Protective Effect Of α-MSH And EPO On Rhabdomyolysis-induced Acute Kidney Injury In Rats And Clinical Study Of AKI In Patients Undergoing Cardiac Surgery

PartⅠprotective effect ofα-MSH and EPO to rhabdomyolysis-induced acute renal failure in rats1.α-Melanocyte-stimulation hormone reduce renal inflammation and protect renal function in rhabdomyolysis-induced acute kidney injury ratsObjective To investigate the effects ofα-MSH on kidney inflammation and renal function of glycerol induced acute kidney injury(AKI) in rats.Methods After 14h fasting forty-eight Sprague-Dawley rats were divided into four groups:normal control group were given 10 ml/kg of saline by i.m.,ARF group rats were injected with 50%glycerol(10 ml/kg,i.m.).α-MSH immediate group andα-MSH delayed group were respectively givenα-MSH(200μg/kg,I.P) immediately or 6h afterward in addition to 50%glycerol injected(10 ml/kg,i.m.),and repeated after 12 h.Blood samples and kidney tissues were taken from anaesthetised rats at 24h, Plasma creatine kinase(CK),urea,creatinine,IL-6 and TNF-αlevels,as well as kidney acute tubular necrosis scores,ED-1 cell,MCP-1 RNA expression and NF-κB p65 DNA combining activity in kidney tissues were investigated.Results Kidney tissues of ARF rats had more ED-1 positive cells(1.46±1.24 vs 16.8±7.0,P<0.05) and more MCP-1 RNA expression(7.8±1.9 vs11.0±3.8,P<0.05) Compared with normal control rats.α-MSH immediate group had less ED-1 positive cells and less MCP-1 RNA expression in kidney compared with ARF group(9.5±8.2 vs 16.8±7.0,P<0.05 and 8.7±5.1 vs 11.0±3.8,P<0.05).NF-κB p65 DNA combining activity in normal control,ARF,α-MSH immediate andα-MSH delayed groups were 3.19±0.99,5.30±0.84,3.34±1.0,5.05±1.1(μg/ml) respectively (P<0.01).Also compared with ARF group,α-MSH immediate group had a lower serum urea[(23.8±9.3) vs(56±10) mmol/L,P<0.05],lower serum creatinine [(152±76) vs(333±60)μmol/L,P<0.05]and lower ATN score(1.7±0.4 vs 2.7±0.4, P<0.05).There was no significant difference betweenα-MSH delayed group and ARF group.Conclusion There was obvious inflammation in kidneys of rhabdomyolysis-induced ARF rats,α-MSH immediately administration attenuated the inflammation and protect acute renal injury. 2.Erythropoietin reduce kidney injury in rhabdomyolysis-induced acute kidney injury in ratsObjective:To observe if Erythropoietin(EPO) can reduce kidney injury in rhabdomyolysis-induced acute renal failure(ARF) in rats and investigate the mechanism.Methods:48 SD rats were divided into four groups:Normal control group were injected 10ml/Kg saline in hind legs muscle.ARF group were injected 50%glycerol(10ml/Kg,I.M).EPO immediate group and EPO-delayed group were injected EPO(2000u/Kg) immediately or 6h later in addition to 50%glycerol injected,and repeated after 12h.The urine volume,renal function and kidney histopathology were investigated.Results:24 hours after modle were made,Compared with ARF group, EPO treated groups(immediate and 6h delayed) have lower blood urea nitrogen(56±10,24±10 and 25.8±9 mmol/L),lower Serum creatinine(333±60,171±103 and 178±98μmol/L) and lower ATN score(2.7±0.4,1.5±0.6和1.54±0.4),(P<0.05).Serum creatinine levels in ARF group at 48h were continously increased,but in EPO immediate group and EPO-delayed group it began to decrease,they were 477±223,119±89 and 117±130μmol/L respectively(P<0.01).24h kidney tissue of ARF group had obvious tubule cell apoptosis,EPO treated groups had less apoptosis cells.Western blot showed Bcl-XL protein was increased in ARF group compared normal control group,Bcl-XL protein expressed more in EPO treated groups than ARF group.Conclusion:EPO,not matter was given immediately or 6h later,can reduce kidney injury in rhabdomyolysis- induced acute renal