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Researchers from the Medical Faculty of the University of Freiburg have gained significant new insights into metabolic processes in the kidney. Scientists from the Institute of Genetic Epidemiology at the Medical Center – University of Freiburg measured tiny molecules, so-called metabolites, which are found in blood and urine and reflect our metabolism, in samples taken from more than 5,000 study participants.
They compared them to the genomes of the people they tested and were able to identify 1,299 genetic changes associated with the metabolites and contributing to their production, degradation or transport. The findings provide a better understanding of processes throughout the body and particularly in the kidney, which produces urine from blood plasma. These findings, which appeared on June 5, 2023, in the journal Genetics of nature, could lead to a better understanding of diseases and new approaches to their treatment. For example, a new class of diabetes therapies called SGLT2 inhibitors work by inhibiting a metabolite transporter in the kidney.
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This study opens up new insights into metabolism and its links to health. It provides valuable information that could help us better understand diseases and thus provide a basis for new treatment options, says Prof. Dr. Anna Kttgen, director of the Institute of Genetic Epidemiology at the University of Freiburg Medical Center and spokesperson for the Collaborative Research Center 1453 Nephrogenetics at the University of Freiburg, which supported the research of the studies. Kttgen is also a member of the Cluster of Excellence CIBSS – Center for Integrative Biological Signaling Studies at the University of Freiburg.
The integration of blood plasma and urine analyzes has produced important results
Conducting a large-scale association study presented particular challenges. Researchers had to analyze large amounts of data and understand complex genetic relationships. First author Dr. Pascal Schlosser of the Faculty of Medicine of the University of Freiburg and the Institute of Genetic Epidemiology at the Medical Center – University of Freiburg explains: In particular, the comparison of metabolites from plasma and urine samples and their genetic basis, known as multi-matrix analysis takes a long time. However, it offers the possibility to distinguish whether certain metabolic changes occur primarily in the kidney itself or are distributed throughout the body. Furthermore, in this way we were able to observe a much larger part of human metabolic processes than by merely studying blood.
Renal enzyme also relevant in hypertension and osteoarthritis
Among other things, the researchers were able to demonstrate that the DPEP1 enzyme not only has important functions in the kidney, but also works in different parts of the body. For example, increased DPEP1 activity was associated with a higher risk of osteoarthritis, but at the same time a lower risk of hypertension. Our findings can therefore help us consider the potential side effects of new drugs already during their development process, says first author Nora Schereralso by the Institute of Genetic Epidemiology at the Medical Center – University of Freiburg.
Reference: Schlosser P, Scherer N, Grundner-Culemann F, et al. Genetic studies of coupled metabolomes reveal enzymatic and transport processes at the interface between plasma and urine. Nat Genet. 2023.doi: 10.1038/s41588-023-01409-8
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