Review of Trend in Incidence and Characteristics of Hospital-acquired Acute Kidney Injury in Hospital Selayang
Conditions: Acute Kidney Injury, Acute Renal Failure, Kidney Failure, Acute, Hospital Acquired Condition
Sponsor: Selayang Hospital

   
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Study Protocol   
   
Review of Trend in Incidence and   
Characteristics of Hospital-acquired   
Acute Kidney Injury in Hospital 
Selayang   
   
Protocol number, version number and date:    
HA-AKI-1, Version 3, 1 November 2017   
   
Name and Institution of Principal investigator:    
Lee Fei Yee, Clinical Research Centre (CRC), Hospital Selayang   
   
Name and Institution of Co-Investigators:    
Dr Wong Hin Seng, Nephrology Department, Hospital Selayang   
Dr Phui Vui Eng, Nephrology Department, Hospital Selayang   
Dr Khairiyah Idris, Nephrology Department, Hospital Selayang   
Dr Jothiswaran Namasoo, Nephrology Department, Hospital Selayang   
Dr Leong Chin Tho, CRC Hospital Pulau Pinang   
Neo Ming Shin, CRC Hospital Selayang   
 
Name and address of Sponsor:    
Self-Sponsored    
   
Study site/s:   
Hospital Selayang   
   
   
  
  
  
  
  
  
  

   
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Table of Contents   
List of Abbreviations ............................................................................................................3 
Research Synopsis ................................................................................................................4 
1.Background and Significance ............................................................................................5 
2. 
Objective .......................................................................................................................5 
2.1 
General Objective ...................................................................................................5 
2.2 
Specific Objectives: ................................................................................................5 
3. 
Methodology .................................................................................................................6 
3.1 
Study Type and Design ..........................................................................................6 
3.2 
Study Population ....................................................................................................6 
3.3 
Inclusion Criteria ....................................................................................................6 
3.4 
Exclusion Criteria ...................................................................................................7 
3.5 
Withdrawal Criteria ................................................................................................7 
3.6 
Study Outcomes......................................................................................................7 
3.7 
Sample Size ............................................................................................................7 
3.8 
Study Duration and Timeline .................................................................................8 
3.9 
Study Visits and Procedures ...................................................................................8 
3.10 
Statistical Analysis Plan ......................................................................................8 
3.11 
Risk and benefit to study participants .................................................................8 
Benefits to the participants............................................................................................9 
3.12 
Risk Benefit Assessment ....................................................................................9 
3.13 
Ethics of Study ....................................................................................................9 
3.14 
Informed Consent/Assent Process ......................................................................9 
3.15 
Privacy and Confidentiality ................................................................................9 
3.16 
Conflict of Interest ..............................................................................................9 
3.17 
Publication Policy ...............................................................................................9 
3.18 
Termination of Study ........................................................................................10 
References...........................................................................................................................10 
 
  
   
  

   
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List of Abbreviations   
   
AKI   
Acute Kidney Injury   
CA-AKI   
Community-acquired Acute Kidney Injury   
HA-AKI   
Hospital-acquired Acute Kidney Injury   
ICU 
Intensive Care Unit 
SCr   
Serum creatinine   
  
  
 

   
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Research Synopsis   
Study title   
Review of Trend in Incidence and Characteristics of Hospital-
acquired Acute Kidney Injury In Hospital Selayang   
Study Population   
Patients admitted into Hospital Selayang from:   
• 
1st July 2001 to 30th June 2002  
• 
1st July 2006 to 30th June 2007  
• 
1st July 2011 to 30th June 2012   
• 
1st July 2016 to 30th June 2017   
 
Study Design   
Retrospective Cohort Study   
General Objective   
To investigate the incidence, risk factors and outcomes of 
Hospital-acquired Acute Kidney Injury in Hospital Selayang over 
15 years (5-yearly trend)   
Specific Objectives   
• 
To determine the incidence pattern of Hospital-acquired 
Acute Kidney Injury in Hospital Selayang    
• 
To study the determinants associated with development of 
Hospital-acquired Acute Kidney Injury in Hospital 
Selayang   
• 
To describe the survival outcomes of admissions with 
Hospital-acquired Acute Kidney Injury, admissions with 
Community-acquired Acute Kidney Injury and admissions 
without Acute Kidney Injury in Hospital Selayang   
Study   
endpoints/outcomes  
Completion of data collection at the end of the study duration   
Sample Size   
170000 (minimum 11345 required) 
Study Duration   
1 year   
   
