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. 2023 Dec 20;11(1):97.
doi: 10.1186/s40635-023-00583-7.

A model of hemodialysis after acute kidney injury in rats

Affiliations

A model of hemodialysis after acute kidney injury in rats

J Mallet et al. Intensive Care Med Exp. .

Abstract

Background: Acute kidney injury (AKI) is frequent among critically ill patients. Renal replacement therapy (RRT) is often required to deal with severe complications of AKI. This technique is however associated with side effects such as hemodynamic instability and delayed renal recovery. In this study, we aimed to describe a novel model of hemodialysis in rats with AKI and depict a dialysis membrane performance.

Methods: Eighteen Sprague-Dawley rats received 0.75% adenine-rich diet to induce AKI. After 2 weeks, nine underwent an arterio-venous extracorporeal circulation (ECC) (ECC group) for 2 h without a dialysis membrane on the circuit and nine received a hemodialysis session (HD group) for 2 h with an ECC circuit. All rats were hemodynamically monitored, and glomerular filtration rate (GFR) was measured by transcutaneous fluorescence after the injection of FITC-Sinistrin. Blood samples were collected at different time points to assess serum creatinine and serum urea concentrations and to determine the Kt/V. Sinistrin concentration was also quantified in both plasma and dialysis effluent.

Results: After 2 weeks of adenine-rich diet, rats exhibited a decrease in GFR. Both serum urea and serum creatinine concentrations increased in the ECC group but remained stable in the HD group. We found no significant difference in serum creatinine and serum urea concentrations between groups. At the end of experiments, mean serum urea was 36.7 mmol/l (95%CI 19.7-46.9 mmol/l) and 23.6 mmol/l (95%CI 15.2-33.5 mmol/l) in the ECC and HD groups, respectively (p = 0.15), and mean serum creatinine concentration was 158.0 µmol/l (95%CI 108.1-191.9 µmol/l) and 114.0 µmol/l (95%CI 90.2-140.9 µmol/l) in the ECC and HD groups, respectively (p = 0.11). The Kt/V of the model was estimated at 0.23. Sinistrin quantity in the ultrafiltrate raised steadily during the dialysis session. After 2 h, the median quantity was 149.2 µg (95% CI 99.7-250.3 µg).

Conclusions: This hemodialysis model is an acceptable compromise between the requirement of hemodynamic tolerance which implies reducing extracorporeal blood volume (using a small dialyzer) and the demonstration that diffusion of molecules through the membrane is achieved.

Keywords: Acute kidney injury; Adenine 0.75%; Animal model; Hemodialysis; Intensive care unit; Renal replacement therapy.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Experimental model. ECC: extracorporeal circulation, HD: Hemodialysis, GFR: glomerular filtration rate, Qs: blood flow; Qd: dialysate flow
Fig. 2
Fig. 2
Adenine 0.75%-induced kidney injury after 2 weeks. Top-left panel shows the bodyweight loss, top-center and top-right panels respectively show blood urea nitrogen and serum creatinine concentration before and after adenine-rich diet. Bottom panel shows a PAS staining of a kidney section. Acute tubular necrosis signs are present alongside crystal’s deposits. ***p < 0.0001
Fig. 3
Fig. 3
Glomerular filtration rate measurement by the transcutaneous FITC-Sinistrin method. GFR: glomerular filtration rate; ECC: extracorporeal circuit group; Dialysis: HD group ** p < 0.01
Fig. 4
Fig. 4
Membrane efficiency. ECC: extracorporeal circuit group; Dialysis: HD group. Top panels show serum urea and serum creatinine evolution during the procedure (ECC group: green curve; HD group: cyan group). Bottom left panel shows plasmatic concentration of Sinistrin at the end of the procedure. Bottom right panel shows the evolution of the Sinistrin quantity during the first 30 min of the dialysis

References

    1. Hoste EAJ, Bagshaw SM, Bellomo R, Cely CM, Colman R, Cruz DN, et al. Epidemiology of acute kidney injury in critically ill patients: the multinational AKI-EPI study. Intensive Care Med août. 2015;41(8):1411–1423. doi: 10.1007/s00134-015-3934-7. - DOI - PubMed
    1. Vanmassenhove J, Kielstein J, Jörres A, Biesen WV. Management of patients at risk of acute kidney injury. Lancet Lond Engl. 2017;389(10084):2139–2151. doi: 10.1016/S0140-6736(17)31329-6. - DOI - PubMed
    1. Benichou N, Gaudry S, Dreyfuss D. The artificial kidney induces acute kidney injury: yes. Intensive Care Med. 2020;46:513–515. doi: 10.1007/s00134-019-05891-9. - DOI - PMC - PubMed
    1. Gaudry S, Hajage D, Schortgen F, Martin-Lefevre L, Pons B, Boulet E, et al. Initiation strategies for renal-replacement therapy in the intensive care unit. N Engl J Med. 2016;375(2):122–133. doi: 10.1056/NEJMoa1603017. - DOI - PubMed
    1. STARRT-AKI Investigators, Canadian Critical Care Trials Group, Australian and New Zealand Intensive Care Society Clinical Trials Group, United Kingdom Critical Care Research Group, Canadian Nephrology Trials Network, Irish Critical Care Trials Group, et al. Timing of initiation of renal-replacement therapy in acute kidney injury. N Engl J Med. 2020;383(3):240‑51. - PubMed

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