Impact of timing of renal replacement therapy initiation on outcome of ptic acute kidney injury
Yu-Hsiang Chou 1†,Tao-Min Huang 2†,Vin-Cent Wu 1,Cheng-Yi Wang 3,Chih-Chung Shiao 4,Chun-Fu Lai 1,
Hung-Bin Tsai 5,Chia-Ter Chao 1,Guang-Huar Young 6,Wei-Jei Wang 7,Tze-Wah Kao 1,Shuei-Liong Lin 1,Yin-Yi Han 5,Anne Chou 5,Tzu-Hsin Lin 6,Ya-Wen Yang 8,Yung-Ming Chen 1,Pi-Ru Tsai 4,Yu-Feng Lin 8,Jenq-Wen Huang 1,
Wen-Chih Chiang 1,Nai-Kuan Chou 6,Wen-Je Ko 6*,Kwan-Dun Wu 1,Tun-Jun Tsai 1and for the NSARF Study Group 9
Introduction
Acute kidney injury (AKI)is a common entity in criti-cally ill patients with an incidence of about 30to 60%[1]as defined by the RIFLE (risk,injury,failure,loss of kidney function,and end-stage renal failure)classifica-tion and is thought to be an independent risk factor for
incread morbidity and mortality [2-4].Sepsis is the leading cau of AKI,contributing to 30to 50%of cas of AKI [4,5].Almost 30%of ptic AKI patients need renal replacement therapy (RRT).This rate is much higher than that obrved for other caus of AKI [6-8].Among critically ill patients,mortality rates of patients with ptic AKI are also higher than among patients with non-ptic AKI [9].Thus,finding better strategies for ptic AKI is the key issue for intensivists.The cur-rent goal is to improve strategies for the treatment of patients with ptic AKI.
*Correspondence:kowj@ntu.edu.tw †Contributed equally 6
Department of Surgery,National Taiwan University Hospital,7Chung-Shan South Road,Taipei 100,Taiwan
Full list of author information is available at the end of the article
Chou et al .Critical Care 2011,15:R134
魁梧近义词/content/15/3/R134
©2011Chou et al.;licene BioMed Central Ltd.This is an open access article distributed under the terms of the Creative Commons Attribution Licen /licens/by/2.0,which permits unrestricted u,distribution,and reproduction in any medium,provided the original work is properly cited.
The pathogenesis of psis is a systemic inflammatory reaction that involves multiple inflammatory mediators. Many strategies for treatment were recommended as part of the early goal-directed thera
py popularized by the Surviving Sepsis Campaign(SSC)[10].Although RRT for refractory fluid overload,as well as electrolyte and acid-ba imbalance,is recommended by the SSC, issues related to when and how to perform RRT are not addresd.Furthermore,continuous RRT(CRRT)with high-volume hemofiltration and a super-high flux dialy-zer was suggested to restore immune homeostasis by removing cytokines and toxic molecules,but the effects on morbidity and mortality are still controversial[11,12]. As inflammatory cytokines play a critical role in the mechanism of ptic AKI as compared with other etiolo-gies of AKI[13],we hypothesized that the timing of RRT initiation in ptic AKI is more important than in other types of AKI.However,certain obrvational stu-dies showed that early initiation of RRT may be better for critically ill patients with vere AKI[14,15].There is still no strong evidence or clear definition of how early is early enough.However,the RIFLE classification was ud widely to categorize the verity of AKI,and was able to predict patient outcomes in some studies [16].The purpo of the current study is to test the hypothesis that the timing of RRT initiation,as defined using sRIFLE criteria,is associated with patient out-comes,using our NSARF(National Taiwan University Hospital Study group on Acute Renal Failure)databa. Materials and methods
Study populations
This retrospective study was bad on the NSARF data-ba,which was established in the64-bed surgical ICU of a tertiary hospital and its three branch hospitals in different cities[17-20].The databa prospectively col-lected data from patients requiring RRT during their ICU stays,and continuously recorded data from all patients for outcome analys.In this study,we enrolled patients who underwent acute RRT becau of ptic AKI between July2002and October2009.Tho enrolled subjects were treated by one multi-modality team,compod of physicians,surgeons,technicians, and nursing personel.Septic AKI was defined as AKI development after psis without other etiology.Sepsis was classified according to the American College of Chest Physicians and the Society of Critical Care Medi-cine connsus[21].Sepsis was defined by the prence of both infection and systemic inflammatory respon syndrome(SIRS).SIRS was considered to:be prent when patients had more than one of the following clini-cal findings:body temperature above38°C or below36°C,heart rate of more than90beats/min,hyperventila-tion evidenced by a respiratory rate of more than20breaths/min or a partial pressure of arterial carbon dioxide of less than32mmHg,and a white blood cell count of more than12×103cells/μl or less than4×103cells/μl.Infection was defined as a pathologic pro-cess caud by the invasion of normally sterile tissue or fluid or body cavity by pathogenic or potentially patho-genic microorganisms.Exclusion criteria included patients aged less than18years,patients with an ICU stay
of less than two days[22],and patients who only underwent acute RRT for less than two days.Approval for this study was obtained from the Institutional Review Board of National Taiwan University Hospital, Taipei,Taiwan(No.31MD03).Informed connt was waived becau there was no breach of privacy and the study did not interfere with clinical decisions related to patient care.
