Fluid resuscitation with preventive peritoneal dialysis attenuates crush injury-related acute kidney injury and improves survival outcome

Abstract

Background: In-hospital renal replacement therapy (RRT) is widely used for the treatments of acute kidney injury (AKI) in crush injury (CI) victims. This study was designed to investigate whether preventive peritoneal dialysis (PPD) is useful for renal protection in CI.

Methods: Animals received hindlimb compressions for 6 h to induce CI. Then, animals were untreated or treated with PPD and/or massive fluid resuscitation (MFR) for 8 h since the onset of compression release. Blood and renal tissue samples were collected at various time points for biological and morphological analysis.

Results: PPD attenuated lactic acidosis and reduced serum K⁺ and myoglobin levels in CI animals. In addition, PPD was effective in removing blood urea nitrogen (BUN) and creatinine, and reduced renal expressions of neutrophil gelatinase-associated lipocalin (NGAL). The combination of PPD and MFR furtherly attenuated AKI with significantly decreased histological scores (p = 0.037) and reduced NGAL expressions (p = 0.0002) as compared with the MFR group. Moreover, MFR + PPD group had a significantly higher survival rate than that in the MFR and the PPD groups (p < 0.05, respectively).

Conclusion: The use of PPD at the onset of compression release is beneficial for renal protection and survival outcome in a rabbit model of CI.

Keywords: Acute kidney injury; Crush injury; Massive fluid resuscitation; Peritoneal dialysis; Survival outcome.

Fig. 1

Study protocol. Phase I (n = 10): animal study for biochemical and morphological analysis; blood samples were collected at the time prior to compression onset (Baseline), the time just after compression release (Compression), and the end of resuscitation (Resuscitation, n ≥ 5). Kidneys were collected at 12 h after compression release (n ≥ 3). Surgical procedure of peritoneal dialysis was performed at 1 h before compression release. Phase II (n = 10): survival analysis without sample collections. In each group, 10 animals were assigned to a 72-h survival observation. MFR = massive fluid resuscitation; PPD = protective peritoneal dialysis; NS = normal saline

Fig. 2

Blood pressure monitoring in all groups. The mean arterial pressure (MAP) was monitored and data were collected with a 2-h interval. Hindlimb compression lasted for 6 h, and the MAP monitoring ended at 8 h after compression release. In each group, the number of animals was ≥5 at all time points. Con = control group; MFR = massive fluid resuscitation; PPD = preventive peritoneal dialysis. ^*** p < 0.001

Fig. 3

Effects of MFR and PPD on CI-induced rhabdomyolysis. At the end of resuscitation, we measured serum K⁺ levels (a), myoglobin concentrations (b), and CK activities (c) to evaluate rhabdomyolysis. To evaluate the clearance ability of different interventions, removal rates of serum K⁺ (d), myoglobin (e) and CK (f) were calculated. Dialysis fluids were collected for the measurements of K⁺ (g), myoglobin (h) levels and CK activities (i). In each group, the number of animals was ≥5 at all time points. Con = control group; MFR = massive fluid resuscitation; PPD = preventive peritoneal dialysis. In each group, number of animals ≥5. ^*p < 0.05, ^** p < 0.01, ^*** p < 0.001 vs. CP group; ^#p < 0.05, ^##p < 0.01, ^###p < 0.001 vs. MFR group. ^∇∇ p < 0.01 vs. PPD group

Fig. 4

Evaluation of kidney injury. To evaluate kidney injury, BUN (a) and creatinine (b) were determined at the end of resuscitation. In addition, specimens of renal tissues were scored (c) after HE stain (e, 200×). Immunofluorescence stain of renal NGAL were performed to evaluate acute kidney injury (d, f). BUN (g) and creatinine (h) were also detectable in dialysis solutions collected from abdominal cavity. BUN = blood urea nitrogen; Con = control group; MFR = volume resuscitation; PPD = preventive peritoneal dialysis; NGAL = neutrophil gelatinase-associated lipocalin. In each group, number of animals ≥5 for biochemical analysis and number of animals ≥4 for morphological assessments. ^**p < 0.01, ^*** p < 0.001 vs. CP group; ^#p < 0.05, ^###p < 0.001 vs. MFR group; ^ΔΔ p < 0.01 vs. PPD group

Fig. 5

Survival analysis. A 72-h survival observation was carried out in all groups (n = 10 in each group). The status of all animals was checked every 6 h during observation. Con = control group; MFR = massive fluid resuscitation; PPD = preventive peritoneal dialysis