acute renal failure ( arf ) is associated with adverse outcomes , especially in children admitted to the pediatric intensive care unit ( picu ) . due to usage of multiple definitions of arf in the literature , causing large variations in the reported incidence and outcome , the term arf was replaced by acute kidney injury ( aki ) recently , to provide the uniformity of definition and standardize the care of patients [ figure 1 ] .
many studies on the incidence of aki in critically ill - children have been conducted in developed countries and are often retrospective in nature . only a few retrospective studies
have been conducted to determine the incidence and profile of aki , in critically ill - children from the developing world in recent years .
this study was performed considering the paucity of data available on the incidence and determinants of aki in indian children and taking into account the retrospective nature of previous studies .
this prospective observational study was conducted over a period of 10 months from june 2010 to march 2011 .
informed consent was obtained from the parents prior to inclusion of subjects into the study . to determine the incidence of aki as defined by the acute kidney injury network ( akin ) classification in critically ill pediatric patients admitted to the picu ; aged 1 month to 13 years . 
 to determine the predictors of fatality in aki in critically ill - childrento study the etiology and short term outcome of aki in critically ill - childrento compare the demographic and clinical parameters among survivors and non - survivors in aki . 
  to determine the predictors of fatality in aki in critically ill - children to study the etiology and short term outcome of aki in critically ill - children to compare the demographic and clinical parameters among survivors and non - survivors in aki .
patients with known chronic kidney disease stage 5 ( estimated glomerular filtration rate < 15 ml / min/1.73 m)bilirubin level > 5 mg / dl . 
 
patients with known chronic kidney disease stage 5 ( estimated glomerular filtration rate < 15 ml / min/1.73 m ) bilirubin level > 5 mg / dl .
the incidence of aki was estimated to be around 30% in picu patients on the basis of current literature .
assuming a variation of 7% in picu , i.e. , absolute precision d = 0.07 , and the chance of this to be at least 95% , the sample size was calculated to be 165 subjects .
results were analyzed using the spss version 16 ( ibm corporation , new york , u.s.a ) .
values for continuous data were expressed as mean  sd ( if normally distributed ) and median ( range ) ( if non - normally distributed ) .
the incidence of aki was defined as its occurrence as a proportion of total admissions .
continuous variables with normal distribution were compared using student t - test while those not normally distributed were analyzed using mann whitney u test .
multivariate binary logistic regression models were used for multivariate analysis of statistically significant variables in univariate analysis ( p < 0.05 ) , to determine predictors of fatality in aki .
several multivariate logistic regression models were constructed by evaluating various combinations of variables based on clinical and statistical significance and then the most effective model was selected .
as per the hospital policy , children hospitalized for any illness in the pediatric wards were transferred to the picu if one or more of the following criteria were present : impaired level of consciousness ( glasgow coma scale < 7 ) , signs suggestive of severe increase in intracranial pressure ( e.g. , hypertension , bradycardia , papilledema ) , hypoventilation or respiratory failure ( oxygen saturation < 90% or arterial oxygen ( pao2 ) < 60 mmhg with supplemental oxygen or arterial co2 ( paco2 )
> 60 mmhg ) , uncontrollable or poorly controlled seizures , hypotension requiring inotropic support , requirement of renal replacement therapy ( rrt ) and fulminant hepatic failure .
the diagnosis of aki was based on akin definition and classification [ figure 1 ] .
either serum creatinine or urine output was used to diagnose and stage aki , using a criterion that led to a higher stage classification .
a total of 2 ml of intravenous blood was withdrawn and centrifuged at 3000 rpm for 10 min .
estimation of serum creatinine was repeated every 24  6 h for 3 consecutive days and daily thereafter until discharge from hospital .
an absolute increase in serum creatinine of 0.3 mg / dl or an increase in serum creatinine of more than or equal to 1.5-fold from the initial serum creatinine was considered as aki .
similarly , a decrease in serum creatinine of more than or equal to 0.3 mg / dl or a decrease in serum creatinine of 1.5-fold from the initial serum creatinine was also considered as aki . if there was a progressive rise in serum creatinine values , re - classification and progression to maximum aki stage during the hospital stay was recorded .
the provisional diagnosis at admission and final diagnosis ( at discharge / death ) were recorded .