  
  
  
  
  
  
  
  
  
  
  
  
  

   
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1.Background and Significance   
   
Acute kidney injury (AKI) is a common problem globally which imposed heavy illness 
burden to the healthcare system, especially in developing countries. (1, 2) AKI can occur 
in the community (termed as Community-acquired AKI (CA-AKI)) or in the hospital 
setting (termed as Hospital-acquired AKI (HA-AKI)). Studies have associated HA-AKI as 
a preventable disorder, and linked HA-AKI with several immediate and long-term 
outcomes adversely, such as length of hospitalization, morbidity, and residual renal 
function. (1, 3, 4) Moreover, delayed recovery to baseline kidney function after AKI 
episode is found to be associated with higher risk of adverse events and mortality. (5) The 
impact of HA-AKI is significantly profound, especially among HA-AKI survivors who lost 
their residual renal function, and remain dialysis dependent. (6)   
   
There was an increasing trend in HA-AKI incidence among hospitalized patients.(6-8) This 
could be attributed to increased exposure to potentially preventable risk factors during 
hospitalization. (6) However, studies pertaining to Asian countries are scarce, especially 
Malaysia. Preventative strategies against HA-AKI could be formulated based on 
understanding of risk factors which could be identified earlier upon hospital admission. (4)    
   
The purpose of this study is to compare the incidence trend of HA-AKI in Selayang 
Hospital for the past 15 years, as well as to determine characteristics predictive of such 
cases. Understanding of clinical variables associated with HA-AKI could facilitate 
strategies and approaches to prevent, recognize HA-AKI early and mitigate the disease 
burden of HA-AKI in future.    
   
2. Objective     
2.1 
General Objective   
To investigate the incidence, characteristics and outcomes of Hospital-acquired Acute  
Kidney Injury in Hospital Selayang over 15 years    
2.2 
Specific Objectives:   
• 
To determine the incidence pattern of Hospital-acquired Acute Kidney Injury in 
Hospital Selayang    
• 
To study the determinants associated with development of Hospital-acquired Acute 
Kidney Injury in Hospital Selayang   

   
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• 
To describe the survival outcome pattern of admissions with Hospital-acquired 
Acute Kidney Injury, admissions with Community-acquired Acute Kidney Injury 
and admissions without Acute Kidney Injury in Hospital Selayang   
   
3. Methodology   
   
3.1 Study Type and Design    
This is a retrospective cohort study involving 5-yearly trend from 2002 to 2017 for analysis. 
Laboratory serum creatinine (SCr) results of all patients admitted during study period will 
be retrieved from the hospital Laboratory Information System. A preliminary screening list 
will be generated by using STATA program from the SCr results. The nephrologist will 
then determine HA-AKI as per inclusion and exclusion criteria. Data collectors will collect 
all relevant data from these patients.   
   
 
   
Figure 1. Flow chart of the study   
3.2 Study Population   
Patients admitted into Hospital Selayang from    
• 
1st July 2001 to 30th June 2002   
• 
1st July 2006 to 30th June 2007  
• 
1st July 2011 to 30th June 2012   
• 
1st July 2016 to 30th June 2017   
3.3 Inclusion Criteria     
   
a) Age of 18 and above at time of hospital admission   
b) HA-AKI is defined by any patient who developed AKI (as per definition below) 
after 48 hours of hospital admission.   
   
c) Definition of AKI(9):    

   
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i. 
An increase in serum creatinine of 0.3 mg/dl (26.5 μmol/l) within 48 
hours  OR   
ii. 
An increase in serum creatinine to more or equal to 1.5 times baseline, 
which is known or presumed to have occurred within the prior 7 days    
   
d) Definition for baseline creatinine(9):   
i. 
The baseline creatinine level is defined as the creatinine level at or 
within 7 days before the hospital admission, OR    
ii. 
at the hospital admission OR    
iii. 
the lowest creatinine (excluding the post dialysis creatinine if dialysis 
is initiated) during the index hospitalisation for those whose baseline creatinine 
were unknown.   
   
