| Background:Both hypertension and acute kidney injury(AKI)are devastating conditions with respect to human and financial costs.900 million of the adult population in 2000 had hypertension,333 million in economically developed countries and 639 million in economically developing countries,and 1.56 billion were projected to have this condition by 2025.Hypertension prevalence varied from 23%to 52%in middle-income countries,Framingham Heart Study reported that the residual lifetime risk of hypertension for middle-aged and elderly individuals was 90%,the prevalence of hypertension was approximately 26.6%-40%in china adults according to tree population-based studies.hypertension had been considered one of the most important risk factors for stroke,heart failure,myocardial infarction,coronary heart disease and renal disease,even the slightly elevated blood pressure tended to be risk factors of cardiovascular diseases,stroke and renal disease.An average reduction of 12-13 mmHg in systolic blood pressure over 4 years of follow-up is associated with a 21%reduction in coronary heart disease,a 37%reduction in stroke,and a 13%reduction in all-cause mortality.Hence,hypertension is one of the leading causes of global burden of diseases.The renal disease contributed by hypertension have been considered as a problem all over the world.Crews DC et al found that the prevalences of chronic kidney disease among those with normal blood pressure was 13.4%,while 27.5%with diagnosed hypertension,and macroalbuminuria(urinary albumin:creatinine ratio>300 mg/g)had a strong association with increasing blood pressure.What is worse,more and more studies have found hypertension was a independent risk factor for AKI,defined as an abrupt decline in renal function,represent as a common complication among hospitalized patients,the prevalence of adult patients is 0.7%-77%depending on different definitions and the populations.There have been many different AKI definitions and staging systems have been used in clinical practice,including RIFLE(Risk,Injury,Failure,Loss,End Stage),AKIN(Acute Kidney Injury Network),KDIGO(Kidney Disease:Improving Global Outcomes),and CK(Creatinine Kinetics)criteria.Although there are some difference between these criteria,The AKI according to them is significantly associated with increased mortality,more financial costs and longer hospital stay.Although each of AKI and hypertension diseases has been extensively studied,little has been published about the incidence and outcomes of in hospital AKI of hypertension adults in developing Asian countries.Though some studies has reported that heart failure,myocardial infarction was risk factors of the development of AKI,if they are independent of hypertension or not were needed to be verified.In addition,some studies had found that hypertension was the risk factor of the development of AKI.Objectives:The primary aims of this study were to estimate the incidence and risk factors and outcomes of hospital-acquired(HA)AKI in a referred cohort of hypertension adult patients in China.Methods:We performed a multicenter retrospective population based cohort study conducted in nine regional central hospitals across northern,central,and southern of China,such as Nan Fang hospital,Zhong Shan hospital,Guangdong Provincial People's Hospital,Tongji Hospital,first affiliated hospital of Zhengzhou university,Hua Shan hospital,Gui Zhou Provincial People's Hospital,Zhong Da Hospital.We obtained the basic nnformation of in hospital patients from the electronic system of every hospital,including age,sex,nation,Residential Address,Birthdate,Admission date,discharge data,operation procedures and dates,in-hospital death,total cost abd serum creatinine(Scr)and so on.We made a Case report form(CRF)by nephrologue for AKI patients and put the databases in EpiData software.the records of the CRF include as follows:(1)personal information:age,sex,national,Occupation,education level,Residential Address(2)personal history:smoking history,drinking history and obsterical history;(3)databases associated with AKI:asmission with AKI or not,be diagnosed with AKI or not;(4)diagnostic message:admitting and discharge diagnosis,pathological diagnosis;(5)operation procedures:date of surgery,and time to AKI after operation;(6)diseases in different systems:hematological system diseases,Cardiovascular Diseases,nervous system disease,Lymphatic Diseases,Digestive Diseases respiratory disease and so on;(7):the names and daily dose of the AECi/ARB,nsaids,the antibiotics harmful to the kidney traditional and Chinese medicine preparation taken by patients;(8)ICU admission time,the time diagnosed with AKI before or after ICU admission;(9)medical history:have been diagnosed with hypertension,acute myocardial infarction,heart failure,Diabetes Mellitus,stroke,Hepatitis,Hepatitis C,tuberculosis,tumor,chronic nephritis?chronic kidney disease?urinary calculus and so on or not,at last we determine the patient's condition by electronic databases