the diagnosis of sepsis was made according to the international pediatric sepsis consensus conference definition .
demographic parameters and short term outcomes ( complete renal recovery , partial renal recovery and death ) were recorded .
shock was defined as the presence of at least two of the following : tachycardia ( heart rate > 2 sd for age ) , feeble pulses , cool peripheries and hypotension ( blood pressure < 2sd for age and sex ) or capillary filling time > 3 s. hypertension was defined as > 95 percentile blood pressure for age , height and gender .
complete renal recovery was defined as normal serum creatinine for age ( 0.2 - 0.4 mg / dl for infants , 0.3 - 0.7 mg / dl for 1 - 12 years , 0.5 - 1 mg / dl for > 12 years ) and normal blood pressure at discharge .
partial renal recovery was defined as elevated serum creatinine for age or persistent hypertension at discharge .
to determine the incidence of aki as defined by the acute kidney injury network ( akin ) classification in critically ill pediatric patients admitted to the picu ; aged 1 month to 13 years . 
 to determine the predictors of fatality in aki in critically ill - childrento study the etiology and short term outcome of aki in critically ill - childrento compare the demographic and clinical parameters among survivors and non - survivors in aki . 
  to determine the predictors of fatality in aki in critically ill - children to study the etiology and short term outcome of aki in critically ill - children to compare the demographic and clinical parameters among survivors and non - survivors in aki
to determine the incidence of aki as defined by the acute kidney injury network ( akin ) classification in critically ill pediatric patients admitted to the picu ; aged 1 month to 13 years .

 to determine the predictors of fatality in aki in critically ill - childrento study the etiology and short term outcome of aki in critically ill - childrento compare the demographic and clinical parameters among survivors and non - survivors in aki . 
  to determine the predictors of fatality in aki in critically ill - children to study the etiology and short term outcome of aki in critically ill - children to compare the demographic and clinical parameters among survivors and non - survivors in aki

 patients with known chronic kidney disease stage 5 ( estimated glomerular filtration rate < 15 ml / min/1.73 m)bilirubin level > 5 mg / dl . 
  patients with known chronic kidney disease stage 5 ( estimated glomerular filtration rate < 15 ml / min/1.73 m ) bilirubin level > 5 mg / dl .
the incidence of aki was estimated to be around 30% in picu patients on the basis of current literature . assuming a variation of 7% in picu , i.e. , absolute precision d = 0.07 , and the chance of this to be at least 95% , the sample size was calculated to be 165 subjects .
results were analyzed using the spss version 16 ( ibm corporation , new york , u.s.a ) .
values for continuous data were expressed as mean  sd ( if normally distributed ) and median ( range ) ( if non - normally distributed ) .
the incidence of aki was defined as its occurrence as a proportion of total admissions .
continuous variables with normal distribution were compared using student t - test while those not normally distributed were analyzed using mann whitney u test .
multivariate binary logistic regression models were used for multivariate analysis of statistically significant variables in univariate analysis ( p < 0.05 ) , to determine predictors of fatality in aki .
several multivariate logistic regression models were constructed by evaluating various combinations of variables based on clinical and statistical significance and then the most effective model was selected .
goodness of fit of the model was ascertained by the hosmer lemeshow test . as per the hospital policy , children hospitalized for any illness in the pediatric wards were transferred to the picu if one or more of the following criteria were present : impaired level of consciousness ( glasgow coma scale < 7 ) , signs suggestive of severe increase in intracranial pressure ( e.g. , hypertension , bradycardia , papilledema ) , hypoventilation or respiratory failure ( oxygen saturation < 90% or arterial oxygen ( pao2 ) < 60 mmhg with supplemental oxygen or arterial co2 ( paco2 )
> 60 mmhg ) , uncontrollable or poorly controlled seizures , hypotension requiring inotropic support , requirement of renal replacement therapy ( rrt ) and fulminant hepatic failure .
the diagnosis of aki was based on akin definition and classification [ figure 1 ] .
either serum creatinine or urine output was used to diagnose and stage aki , using a criterion that led to a higher stage classification .
a total of 2 ml of intravenous blood was withdrawn and centrifuged at 3000 rpm for 10 min .
estimation of serum creatinine was repeated every 24  6 h for 3 consecutive days and daily thereafter until discharge from hospital .
