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Press release: New therapeutic approach for cystic kidneys

Projects A2 and A3: Research teams from Regensburg and Erlangen find a promising approach to the treatment of the familial cystic kidney disease ADPKD

August 28, 2020   Artikel auf Deutsch

"Cystic kidneys" are one of the most common inherited diseases worldwide, requiring dialysis in advanced stages. This is caused by the appearance of cysts (fluid-filled cavities) in both kidneys, which continuously increase in size and thus displace healthy tissue. The therapeutic options available to date are only very limited in their effectiveness and are accompanied by side effects. Researchers at the University of Regensburg and the University Hospital Erlangen have now shown in a comprehensive study that the chloride channel TMEM16A (anoctamine 1) contributes significantly to cyst growth and that pharmacological inhibition of TMEM16A significantly reduces cyst growth. This is achieved in part by two drugs already approved for other purposes in human medicine. The results have now been published in the journal Nature Communications.

About one in a thousand people suffer from the autosomal dominant polycystic kidney disease ADPKD, which in turn leads to irreversible loss of kidney function in about 50% of cases from the middle of the fifth decade of life. For patients, this means lifelong hemodialysis or kidney transplantation and a shortened life expectancy. In addition, those affected suffer from high blood pressure, pain and infections as a result of their kidney disease. It has been known for some time that continuous cyst growth is a major contributor to all these problems. The therapeutic options available to date have only very limited efficacy and are accompanied by relevant side effects.

An essential mechanism for cyst growth is the transport of fluid into the interior of the cysts. The research teams led by Professor Dr. Karl Kunzelmann and Professor Dr. Rainer Schreiber from the Institute of Physiology at the University of Regensburg and PD Dr. Björn Buchholz at the University Hospital Erlangen now report a potential breakthrough: Their research groups show that genetic inactivation of the chloride channel TMEM16A in an ADPKD mouse model led to a significant reduction in cyst growth. In a next step, they found that the highly specific pharmacological agent Ani9 achieved comparable inhibition of cyst growth. In their goal toward treating patients with renal cysts, they identified two promising compounds that suppressed cyst growth in mice and in cell experiments. These are benzbromarone, which has long been used to lower uric acid, and niclosamide, also an approved drug.

In their joint publication, the authors reveal the precise mechanism of action leading to cyst formation and its pharmacological inhibition: "Further studies are now needed to show good efficacy and tolerability in patients as well." In this context, the researchers refer to the Collaborative Research Center 1350 "Tubule System and Interstitium of the Kidney: (Patho-) Physiology and Crosstalk," in which they are involved with their research groups: "Collaborative Research Center 1350 offers us optimal conditions for conducting the experiments and for our close collaboration," Karl Kunzelmann and Björn Buchholz agree.

Original publication:
Ines Cabrita, Andre Kraus, Julia Katharina Scholz, Kathrin Skoczynski, Rainer Schreiber, Karl Kunzelmann, Björn Buchholz: Cyst growth in ADPKD is prevented by pharmacological and genetic inhibition of TMEM16A in vivo. In: Nature Communications.
DOI http://dx.doi.org/10.1038/s41467-020-18104-5

AG Kunzelmann © Prof. Dr. Karl Kunzelmann
Press release: Cystic fibrosis test to drink

Project A2: The role of a gene in the kidney allows a simple diagnostic method to be developed

29th July 2020  Artikel auf Deutsch

Cystic fibrosis is primarily a severe lung disease, but it also affects other organs, such as the pancreas and intestines. Cystic fibrosis is caused by mutations in the so-called CFTR (Cystic Fibrosis Transmembrane Conductance Regulator) gene. This gene codes for a chloride channel that is typically found in organs that need to transport a lot of salt. The kidney is also such an organ. It is therefore all the more surprising that the kidney does not appear to show any functional impairment in the disease cystic fibrosis. The research teams led by Prof. Jens Leipziger in Aarhus/Denmark and from the Regensburg laboratory of the research duo Prof. Dr. Karl Kunzelmann and Prof. Dr. Rainer Schreiber have now made significant progress in understanding the role of CFTR in the kidney as part of Collaborative Research Center 1350.

CFTR is mainly found in specialized cells of renal tubules that help to adjust the pH of the blood. The paper by the Aarhus and Regensburg scientists, which has now been published in the Journal of the American Society of Nephrology, describes the precise cellular mechanism of pH regulation and the central role played by CFTR in this process. CFTR is activated by the digestive hormone secretin, which intervenes in a regulatory manner. One would now expect to find conspicuous changes in blood pH on a regular basis in cystic fibrosis patients. However, this is not the case, since other parts of the kidney and, above all, respiration are in the foreground in blood pH regulation in healthy people. However, an elevated pH, a so-called alkalosis, has been repeatedly reported in cystic fibrosis patients.

Currently, the diagnosis of cystic fibrosis disease is not straightforward because there are well over 2,000 different mutations. Current diagnostic procedures are either inaccurate, laborious, or burdensome and usually do not directly test CFTR function or residual function. The fact that cystic fibrosis patients cannot adequately regulate blood pH in the presence of alkalosis gave the researchers the idea of using this to diagnose cystic fibrosis: "The sick children or even older patients would simply have to drink a beverage that raises the blood pH for a short time. An increased pH value and the excretion of so-called bases could then be detected in the subsequently excreted urine," explains Prof. Leipziger. "If cystic fibrosis is present, this excretion would be absent," adds Prof. Kunzelmann. Precisely these findings have now been demonstrated in animal models of cystic fibrosis and in cystic fibrosis patients. Furthermore, the researchers were able to show that such a simple drinking test can be reliably used as a success control for therapy with recently developed CFTR repair drugs, so-called CFTR modulators. Such a simple test could also help save costs of the very expensive therapy. "As a next step, we are planning clinical trials to assess the everyday suitability of this simple and cost-effective cystic fibrosis test," the team is already looking ahead.

Original publication:
Peder Berg, Samuel L. Svendsen, Mads V. Sorensen, Casper K. Larsen, Jesper Frank Andersen, Soren Jensen-Fangel, Majbritt Jeppesen, Rainer Schreiber, Ines Cabrita, Karl Kunzelmann and Jens Leipziger: Impaired renal HCO3- excretion in Cystic Fibrosis, Journal of the American Society of Nephrology
DOI: https://doi.org/10.1681/ASN.2020010053

Rainer Greger Promotionspreis for Dr. Andre Kraus and poster prize for Julia Scholz at the Congress for Nephrology of the DGfN 2019.
Academic Awards_Congress for Nephrology of the DGfN 2019

Project B3: Rainer Greger Promotionspreis for Dr. Andre Kraus and prize for one of the best abstracts for Julia Scholz

Award of the Rainer Greger Promotionspreis for Dr. Andre Kraus (at the right) and prize for one of the best 11 abstracts for Julia Scholz (at the left), both from the working group of Prof. Björn Buchholz (in the middle) - Project B3, at the Congress for Nephrology of the DGfN 2019.

  1. Deutsche Forschungsgemeinschaft (DFG)
  2. Friedrich-Alexander Universität Erlangen-Nürnberg


"Interdisciplinary kidney research to advance understanding of disease mechanisms and develop new therapeutic concepts"


Nierenzentrum REN

Dr. Michaela Kritzenberger
Tel.: ++49 (0)941/943-2885

Nierenzentrum REN

Molecular Medicine