LITHUANIAN UNIVERSITY OF HEALTH SCIENCES DEPARTMENT OF ICU TAREK RIDA FACULTY OF MEDICINE VI GROUP 32

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1 LITHUANIAN UNIVERSITY OF HEALTH SCIENCES DEPARTMENT OF ICU TAREK RIDA FACULTY OF MEDICINE VI GROUP 32 MORTALITY AND OUTCOMES OF ACUTE KIDNEY INJURY IN INTENSIVE CARE UNIT. 1

2 Table of contents 1. Title page (pg.1) 2. Table of content (pg.2) 3. Summary (pg.3-4) 4. Acknowledgments (pg.4) 5. Conflicts of interest (pg.4) 6. Ethics Committee Clearance (pg.5) 7. Abbreviations (pg.6) 8. Terms (pg.6) 9. Introduction (pg.7) 10. Aims and Objectives (pg.8-9) 11. Literature Review (pg.9-13) 12. Methodology and Methods (pg.13-15) 13. Results and their Discussion(pg.15-25) 14. Conclusion (pg.26) 15. References (pg.27-29) 2

3 Summary: Acute kidney injury is known to be one of the common diseases who have increase number of admitting to ICU, having a variety of outcomes associated with comorbidities, risk factors and blood tests that interfere with the severity of the disease. We tried to evaluate and determine whether creatinine does play an impact role by assessing AKI patients outcomes and determine the prognosis of AKI patients who require dialysis.the research instrument we used was based on (creatinine, BUN, GFR, risk factors and comorbidities) of admitted patients during 2 consecutive years 2014 and Our objectives was to classify AKI patient into 2 stages according their creatinine values (<2,7 mg/dl and > or equal to 2,7 mg/dl), to asses AKI-associated risk factor and to determine AKIinterferes with comorbidities, as well as to determine the prognosis for patients who required dialysis in their treatment. We detailed the values from inpatient by a retrospective study containing of (n=30) in LSMU Kauno Klinikos between dates 2014 and 2015, given blood tests where analyzed, correlation between all 3 (creatinine, BUN and GFR) was assessed, frequency of comorbidities was determined, staging of AKI was done according to given creatinine values, comorbidities in AKI and CKI was calculated and explained, patients comorbidities was shown and staged according creatinine levels (< 2,7 mg/dl and >or equal from 2,7 mg/dl) and last but not least, the frequency of risk factors for patients with kidney diseases and classifying them into AKI and CKD furthermore according there creatinine levels was assessed. Results showed: an age of (64,79 +/- 18) for AKI and (66,55 +/- 22,5) for CKI. The deference in blood parameters in (2014/2015) was not significant. The decrease in creatinine strongly affect GFR rate, whereas correlation between creatinine and GFR was not statistically significant, but an increase in creatinine levels have influence on increasing BUN levels, this highlight the fact that creatinine value affect GFR ad BUN rate. The highest comorbidities frequency was other diseases including infectious disease and sepsis (40%), kidney disorders (16.7%) and lung involvement (13.3%), which in turn clarify that development of these comorbidities have influence on worse outcome for patients. Staging according creatinine values where (36.7 %) for (< 2,7mg/dl) and (63,3 %) for (>or equal to 2,7mg/dl). Patients with chronic kidney injury required more dialysis than patients with acute kidney injury, as well as they had an increase levels in their creatinine levels and lower levels 3

4 in GFR rate, worsening the chronic phase. Comorbidities in patients with acute and chronic kidney injury demonstrate that AKI had kidney and liver disorders, cardiovascular diseases and lung manifestations more frequent than CKI. Creatinine values were higher in patients who had more comorbidities, this sum up the concept of developing a comorbidities can worse the phase of injury. The most frequent risk factors in patients with kidney injury was hypertension (70%), which emphasize for us that increase blood pressure has bad influence on kidney injury. Patients with chronic kidney injury had hyperparathyroidism as risk factor more frequent than AKI patients and it was significant (P=0,047), whereas AKI patients were prone to have DM II and hypertensive cardiomyopathy more frequently than CKI patients. Obese patients didn t had elevation in their creatinine value significantly (P = 0.03) opposing other risk factors, which clarify that a high body mass index doesn t affect severity of the disease. Acknowledgements The fact that this study took a hard work, sqezzing informations and comparing them with others to finding their effect which may help us and other coming up studies to evaluate and go further with development of better disease understanding. I would like to thanks Dr. Vidas Pilvinis for his help and insure that with his leading it was easier to reach better results. Conflict of interests The author supports no conflicts of interest. 4