Data collection
All data were prospectively collected.Data variables included demographic data,comorbid dias,ptic AKI developed post-surgery(or not),and the indications for RRT.Biochemistry data such as complete blood cell count,blood urea nitrogen(BUN),rum creatinine (sCr),rum glutamate oxaloacetate transamina (GOT),rum total bilirubin,rum albumin,and rum potassium(sK+)were recorded upon ICU admission and RRT initiation[18,20].Moreover,the clinical parameters and verity score were also recorded at the two time points.The clinical parameters included heart rate,sys-tolic and diastolic blood pressures,central venous pres-sure(CVP)level,partial pressure of arterial blood gas oxygen and fraction of inspired oxygen.Severity scores included Glasgow Coma Scale(GCS)score,Acute Phy-siology and Chronic Health Evaluation II(APACHE II) score[23],Sequential Organ Failure Asssment(SOFA) score[24],and Simplified Acute Physiology Score III (SAPS III)[25].The usage of mechanical ventilation was recorded and the inotropic equivale
nt do was calcu-lated[26].Definitions were made as follows:hyperten-sion was blood pressure above140/90mmHg or usage of anti-hypertension agents;diabetes was previous usage of insulin or oral hypoglycemic agents;congestive heart failure was low cardiac output with a CVP above12 mmHg and dopamine equivalent above5μg/kg/min [26];and chronic kidney dia(CKD)was sCr of1.5 mg/dl or greater documented prior to this admission. The indications for RRT were:(1)azotemia(BUN> 80mg/dL and sCr>2mg/dl)with uremic symptoms;
(2)oliguria(urine amount<100ml every eight hours) or anuria refractory to diuretics;(3)fluid overload refractory to diuretics with a CVP level above12mmHg or pulmonary edema with a partial pressure of arterial oxygen/fraction of inspired oxygen ratio below300 mmHg;(4)hyperkalemia(sK+>5.5mmol/L)refractory
to medical treatment;and(5)metabolic acidosis(pH <7.2in arterial blood gas)[27].
According to previous studies[2,28,29],simplified RIFLE classification was ud only with the glomerular filtration rate(GFR)criterion for classification becau the eight-hourly urine volumes in our databa did not match the6-or12-hourly urine output criterion in the RIFLE classification.The baline sCr was the data acquired at hospital discharge from the prior admission among the patient
s with more than one admission[2], or the data estimated using the Modification of Diet in Renal Dia(MDRD)equation[30]in tho with only one admission(assuming an average estimated GFR of 75ml/min/1.73m2).The peak sCr was defined as the highest sCr before RRT initiation in ICU.Tho who initiated RRT when in sRIFLE-R(risk)or sRIFLE-0[31], that is not yet reaching the sRIFLE-R level,were defined as the early dialysis(ED)group,while tho in the sRI-FLE-I(injury)or sRIFLE-F(failure)groups were classi-fied as the late dialysis(LD)group.
