Aufklärung der Pathophysiologie und der Faktoren des suizidalen Erythrozytentods bei chronischer Nierenerkrankung

01/10/2023 to 30/09/2026

Renal anemia is a typical complication of chronic kidney disease, significantly impacting the performance and quality of life of affected patients. Currently, renal anemia is treated through interventions such as iron substitution, erythropoietin administration, and HIF stabilizers. Studies from our own research group indicate that a shortened lifespan of red blood cells also plays a crucial role in the development of renal anemia. Remarkably, despite substantial erythropoietin production, the anemia persists. A better understanding of the underlying reasons for this pronounced breakdown of red blood cells could significantly contribute to improving the therapy for renal anemia.

In the context of the proposed experimental project, the influence of various environmental factors related to chronic kidney insufficiency on premature suicidal death of erythrocytes and thus renal anemia will be examined. Specifically, the impact of the uremic environment, secondary hyperparathyroidism, as well as hypoxia or the Rapaport-Luebering cycle and the HIF signaling pathway will be investigated and better understood. Additionally, the interplay between suicidal erythrocyte death and renal anemia will be explored in patients before and after kidney transplantation, with a particular focus on the influence of different immunosuppressants on suicidal erythrocyte death.

The primary focus of the respective animal experiments is on therapeutically influencing the specific environment and investigating its effects on the elimination of erythrocytes from the bloodstream. To achieve this, various interventions with medications (Sevelamer, Ketoprofen) and diets (low-protein diet, low-phosphate diet), readily available in clinical practice, will be implemented in established animal models. Furthermore, relevant signaling pathways (Rapaport-Luebering cycle and HIF signaling pathway) will be examined in terms of their functionality in chronic kidney insufficiency and their relevance to the survival of erythrocytes will be assessed.

In summary, the insights gained from this study may contribute to elucidating the influence of various factors on suicidal erythrocyte death, which holds pathophysiological relevance in the context of chronic kidney insufficiency, and deriving improved therapeutic approaches for the treatment of renal anemia.