5 Ethics Committee Clearance : Nr. BEC-MF-67 Date

6 Abbreviations list BUN(blood urea nitrogen), AKI(acute kidney injury), GFR(glomerular filtration rate), ICU(intensive care unit), KDIGO(Kidney Disease Improving Global Outcomes), RRT(renal replacement therapy), AKIN(acute kidney injury network), ESRD(end stage renal disease), ACEI(Angiotensin converting enzyme inhibitor), ATN(acute tubular necrosis), BPH(benign prostatic hyperplasia), RIFLE(risk injury failure loss end stage kidney disease), BMI(body mass index), APACHP I(acute physiology and chronic health physiology), CVVH(continuous veno-venous hemofiltration), CVVHDF(continuous arteriovenous hemodiafiltration), IHD(intermittent hemodialysis), (SLED)slow low efficiency dialysis, SPSS 17.0 (Statistical Package for the Social Sciences), Absolute (n), percentage (%),arithmetic averages (m), standard deviation (sd), Chi-squared test (χ 2 ), Four-field (2x2), Spearman correlation coefficient (r), (0< r 0.3)the dependence is weak, (0.3< r 0.8)the dependence is moderate, (0.8< r 1) dependence is variables, (p 0.05) significance level, HTN(hypertension). Terms: AKI (acute kidney injury), CKI (chronic kidney injury), dialysis, ESKD (end stage kidney disease), hypovolemia, cardiovascular diseases, sepsis, infectious diseases, hypertension, hyperparathyrodisim, thyrotoxicosis, DM II (diabetes mellitus type 2), anemia, cirhosis, hepatorenal insuffeciency, BPH (benin prostatic hyperplasia), congestive heart failure. 6

7 Introduction : Acute kidney injury defined as a rapidly decrease in kidney function and GFR, leading to unbalance in nitrogenous metabolites and water electrolytes retention[2], a rapid increase in creatinine by 0,3 mg/dl (and/or) reduction in urine count by 0,5ml/kg/h in 6 hours defines an AKI episode [2]. Usually all kind of kidney injured patients will have an increase in their creatinine levels, due to the fact that kidney is damaged. Risk factors which influence a bad prognosis on AKI include: age>65 years, overweight, HTN, surgical history, cardiovascular disorders, sepsis, prolonged hospital stay, decrease urine output and few more [2]. The most effective diagnostic test so far is evaluation of creatinine levels for AKI in addition to urine output per 24hours, serum creatinine considered to be rapid valuation with high specificity controversy with BUN levels which is not specific just for renal function [13]. AKI can be caused by 3 major stages, starting from prerenal stage which could be due to hypovolemia causing lowering of blood flow through glomerulus, following by a renal stage which usually occurred due to untreated prerenal blood pressure flow, reaching the last stage, the post-renal, this part is mostly due to obstruction caused by stones tumors or other closing the ureters pathway. Treatment of AKI usually depend in the incidence starting from supportive treatment reaching renal replacement therapy, the common RRT used is CVVH and further using CVVHDF, whereas low amount of patients require IHD[17]. The need of dialysis for AKI patients clarify that kidney function is coming to its worse phases and may end in end stage kidney disease (ESKD). Comorbidities and risk factors play a significant role in worsening kidney function and by assessing which has more negative influence on this disease and try to control them, it may help reach a better outcome and prognosis for AKI patients. Our goal is to sum up some evidence about finding out the most common comorbidities and risk factors, including staging of AKI according their creatinine levels. We specified the evaluation of given values from an inpatients of ICU by a retrospective cohort study including n=30 patients between 2 consuctive years 2014/2015, for better understanding of outcomes of AKI patients admitted to ICU, and determine the prognosis for patients requiring dialysis. 7

8 Aim and objectives of the thesis: The direction of the study and indication of analyzed problems: A very few researches which demonstrate the epidemiological information of an AKI patient in ICU department and concerning its riskiness and acutness through out different ICU departments linked to AKIN criteria. Wide varaity of cohort studies of AKI patients in ICU was centering there main concept on the intensity for AKI which may require the last step of treatment before kidney transplantation, dialysis, or on other hand pointing on the very first day of admission for AKI in ICU to evaluate their mortality. An evidence based medicine showing that a small elevation in serum creatinine may contribute with worse prognosis for those patients, But these evidence are limited to few cases where a patient obtaining a heart operations and the use of contrast such as cardiac cathetirization. There is a restrictive information about varaity of data requiring the patients who is suffering from AKI about his definitive disease. Therefore if we didn t have a clear concept about how the association between acuteness and Acute kidney Injury and Intensive care unit consequences it will make it harder to reach a better prognosis and outcome results to help us achieve better quality of management and even prophylaxis from sever complication could be avoided. Research process and research instruments: The process and intruments used in this research was based on the given values in the patients case histories about different blood tests including: serum creatinine, blood urea nitrogen (BUN) and further history of patients including ( age, gender, date of admission, the diagnosis upon admission to ICU depatment, the risk factors which may affect their hospital stay and intense of the disease, glomerular filtration rate (GFR), and comorbidities). In this research we collect the informative data found in the patients case histories and performed a systematic review to gather and conflict the prognosis and functional outcomes of patients with AKI admitted to ICU department. Objectives of the thesis: 1) Classification of AKI stages with further assessment of prognosis. 2) Better realization on which risk factors contribute with worse AKI outcome. 3) Determine the comorbidities that have more negative influence on AKI than others. 4) Assess the prognosis of patients requiring dialysis. 8