failure in rats,one mechanism may be it can reduce tubule cell apoptosis. PartⅡmultiple analysis of etiology,prognostic factors and Risk factors of acute kidney injury in patients undergoing cardiac surgery.1.Risk factors for development of acute kidney injury in patients undergoing cardiac surgeryObjective:To evaluate risk factors of acute kidney injury(AKI) or acute renal failure(ARF) in patients underwent cardiac surgery.Methods:Retrospective cases control study was carried out in patients underwent cardiac surgery from 1994 to 2002 in one central,with 108 cases in AKI group and 152 cases randomly selected patients without ARF as control group.10 of Perioperative variables were analyzed by univariate and Logistic Regression.ARF (AKI) was difined as serum creatinine increased more than 0.5mg/dl(44.2μmol/L) in 48h,or increased over 50%from baseline.Results:ARF group had decreased baseline creatinine clearance rate (CCr)(65.2±26.7ml/min vs 91.4±28.1ml/min,P<0.001),lower ejection fraction (0.54±0.09 vs 0.58±0.07,P<0.001),prolonged cardiopulmonary bypass(CPB) (145.8±111min vs 99.9±46.0min,P<0.001) and surgery duration(6.1h±3.5h vs 3.9h±1.5h,P<0.001),more blood transfusion(1360 ml±1076ml vs 847 ml±400ml, P<0.001).There were no difference of perfusion pressure,average perfusion flow rate and mannitol infusion during CPB between the two groups.Forward stepwise logistic regression showed that baseline CCr,heart NYHA class states,postoperative lower blood pressure,reoperation and duration of surgery were the significant risk factors prognosing ARF in those patients.Conclusion:This study identifies the perioperative risk factors of ARF in patients undergoing cardiac surgery.Pay more attention to patients with those risk factors before operation,shorten operation time and avoiding complications during and after operation may reduce the incidence of ARF in those patients. 2.Analysis of etiology and prognostic factors in 108 patients undergoing acute renal failure following cardiac surgeryObjective:To analyse etiology and prognostic factors in patients with ARF after cardiac surgery.Methods:The characters of 108 patients undergonging ARF after heart operation were retrospectively analyzed.Causes of ARF,cause of dead and prognostic factors were analysised.ARF was difined as serum creatinine increased more than 0.5mg/dl(44.2μmol/L) in 48h,or increased over 50%from baseline.Results:Cause of ARF:cardiac hypotension 50 cases;severe infection 3 cases, respiratory failure 4 cases,hemolysis 8 cases,interstitial nephritis 1 case,the rest 42 were uncertain.Renal function recovered in 47.38 patients survived(35.2%),70 died. The causes of death:MODS 33 cases,cardiac causes 26,respiratory failure 2, hyperkalemia 4,hemorrhage shock 2,brain damage 1,DIC 1,asphyxia 1.Univariate analysis showed that the mortality rates were significantly higher in patients with oliguria(OR:10.4),persistent hypotension(OR:21.4),mechanical ventilation support more than 3 days(OR:18.3),coma(OR:9.4),Digestive tract bleeding(OR:4.11).Cox Regression analysis showed that oliguria,persistent hypotension and mechanical ventilation support more than 3 days were the most important factors correlated with death(β:1.19,1.13 and 1.11 respectively;P:<0.001,＝0.001 and 0.019).To 76 oliguria patients,mortality was higher in no dialysis group(Odds R=4.829,95%CI: 1.002～23.275).Conclusion:Persistent hypotension owing to heart failure was not only the main cause of ARF,but also the main cause of death in patents with cardiac surgery. Oliguria,persistent hypotension and mechanical ventilation support more than 3 days were the most important factors correlated with death.Early blood purification may amelioration the prognosis of oliguria patients.