an absolute increase in serum creatinine of 0.3 mg / dl or an increase in serum creatinine of more than or equal to 1.5-fold from the initial serum creatinine was considered as aki . similarly ,
a decrease in serum creatinine of more than or equal to 0.3 mg / dl or a decrease in serum creatinine of 1.5-fold from the initial serum creatinine was also considered as aki .
if there was a progressive rise in serum creatinine values , re - classification and progression to maximum aki stage during the hospital stay was recorded .
the provisional diagnosis at admission and final diagnosis ( at discharge / death ) were recorded .
the diagnosis of sepsis was made according to the international pediatric sepsis consensus conference definition .
demographic parameters and short term outcomes ( complete renal recovery , partial renal recovery and death ) were recorded .
shock was defined as the presence of at least two of the following : tachycardia ( heart rate > 2 sd for age ) , feeble pulses , cool peripheries and hypotension ( blood pressure < 2sd for age and sex ) or capillary filling time > 3 s. hypertension was defined as > 95 percentile blood pressure for age , height and gender .
complete renal recovery was defined as normal serum creatinine for age ( 0.2 - 0.4 mg / dl for infants , 0.3 - 0.7 mg / dl for 1 - 12 years , 0.5 - 1 mg / dl for > 12 years ) and normal blood pressure at discharge .
partial renal recovery was defined as elevated serum creatinine for age or persistent hypertension at discharge .
54 children had aki , giving incidence of 25.1% . the median age of patients with aki was 21 months ( range 1 - 144 months ) and 53.7% of patients were boys .
the mean level of maximum creatinine value during the hospital stay was 1.9 ( sd 1.7 ) mg / dl .
aki stage 1 , stage 2 and stage 3 were detected in 19 ( 35.2% ) , 14 ( 25.9% ) and 21 ( 38.9% ) of patients respectively .
demographic parameters of critically ill - children with aki the etiology of aki observed is summarized in table 2 .
tropical febrile illnesses ( dengue , scrub typhus , tuberculosis ( tb ) and malaria ) constituted 9.3% of aki patients .
sepsis ( without localizing signs ) was diagnosed in 9 children , 5 were culture positive .
organisms isolated were pseudomonas aeruginosa ( 2 patients ) , escherichia coli ( 1 patient ) , klebsiella pneumoniae ( 1 patient ) and streptococcus pneumoniae ( 1 patient ) .
other common etiologies were acute post - streptococcal glomerulonephritis ( psgn ) , snake envenomation , hemolytic uremic syndrome ( hus ) and congestive cardiac failure .
etiological profile of aki in critically ill children ( n=54 ) mortality rate in children with aki was 46.3% . in aki stage 1 ,
7 ( 36.8% ) patients died while in stage 2 and stage 3 , 8 ( 57.1% ) and 10 ( 47.6% ) patients died respectively ( differences not significant ) .
mortality was nil in psgn , diarrhea , snake envenomation and tb , but highest in pneumonia ( 66.7% ) .
mortality in babies aged less than 10 months was 65% while it was 35.3% above 10 months ( p = 0.049 ) .
the age , etiological profile and maximum serum creatinine values were not different among the survivors and non - survivors [ table 3 ] .
the length of hospital stay was 10.1  5.8 days among survivors . among the non - survivors , the corresponding value was 6.3  4.3 days .
comparison of survivors and deaths in critically ill - children with aki ( n=54 ) a total of 23 ( 79.3% of survivors ) children with aki had complete renal recovery while 6 ( 20.7% of survivors ) had partial renal recovery at discharge . in aki stage 1 , out of the survivors , 11 ( 91.7% ) had complete renal recovery while 1 ( 8.3% ) had partial renal recovery at discharge . in aki stage 2 ,
4 ( 66.7% ) had complete renal recovery while 2 ( 33.3% ) had partial renal recovery at discharge . in aki stage 3 ,
8 ( 72.7% ) had complete renal recovery , while 3 ( 27.3% ) had partial renal recovery at discharge ( differences not significant ) .
the mortality among children requiring rrt was similar to children not requiring rrt ( 46.7% vs. 46.2% ) .