9 Aim: The aim of this research is to have better understanding of most common risk factor and comorbidites which can have bad influnce AKI patients admitted to the ICU department during 2 consequtive years 2014/2015, and help determine the prognosis of patients indicated for them the need of dialysis. Literature Review: Acute kidney injury (AKI) indicates a rapidly decrease in kidney function associated with deterioration of Glomerular filtration rate (GFR) leading to incapability of kidney to manifest its normal function by retaining nitrogenous metabolites and water electrolyte imponderables in the body [2]. Although kidney known to have various functions whereas the rapid and immediate elevation of serum creatinine by 0.3mg/dl (and/or ) reduction in urine count to less than 0.5ml/kg/h in a duration exceeds to approximately 6 hours, is the accurate definition so far[2]. A huge apprehension in intensive care unit about patients who continue their lives after recovery from AKI to determine their quality of life and risk assessment of long term outcomes after discharge from ICU, in turn the evidence that shows patient who had the need for a renal replacement therapy(rrt) concerning their quality of life it was insufficient [10]. Over review: During the time patient admitted to ICU with increase in his serum creatinine and blood urea nitrogen and an indication for an invasive mechanical ventilation it shown to have an increased risk for AKI, in addition to that, a long ICU stay associated with sepsis, adding to it a low GCS score, elevation in patients SOFA score was showing an increased risk for AKI as well [2]. The happening of AKI is much more than ESRD which have incidence to develop with the patients suffering from cardiovascular, nutritional and metabolic disturbance leading to bleeding issues and emergent ICU admission [3, 4]. In turn ESKD is connected with weaken health related quality of life (HRQL) and the beneficial of health [1]. AKI without doubt can affect patient morbidity and mortality from developing severe complications, up to 40% of critically ill patients with AKI associated with KDIGO stage 3 (Kidney Disease Improving Global Outcomes) there life will be ended within approximately 9

10 90 days [6]. And for patients whose under renal replacement therapy (RRT) a 30% linked with AKI there life expectancy is 5 years after their stay in ICU [6]. Moreover the mortality of AKI is connected with its acuity of damage, liver and lung diseases involvement in addition to multiple organ damage which they are linked to a rise in mortality rate regardless of any progress in the renal replacement therapy [7, 11]. As AKI is a comorbidity associated disease for most of the times, therefore patients may stay with elevated risk mortality and morbidity even though after a recapture from disease [9]. A huge apprehension in intensive care unit about patients who continue their lives after recovery from AKI to determine their quality of life and risk assessment of long term outcomes after discharge from ICU, in turn the evidence that shows patient who had the need for a renal replacement therapy (RRT) concerning their quality of life it was insufficient [10]. RIFLE classification is critically important investigation to evaluate AKI, in addition the injury or failure class of RIFLE criteria are contributed with elevation in hospital mortality, as well as patient which show a risk class are also more prone to develop to injury or failure class and by then to increase hospital mortality [14]. Epidemiology: AKI cover 15% from the average of hospitalized patients, out of these patients there is up to 40% got the need for admission into ICU department, moreover 80% of the patients require ICU department die and the rest 13 % seek dialysis [2]. As soon as the disease is diagnosed therefore it will help in decreasing the risk of complications and better recovery [5].Even a small increase in serum creatinine show a rise in mortality rate [12]. According patient who continue to live from AKI, a notable significant detailed evidence have shown that AKI can be associated in a risk factors following a long period of time increase in developing to end stage kidney disease, contributing to main risk factors such as sepsis, fractures and heart problems [1]. Etiology: AKI causes can be classified into three main stages, the first is prerenal which is associated with decrease in blood pressure and decrease in flow via GFR due to hypovolemia linked to shock, as well as excessive vasodilation connected with septicemia and in addition to certain type of drugs such as anti-prostaglandins and Angiotensin converting enzyme inhibitor (ACEI) developing an increase in serum creatinine and Blood urea nitrogen (BUN) known as azotemia [2]. 10

