Cytokines in the Urine of AKI patients regulate TP53 and SIRT1 and can be used as biomarkers for the early detection of AKI

Erichsen, L.; Thimm, C.; Wruck, W.; Kaierle, D.; Schless, M.; Huthmann, L.; Dimski, T.; Kindgen-Milles, D.; Brandenburger, T.; Adjaye, J.

doi:10.1101/2023.01.20.524775

bioRxiv · 10.1101/2023.01.20.524775

Cytokines in the Urine of AKI patients regulate TP53 and SIRT1 and can be used as biomarkers for the early detection of AKI

Erichsen, L.·Thimm, C.·Wruck, W.·Kaierle, D.·Schless, M.·Huthmann, L.·Dimski, T.·Kindgen-Milles, D.·Brandenburger, T.·Adjaye, J.

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Abstract

Acute kidney injury (AKI) is a major kidney disease with a poor clinical outcome. It is a common complication with an incidence of 10-15% of patients admitted to hospital. This rate even increases for patients who are admitted to the intensive care unit with an incidence of >50%. AKI is characterized by a rapid increase in serum creatinine, decrease in urine output, or both. Associated Symptoms include feeling sick or being sick, diarrhoea, dehydration, decreased urine output-although occasionally urine output remains normal, fluid retention-causing swelling in the legs or ankles, shortness of breath, fatigue and nausea. However, sometimes acute kidney injury causes no signs or symptoms and is detected by lab tests. Therefore, an urgent demand for non-invasive biomarkers for early detection of AKI are highly desirable. This might enable the prevention of the progression from AKI to CKD. In this study, we analysed the secretome of urine of an AKI patient cohort employing a kidney-biomarker cytokine assay. Based on these results we suggest, ADIPOQ, EGF and SERPIN3A as potential biomarkers, which might be able to detect AKI as soon as 24 h post-surgery. For the later stages, common biomarkers for the detection of AKI in both male and female patients we suggest, VEGF, SERPIN3A, TNFSF12, ANPEP, CXCL1, REN, CLU and PLAU. These markers in combination might present a robust strategy to identify the development of AKI as early as 24h or 72h post-surgery. Furthermore, we evaluated the effect of patient and healthy urine on human podocyte cells. We conclude that cytokines in the urine of AKI patients trigger processes which are needed to repair the damaged nephron and activate TP53 and SIRT1 to maintain the balance between proliferation, angiogenesis, and cell cycle arrest. In conclusion, the Renin-Angiotensin pathway seems to have major implications.

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Erichsen, L., Thimm, C., Wruck, W., Kaierle, D., Schless, M., Huthmann, L., Dimski, T., Kindgen-Milles, D., Brandenburger, T., Adjaye, J.. 2023-01-23. Cytokines in the Urine of AKI patients regulate TP53 and SIRT1 and can be used as biomarkers for the early detection of AKI. https://doi.org/10.1101/2023.01.20.524775

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