Abstract
Different animal models for peritoneal dialysis (PD) have been used in the past decades to develop PD fluids compatible with patient life and to identify markers of peritoneal fibrosis and inflammation. Only few of those studies have taken into account the importance of uraemia-induced alterations at both systemic and peritoneal levels. Moreover, some animal studies which have reported about PD in a uremic setting did not always entirely succeed in terms of uraemia establishment and animal survival. In the present study we induced uraemia in the recently established mouse PD exposure model in order to obtain a more clinically relevant mouse model for kidney patients. This new designed model reflected both the slight thickening of peritoneal membrane induced by uraemia and the significant extracellular matrix deposition due to daily PD fluid instillation. In addition the model offers the opportunity to perform long-term exposure to PD fluids, as it is observed in the clinical setting, and gives the advantage to knock out candidate markers for driving peritoneal inflammatory mechanisms.
Highlights
End Stage Renal Disease (ESRD) affects more than 200,000 people in Europe per year and 20,000 of those are peritoneal dialysis (PD) patients
In order to mimic in mice the clinical situations of peritoneal dialysis patients, uraemia was induced by performing 5/6 nephrectomy
This demonstrates that chronic instillation of peritoneal dialysis fluid (PDF) in our mouse model caused peritoneal thickening and inflammation of the submesothelial compact zone comparable with the clinic situation of a patient
Summary
End Stage Renal Disease (ESRD) affects more than 200,000 people in Europe per year and 20,000 of those are peritoneal dialysis (PD) patients. Uraemia is represented by accumulation in the body of urea and other organic waste products of metabolism normally filtered out by the kidneys It can only be treated by replacing kidney function that nowadays, due to the insufficient number of kidneys available worldwide for transplantation, occurs mainly by dialysis. PD rodent models have been used to introduce in the market PD fluids more compatible with the patient life and have offered opportunities to study PD fluid additions Those models allowed identifying important biomarkers driving peritoneal inflammatory mechanisms that occur during long-term exposure to PD fluids and, as a matter of fact, the failure of the technique itself
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