11 Whereas in causes associated in renal stage, there is a common etiology starts as a prerenal by uncorrected decrease flow of blood through Glomerulus causing a prolonged hypoperfusion and ischemia of the renal tissue leading to acute tubular necrosis (ATN), in addition to other renal causes such as acute tubule-interstitial nephropathy happened due to allergy from a drug forming destruction of the tubule-interstitial [2]. A post-renal stage is associated with obstruction by stones, malignancy or benign prostatic hyperplasia (BPH) developing an increase in pressure kidney stopping the glomerular filtration rate (GFR), another causative factor is a decrease in bladder contractility due to infection autonomic neuropathy and anticholinergic drugs [2]. Diagnostic criteria: Diagnosis of AKI require serum creatinine and the amount of urine the patient does per 24hours contributing with Glomerular filtration rate (GFR), whereas it does show exact incidence about the site of kidney damage[12]. As AKI defined by a rise in serum creatinine of 0.3mg/dl/hour in a period of 6 hours shows an indication [2]. Serum creatinine considered to be fast measurement with high specificity controversy with blood urea nitrogen (BUN) which is not specific just for renal function [13]. Urine output is not a sensitive test to be done for AKI unless an oliguria (less than 500ml/24 hours) or anuria (less than 100ml/24hours) have been confirmed, intense appearance of AKI can happen without an urine output stage as for an non-oliguric AKI, whereas urine output can be showen before biochemical markers start to develop[13]. Morbidity: Morbidity is associated with a prolonged stay of patients suffering from AKI in Intensive care units (ICU) making them more susceptible for increase morbidity as well as for increasing risk to develop chronic kidney disease (CKD) and furthermore an end stage kidney disease (ESKD) may also influence the morbidity high risk [17]. Unfortunately a developing evidence showing that treating patients hypovolemia by excess in fluid administration in will in turn cause an increase in morbidity and further more developing an AKI risk mortality [16]. Mortality: Recent studies have shown that patients suffering from AKI are in the range of geriatric (more than 65 years old) associated with underlining diseases and have high risk to develop a 11

12 septic shock and frequent comorbidities such as (chronic kidney disease, cardiovascular events and furthermore) and less episodes of recovery they can manage following an organ damage [15] Regardless of high quality care and Renal replacement therapy (RRT) mortality rate remains elevated in up to at least 50% of the severely affected patients. A score of 30% mortality from hospitalized patients was there leading cause to AKI is a drug induced such as antprostaglandins and angiotensin converting enzyme inhibition (ACEI), and a 90% mortality rate for patients developed AKI due to multiple organ damage [17]. An evidence based medicine showed an increase in mortality rate associated with a delay in nephrology consultation for AKI patients who require dialysis, the last therapeutic treatment before kidney transplantation or even who doesn t have indication for dialysis adding to it an obvious prolongation to the patients stay in hospital making him more prone to risk complications [17]. Outcomes: To calculate the outcome measurement is essential for effective enforcement [13]. An outcome is to clarify 1 of these 2 main issues: 1 st the measurement and/or 2 nd the incident such as end of life or requiring dialysis [13]. Therefore it s important and essential for an outcome to demonstrate it and as importance as for the primary outcome to be specified as well [13]. A consultation of nephrologist participation in the AKI patients and suggesting his experience with ICU doctors may indeed help in progression for patients outcomes [17]. According to majority of nephrologist which they emphasize that a reduction in kidney function has to do with long-term outcomes, in turn the modulation can t be accurately confirmed unless there is a follow up within few years to investigate a precise result, coming to a point that insufficient renal recovery can determine just the mortality during a period of time between the (1 st and 12 th month) [8]. Recovery: According recovery of patients from AKI it have been classified into 2 major stages: 1 st is complete renal recovery defined as returning to the limit range levels linked to RIFLE criteria and 2 nd fractional renal recovery which intermits a constant alternation in the RIFLE criteria especially, but without the need for (RRT) [13]. 12

