Cyclic uremia without kidney injury drives cardiovascular disease with rapid onset of immunosenescence and heart failure
- 1University Hospital RWTH Aachen
Abstract
End-stage kidney disease (ESKD) is a major driver of cardiovascular disease (CVD) and requires dialysis treatment leading to a unique metabolic phenotype with cyclic transitions between accumulation and clearance of uremic toxins. Although ESKD patients display the highest cardiovascular mortality among CKD patients, the effect of cyclic uremia on cardiovascular disease remains subject to discussion. Existing mouse models rely on induction of kidney injury and do not resolve the interconnected pathophysiological effects of metabolic, hypertensive and endocrine renal failure. They are therefore unable to distinguish uremia-driven effects from well-established drivers of cardiovascular disease such as hypertension. Here, we established a simple, reproducible, and sex-inclusive mouse model of uremia in absence of kidney injury or hypertension leveraging a bistable vesico-peritoneal shunt (VPS). Strikingly, we identify cyclic uremia as an independent driver of ESKD-induced CVD, that induces heart failure with preserved ejection fraction (HFpEF), vascular inflammation and immunosenescence. As such, the VPS represents the first preclinical model that enables investigation of cyclic uremia as a driver of cardiovascular disease.
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BibTeX
@misc{schaefer2026cyclic,
title = {{Cyclic uremia without kidney injury drives cardiovascular disease with rapid onset of immunosenescence and heart failure}},
author = {G. J. Schaefer and P. Droste and C. Schikarski and X. Li and M. Kohl and N. Lutterbach and H. de Loor and L. Koch and S. Menzel and L. Zhang and Q. Long and K. Vogt and A.-S. Andries and A. Babler and D. Schumacher and K. Schneider and A. Hoeft and P. Boor and B. Meijers and R. K. Schneider and C. V. Schneider and A. Honne and R. Kramann and K. Hoeft},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.29.755324},
url = {https://www.biorxiv.org/content/10.64898/2026.09.29.755324v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Cyclic uremia without kidney injury drives cardiovascular disease with rapid onset of immunosenescence and heart failure
AU - G. J. Schaefer
AU - P. Droste
AU - C. Schikarski
AU - X. Li
AU - M. Kohl
AU - N. Lutterbach
AU - H. de Loor
AU - L. Koch
AU - S. Menzel
AU - L. Zhang
AU - Q. Long
AU - K. Vogt
AU - A.-S. Andries
AU - A. Babler
AU - D. Schumacher
AU - K. Schneider
AU - A. Hoeft
AU - P. Boor
AU - B. Meijers
AU - R. K. Schneider
AU - C. V. Schneider
AU - A. Honne
AU - R. Kramann
AU - K. Hoeft
PY - 2026
DA - 2026/09/29
PB - bioRxiv
DO - 10.64898/2026.09.29.755324
UR - https://www.biorxiv.org/content/10.64898/2026.09.29.755324v1
AB - End-stage kidney disease (ESKD) is a major driver of cardiovascular disease (CVD) and requires dialysis treatment leading to a unique metabolic phenotype with cyclic transitions between accumulation and clearance of uremic toxins. Although ESKD patients display the highest cardiovascular mortality among CKD patients, the effect of cyclic uremia on cardiovascular disease remains subject to discussion. Existing mouse models rely on induction of kidney injury and do not resolve the interconnected pathophysiological effects of metabolic, hypertensive and endocrine renal failure. They are therefore unable to distinguish uremia-driven effects from well-established drivers of cardiovascular disease such as hypertension. Here, we established a simple, reproducible, and sex-inclusive mouse model of uremia in absence of kidney injury or hypertension leveraging a bistable vesico-peritoneal shunt (VPS). Strikingly, we identify cyclic uremia as an independent driver of ESKD-induced CVD, that induces heart failure with preserved ejection fraction (HFpEF), vascular inflammation and immunosenescence. As such, the VPS represents the first preclinical model that enables investigation of cyclic uremia as a driver of cardiovascular disease.
ER -