requirement of rrt was not related to age or the etiology of aki . the complications and co - morbidities observed among the study subjects included severe metabolic acidosis in 32 ( 59.3% ) , hyponatremia in 14 ( 25.9% ) , hypernatremia in 8 ( 14.8% ) , hyperkalemia in 13 ( 24.1% ) , hypertension in 8 ( 14.8% ) , encephalopathy in 19 ( 35.2% ) , thrombocytopenia in 21 ( 38.9% ) , mechanical ventilation in 43 ( 79.6% ) and shock in 47 ( 87% ) children .
there was no correlation between stages of aki and etiological profile , mortality or length of hospital stay .
the predictors of mortality on univariate analysis were : age less than 10 months , shock and requirement of mechanical ventilation [ table 4 ] . in the multivariate model ,
requirement of mechanical ventilation was found to be an independent predictor of fatality ( r = 24.3% ; odds ratio 9.7 ; 95% confidence interval [ ci ] : 1.1 - 85.5 ; p value 0.041 ) . predictors of fatality in aki on univariate analysis
detection of incidence , etiological profile and outcome of aki is important for the institution of appropriate management as well as comparison of epidemiological studies for improved clinical decision making .
the present prospective observational study from a tertiary center in southern india found the incidence of aki to be 25.1% in critically ill - children admitted to the picu .
some recent pediatric studies on aki using risk , injury , failure , loss , end - stage criteria or its modifications have reported the incidence of aki to be widely varying from 10% to 82% , highlighting the heterogeneity of patient populations , diverse regional differences , sample sizes and study designs .
one of these studies was a retrospective analysis of prospectively collected clinical data in 3396 critically ill - children ; 15.7% had some degree of aki at admission and 10% had aki develop during hospital course .
another study from texas in 150 mechanically ventilated children found the incidence of aki to be 82% .
of these children , 11 required dialysis . in another retrospective study from the netherlands , among 103 children requiring mechanical ventilation , 58% developed aki ; 6 patients received rrt . in yet another study from california , in 123 children with
burn injury of 10% or more of body surface area , incidence of aki was 45.5% .
a wide spectrum of etiologies for aki has been found in studies across the world .
while sepsis , glomerulonephritis , hus and acute tubular necrosis predominate in developing countries , these have been replaced by hemato oncologic complications and pulmonary failure as causes of aki in the west .
one study from turkey on 100 children with aki described the most common causes as bone marrow transplantation , renal disease , dehydration , nephrotoxic medication and cardiac surgery . in another study from the same country , on 472 children with aki ( including 32.6% neonates ) , hypoxic ischemic injury and sepsis were leading causes of aki . at kolkata , india , glomerulonephritis and snake bite were the two most important causes of aki in 37 children , making up 70% of all cases .
we found that the common etiologies were infections , psgn , snake envenomation , hemolytic uremic syndrome ( hus ) and congestive cardiac failure .
pneumonia constituted one - fourth of all infections associated with aki and was associated with high mortality .
mortality was not seen in psgn , diarrhea , snake envenomation and tb , but was quite common in pneumonia ( 66.7% ) . increased risk of developing aki has been mentioned with pneumonia , but seems to have been under - reported in children . in a prospective study from scotland , out of 1241
tropical febrile illnesses have been significantly associated with aki , especially in adults . in our study too , tropical febrile illnesses ( dengue , scrub typhus , tb and malaria ) constituted 9.3% of children with aki .
mechanisms for aki in tropical illnesses include direct invasion by the micro - organism leading to acute interstitial nephritis ( in dengue and tb ) , hemodynamic perturbation and renal ischemia ( in malaria ) .
severe diarrhea and psgn form a large proportion of children with aki in india . in our study , acute glomerulonephritis ( predominantly psgn ) accounted for 7.6% of patients .
probably , awareness regarding the usage of oral rehydration solution has led to fewer cases of severe dehydration and thereby aki , being referred to our institute .
three patients developed aki owing to snake envenomation in our study , which is an important problem in some regions of india .
the mortality in aki in children also has been reported to vary widely from 16% to 43.8% . in our study , it was 46.3% , which is comparable to a recent study from kuwait reporting 43.8% mortality .
a retrospective study of 311 children with arf over a 22 year period from thailand reported mortality as 41.5% .
