Pulmonary complications after solid-organ transplantation, and particularly infections, are able to compromise the extremely good results of the transplant procedures. Solid-organ transplantation recipients challenge the ICU physician with unique aspects of their post-transplant course, adding, in an already critical patient, the immunosuppressed state and the quality of the functional recovery of the graft.
Sepsis is a major clinical problem associated with significant organ dysfunction and high mortality. The ATP‐sensitive P2X7 receptor activates the NLRP3 inflammasome and is a key component of the innate immune system. We used a fluid‐resuscitated rat model of fecal peritonitis and acute kidney injury (AKI) to investigate the contribution of this purinergic receptor to renal dysfunction in sepsis. Six and 24 h time‐points were chosen to represent early and established sepsis, respectively. A selective P2X7 receptor antagonist (A‐438079) dissolved in dimethyl sulfoxide (DMSO) was infused 2 h following induction of sepsis. Compared with sham‐operated animals, septic animals had significant increases in heart rate (−1(−4 to 8)% vs. 21(12–26)%; P = 0.003), fever (37.4(37.2–37.6)°C vs. 38.6(38.2–39.0)°C; P = 0.0009), and falls in serum albumin (29(27–30)g/L vs. 26(24–28); P = 0.0242). Serum IL‐1β (0(0–10)(pg/mL) vs. 1671(1445–33778)(pg/mL); P < 0.001) and renal IL‐1β (86(50–102)pg/mg protein vs. 200 (147–248)pg/mg protein; P = 0.0031) were significantly elevated in septic compared with sham‐operated animals at 6 h. Serum creatinine was elevated in septic animals compared with sham‐operated animals at 24 h (23(22–25) μmol/L vs. 28 (25–30)μmol/L; P = 0.0321). Renal IL‐1β levels were significantly lower in A‐438079‐treated animals compared with untreated animals at 6 h (70(55–128)pg/mg protein vs. 200(147–248)pg/mg protein; P = 0.021). At 24 h, compared with untreated animals, A‐438079‐treated animals had more rapid resolution of tachycardia (22(13–36)% vs. −1(−6 to 7)%; P = 0.019) and fever (39.0(38.6–39.1)°C vs. 38.2(37.6–38.7)°C; P < 0.024), higher serum albumin (23(21–25)g/L vs. (27(25–28)g/L); P = 0.006), lower arterial lactate (3.2(2.5–4.3)mmol/L vs. 1.4(0.9–1.8)mmol/L; P = 0.037), and lower serum creatinine concentrations (28(25–30)μmol/L vs. 22(17–27)μmol/L; P = 0.019). P2X7A treatment ameliorates the systemic inflammatory response and renal dysfunction in this clinically relevant model of sepsis‐related AKI.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.