13 Risk factor: There is some risk factors which correlate with increase mortality and disease aggressiveness include: geriatric patients (more than 65 years old), elevated BMI ( more than 30), history of elevated blood pressure, recent surgery, cardiovascular manifestation, sepsis, long hospital and ICU stay, hypovolemia, decrease urine output by (less than 500ml/dl/24 hours), polytrauma patients and few more in addition to increased score of Acute Physiology And Chronic Health Physiology (APACHP I) [2]. Treatment: Treatment of AKI require symptomatic treatment and additional to that renal replacement therapy (RRT) if indicated [17]. The most common form of renal replacement therapy used is continuous veno-venous hemofiltration (CVVH) and thereafter to continuous arteriovenous hemodiafiltration (CVVHDF), whereas a low number of ICU patients with AKI require the use of intermittent hemodialysis (IHD) which is the major process of renal replacement therapy (RRT) continuing with the lowest percentage from patient with AKI who is using the slow low efficiency dialysis (SLED), coming to the preference of patients, up to half of them will choose the (CVVHDF) and a score of 10% they will choose intermittent hemodialysis (IHD) or hybrid therapy [17]. Dialysis: Patients who require dialysis in acute kidney injury are under weak prognosis, whereas the information for these evidence is quit constricted. Even though the increase of AKI patients who required dialysis was happening, there was and developing in the use of CCRT (continuous renal replacement therapy), in addition to acute renal replacement therapy(rrt) for patient reaching the age above 75 years [21]. Research methodology and methods: A multi researches was showing the different incidence how to evaluate and discuss the severity of AKI illness and finding out a new test if could be relevant and more specific for AKI than (serum creatinine, Blood urea nitrogen and/or urine output) such as cystatin C, whereas it could find a lack for certain information in a trauma patients [5]. Although urine 13

14 output might not correlates for specificity of AKI whereas it does add specificity when the urine output is severely decrease such as an oliguric phases (less than 400ml/24hours) or an anuria phase (less than 100ml/24 hours) [13]. Object of the study: In our research study we tried to look for the prognosis and outcomes of the AKI patients found in ICU department from January 2014 till March 2015 in Lithuanian ICU department and how does their risk factors affect their prognosis. This study was done to show the different evidence of patients assessment during 2 consecutive years and showing the disease AKI prognosis if have been developed to a better outcome. Research planning: we research the patient history given on his case and collected several data such as (age, gender, date of admission, the diagnosis on admission, 2 specific tests for AKI serum creatinine and blood urea nitrogen (BUN), GFR, in addition to the risk factors of patient). These risk factors are: 1- blood pressure levels 2- High body mass index (obesity) 3- Recent AKI 4- Cardiovascular diseases 5- Sepsis Adding the comorbidities: 1- Smoking 2- Chronic kidney disease 3- Congestive heart failure 4- Diabetes mellitus [2,3]. Research methods and methods of data analysis: SPSS was used 17.0 (Statistical Package for the Social Sciences) and MS Excel Absolute (n) and percentage (%) rates of descriptive statistics have been applied to evaluate distribution of analyzed variables in the selected sample. Quantitative data was presented as arithmetic averages (m) with standard deviation (sd). Evaluation rate of quantitative variables were specified. Related variables lists was demonstrated to evaluate 14

15 signs relations. Chi-squared test (χ 2 ) evaluate variables dependence. Fisher s method determined additionally, if data was describing the Four-field (2x2) frequency table and at least one expected sample was less 5. Z-test verified the ratio equivalence. Mann-Whitney U test evaluate the contrast between non-parametric variables average values of two independent samples. Spearman correlation coefficient (r) done to evaluate strength of dependence of two variables. If 0< r 0.3, the dependence is weak, if 0.3< r 0.8 the dependence is moderate and if 0.8< r 1 variables are strong dependent. Correlation coefficient is positive if one size tends to increase when another increases and negative if one size tends to decrease when another increases. If the significance level p 0.05, the difference of variables in analyzed groups is statistically significant. The results are presented in graphs and tables. We detailed the examination of elements and given values from an inpatients of ICU by a retrospective cohort study containing as part of the whole being considered patients a number of (n=30) was assumptive in ICU of Hospital of Lithuanian University of Health Sciences (Kauno Klinikos) between the dates of January 2014 and March )We evaluated the creatinine levels during their stay in ICU, 2) calculated their glomerular filtration rate for whom less than (15 ml/min/1,73m3), 3)classification of cases according 2 stages. Cases were classified into two sections: 1- Mild to moderate: creatinine < 2.7 mg/dl 2- Highly moderate to severe: creatinine 2.7 mg/dl. Risk method: this research has showed the feature of quality for each different patient concerning their risk factors and comorbidities related to it, such as (blood pressure levels, high body mass index (obesity), recent AKI, cardiovascular diseases, sepsis, smoking, chronic kidney disease, congestive heart failure, diabetes mellitus) [2,3]. This means that the more risks the patient has the more worse his outcome will be. Therefore this risk method can foretell mortality risk for the examining patients. Results and their discussion : 1. The distribution of the subjects In this research was collected the informative data found in the patients histories in patients with kidney injury were analyzed: 16 men (53.3 %) and 14 women 15