The choice of RRT modality
The modality of RRT was chon according to the hemodynamics of the patients.Continuous venovenous hemofiltration was performed if more than15points of inotropic equivalent(IE)[26]were required to maintain systemic blood pressure up to120mmHg. The effluent flow and blood flow were35ml/kg/hour and200ml/min,respectively.Extended RRT such as sustained low efficiency RRT(SLED)with or without hemofiltration(SLED-f)was performed if IE was between5and15points.For SLED,blood flow and dialysate flow were200ml/min and300ml/min, respectively.When hemofiltration was added,the hemofiltration rate was35ml/kg/hour.The duration of hemofiltration was about6to12hours,according to the amount of ultrafiltration.Intermittent hemodia-lysis,which was chon if IE was less than five points, was performed for four hours every ssion with a dia-lysate fl
ow of500ml/min,and blood flow of200ml/ min.As hemodynamics change,the patients may receive different RRT modalities[19].
Outcomes
The endpoint of this study was in-hospital mortality. The survival period was calculated from RRT initiation to mortality(in non-survivors)or to hospital discharge (in survivors).
Statistics
Statistical analys were performed using SAS,version 9.1.3(SAS Institute Inc.,Cary,NC,USA),statistical soft-ware.In statistical testing,a two-sided P value of less than0.05was considered statistically significant.Continuous data were expresd as mean±standard deviation unless otherwi specified.Frequency and per-centage were calculated for categorical variables.Stu-dent’s t test was ud to compare the means of continuous data between two groups,whereas Chi-squared test or Fisher’s exact test was ud to analyze categorical proportions.
Then we ud the backward stepwi likelihood ratio model of Cox proportional hazard method to analyze the independent predictors of in hospital mortality as model1.The independent variables wer
e lected for multivariate analysis if they had a P≤0.2on univariate analysis.The basic model-fitting techniques for(1)vari-able lection,(2)goodness-of-fit asssment,and(3) regression ,residual analysis,detection of influential cas,and check for multicollinearity)were ud in our regression analyzes to ensure the quality of the analysis results.
Propensity matching
To balance the lection bias in an obrvational trial such as the current study,we ud propensity score lection and the matching method[32,33].Further models were adapted in our study.In model2,we con-ducted Cox proportional hazard models using a propen-sity score,and included all patients bad on the probability of late RRT.In model3,we identified factors associated with late RRT in the entire cohort,using stepwi logistic regression.Bad on the factors identi-fied,we matched patients with1:1,2:2,3:3,or4:4blocks manually[32].We subquently compared outcomes between patients undergoing early dialysis or late dialy-sis.In addition,a nsitivity analysis was also carried out among the subt of patients undergoing dialysis due to azotemia,which reprented the largest proportion of our study population.
Finally,Kaplan-Meier curves obtained with the log-rank test were plotted to demonstrate the differences in patient survival between the two groups(ED versus LD). Results
From our databa,we identified1,258patients who underwent RRT during the study period.Among the patients,370fulfilled our enrollment and exclusion cri-teria for ptic AKI.The mean age of enrolled patients was65.4±15.9years on the day of RRT.Males accounted for67.0%of patients.The basic demographic data on enrollment and on ICU admission and acute physiology scores are shown in the upper part of Table 1.Finally,192(51.9%)patients underwent early RRT and the rest(48.1%)received late RRT.In-hospital mor-tality affected279patients(70%).Hospital mortality rates were comparable in the two groups(70.8%vs.
69.7%,respectively;P=0.98).
