November 4th, 2023 - The focus of this year's congress of the German Society for Nephrology (DGfN) in Berlin was molecular therapies and individualized medicine. These topics are particularly relevant for rare kidney diseases, as they are often caused by genetic changes that represent targets for potential therapies. One of the most common rare hereditary diseases is ADTKD – Autosomal Dominant Tubulointerstitial Kidney Disease.

You are reading the version for healthcare professionals. This report is available here in a version for patients.

ADTKD Vision Cure, the german organization for patients with ADTKD, has been in existence for almost two years. It was represented for the first time at the Conference of the German Society of Nephrology (DGfN) 2023 in Berlin with its own poster. The aim: to raise awareness among nephrologists.

ADTKD is a relatively "young" disease. The underlying mutations were only discovered in 2013 and the disease was reclassified as such in 2015 [1]. Previously, it was also known as "medullary cystic kidney disease". Depending on the genetic cause, a distinction is currently made between five subtypes, which are called ADTKD-UMOD, ADTKD-MUC1, ADTKD-REN, ADTKD-HNF1B and ADTKD-SEC61A1. The UMOD and MUC1 sub-entities are the most common.

NONSPECIFIC CLINICAL SIGNS

The striking thing about ADTKD is its relative inconspicuousness. This is also the main reason why the disease is often not diagnosed or misdiagnosed. Experts therefore assume that the number of unreported cases is high. "Every nephrologist has an ADTKD family," suspects US ADTKD expert Anthony Bleyer, who has been researching the disease for the longest time. 

The first and often only sign is a - usually slow - rise in creatinine levels.Proteinuria or hematuria are rarely found in the urine.The kidneys themselves are of normal size or rather small. Even a kidney biopsy does not provide a clear diagnosis; fibrotization is often found. This is caused by the deposition of a defective protein in the tubule cells, which accumulates and thus "clogs" certain structures and signaling pathways.This results in chronic renal insufficiency.

The disease is inherited autosomal-dominantly, which means that the risk is 50% from one generation to the next. ADTKD has a very variable course. Although the same genetic defect is present within a family, the age range of manifestation is very wide and the speed of progression also varies greatly.

BOTTLE NECK DIAGNOSTICS 

The only reliable method of diagnosis is a genetic test.Diagnosis of the MUC1 subtype in particular is difficult and involves a great deal of effort.One of the most common MUC1 variants cannot be detected by panel testing or next generation sequencing (NGS) for technical reasons.This is the insertion of an additional cytosine (dupC) in a VNTR domain of the MUC1 gene. [2]

In Germany, there are currently two laboratories in Erlangen and Mainz that have the necessary SNaPshot technology and corresponding expertise. It is therefore very important to run the entire genetic diagnostics process through one of these two laboratories from the outset in the event of a clinical suspicion of ADTKD.

THERAPY ON THE HORIZON

The goal of Vision Cure is a therapy for ADTKD patients.The hope for this is well-founded. A potentially effective substance has already been identified in preclinical studies [3]. International clinical trials are in preparation.German patients should also be able to take part. The coordinating center is the University Hospital Erlangen. A national ADTKD registry already exists here and an application has been made to set up a European registry.