combined with CRF databases.The study included 87189 hypertension adult hospitalizations occurring between January 1 and December 31,2013,after excluding patients who younger than 15years older and older than 100years older,or with stages 4-5 CKD and have receiving maintenance dialysis or renal transplantation.the analysis set conclude the hospitalizations had at least two serum creatinine(SCr)tests within any 7-day window during their first 30 days of hospitalization and without community-acquired(CA)AKI and rehospitalizations in the study cohort,that 26389 patients was selected as the analysis set.For patients with multiple hospitalizations,we included only the first hospitalization.To classify the patients with HA-AKI,First,we defined CA-AKI by the following criteria:(1)admitted with AKI according to diagnosis code;(2)was diagnosised with AKI within 48 hours of admission according to the KDIGO definition;(3)SCr on admission was?1.1 mg/dl in women or ?1.4 mg/dl in men(corresponding to 1.5-fold of the SCr level in a 60-year-old man or woman with an eGFR of 90ml/min per 1.73m2)and ?1.5 fold of the minimal SCr level during hospitalization.In these cases,the baseline Scr was defined as the lowest SCr during hospitalization.Second,we defined the AKI by KDIGO criteria as follows:we sorted the SCr data during hospitalization in increasing order according to the test time,the baselines Scr dynamically defined as the mean of Scr levels within the 7 days before t(any point in time),then,we compared any available SCr data within 7 days after t with the baseline Scr,The earliest day that the SCr change met the right criteria was defined as the date of AKI onset.Patients who developed AKI by KDIGO criteria but did not meet CA-AKI criteria were identified as having hospital-acquired(HA)AKI.The peak SCr was defined as the the highest measured SCr after been diagnosed as HA-AKI during hospitalization,HA-AKI was subdivided into three severity stages(stage1,stage2,stage3)based upon increases from an baseline Scr to the peak SCr.:stage I was defined as an increase by 0.3 mg/dL or more or an increase to 150%to 200%of the baseline Scr;stage ? was defined as an increase to 200%to 300%of the baseline value;and stage ? was defined as an increase to more than 300%of the baseline value,or a value greater than 4.0mg/dL,or the need for renal replacement therapy(RRT).The Chronic Kidney Disease Epidemiology Collaboration(CKD-EPI)was used to estimate glomerular filtration rate(GFR),that eGFR = 141×min(Scr/?,1)?×max(Scr/?,1)-1.209×0.993Age×1.018[if female],where ? is 0.7 for females and 0.9 for males,? is-0.329 for females and-0.411 for males,min indicates the minimum of Scr/? or 1,and max indicates the maximum of Scr/? or 1.Precreesing CKD was defined as fowllows:1 identified with CKD by the diagnosis codes;2 a baseline eGFR<60 ml/min per 1.73 m2 in patients with AKI(CA-AKI or HA-AKI);3 the highest eGFR<60 ml/min per 1.73 m2 in patients without AKI(CA-AKI or HA-AKI).All comorbidities was determined based on the diagnosis codes at admission and discharge,Charlson comorbidity index was used to assess the severity of complications in patients.Continuous data were presented as mean ±SD or median(Q1,Q3),and categorical data were reported as number(percentage).we used the Chi-square tests for categorical variables,t test for normally distributed continuous variables to evaluate statistical significance.All tests were two-sided,and a p value of<0.05 was considered significant,We performed univariate analysis to identify the potential risk factors for the development of HA-AKI,all variables(p<0.1)from the univariate analysis were entered into the multivariable cox model analysis to identify independent risk factors for the development of HA-AKI,We also estimated the population attributable fractions(PAF)of the significant risk factors.We further performed an analysis with the Cox model to identify the risk factors of in hospital death in HA-AKI patients.We estimated the determination of in hospital death and AKI stages with multivariable Cox proportional hazards models adjusted for age,sex,comorbidities,and clinical procedures.A multivariate linear regression model with log transformation of the response variable was used to compared the effect of AKI on average daily cost during hospitalization and LOS,Multiple logistic regression analysis was made to identify the independent association between Intensive Care Unit stay and HA-AKIAll statistical analyses were performed using R software,version 3.2.0,and epicalc package,version 2.15.1.0.Result:There was 26389hospitalazations with 8.4%incidence rate of HA-AKI in in the analysis set.The incidence of HA-AKI for Stage?,Stage ?,and Stage? were 5.9%,1.2%,and 1.3%.There are 98.9%essential hypertension patients with 15.0%low risk,5.2%med risk,17.0%high risk and 61.7%very heigh risk in the analysis set.the proportion of females was 40.7%,the mean age was 65.5(sd=13.4)years,the mean baseline eGFR was 80.2(sd=22.6)ml/min