Thesis Abstract

<p> </p><h2>Abstract
</h2><div><div><h3><br></h3><p>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.</p></div><div><h3><br></h3><p>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.</p></div><div><h3><br></h3><p>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.</p></div><div><h3><br></h3><p>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.</p></div><div><h3><br></h3><p>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.</p></div></div><div><strong>Keywords </strong>Acute kidney injury, critically ill-children, pediatric intensive care unit</div> <br><p></p>

Thesis Overview

<p> </p><div><h2>Introduction</h2><p>Acute renal failure (ARF) is associated with adverse outcomes, especially in children admitted to the pediatric intensive care unit (PICU).[<a target="_blank" rel="nofollow" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3796898/#ref1">1</a>] 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,[<a target="_blank" rel="nofollow" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3796898/#ref2">2</a>,<a target="_blank" rel="nofollow" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3796898/#ref3">3</a>] to provide the uniformity of definition and standardize the care of patients [<a target="_blank" rel="nofollow" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3796898/figure/F1/">Figure 1</a>]. Many studies on the incidence of AKI in critically ill-children have been conducted in developed countries and are often retrospective in nature.[<a target="_blank" rel="nofollow" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3796898/#ref4">4</a>,<a target="_blank" rel="nofollow" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3796898/#ref5">5</a>,<a target="_blank" rel="nofollow" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3796898/#ref6">6</a>,<a target="_blank" rel="nofollow" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3796898/#ref7">7</a>] 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.[<a target="_blank" rel="nofollow" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3796898/#ref8">8</a>,<a target="_blank" rel="nofollow" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3796898/#ref9">9</a>,<a target="_blank" rel="nofollow" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3796898/#ref10">10</a>] 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.</p><div><a target="_blank" rel="nofollow" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3796898/figure/F1/"></a><div><a target="_blank" rel="nofollow" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3796898/figure/F1/"></a><a target="_blank" rel="nofollow" href="https://www.ncbi.nlm.nih.gov/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=Click%20on%20image%20to%20zoom&amp;p=PMC3&amp;id=3796898_IJCCM-17-207-g001.jpg"><div></div><img alt="An external file that holds a picture illustration etcObject name is IJCCM-17-207-g001jpg" src="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3796898/bin/IJCCM-17-207-g001.jpg"></a></div><div><div><a target="_blank" rel="nofollow" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3796898/figure/F1/">Figure 1</a></div><div><p>Definition and classification of AKI</p></div></div></div></div><div><div><a target="_blank" rel="nofollow" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3796898/#">Go to:</a></div><h2>Materials and Methods</h2><p>This prospective observational study was conducted over a period of 10 months from June 2010 to March 2011. The study was approved by the institutional ethics committee. Informed consent was obtained from the parents prior to inclusion of subjects into the study.</p><div><h3>Objectives</h3><div><p></p><h4>Primary objective</h4><p>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.</p></div><div><p></p><h4>Secondary objectives</h4><p></p><ul><li><p>To determine the predictors of fatality in AKI in critically ill-children</p></li><li><p>To study the etiology and short term outcome of AKI in critically ill-children</p></li><li><p>To compare the demographic and clinical parameters among survivors and non-survivors in AKI.</p></li></ul><p></p></div></div><div><h3>Inclusion criteria</h3><p>Consecutive patients aged 1 month to 13 years, admitted to the PICU.</p></div><div><h3>Exclusion criteria</h3><p></p><ul><li><p>Patients with known chronic kidney disease stage 5 (estimated glomerular filtration rate &lt; 15 ml/min/1.73 m2)</p></li><li><p>Bilirubin level &gt; 5 mg/dL.</p></li></ul><p></p><p>The incidence of AKI was estimated to be around 30% in PICU patients on the basis of current literature.[<a target="_blank" rel="nofollow" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3796898/#ref7">7</a>,<a target="_blank" rel="nofollow" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3796898/#ref11">11</a>] Assuming a variation of 7% in PICU, i.e., absolute precision <em>d</em>&nbsp;= 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). Categorical variables were reported as proportions. The incidence of AKI was defined as its occurrence as a proportion of total admissions. Continuous variables with normal distribution were compared using Student <em>t</em>-test while those not normally distributed were analyzed using Mann Whitney U test. Categorical data were analyzed using Pearson Chi-square test or Fischer exact test. Multivariate binary logistic regression models were used for multivariate analysis of statistically significant variables in univariate analysis (<em>P</em>&nbsp;&lt; 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.</p><p>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 &lt; 7), signs suggestive of severe increase in intracranial pressure (e.g., hypertension, bradycardia, papilledema), hypoventilation or respiratory failure (oxygen saturation &lt; 90% or arterial oxygen (PaO2) &lt;60 mmHg with supplemental oxygen or arterial CO2 (PaCO2) &gt;60 mmHg), uncontrollable or poorly controlled seizures, hypotension requiring inotropic support, requirement of renal replacement therapy (RRT) and fulminant hepatic failure.