Effects and Mechanisms of Peritoneal Resuscitation on Acute Kidney Injury After Severe Burns in Rats

Abstract

Introduction Acute kidney injury (AKI) is a common complication in severe burn patients with poor prognosis and high mortality. Reduced kidney perfusion induced by the decreased effective circulating blood volume after severe burn is a common cause of AKI. Routine intravenous resuscitation (IR) is difficult or delayed in extreme conditions such as war and disaster sites. Peritoneal resuscitation (PR) is a simple, rapid resuscitation strategy via a puncture in the abdominal wall. This study investigated whether PR is a validated resuscitation strategy for AKI after severe burns in rats and explored its mechanisms. Materials and Methods Eighty Sprague–Dawley rats were randomized into four groups: (1) sham group; (2) IR group, which was characterized by the full thickness burn of 50% of the total body surface area received IR immediately post-injury; (3) early PR group, in which rats with the same burn model received PR immediately post-injury; and (4) delayed resuscitation (DR) group, in which rats with the same burn model received no resuscitation within 3-hour post-injury. PR and DR groups animals received IR after 3-hour post-injury. The survival rate, mean arterial pressure, renal histopathology, renal function, indicators of renal injury, and renal hypoxia-inducible factor-1α and NADPH oxidase 4 (NOX4) proteins of rats were measured at 3 h, 12 h, and 24 h post-injury. Results Compared with rats in the DR group, rats in the PR group had a significantly improved survival rate (100% vs. 58.3% at 24 h, P = 0.0087), an increased mean arterial pressure (92.6 ± 6.6 vs. 65.3 ± 10.7, 85.1 ± 5.7 vs. 61.1 ± 6.9, 90.1 ± 8.7 vs. 74.9 ± 7.4 mmHg, at 3 h, 12 h, and 24 h, P < 0.01), a reduced renal water content rate (51.6% ± 5.0% vs. 70.1% ± 6.8%, 57.6% ± 7.7% vs. 69.5% ± 8.7%, at 12 h and 24 h, P < 0.01), attenuated histopathological damage, reduced serum creatinine expression (36.36 ± 4.27 vs. 49.98 ± 2.42, 52.29 ± 4.31 vs. 71.32 ± 5.2, 45.25 ± 2.55 vs. 81.15 ± 6.44 μmol/L, at 3 h, 12 h, and 24 h, P < 0.01) and BUN expression (7.62 ± 0.30 vs. 10.80 ± 0.58, 8.61 ± 0.32 vs. 28.58 ± 1.99, 8.09 ± 0.99 vs. 20.95 ± 1.02 mmol/L, at 3 h, 12 h, and 24 h, P < 0.01), increased kidney injury markers neutrophil gelatinase-associated lipocalin expression (95.09 ± 7.02 vs. 101.75 ± 6.23, 146.77 ± 11.54 vs. 190.03 ± 9.87, 112.79 ± 15.8 vs. 194.43 ± 11.47 ng/mL, at 3 h, 12 h, and 24 h, P < 0.01) and cystatin C expression (0.185 ± 0.006 vs. 0.197 ± 0.006, 0.345 ± 0.036 vs. 0.382 ± 0.013, 0.297 ± 0.012 vs. 0.371 ± 0.028 ng/mL, at 3 h, 12 h, and 24 h, P < 0.01), and reduced renal hypoxia-inducible factor-1α and NADPH oxidase 4 protein expression (P < 0.01). There was no significant difference between rats in the PR group and the IR group in the above indicators. Conclusions Early PR could protect severe burn injury rats from AKI. It may be an alternative resuscitation strategy in severe burn injury when IR cannot be achieved.