HIF-stabilizing agents at ADTKD-MUC1
Anemia drug accelerates disease progression
7/12/2023 - Anemia (anaemia) should rather not be treated with HIF-stabilizing agents in patients with the disease ADTKD-MUC1 who do not require dialysis. This is suggested by the results of a preclinical study published by researchers at the University of Erlangen. The reason: the drugs apparently lead to an increased expression of the mutated MUC1 protein. This increases the risk that the disease will progress faster.
HIF-stabilizing agents are modern drugs used to treat anemia that occurs as a result of chronic kidney disease (CKD). HIF means hypoxia-inducible factor. This reacts when there is a lack of oxygen (hypoxia) in the cells. This is the case with anemia because the number of oxygen-carrying red blood cells (erythrocytes) decreases due to kidney disease. When the oxygen content is reduced, HIF activates the production of erythropoietin (EPO) and thus the formation of erythrocytes.
HIF-stabilizing agents are given in tablet form. In Europe and the U.S. the HIF stabilizer Roxadustat (Evrenzo) is approved for the treatment of renal anemia before and during dialysis.
HIF increases the expression of MUC1 in the kidney
The researchers from Erlangen investigated the connection between HIF and MUC1 in cells of the kidney tubules of affected patients. They found that during the use of HIF-stabilizing agents there was an increased formation of the harmful protein mucin-1 in all variants of MUC1 changes examined. The overexpression of this protein is the cause of ADTKD-MUC1 disease as it accumulates in the renal tubules and is no longer cleared away. The authors therefore recommend caution when using HIF stabilizers in people with ADTKD-MUC1. These findings also underscore the need for genetic testing of patients with CKD of unknown cause.
Renal anemia: causes and treatment
Most anemias in patients with renal insufficiency are due to a lack of the hormone EPO. Typical symptoms of the resulting lack of oxygen occur primarily during physical exertion. The patients are pale, tire more easily, have breathing problems and are less resilient. The heart rate is often increased because the body is trying to compensate for the deficiency with faster blood flow. Renal anemia is usually treated with injections of genetically engineered EPO. Alternatively, HIF-stabilizing agents are now also available.
Expert advice: Prof. Dr. Michael Wiesener, Erlangen (Germany)
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