Table1Comparisons of demographic data and clinical parameters among the whole cohort as well as early,and late RRT groups(n=370)wifi连接超时
Enrolled patients(n=370)Early RRT(n=192)Late RRT(n=178)P-value Demographic data
Age(years)65.4±15.964.1±16.566.7±15.20.34馒头记
Male(%)248(67.0)119(62)129(72.5)0.04
DM(%)126(34.1)63(32.8)63(35.5)0.68 Hypertension(%)175(47.3)92(47.9)83(46.6)0.93
CHF(%)68(18.4)44(22.9)24(13.5)0.02
CKD(%)92(24.9)56(29.2)36(20.2)0.06
Post-operative(%)237(64.1)113(58.9)124(69.7)0.03 Admission creatinine(mg/dL) 2.0±0.2 2.7±1.7 1.5±1.0<0.01 (μmol/L)176.6±17.7238.7±150.3132.6±88.4
Mechanical ventilation(%)322(87.0)163(84.9)159(89.3)0.27
Data at ICU admission
Hematocrit(%)32.2±9.532.3±12.032.1±5.90.83
BUN(mg/dL)50.7±33.759.8±34.1,41.0±30.4,0.05 (mmol/L)18.1±12.021.3±12.214.6±10.9
Creatinine(mg/dL) 2.5±1.7 2.6±1.8 2.3±1.60.06 (μmol/L)221±150.3232.5±156.5200.7±141.4做包子的配方
Albumin(g/dL) 2.9±0.73,0±0.7 2.9±0.70.08 (g/L)29±730±729±7
APACHE II scores11.3±6.411.8±6.610.7±6.00.37
SOFA scores8.1±3.88.7±3.77.4±3.80.18
SAPS III score63.1±13.064.7±7.362.2±7.60.30
排卵期出血是什么原因造成的
Pre-RRT data
Hematocrit(%)30.0±5.830.1±6.329.8±0.60.62
BUN(mg/dL)81±40.678.2±41.284.0±39.80.19 (mmol/L)28.9±14.527.9±14.730.0±14.2
Creatinine(mg/dL) 3.4±0.4 3.4±0.3 3.4±0.80.17 (μmol/L)298.8±35.4297.9±23.9299.7±70.7
Albumin(g/dL) 3.0±1.2 3.1±1.5 2.9±0.60.09 (g/L)30±1231±1529±6
Potassium(mEq/L) 4.8±12.1 5.0±1.0 4.3±0.90.32 Lactate(mg/dL) 3.4±3.6 3.5±3.9 3.1±3.50.10 (mmol/L)0.4±0.40.4±0.40.3±0.4
GCS scores11.8±3.711.5±4.311.0±4.50.72 Systolic blood pressure122.7±25.7122.8±26.5123.7±25.70.84 Diastolic blood pressure61.2±39.061.5±14.160.1±14.00.36 Central venous pressure13.8±5.514.16±5.913.4±5.20.22 APACHE II scores13.1±6.412.3±7.014.0±5.50.52
SOFA scores11.2±3.910.8±4.011.6±3.70.80
SAPS III score67.3±6.866.2±6.768.6±6.70.61 Indications for dialysis
Azotemia with uremic symptoms265(71.6)119(62.0)146(82.0)<0.01 Oligouria or anuria241(65.1)113(58.9)128(63.0)0.01
吃阿胶
Fluid overload81(21.9)41(21.4)40(22.5)0.29 Electrolyte imbalance23(6.2)8(4.2)15(8.4)0.14
Acid ba imbalance25(6.8)12(6.4)13(7.3)0.84 Rhabdomyolysis7(1.9)5(2.7)2(1.1)0.51 Hospital mortality259(70.0)135(70.8)124(69.7)0.98
Values are prented as mean±standard deviation or number(percentage)unless stated otherwi.
APACHE II:Acute Physiology and Chronic Health Evaluation II;BUN:blood,urea,nitrogen;CHF:congestive heart failure;CKD:chronic kidney dia;DM: diabetes mellitus;GCS:Glasgow Coma Scale;RRT:renal replacement therapy;SAPS:Simplified Acute Physiology Score;SOFA:Sequential Organ Failure Asssment.