much of the data on the incidence and mortality of aki are limited to the developed world . apart from mortality , 20.7% of children with aki who survived , had partial renal recovery at discharge ( majority being aki stage 3 ) , pointing toward significant morbidity resulting from aki . in the present study , requirement of mechanical ventilation
however , the wide ci of the odds of death indicates that the estimate lacks precision since the study was not powered to look at the predictors of fatality . though age less than 10 months and shock predicted fatality on univariate analysis , they were eliminated on multivariate logistic regression analysis .
mortality in aki is primarily related to etiology ; psgn and gastroenteritis having a much better outcome than sepsis , malignancy or major surgery .
multiple factors have been described as predictors of outcome in aki , again reflecting heterogeneity of patient populations .
sepsis and hus with prolonged anuria have been associated with poor outcome . in rapidly progressive glomerulonephritis
delay in seeking health - care , infections and cardiovascular / respiratory complications result in poor outcome . in critically ill - patients with aki undergoing hemodialysis ,
cardiovascular co - morbidities , metabolic acidosis and acute respiratory distress syndrome led to poor outcome .
age below 2 years , shock , fluid overload , need for mechanical ventilation , multi - organ failure and late referral predicted poor outcomes in a study from kuwait .
children with aki may have long - term residual renal injury e.g. , microalbuminuria , hypertension or elevated creatinine levels .
lack of information on the long - term outcome does not permit evaluation of the impact of mild aki on renal function .
secondly , the study was conducted at a tertiary hospital ; the clinical profile of patients would be affected by a referral bias .
we did not compare children with aki and those without aki as this was not the objective of our study .
thirdly , data regarding non aki patients was not collected and hence increased odds of mortality with aki could not be analyzed .
finally , the study was not powered to examine predictors of mortality in aki as this was not the primary outcome variable ; and larger studies would be required . in summary , we emphasize that the incidence of aki is high in critically sick hospitalized children .
a clearer understanding of the long - term outcomes of this condition would allow optimization of follow - up strategies .
the present prospective observational study from a tertiary center in pondicherry , southern india found the incidence of aki to be 25.1% in critically ill - children admitted to the picu .
the mortality was 46.3% in children with aki admitted to the picu and 20.7% of children with aki who survived ( majority being aki stage 3 ) , had partial renal recovery at discharge .
the etiological profile of aki was dominated by infections , including pneumonia , sepsis , meningoencephalitis and tropical febrile illnesses .
on multivariate logistic regression analysis , requirement of mechanical ventilation was found to be an independent predictor of fatality in children with aki .
 background : although the term acute renal failure was replaced by acute kidney injury ( aki ) recently , there is a paucity of data on the incidence and profile of aki in critically ill children from the developing world.objectives:the objective of this study is to determine the incidence , etiology , short term outcome and predictors of fatality in critically ill children admitted to the pediatric intensive care unit ( picu ) with aki , aged 1 month to 13 years.materials and methods : in this prospective observational study , from june 2010 to march 2011 , 215 children admitted to the picu were screened for aki , defined according to the aki network criteria . 
 the patients with aki were followed - up until discharge / death . 
 their clinical and biochemical data were recorded.results:the incidence of aki among 215 patients screened was 54 ( 25.1% ) . 
 the common etiologies were infections , [ 34 ( 62.9% ) ] , acute glomerulonephritis ( 7.6% ) , snake envenomation ( 5.7% ) , hemolytic uremic syndrome ( 3.8% ) and congestive cardiac failures ( 3.8% ) . among infections , pneumonia and septicemia constituted 26.5% each , meningoencephalitis accounted for 23.5% , and dengue , scrub typhus , tuberculosis and malaria constituted 9.3% of children with aki . 
 27.8% of patients required dialysis . 
 overall mortality was 46.3% . on logistic regression analysis , requirement of mechanical ventilation was an independent predictor of fatality in aki.conclusions:besides the high incidence of aki in critically ill - children admitted to the picu ( 25.1% ) , the condition was associated with adverse outcomes , including high mortality ( 46.3% ) and need for dialysis ( 27.8% ) . 
 infections dominated the etiological profile . 
 requirement of mechanical ventilation predicted an adverse outcome in our patient population . 
Introduction
Materials and Methods
Objectives
Primary objective
Secondary objectives
Inclusion criteria
Exclusion criteria
Results
Discussion
Conclusions