| BackgroundIn the United States,more than 1 million patients are admitted annually for acute decompensated heart failure(ADHF).Acute kidney injuery(AKI)occurs commonly in patients with ADHF and was defined as "Type 1 cardiorenal syndrome(CRS1)".Recent studies have demonstrated that even smaller increases in serum creatinine(SCr)might also be associated with a prolonged length of stay and adverse in-hospital outcomes.Thus,Identifying predictors for development of AKI in hospitalized ADHF,so as to prevent and early intervent CRS1,is not only a difficult problem for clinical diagnosis and treatment,but also the current hot areas of research.Previous studies showed aged,chronic kidney diease(CKD),were the independent predictors for development of AKI in patients with ADHF.Theoretically,the elderly are much more vulnerable to suffer AKI than younger patients because of their degeneration of physiology.And patients with prior CKD,is also a susceptible population for development of AKI due to pre-existing disfunction of kidney.It might make sense for clarifying the characteristics of development of AKI in ADHF that analyze these population in ADHF subgroups.The present study was preformed prospectively in multicenter to investigate predictors for development of in-hospital AKI in ADHF patients and its subgroups.Patients and Methods1.Study population436 patients with ADHF enrolled on the first day of admission were recruited from 6 centers(Nanfang Hospital,Guangdong Provincial People’s Hospital,Guizhou Provincial People’s Hospital,Futian Hospital,Beijing An Zhen Hospital,Affiliated Hospital of Guangdong Medical College)in 5 cities(GuangZhou,Guiyang,Shenzhen,Beijing,Zhanjiang).Eligible subjects were ADHF patients and(1)aged 18-80years who were admitted to the 6 participating hospitals;(2)with at least three measurements of SCr over a 6-month period before admission.Exclusion criteria included exposure to nephrotoxin within 4 weeks before admission or during their hospital stay,pre-existing advance CKD(chronic dialysis or pre-admission estimated glomerular filtration rate[eGFR]<30 ml/min/1.73m2),urinary tract infection or obstruction,cancer,a concurrent diagnosis of an acute coronary syndrome,cardiogenic shock or need for inotropes,a history of cardiac transplantation and/or ventricular assist devices,and heart failure following cardiac surgery,patients who had AKI on admission(those with a 50%increase in SCr from pre-admission level on the day of hospitalization)were also excluded.2.P rocedures2.1 Data collectionEach patient was identified a unique number.Data were collected on the patient’s demographic characteristics,primary cause,coexisting conditions,clinical manifestations,laboratory analysis on admission.SCr was measured on admission and at least twice a day during the first 3 days and daily thereafter.This was an observational study in which all of study patients received the standard care for ADHF.2.2 Sample collectionSpot urine and blood samples were collected immediately after admission before any in-hospital treatment initiation and every 24 hours for the first 7 days during hospitalization.The remaining urine and blood samples were obtained at the time of routine morning sample collection for clinical care purpose until discharge.The urine and blood samples were centrifuged at 3,0OO×g for 10 minutes and the supernatants were stored at-80 ℃,All of the samples were labeled as the patient’s number without personal identity or clinical information.2.3 Laboratory measurementsUrine and blood samples collected from the participating hospitals were shipped by commercial cold chain transportation.Urine creatinine and albumin were measured in a central laboratory using a standard protocol by 2 specific measurers.To ensure continuity and integrity of laboratory parameters,supplementary measurements of spot urine or blood from samples library were performed for missing values.2.4 Primary outcome and definitionPrimary outcome was development of in-hospital AKI which defined as an increase in SCr by 26.5 μmol/L(0.3 mg/dl)within 48 hours of admission or a 50%increase in SCr from pre-admission level(mean of at least three measurements over a six-month period before admission)within 7 days of admission according to the Kidney Disease Improving Global Outcomes(KDIGO)Clinical Practice Guidelines for Acute Kidney Injury.We did not use urine output criteria(<0.5 ml/kg/h for>6 h)for AKI diagnosis because of limited sensitivity when diuretics are administered,reduced specificity in the presence of dehydration,and lack of practicality in measurement when an indwelling urinary catheter is not present.We assigned study subjects to AKI or Non-AKI group according to the development of AKI.2.5 Criteria and definition of subgroups2.5.1 AgedPatients whose age>60 years were defined as Aged.The total cohort was further subdivided into 2 groups according to age.2.5.2 CKDPre-admission SCr level was calculated as mean of at least three measurements over a six-month period before admission.We estimated glomerular filtration rate(eGFR)with the Chronic Kidney Epidemiology Collaboration equation(CKD-EPI).Prior CKD was defined as Pre-admission eGFR<60 ml/min/1.73m2.The total cohort was further subdivided into 2 groups according to prior CKD.2.6 Other diagnostic criteriaThe diagnosis of ADHF was based on European Society of Cardiology Criteria.Heart function classification was based on New York Heart Association.Medical treatment before admission was defined as receiving the drugs for