| Objective: 1.We aimed to evaluate the etiology,epidemiological characteristics,clinical diagnosis,outcomes and the risk factors of clinical prognosis of the hospitalized patients with AKI in Xinjiang.To compare the long-term outcomes of hospital-and community-acquired acute kidney injury in Xinjiang and investigate prognostic factors of 3-years all-cause mortality for AKI patients.2.To evaluate the clinical significance of serum Klotho protein levels in the early diagnosis and prognosis of AKI among adult patients in the intensivecare units(ICU).3.To investigate the effect of Klotho on endoplasmic reticulum stress during ischemia / reperfusion(I / R)AKI.Methods: 1.A multi-center retrospective survey of adult patients in 4hospitals from Xinjiang in January 2013 and July.Patients with AKI were screened out based on inclusion and exclusion criteria.Clinical variables of patients with AKI were collected.Then,352 patients admitted to the First Affiliated Hospital of Xinjiang Medical University were divided into hospital-acquired acute kidney injury(HA-AKI)group and community-acquired AKI(CA-AKI)group in terms of time of onset of AKI.All patients were followed up for 3 years.Clinical data and the results of laboratory examination were collected.Comparison of long-term outcomes between patients with HA-AKI group and those with CA-AKI was performed using the Log rank test,and prognostic factors of 3-years all-cause mortality in AKI patients were analyzed using the Cox regression.2.The study was prospective and observational.Blood samples and clinical data of AKI patients admitted to the ICU of the First Affiliated Hospital of Xinjiang Medical University between July 1 and August 31 2016 were collected.ELISA was used for the detection of Klotho and NGAL.Receiver operating characteristic curve(ROC)and the area under the curve(AUC)were used to compare the predictive performance among Klotho,NGAL and serum creatinine,evaluating the sensitivity and specificity of Klotho on the diagnosis of AKI.The correlation between Klotho and prognosis of AKI was investigated by comparing serum Klotho levels and early AKI predictors.3.A rat model of acute renal ischemia / reperfusion injury was established and randomly divided into normal + NS group,Sham operation + NS group,Surgical + NS group,sham operation group + Klotho Group(Sham + Kl),Surgical + Klotho group(IR + Kl).Klotho protein(0.01 mg /kg)or NS(same dose)was intraperitoneally injected 30 minutes,60minutes,3hours,5hours,12 hours and 24 hours after the successful modeling.The serum and kidney tissues of rats at 1,5,12,24 h after injury were collected to detect the renal function.Serum Klotho levels were detected by ELISA.The pathological changes of renal tubules and the renal tubular epithelial cells at different time points were evaluated by HE staining and TUNEL staining.The levels of apoptosis protein CHOP,JNK and Caspase12 in animal specimens were detected by Western-blot and RT-PCR at each time point.Results: 1.Among 32,157 adult hospitalized patients,719 patients suffering from AKI for 722 episodes were enrolled in this study.The detection rate of AKI was 2.25%(722 of 32157)by KDIGO criteria.The majority of AKI patients were male,accounting for 65.79%.The mean age was 58.15 ± 16.82 years.AKI was the highest in 60-79 years(320 cases,44.51%).In all departments,the most commonly occurring AKI was ICU,followed by cardiology,and nephrology was the third.The main causes of AKI were 338 cases(51.76%)of prerenal etiologies,followed by 188 cases(28.79%)with renal parenchyma and 127 cases(19.45%)with renal parenchyma.The major risk factors of prerenal AKI were cardiac output and hypovolemia.Acute tubular necrosis is the primary factor of renal AKI,followed by renal interstitial factors.The non-recognition rate of AKI was 72.4%(407/557).In the short-term prognostic analysis,the overall mortality rate was 12.8%(92/719).Of the 323 patients with AKI who survived discharge,43.7%(141)had renal function recovery;40.2%(130)did not fully recover their renal function but did not continue dialysis;16.4%(53)were still on dialysis at discharge.Multivariate Cox regression model suggested that DIC,shock and department of obstetrics were