16 percentage (46.7 %). The youngest patient with kidney injury was 23 years old and the oldest patient was 86 years old. More men had chronic kidney injury, though difference between males and females was not significant (P = 0.47) (Table 1). Table 1 Distribution by gender and diagnosis of hospitalization (N=30) Socio-demographics Acute kidney Chronic kidney characteristics injury (n=19) injury (n=11) p Gender (n / percent)* Male 9 / / Female 10 / / 36.4 Age (m ± sd)** ± ± *- Fisher's Exact test; **- Mann-Whitney U test The average of the subjects with acute kidney injury was ± 18.0 years and with chronic was ± The youngest patient with acute kidney injury was 24 years old and the oldest 86 years old. The youngest patient with chronic kidney injury was 23 years old and the oldest 84 years old. Picture 1 Need for dialysis of patients with different kidney injuries (N=30) ,7 Nondialyzed (Black) Dialyzed (Red) 73,7 * ,3 Acute kidney injury 26,3 Chronic kidney injury *- Chi-square test, p=0,023 16

17 Patients with chronic kidney injury have an increased need for dialysis than patients with AKI. This difference is statistically significant (p<0.05). The need for dialysis of patients with different kidney injuries is shown in 1 st picture. Indicate the worsening prognosis of chronic kidney phase comparing with that of acute one. 2. Blood tests parameters and comorbidities Creatinine, blood urea nitrogen and GFR, are analyzed for patient s blood tests. The averages of these parameters are shown in Table 2. Table 2 Averages of blood tests parameters for patients having different kidney injuries (N=30 Blood tests parameters Acute kidney Chronic kidney injury (n=19) injury (n=11) p* Creatinine (mg/dl) m ± sd 4,23±2,8 6,13±2,9 0,023 Min 1,36 2,66 Max 12,64 11,34 Blood Urea Nitrogen (mg/dl) m ± sd 24,77±12,7 22,49±12,1 0,491 Min 7,7 9,0 Max 66,6 51,7 Glomerular Filtration Rate (GFR) m ± sd 19,63±11,3 10,27±4,8 0,016 Min 7 5 Max *-Mann-WhitneyUtest Results of averages of blood tests parameters showed that patients with chronic kidney injury have higher level of creatinine and lower level of GFR than patients with AKI. These differences are statistically significant (p<0.05). This result highlights for us the severity of chronic phase and how it will influence with bad prognosis on patients assessment. 17

18 Blood Urea Nitrogen (mg/dl) Table 3 Averages of blood tests parameters of dialyzed and non-dialyzed patients (N=30) Blood tests parameters Dialyzed Non-dialyzed (n=13) (n=17) p* Creatinine (mg/dl) m ± sd 6,79±3,0 3,50±2,0 0,001 Min 2,69 1,36 Max 12,64 7,97 Blood Urea Nitrogen (mg/dl) m ± sd 27,21±16,6 21,43±7,4 0,509 Min 9,1 7,7 Max 66,6 33,6 Glomerular Filtration Rate (GFR) m ± sd 10,31±4,0 20,71±11,6 0,007 Min 5 7 Max The differences of creatinine and GFR levels also are between dialyzed and nondialyzed patients. Dialyzed patients had higher level of creatinine and lower level of GFR than non-dialyzed patients statistically significant (p<0.05) (Table 3). Picture 2 Correlation between Creatinine and BUN rate Creatinine (mg/dl) r = 0.344, P =

19 Glomerulal Filtration Rate The correlation between Cr and BUN rate was not statistically significant (P = 0.06), but increased amount of creatinine is trend to increase amount of blood urea nitrogen, this shows the correlation between the 2 tests, creatinine and BUN values. (Picture 2) Picture 3 Correlation between Creatinine rate and GFR (N=30) Creatinine (mg/dl) r = , P = The decrease of creatinine strongly affects GFR. The correlation between these parameters is strong negative (r = -0.8) and significant (P = 0.001) (picture 3). Since creatinine levels is significant and important for AKI mortality [18], therefore creatinine levels will reflect the levels of glomerular filtration rate and can help in evaluation of AKI patient prognosis and influence a huge role in diagnosing and classifying AKI patients. 19