3.4 Exclusion Criteria   
o End Stage Renal Failure and on Renal Replacement Therapy (HD, PD or Renal  
Transplant)     
3.5 Withdrawal Criteria     
Not applicable    
3.6 Study Outcomes   
   
1. Incidence of Hospital-acquired AKI at our centre during study period 
2. Renal recovery at 90 days after AKI diagnosis   
Definition for renal recovery:    
a. Full recovery: Return of serum creatinine to or below baseline or within 20% of 
baseline creatinine    
b. Partial recovery: Serum creatinine remaining 20% above the baseline, but below 
50% of the baseline and not dialysis dependent or if previously requiring dialysis 
and now is dialysis Independent.    
c. Failure to recover: Serum creatinine remains 50% above the baseline or dialysis 
dependent.    
   
3. In-hospital mortality (from date of AKI diagnosis until date of death in hospital)   
3.7 Sample Size     
The primary outcome of interest is development of HA-AKI during admission at our centre. 
The incidence of Hospital-acquired AKI at our centre at March 2017 was 1.19% based on 
one ongoing study (A prospective, multicenter, observational study to determine the 
incidence and outcome of Acute Kidney Injury among hospitalised patients in Malaysia). 
The nine variables to be investigated for predictors of HA-AKI are age, gender, ICU 

   
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admission, race, nephrotoxin use, diabetes mellitus, hypertension, congestive heart failure 
and chronic obstructive pulmonary disease. With an estimation of 15 events per predictor, 
a minimum of 135 events would be needed, translating to a minimal of 11345 patients at 
our centre required for the study. The study population fits the minimum sample size 
requirement as 170283 adult admissions were recorded in total (22788 for Year 2002, 41731 
for Year 2007, 46330 for Year 2012 and 59434 for Year 2017).  
3.8 Study Duration and Timeline    
Proposed study will be conducted from 1 November 2017- 1 November 2018 in the stages 
shown below:   
• 
Stage 1, review of medical records – 5 months   
• 
Stage 2, data collection and data analysis –5 months   
• 
Stage 3, presentation and publication – 2 months   
   
3.9 Study Visits and Procedures   
No study visits and follow up is required as this is a retrospective study through utilisation 
of existing patient records for data collection.   
  
3.10 Statistical Analysis Plan   
The analyses will be performed using IBM SPSS Statistics for Windows (Version 23.0. 
Armonk, NY: IBM Corp.). Descriptive statistics will be utilized for selected variables. The 
results will be presented as frequencies and percentage for Categorical Data. Numerical 
Data which is normally distributed will be presented as mean and standard deviation while 
median and interquartile range will be presented for Numerical Data which is not normally 
distributed.    
   
Comparing Numerical Data which is normally distributed between two groups will be 
analysed using the Independent t-test while Mann-Whitney test will be used if not normally 
distributed. Multiple logistic regression will be used to study association between risk 
factors (Numerical Data/Categorical Data) and outcome (Categorical Data). The survival 
analyses and survival curves from the date of diagnosis until death will be performed using 
the Kaplan-Meier method, to estimate the index hospitalisation survival rate. All 
probability values will be two-sided and a level of significance of less than 0.05 (p-value 
< 0.05) will be considered as statistically significant.   
   
3.11 Risk and benefit to study participants    
As this is a retrospective data collection of the participants, no intervention, procedure or 
treatment will be imposed to the participants during the whole course of the study. Thus, 
there is minimal risk to the participants.   
   

   
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Benefits to the participants   
This study does not present any direct benefit to the participants. However, understanding 
of HA-AKI patterns at our centre will help in formulating preventative strategies related 
with HA-AKI.   
   
