A Uremic Pig Model for Peritoneal Dialysis.

A Uremic Pig Model for Peritoneal Dialysis.
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DOI:
10.3390/toxins14090635
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发表时间:
2022-09-14
期刊:
影响因子:
4.2
通讯作者:
Gerritsen KGF
Gerritsen KGF
中科院分区:
医学2区
文献类型:
--
作者:
de Vries JC;van Gelder MK;Monninkhof AS;Ahmed S;Hazenbrink DHM;Nguyen TQ;de Kort GAP;Vonken EPA;Vaessen KRD;Joles JA;Verhaar MC;Gerritsen KGF

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随着人们对家庭透析越来越感兴趣,需要一种转化的尿毒症大动物模型来评估腹膜透析(PD)的技术创新。为此,我们建立了一个肾衰竭的猪模型。通过双侧肾动脉次全栓塞诱导稳定的慢性肾损伤。在应用PD之前,通过给予庆大霉素(10 mg/kg i. v.每日两次,持续7天)诱导尿毒症暂时加重,以获得透析患者范围内的尿毒症溶质水平。使用标准腹膜渗透性评估(SPA)评估腹膜转运。栓塞后,尿素和肌酐浓度分别从1.6 ± 0.3 mM和103 ± 14 µ M短暂升高至7.5 ± 1.2 mM和338 ± 67 µM,随后在1-2周内分别稳定至2.5 ± 1.1 mM和174 ± 28 µM。庆大霉素诱导暂时性慢性加急性肾损伤,峰值尿素和肌酐浓度分别为16.7 ± 5.3 mM和932 ± 470 µM。成功应用了腹膜透析,但经常并发腹膜炎。SPA显示低转运状态(4 h时D/P肌酐为0.41(0.36-0.53)),尿素、肌酐和磷酸盐的传质面积系数分别为9.6 ± 3.1、4.6 ± 2.6、3.4 ± 2.3 mL/min。总之,这种尿毒症按需加重的猪模型适用于PD,尽管腹膜转运的特征在于低转运状态。
With increasing interest in home dialysis, there is a need for a translational uremic large animal model to evaluate technical innovations in peritoneal dialysis (PD). To this end, we developed a porcine model with kidney failure. Stable chronic kidney injury was induced by bilateral subtotal renal artery embolization. Before applying PD, temporary aggravation of uremia was induced by administration of gentamicin (10 mg/kg i.v. twice daily for 7 days), to obtain uremic solute levels within the range of those of dialysis patients. Peritoneal transport was assessed using a standard peritoneal permeability assessment (SPA). After embolization, urea and creatinine concentrations transiently increased from 1.6 ± 0.3 to 7.5 ± 1.2 mM and from 103 ± 14 to 338 ± 67 µM, respectively, followed by stabilization within 1–2 weeks to 2.5 ± 1.1 mM and 174 ± 28 µM, respectively. Gentamicin induced temporary acute-on-chronic kidney injury with peak urea and creatinine concentrations of 16.7 ± 5.3 mM and 932 ± 470 µM respectively. PD was successfully applied, although frequently complicated by peritonitis. SPA showed a low transport status (D/P creatinine at 4 h of 0.41 (0.36–0.53)) with a mass transfer area coefficient of 9.6 ± 3.1, 4.6 ± 2.6, 3.4 ± 2.3 mL/min for urea, creatinine, and phosphate respectively. In conclusion, this porcine model with on-demand aggravation of uremia is suitable for PD albeit with peritoneal transport characterized by a low transport status.
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