20 Ascites Dyslipiemia Sepsis Coma Shock Carcinomas Astma non-allergica Liver manifestations Cardiovascular diseases Lung invovlement Kidney manifestations Anemia 3,3 3,3 3,3 3,3 3,3 3,3 6,7 6,7 6,7 13,3 16,7 33, percentage Picture 4 Frequency of comorbidities (N = 30) There was large amount of comorbidities in the patients with kidney injuries. All of comorbidities were divided into groups by affected systems. Carcinomas group included ovarian carcinoma only. Liver manifestations included hepatorenal insufficiency, acute liver failure and cirrhosis cases. Cardiovascular diseases included angina ischemic cardiomyopathy and status post thrombotic cases. Lung involvement included acute pulmonary insufficiency and pneumonia cases. Kidney manifestations group included hepatorenal insufficiency, chronic exacerbations, glomerulonephritis, pyelonephritis and nephrotic syndrome cases. In addition to anemia, coma, shock, sepsis, dyslipidemia, ascites and asthma non-allergic cases. The most frequent comorbidities were infectious diseases (40.0 %), kidney manifestations (16.7 %) and lung involvement (13.3 %). A similar study done and showed also an increase in comorbidities such as infectious diseases and kidney disorders to affect AKI [18]. Therefore to control patients comorbidities which affect patients outcomes and AKI development is critically important and may decrease the mortality rate for patients or at least prolong their life expectations. The frequency of comorbidities is shown in (picture 4). 20

21 percentage 3. Staging of Acute Kidney Disease according to creatinine values , ,7 0 Creatinine < 2,7 mg/dl Creatinine 2,7 mg/dl 5 picture Stages according creatinine values (N = 30) The objective of research was to stage AKI according to creatinine values: Cases were divided into two stages: creatinine < 2.7 mg/dl (36,7%) and 2.7 mg/dl (63,3%) (picture 5). This shows that the higher creatinine value is during admission of patients to ICU associated with other risk factors such as BUN and comorbidities in addition to sepsis during the hospital stay, the worse existence of morbidity for patients will be, and a longer hospital stay. [2]. 4. Assessment of patients with kidney injury: Table 4 Comorbidities in patients with different kidney injury Comorbidities Acute kidney Chronic kidney n / percent injury (n=19) injury (n=11) p* Kidney manifestations 4 / / Lung involvement 3 / / Cardiovascular diseases 2 / Liver manifestations 2 / Carcinomas 1 / Others diseases 7 / / *- z test 21

22 The patients with AKI had kidney and liver manifestations, cardiovascular diseases and lung involvement more frequent than the patients with chronic kidney injury, but the difference was not significant (P > 0.05). Usually a chronic kidney injury known to have severe outcomes than AKI, whereas according to comorbidities, it has been shown that AKI is more prone to develop with increased comorbidities than a chronic phase. (table 4). Table 5 Creatinine stages and comorbidities Comorbidities Creatinine < 2,7 mg/dl Creatinine 2,7 mg/dl n / percent (n=11) (n=19) p* Kidney manifestations 2 / 18,2 3 / Lung involvement - 4 / Cardiovascular diseases 1 / / Liver manifestations 1 / / Carcinomas 1 / Others diseases 5 / / *- z test Creatinine values were higher in patients who had more comorbidities, which coming further to the point we are trying to explain that high creatinine levels are influencing on AKI patients by worse prognosis and mortality [18], but in our patients the difference was not significant (P > 0.05) (table 5). Based on these results, even though comorbidities are an important evidence for developing a disease whereas the conclusion is that comorbidities are not a factor of kidney injury. There is no dependence from comorbidities to acute kidney injury and chronic kidney injury exacerbation. 5. Assessment of risk factors in patients with kidney injury The most frequent risk factor in patients with kidney injury was hypertension % of subjects had this factor (picture 6). Other factors included thyroiditis and psychiatric disorder. Indicating that one of the major risk factors for kidney injury and in our research for AKI is hypertension, influencing the development of AKI disease. 22

23 Other factors 6,7 Diabetes mellitus T II Hypertensive cardiomyopathy Hyperparathyroidism 13,3 13,3 13,3 Obesity 23,3 Hypertension 70, percentage Picture 6 Risk factors in patients with kidney injury Patients with chronic kidney injury had hyperparathyroidism more frequent than patients with AKI, can more or less indicate that hyperparathyroidism has something to do with long duration of kidney injury (CKI) more than suddenly appearing (AKI) and it was significant (P = 0.047). Whereas patients with AKI were trend to have hypertensive cardiomyopathy and diabetes mellitus Type II more than patients with CKI, this truly shows the association between DM II and hypertensive cardiomyopathy with AKI, although the difference was not significant (table 6). Table 6 Risk factors in patients with acute and chronic kidney injury Risk factors Acute kidney Chronic kidney n / percent injury (n=19) injury (n=11) p* Hypertension 13 / / Obesity 4 / / Hyperparathyroidism 1 / / Hypertensive cardiomyopathy 3 / / Diabetes mellitus T II 3 / / Others factors 1 / / *- z test 23