per 1.73 m2.Preexisting CKD((HR=2.41,95%CI=2.19-2.65),pneumonia(HR=1,53,95%CI=1.37-1.69),heart failure(HR=1.42,95%CI =1.27-1.58),shock(HR=3.6,95%CI=2.99-4.33),acute myocardial infarction(HR= 2.15,95%CI=1.8-2.56),gastrointestinal bleeding(HR=1.73,95%CI =1.41-2.13)),urinary tract obstruction(HR=1.34,95%CI =1.00-1.79)were independent risk factors for the development of AKI,the PAF values were 20.4%?9.5%?9.1%?5.1%?4.1%?1.9%and 0.6%,respectively.The top three risk factors ranked in order of decreasing PAF were Preexisting CKD(20.4%),pneumonia(9.5%)and heart failure(9.1%).In HA-AKI patients,shock(HR=5.26,95%CI=3.82-7.24),pneumonia(HR=1.64,95%CI=1.23-2.21),preexisting CKD(HR=1.43,95%CI=1.08-1.9),stroke(HR=1.36,95%CI=1.02-1.82),solid cancer(HR=1.49,95%CI=1.07-2.07),acute myocardial infarction(HR=1.74,95%CI=1.11-2.72),trauma(HR=3.19,95%CI=1.24-8.22)were significantly associated with higher in hospital death risk.while cardiac surgery HR=0.3,95%CI=0.14-0.65)and noncardiac surgery(HR=0.65,95%CI=0.48-0.87)presented lower in hospital death risk in HA-AKI patients.Heart failure,gastrointestinal bleeding,urinary tract obstruction was not independent risk factor for increased mortality in the HA-AKI patients in our analysis set.Higher mean age were also associated with a higher incidence of HA-AKI,however,higher mean age were not significantly associated with the developing HA-AKI in a multivariate Cox proportional hazards models adjusted for sex,age and clinical settings.Compared with patients aged 15 to 39 years old,the HR(95%CI)for patients aged 40 to 59 years old,60 to 79 years old,80 to 100 years old were 0.85(0.65-1.11),0.78(0.60-1.02)and 0.78(0.59-1.04).The risk factors of HA-AKI were different between sex.In females,compare to age 15 to 39 years old age group,the HR(95%CI)for 40 to 59 years and 60 to 79 years old were 0.54(0.34-0.84)and 0.55(0.36-0.86),respectivly,while the risk for 80 to 100 years old a was not significantly different,sepsis(HR=1.88,95%CI=1.13-3.14)was also significantly risk factors of HA-AKI in females,but age and sepsis were not significantly associated with the development of HA-AKI in males.In the essential hypertension patients,the very high risk had 24%higher risk for the development of HA-AKI compared with low risk group of hypertension.The presence of hypertensive cvd disease,hypertensive brain disease was not significantly associated with the development of HA-AKI,while hypertensive renal disease was a significant risk factor for HA-AKI.The transient HA-AKI in stage?,stage ?,stage? were 22.4%,8.3%and 5.3%,respectively,28%of patients with HA-AKI had fully recovered renal function at discharge,and 32.2%,24.7%and 11.8%in stage?,stage ?,stage?,respectively.3%of those with HA-AKI required dialysis during hospitalization.threre were significantly lower in hospital mortality in transient HA-AKI patients compare with other kind of HA-AKI,and significantly lower in hospital mortality in patients with fully recovered renal function at discharge than did not.We found the association between the severity of AKI and worse outcomes,including in hospital mortality,length of hospitalization(LOS),higher daily cost in hospital in hypertensive adults,compare with patients without HA-AKI,the HRs(95%confidence intervals)of in hospital death for HA-AKI stages(stage?,stage ?,stage?)were 3.47(2.55-4.70),8.52(6.16-11.77)andll.20(7.47-13.93),respectively,the ORs(95%confidence intervals)for needing of ICU stay were 1.15(1.13-1.17)?1.20(1.16-1.24)?1.24(1.20-1.29),,stage 1,stage 2,and stage 3 AKI were associated with 19%,34%,and 23%longer LOS and 21%,42%and 51%higher daily cost.Conclusion:1.In hypertension patients,the prevalence of HA-AKI was 13.8%,preexisting CKD,pneumonia,heart failure,shock,acute myocardial infarction,gastrointestinal bleeding and urinary tract obstruction were significantly risk factors of HA-AKI.Preexisting CKD was the most serious risk factors of HA-AKI.Heart failure,gastrointestinal bleeding,urinary tract obstruction was not independent risk factor for increased mortality in the HA-AKI patients in our analysis set.2.In essential hypertension patients,the very high risk had 24%higher risk for the development of HA-AKI compared with low risk group of hypertension.the presence of hypertensive cvd disease,hypertensive brain disease was not significantly associated with the development of HA-AKI,while hypertensive renal disease was significantly associated with the development of AKI in hypertension patients3.In hypertension adults,higher mean age were associated with a higher incidence of HA-AKI,however age were not significantly associated with the developing HA-AKI,sepsis were independent risk factors of HA-AKI in females but not in males4.The presence of HA-AKI in hypertensivon Adults was associated with worse outcomes,including increased length of hospitalization,a future higher risk of in hospital death and higher daily cost in hospital. |
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