3.12 Risk Benefit Assessment   
As stated above, there is no risk from this study. Study findings shall potentially greatly 
improve treatment outcomes. The expected benefit outweighs the minimal risk to subjects 
and thus this study should be supported.    
   
3.13 Ethics of Study   
Study will be conducted in compliance with ethical principles outlined in the Declaration 
of Helsinki and Malaysian Good Clinical Practice Guideline.   
   
3.14 Informed Consent/Assent Process   
Not applicable. Consent waiver is permitted from Medical Research Ethics Committee, 
Ministry of Health Malaysia for this retrospective study and there are no additional study 
procedures/visits pertaining to this study. Participants’ data will be de-identified as there is 
no collection of personal, identifiable data.    
3.15 Privacy and Confidentiality 
Subject’s names will be kept on a password-protected database and will be linked only with 
a study identification number for this research. The identification number instead of patient 
identifiers will be used on subject data sheets. All data will be entered into a computer that 
is password protected. On completion of study, data in the computer will be copied to CDs 
and the data in the computer erased. CDs and any hardcopy data will be stored in a locked 
office of the investigators and maintained for a minimum of three years after the completion 
of the study. The CDs and data will be destroyed after that period of storage. Subjects will 
not be allowed to view their personal study data, as the data will be consolidated into a 
database.    
 
3.16 Conflict of Interest   
The investigators declare they have no conflict of interest.  
 
3.17 Publication Policy   
No personal information will be disclosed and subjects will not be identified when the 
findings of the survey are published.   
   

   
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3.18 Termination of Study   
The study is anticipated to be terminated at November 1, 2018. The investigators may decide 
to terminate the study at an earlier date, with written notification given to Medical Research 
Ethics Committee.    
     
   
References   
   
1. 
Khwaja A. KDIGO clinical practice guidelines for acute kidney injury. Nephron 
Clin Pract. 2012;120(4):c179-84.   
2. 
Kumar S, Raina S, Vikrant S, Patial RK. Spectrum of acute kidney injury in the 
Himalayan region. Indian J Nephrol. 2012;22(5):363-6.   
3. 
Jannot AS, Burgun A, Thervet E, Pallet N. The Diagnosis-Wide Landscape of 
Hospital-Acquired AKI. Clin J Am Soc Nephrol. 2017;12(6):874-84.   
4. 
Cely JE, Mendoza EJ, Olivares CR, Sepulveda OJ, Acosta JS, Baron RA, et al. 
Incidence and Risk Factors for Early Acute Kidney Injury in Nonsurgical Patients: A 
Cohort Study. Int J Nephrol. 2017;2017:5241482.   
5. 
Swaminathan M, Hudson CC, Phillips-Bute BG, Patel UD, Mathew JP, Newman 
MF, et al. Impact of early renal recovery on survival after cardiac surgery-associated acute 
kidney injury. Ann Thorac Surg. 2010;89(4):1098-104.   
6. 
Rewa O, Bagshaw SM. Acute kidney injury-epidemiology, outcomes and 
economics. Nat Rev Nephrol. 2014;10(4):193-207.   
7. 
Nash K, Hafeez A, Hou S. Hospital-acquired renal insufficiency. Am J Kidney Dis. 
2002;39(5):930-6.   
8. 
Hou SH, Bushinsky DA, Wish JB, Cohen JJ, Harrington JT. Hospital-acquired renal 
insufficiency: a prospective study. Am J Med. 1983;74(2):243-8.   
9. 
Kellum JA, Lameire N, Group KAGW. Diagnosis, evaluation, and management of 
acute kidney injury: a KDIGO summary (Part 1). Crit Care. 2013;17(1):204.   
10. 
Ali T, Khan I, Simpson W, Prescott G, Townend J, Smith W, et al. Incidence and 
outcomes in acute kidney injury: a comprehensive population-based study. J Am Soc 
Nephrol. 2007;18(4):1292-8.   
11. 
Lemeshow S, World Health Organization. Adequacy of sample size in health 
studies. Chichester England ; New York, NY, USA: Published on behalf of the World 
Health Organization by Wiley ;Distributed in the U.S.A., Canada, and Japan by Liss; 1990. 
xii, 239 p. p.