Cyclic uremia without kidney injury drives cardiovascular disease with rapid onset of immunosenescence and heart failure
Schaefer, G. J.; Droste, P.; Schikarski, C.; Li, X.; Kohl, M.; Lutterbach, N.; de Loor, H.; Koch, L.; Menzel, S.; Zhang, L.; Long, Q.; Vogt, K.; Andries, A.-S.; Babler, A.; Schumacher, D.; Schneider, K.; Hoeft, A.; Boor, P.; Meijers, B.; Schneider, R. K.; Schneider, C. V.; Honne, A.; Kramann, R.; Hoeft, K.
Show 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.
Matching journals
The top 8 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Single-cell profiling of healthy human kidney reveals features of sex-based transcriptional programs and tissue-specific immunity 93%
- IL-27 receptor signaling regulated stress myelopoiesis drives Abdominal Aortic Aneurysm development 93%
- Defining cellular complexity in human autosomal dominant polycystic kidney disease by multimodal single cell analysis 92%
Similar papers in this journal
Similar papers in this journal
- Circulating argonaute-bound microRNA-126 reports vascular dysfunction & response to treatment in acute & chronic kidney disease 92%
- Mortality in hemodialysis: Synchrony of biomarker variability indicates a critical transition 91%
- A comprehensive mouse kidney atlas enables rare cell population characterization and robust marker discovery 90%
Similar papers in this journal
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.