Ulinastatin ameliorates acute kidney injury following liver transplantation in rats and humans

Abstract

Acute kidney injury (AKI) is a common complication following orthotopic liver transplantation (OLT) that evidently affects prognosis. However, no effective treatment exists for AKI. The aim of the present study was to elucidate whether ulinastatin application during OLT in humans can reduce kidney damage and improve renal function. In addition, the underlying mechanisms of ulinastatin were investigated on a rat autologous OLT (AOLT) model. In total, 60 patients undergoing an OLT were randomly selected to receive ulinastatin (U group; n=30) or saline (C group; n=30) during the OLT surgery. The patient demographics, AKI incidence rate, recovery indicators and renal injury indexes were measured during the perioperative period. In addition to the clinical trials, 40 rats were subjected to an AOLT and were divided into the control (C-R), sham-operation and ulinastatin treatment groups. Pathological renal damage, biomarkers of inflammation and oxidative stress were measured to investigate the effects and possible mechanisms of ulinastatin on AKI. In the clinical trials, ulinastatin application was shown to attenuate the incidence of AKI following OLT (P<0.05) and reduce the serum levels of cystatin C and urinary β2 microglobulin within 24 h of the OLT (P<0.05). Furthermore, ulinastatin was found to significantly improve the recovery of patients by reducing the time spent in the intensive care unit (P<0.01 vs. C group), the ventilation time and the hemodialysis rates (P<0.05 vs. C group). In the rat AOLT model, ulinastatin application was also shown to relieve renal pathological damage by reducing the serum cystatin C and creatinine levels. Notably, the levels of tumor necrosis factor-α, interleukin-6, hydrogen peroxide and reactive oxygen species were evidently reduced, while the level of superoxide dismutase was increased in the ulinastatin groups (P<0.05, vs. C-R group). In conclusion, ulinastatin application was demonstrated to protect against AKI following OLT by inhibiting inflammation and oxidation.

Ulinastatin Protects against Acute Kidney Injury in Infant Piglets Model Undergoing Surgery on Hypothermic Low-Flow Cardiopulmonary Bypass

“…Recently, Li and colleagues [ 7 ] report that ulinastatin could be an effective treatment for AKI following liver transplantation in rats and humans and their study suggests that ulinastatincan protect against AKI following orthotopic liver transplantation by inhibiting inflammation and oxidation. However, the effectiveness of ulinastatin in the treatment of AKI caused by HLF and its mechanisms are still unknown.…”

Ulinastatin Inhibits Osteoclastogenesis and Suppresses Ovariectomy-Induced Bone Loss by Downregulating uPAR

“…Mice were separated into three groups ( n = 10 mice/group) at random: bilateral ovariectomized mice intraperitoneal injected with ulinastatin (1 × 10 5 units/kg per day) (OVX + ulinastatin), bilateral ovariectomized mice intraperitoneal injected with isopyknic DMSO (OVX), sham-operated mice intraperitoneal injected with isopyknic DMSO (SHAM). The injection dose of ulinstatin refers to previous studies and the dose is similar to therapeutic dose ( Shen et al, 2014 ; Li et al, 2015 ). Ulinstatin solution and DMSO were administered by intraperitoneal injection in the mice seven times a week for 6 weeks.…”

Renoprotective effect of vildagliptin following hepatic ischemia/reperfusion injury

“…Similar findings were observed in previous studies [5,11,[14][15][16][17] suggesting that hepatic I/R injury damages both the morphology and the function of the kidney [16,18,19]. Moreover, several studies reported pathological alterations in kidneys according to the period of reperfusion ranging from 1 to 24 h. After 1-h kidney showed moderate hemorrhage and congestion [20], eosinophilic appearance and perinuclear vacuolic formation in tubular cells [17] after 8 h showing loss of brush border and tubular epithelium with hyaline casts and congestion [21], while other researches showed tubular dilatation and necrosis, cellular swelling, and granular casts after 24-h reperfusion [5,14,22]. Kadkhodaee et al [23] showed that hepatic and renal dysfunction were seen markedly after 4 h than 24-h reperfusion.…”