independent risk factors for death during hospitalization of AKI.In addition,the risk of death for AKI from department of obstetrics and gynecology patients was higher than that of other departments.In the single-center 352 patients with AKI,the 1-year all-cause mortality was significantly different between patients with CA-AKI(41.8%,89/213)and HA-AKI(56.8%,79/139)(P< 0.05),but the 3-year all-cause mortality showed no significant differences between the two groups(60.1%(128/213)of the CA-AKI group and 64%(89/139)of the HA-AKI group).The multivariate Cox regression model with data from 352 AKI patients indicated that the risk factors related to 3-year outcomes in the AKI patients included increased MODS scores,increased total cholesterol,reduced plasma albumin,decreased ratio of neutrophile granulocyte and leukomonocyte,reduced platelet counts,and low mean arterial pressure.2.The patients were divided into AKI group of 52 cases and non-AKI group of 98 cases.The baseline serum Klotho level in AKI group was significantly lower than that in non-AKI group(P<0.001).The AUC of Klotho predicting for AKI was 0.945(95% CI: 0.892-0.997)for AKI and the best cutoff value was 1.76 ?g/L(sensitivity 92%,specificity 94%).The predictive ability of Klotho was significantly higher than serum creatinine(Scr),and the sensitivity is higher than NGAL(sensitivity 87%,specificity 96%).Serum Klotho combined with Scr predicted better(AUC=0.958,95% CI: 0.915-1.000,sensitivity 96%,sensitivity 92%).The level of Klotho in patients with AKI was significantly different between the renal function recovery group and non-recovery group(P=0.047),while there was no significant difference between the two groups in the level of NGAL and Scr(P>0.05).There was no significant correlation between the Klotho level at diagnosis of AKI and peak Scr,peak e GFR,Scr at discharge and e GFR at discharge(r=0.026,P=0.853;r=-0.127,P=0.368;r=0.243).3.(1)Compared with Norm + NS group and Sham + NS group,the Klotho protein and Klotho m RNA of Klotho protein decreased in the I / R + NS group from the beginning of the injury to the 24 hour after injury,There was significant difference between each group(P<0.05).Serum Klotho protein level,tissue Klotho protein level and Scr were negatively correlated(r=-0.488,P=0.016;r=-0.570,P=0.021).(2)24hours after ischemia-reperfusion,HE staining of IR + NS group showed that renal tubular epithelial cells were edema,degeneration,necrosis,shedding and tubule formation.Compared with the Sham + NS group,the score of renal tubular injury began to increase 1hour after operation in I / R + NS group and reached the peak at 24 h,with significant difference(P<0.05).Compared with Norm + NS group and Sham + NS group,the apoptosis of renal tubular epithelial cells was detected by TUNEL in renal tubular epithelial cells 24 hours after ischemia-reperfusion injury in I / R + NS group The number of IOD in I / R + NS group was significantly higher than that in other two groups(P<0.05).Conclusion: 1.Middle-aged and elderly men are at-risk AKI patients.The most common reason for AKI in hospitalized patients in Xinjiang was prerenal injury.The main risk factors were low cardiac output and low blood volume.The omission diagnosis of AKI was serious.The prognosis of AKI was poor,DIC,shock,hospitalization in obstetrics were independent risk factors for death in patients with AKI.There was no difference in 3-year all-cause mortality between HA-AKI group and CA-AKI group.MODS scores,total cholesterol,plasma albumin,ration of neutrophile granulocyte and leukomonocyte,blood platelet and mean arterial pressure is related to prognosis of AKI patients.2.Serum Klotho may be a potential biomarker for early diagnosis of AKI,but the association between serum klotho and the prognosis of AKI requires further study.3.The Klotho expression is down-regulated after I / R AKI,and the decrease of Klotho protein may be related to the apoptosis of renal tissue.endoplasmic reticulum stress involved in the process o I / R AKI and promote renal tubular epithelial cell apoptosis.Klotho protein may play an anti-apoptotic role by inhibiting endoplasmic reticulum stress. |
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