</p><p>The diagnosis of AKI was based on AKIN definition and classification [<a target="_blank" rel="nofollow" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3796898/figure/F1/">Figure 1</a>].[<a target="_blank" rel="nofollow" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3796898/#ref3">3</a>] Either serum creatinine or urine output was used to diagnose and stage AKI, using a criterion that led to a higher stage classification. Urine output was measured 6 hourly.</p><p>At admission, all subjects underwent serum creatinine measurement. A total of 2 ml of intravenous blood was withdrawn and centrifuged at 3000 rpm for 10 min. Serum creatinine estimation was performed by modified Jaffe method[<a target="_blank" rel="nofollow" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3796898/#ref12">12</a>] using the autoanalyzer. This measured value was considered as “initial” serum creatinine. 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. Indications for RRT were as per standard hospital protocols.</p><p>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.[<a target="_blank" rel="nofollow" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3796898/#ref13">13</a>] Demographic parameters and short term outcomes (complete renal recovery, partial renal recovery and death) were recorded. Pediatric risk of mortality III score was used for assessment of severity of illness. Shock was defined as the presence of at least two of the following: Tachycardia (heart rate &gt; 2 SD for age), feeble pulses, cool peripheries and hypotension (blood pressure &lt;−2SD for age and sex) or capillary filling time &gt; 3 s. Hypertension was defined as &gt;95th percentile blood pressure for age, height and gender.[<a target="_blank" rel="nofollow" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3796898/#ref14">14</a>] Patients were followed-up until discharge. 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 &gt;12 years) and normal blood pressure at discharge. Partial renal recovery was defined as elevated serum creatinine for age or persistent hypertension at discharge.</p></div></div><div><div><a target="_blank" rel="nofollow" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3796898/#">Go to:</a></div><h2>Results</h2><p>Overall, 215 patients were screened for AKI in the PICU. 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. The demographic parameters of children with AKI are depicted in <a target="_blank" rel="nofollow" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3796898/table/T1/">Table 1</a>.</p><div><h3>Table 1</h3><div><p>Demographic parameters of critically ill-children with AKI</p></div><div><br></div></div><p>The etiology of AKI observed is summarized in <a target="_blank" rel="nofollow" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3796898/table/T2/">Table 2</a>. Pneumonia constituted 26.5% of all infections associated with AKI. 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 <em>Pseudomonas aeruginosa</em>&nbsp;(2 patients), <em>Escherichia coli</em>&nbsp;(1 patient), <em>Klebsiella pneumoniae</em>&nbsp;(1 patient) and <em>Streptococcus pneumoniae</em>&nbsp;(1 patient). Other common etiologies were acute post-streptococcal glomerulonephritis (PSGN), snake envenomation, hemolytic uremic syndrome (HUS) and congestive cardiac failure.</p><div><h3>Table 2</h3><div><p>Etiological profile of AKI in critically ill children (<em>n</em>=54)</p></div><div><img alt="An external file that holds a picture illustration etcObject name is IJCCM-17-207-g003jpg" src="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3796898/bin/IJCCM-17-207-g003.jpg"></div><div><a target="_blank" rel="nofollow" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3796898/table/T2/?report=objectonly">Open in a separate window</a></div></div><p>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 (<em>P</em>&nbsp;= 0.049).</p><p>The age, etiological profile and maximum serum creatinine values were not different among the survivors and non-survivors [<a target="_blank" rel="nofollow" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3796898/table/T3/">Table 3</a>]. 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.</p><div><h3>Table 3</h3><div><p>Comparison of survivors and deaths in critically ill-children with AKI (<em>n</em>=54)</p></div><div><img alt="An external file that holds a picture illustration etcObject name is IJCCM-17-207-g004jpg" src="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3796898/bin/IJCCM-17-207-g004.jpg"></div></div><p>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).</p><p>A total of 15 patients (27.8%) required dialysis. Nine (60%) underwent peritoneal dialysis while 6 (40%) underwent hemodialysis. 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.</p><p>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.</p><p>The predictors of mortality on univariate analysis were: Age less than 10 months, shock and requirement of mechanical ventilation [<a target="_blank" rel="nofollow" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3796898/table/T4/">Table 4</a>]. In the multivariate model, requirement of mechanical ventilation was found to be an independent predictor of fatality (<em>R</em>2 = 24.3%; odds ratio 9.7; 95% confidence interval [CI]: 1.1 - 85.5; <em>P</em>&nbsp;value 0.041).</p><div><h3>Table 4</h3><div><p>Predictors of fatality in AKI on univariate analysis</p></div><div><img alt="An external file that holds a picture illustration etcObject name is IJCCM-17-207-g005jpg" src="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3796898/bin/IJCCM-17-207-g005.jpg"></div><br> </div></div><br><p></p>