more than 4 weeks before admission.3.Statistical analysisIn statistical data,continuous variables were presented as mean ±standard deviation(SD)or median(range)and categorical variables were presented as percentages.All variables were tested for normal distribution using the Kolmogorov-Smirnov test.One-way analysis of variance(one-way ANOVA)test or the Kruskal-Wallis H test for continuous variables according to their distribution;Fisher’s exact test or the chi-square test were applied to assess categorical data.To elucidate the predictors for development of AKI,multiple-variable logistic regression analyses was conducted,variables at p<0.05 in the univariate analysis and those considered clinically important were entered a multiple-variable logistic regression model.The Hosmer-Lemeshow test was employed to determine the goodness-of-fit of the model,P>0.05 was regarded as an acceptable model.The results of multivariate logistic regression analysis were summarized by estimating odds ratios(OR)and respective 95%confidence interval(CI).We considered double-sided P<0.05 as statistically significant.Data were analyzed using the SPSS version 13.0.Results1.Characteristics of ADHF patients on admission572 ADHF patients(all Chinese)enrolled from 6 centers were screened for potential participation.136 were excluded according to the exclusion criteria.A total of 436 patients,mean aged 64.5±15.4 years,were included in the study,of which 281(64.4%)were male,106(24.3%),211(48.4%),117(26.8%),234(53.7%)patients had pre-exisiting CKD,hypertension and diabetes,previous history of heart failure,respectively.The mean SCr was 107.8±47.8umol/L.2.Primary outcome in total cohort and subgroups141(32.3%)of 436 ADHF patients developed AKI during hospitalization.ADHF patients with prior CKD had a higher incidence of AKI than those without(56.6%vs.24.5%,P<0.001).Aged ADHF patients had a higher incidence of AKI than those younger patients(40.1%vs.17.4%,P<0.001).3.Predictors for development of AKI in ADHF3.1 Multivariate logistic regression analysis:independent predictors for development of AKI in total cohortIn ADHF patients,the independent predictors for development of AKI included age(per lyear increased,OR 1.039;95%CI 1.021～1.057,P<0.001),prior CKD(OR 2.433;95%CI 1.438-4.115,P=0.001),level of serum albumin(per 1g/L decreased,OR 1.099;95%CI1.056～1.145,P<0.001),N-terminal pro-Brain natriuretic peptide(NT-proBNP,per 1000pg/mL increased,OR 1.030;95%CI 1.001～1.061,P=0.046),urine albumin to creatinine ratio(UACR,per 10 mg/gCr increased,OR 1.008;95%CI 1.002-1.015,P=0.007).The factors which represented statistically significant in univariate analysis,included hypertension,diabetes,heart function,hemoglobin level,were not the independent predictors for development of AKI.3.2 Multivariate logistic regression analysis:predictors for development of CRS stratified by ageIn Aged ADHF patients,the independent predictors for development of AKI included prior CKD(OR 3.388;95%CI 1.859～6.174,P<0.001),level of serum albumin(per lg/L decreased,OR 1.099;95%CI 1.047～1.155,P<0.001),UACR(per 10 mg/gCr increased,OR 1.014;95%CI 1.004-1.025,P=0.009).The factors which represented statistically significant in univariate analysis,included hypertension,diabetes,hemoglobin level,NT-proBNP,were not the independent predictors for development of AKI.In younger ADHF patients,the independent predictors for development of AKI included heart function(NYHA classification Ⅳ,OR 4.718;95%CI 1.605～13.865,P=0.005),level of serum albumin(per 1g/L decreased,OR 1.125;95%CI 1.038～1.218,P=0.004),NT-proBNP(per 1000pg/mL increased,OR 1.118;95%CI 1.032～1.213,P=0.001).The factors which represented statistically significant in univariate analysis,included prior CKD,hemoglobin level,were not the independent predictors for development of AKI.3.3 Multivariate logistic regression analysis:independent predictors for development of CRS stratified by prior CKDIn ADHF patients with prior CKD,the independent predictors for development of AKI only included age(per lyear increased,OR 1.045;95%CI 1.013～1.077,P=0.005)and hemoglobin level(per lg/L decreased,OR 1.019;95%CI 1.003-1.035,P=0.020).Hypertension,The factors which represented statistically significant in univariate analysis,was not the independent predictors for development of AKI.In ADHF patients without prior CKD,the independent predictors for development of AKI included aged(per lyear increased,OR 1.030;95%CI 1.008～1.051,P=0.006),level of SCr(per 1umol/L increased,OR 1.013;95%CI 1.001～1.025,P=0.029),serum albumin(per 1g/L decreased,OR 1.114;95%CI 1.060～1.168,P<0.001),NT-proBNP(per 1000pg/mL increased,OR1.054;95%CI 1.009～1.100,P=0.017),UACR(per 10 mg/gCr increased,OR1.010;95%CI 1.002～1.018,P=0.010).The factors which represented statistically significant in univariate analysis,included hypertension,diabetes,heart function,hemoglobin level,were not the independent predictors for development of AKI.ConclusionsOur study showed a high incidence of in-hospital AKI in ADHF patients.Moreover,the incidence were higher whether in Aged or pre-exisiting CKD patients with ADHF as compared to general ADHF patients.The independent predictors for the development of in-hospital AKI in ADHF patients represented significantly difference according to Aged or prior CKD.Prediction on the basis of different characteristics of ADHF patients may be more beneficial to prevent and early intervent the development of CRS,as well as save medical resources. |
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