both patient recruitment for trials and the selection of endpoints. Nevertheless, she saw cause for optimism, as in recent years around half of all approvals for new medicines have been in the field of rare diseases.
Several factors contribute to this success:
- Regulatory frameworks such as the Orphan Drug Act offer financial incentives that make the development of medicines for rare diseases more attractive to the industry. (Such programs are also available in Europe.)
- Furthermore, approval programmes have been established to accelerate the development of therapies for serious and life-threatening diseases with unmet medical needs. Such pathways are particularly relevant for diseases such as ADTKD.
The development of ‘toolkits’ for rare diseases is also important. Thompson referred to ongoing initiatives aimed at better characterising the disease progression in ADTKD and identifying measurable indicators – such as blood, urine or imaging markers – that can serve as endpoints in clinical trials.
Does calorie restriction inhibit progression in ADTKD-UMOD?
Mariapia Cratere - IRCCS San Raffaele Scientific Institute, Segrate (Italy)
The researcher investigated the influence of calorie restriction on the progression of ADTKD-UMOD
[1]. She reported that a 30% calorie restriction in a mouse model not only slowed the progression of the disease but was also able to partially reverse existing damage:
- reduction of uromodulin aggregates in the cells,
- improvement in the cells’ ‘self-cleansing’ (autophagy),
- reduction in inflammation, tubular damage and interstitial fibrosis,
- stabilisation of kidney function (e.g. urea levels).
The timing was irrelevant: the positive effects were evident in both early and late stages of the disease. This may also apply to ADTKD-MUC1 – however, there are no study data available on this as yet.
Important: Dieting or fasting is currently not recommended. The results are derived exclusively from animal models. Direct extrapolation to humans is not possible, partly due to differences in metabolism.
Recording of the scientific programme (Day 1)
Recording of the patient day (Day 2)
Literature
[1] Cratere MG et al. Calorie Restriction Leads to Degradation of Mutant Uromodulin and Ameliorates Inflammation and Fibrosis in UMOD -Related Kidney Disease. J Am Soc Nephrol. 2026 Feb 3. doi: 10.1681/ASN.0000001032