24 Table 7 Risk factors in patients by creatinine stages Risk factors Creatinine < 2,7 mg/dl Creatinine 2,7 mg/dl n / percent (n=11) (n=19) p* Hypertension 8 / / Obesity 5 / / Hyperparathyroidism 2 / / Hypertensive cardiomyopathy - 4 / Diabetes mellitus T II 2 / / Others factors 1 / / *- z test Obese patients had less creatinine level than others significantly (P = 0.03) (table 7). We gather the risk factors of our patients and arrange them in 2 categories, the first is with creatinine levels less than 2,7 mg/dl and the second category having creatinine levels more than or equal to 2,7 mg/dl, and thereby we calculated the patients who should be in which category. As a result obese patients had less creatinine values than others significantly (P = 0.03), allowing us to investigate that a high body mass index is not evaluated for high creatinine levels and don t influence its major risk factor on AKI patients, whereas it has shown the opposite that obese patients have lower levels of creatinine. (table 7). In comparison to other experiments in the field: - A similar study was made at Westeren Parana State University (UNIOESTE), on patients admitted to ICU between (August/2012) and (June/2013) for a total of

25 patients where 100 patients (66%) suffer from AKI, with the mean age of 57.1 (+/- 20 years) almost similar to our mean age patients ( /- 18 years old) showing an elevated creatinine and urea levels upon admission has to do with the risk assessment of patient were the risk factor patients was detected by appearance of comorbidities, sepsis and the indication for mechanical ventilation during their hospital stay. In our study we calculated the comorbidities, sepsis development during patients hospital stay, elevation of creatinine, BUN and GFR (which helped us determine the prognosis of the patient) - Another similar study was done in September 2009, consisted of large amount of patients who was admitted to Veterans Affairs ICUs, a 22% of patients developed AKI, they was classified into 3 stages according their creatinine levels, 1 st stage (0,3mg/dl increase to less than 2 folds) showed 17.5%, 2 nd stage (more than or equal to 2 or less than 3 times increase) showed 2,4%, 3 rd stage (more than ot equal to 3 times increase or dialysis requirement) showed only 2% [18]. Whereas in our study the difference we made is that we arranged the patients into 2 categories or creatinine levels: 1 st category patients (less than 2,7 mg/dl) showed 36,7% and 2 nd category patients (more than or equal to 2,7 mg/dl) showed 63,3%. What makes our study different is the fact that we added the dialysis requirement for patients according their creatinine levels. - A study made at jan/2016 on assessing the impact of dialysis patterns on outcomes in acute kidney injury in Intensive Care Unit, they evaluated a patient n=162, divided them into n=69 during years (2004 till 2007) and the rest n=93 during the years (2008 till 2011), the mean age was / years and 76.6 % were male, they found that the overall mortality was up to 68 % [19]. In our study we tried to find the prognosis of patients who required dialysis and found out that dialyzed patients had higher level of creatinine and lower level of GFR than non-dialyzed patients statistically significant (p<0.05), and patients with chronic kidney injury have an increased need for dialysis than patients with AKI it was as well statistically significant (p<0.05), this in turn worsening the prognosis of dialyzed patients and the chronic kidney injury phase respectively. 25

26 Conclusion: The main concept of this study was to evaluate between AKI (acute kidney injury) patients and CKI (chronic kidney injury) patients who require dialysis more often and in contribution with their risk factors and comorbidities. As well we tried to high light on assessing which patients having those diseases AKI or CKI will suffer from worse blood test results. Finally we come to a conclusion that chronic kidney injury have a worst impact for patient s assessment of their prognosis, and have increased probability for the need of dialysis comparing it with patients suffering from AKI. Wondering further studies to assess how to control kidney injuries and avoid development of a chronic phase. 26

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29 19. Annigeri R, Nandeesh V, Karuniya R. Impact of dialysis practice patterns on outcomes in acute kidney injury in Intensive Care Unit. Indian Journal of Critical Care Medicine. 2016;20(1): Carlson N e. Dialysis-Requiring Acute Kidney Injury in Denmark : Time Trends of Incidence and Prevalence of Risk Factors-A Nationwide Study. - PubMed - NCBI [Internet]. Ncbi.nlm.nih.gov [cited 3 May 2016]. Available from: Carlson N, Hommel K, Olesen J. Dialysis-Requiring Acute Kidney Injury in Denmark : Time Trends of Incidence and Prevalence of Risk Factors A Nationwide Study. PLOS ONE. 2016;11(2):e