Model1:general model(Table2)
购买能力
Cox proportional hazard model were conducted with the whole cohort to identify factors associated
with in-hospi-tal mortality.We found that patients underwent opera-tions before RRT(hazard ratio(HR)=0.631,P=0.0011), pre-RRT CVP(HR=1.030,P=0.0140),pre-RRT diasto-lic blood pressure(HR=0.987,P=0.0089),pre-RRT GCS scores(HR=0.929,P<0.001),pre-RRT plasma lac-tate(mM)(HR=1.086,P<0.001),SOFA score on ICU admission(HR=0.941,P=0.0015),and SOFA scores on RRT commencement(HR=1.068,P=0.0058)were independently associated with in-hospital mortality. Model2:propensity score adjusted methods(Table2) The Cox proportional hazard model was conducted using the whole cohort,including propensity score as a covariate,and identified pre-RRT diastolic blood pres-sure(HR=0.987,P=0.013),pre-RRT GCS scores(HR =0.923,P<0.001),pre-RRT lactate(mM)(HR=1.073, P<0.001),pre-RRT SOFA score(HR=1.104,P< 0.001),and SOFA score on ICU admission(HR=0.934, P<0.001)predicted in-hospital mortality when propen-sity scores were conditioned(HR=0.085,P<0.001). Model3:propensity score matching method
By logistic regression,we identified differences between early RRT and late RRT groups,and found that male patients(odds ratio(OR)=1.588,95%confidence inter-val(CI)=1.012to2.492,P=0.0444),patients with CHF(OR=0.520,95%CI=0.297to0.909,P=0.0217), patients receiving operations(OR=1.618,95%CI= 1.041to2.516,P=0.0326),and patients with higher admission creatinine(OR=1.184,95%CI=1.051to 1.333,P=0.0055)could predicted late dialysis.This m
odel had a good discriminating power(c-index= 0.637),and validation(Hosmer-Lemshow’s statistics,P= 0.07,with chi squared=14.6,df=8)was fair.
We matched patients by1:1fashion according to each patient’s propensity to late RRT.After careful matching,there were178patients in each cohort.Table3showed the demographic data of the matched cohort.No differ-ences about hospital mortality were detected in both groups according to head-to-head comparison of demo-graphic data.Log Rank test of Kaplan-Meier curves(Fig-ure1)was insignificant between the two groups(HR= 1.13,P=0.33).
Further nsitivity analyzes were undertaken using patients undergoing RRT becau of uremic symptoms. Hospital mortality was associated with post-operative status(HR=0.651,P=0.002),pre-RRT CVP level(HR =1.031,P=0.002),pre-RRT diastolic blood pressure (HR=0.9687,P=0.0029),pre-RRT GCS scores(HR= 0.969,P<0.0001),pre-RRT lactate level(HR=1.091,P <0.0001),SOFA score on ICU admission(HR=0.921, P=0.0033),and SOFA score on starting RRT(HR= 1.071,P=0.0021).
男人帮台词Discussion
Whether or not to perform and when to start RRT in patients with AKI are two dilemmas facing intensivists. There is still no connsus and the initiation of RRT is extremely variable and bad pri
marily on empiricism, local institutional practice,and resources[5,34,35].Tra-ditional indications for RRT among end-stage renal dis-ea patients were not appropriate for AKI patients.The concepts of renal support for AKI patients were estab-lished in2001by Mehta[36].Some indicators for RRT and renal support are the same in life-threatening condi-tions such as vere hyperkalemia,marked acid-ba dis-turbances,or diuretic-resistant pulmonary edema.Other indications may differ between patients with end-stage renal dia and AKI.For instance,many studies have found that even mild increas in sCr in AKI patients have significant impact on outcome[37].Interventions should be performed earlier and dialysis may be consid-ered if residual renal function cannot support the patient. As patients who received dialysis too early would be expod to unnecessary risk of dialysis,while tho
Table2Independent predictors of in-hospital mortality obtained using the Cox proportional hazards model Variables Unadjusted(model1)Propensity score adjusted(model2)
HR95%CI P-value HR95%CI P-value Post-operative,yes0.6310.478-0.8320.0011
Pre-RRT CVP(mmHg) 1.030 1.006-1.0550.0140
Pre-RRT DBP(mmHg)0.9870.977-0.9970.00890.9870.977-0.9970.013 Pre-RRT GCS scores0.9290.
898-0.962<0.0010.9230.890-0.958<0.001 Pre-RRT lactate(mM) 1.086 1.048-1.124<0.001 1.073 1.034-1.113<0.001 SOFA score on ICU admission0.9410.907-0.9770.00150.9340.900-0.970<0.001 SOFA score pre-RRT 1.068 1.019-1.1200.0058 1.104 1.051-1.160<0.001 Propensity scores---0.0850.027-0.2680.085
95%CI:95%confidence interval;CVP:central venous pressure;DBP:diastolic blood pressure;GCS:Glasgow Coma Scale;HR:hazard ratio;RRT:renal replacement therapy;SOFA:Sequential Organ Failure Asssment.
