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Indian Pediatr 2018;55:311-314 |
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Predictors and Outcome
of Acute Kidney Injury in Children with Diabetic Ketoacidosis
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Mullai Baalaaji, Muralidharan Jayashree, Karthi
Nallasamy, Sunit Singhi and Arun Bansal
From the Pediatric Emergency and Intensive Care
Units, Department of Pediatrics, Post Graduate Institute of Medical
Education and Research, Chandigarh, India
Correspondence to: Dr Jayashree Muralidharan,
Professor and Chief, Pediatric Emergency and Intensive Care Units,
Department of Pediatrics, Post Graduate Institute of Medical Education
and Research, Chandigarh, India.
Email: [email protected]
Received: March 01, 2017;
Initial review: June 19, 2017;
Accepted: January 23, 2018.
Published online:
February 09, 2018.
PII:S097475591600113
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Objective: To identify predictors and outcome of
acute kidney injury (AKI) in children with diabetic ketoacidosis (DKA)
admitted to a Pediatric Intensive Care Unit (PICU). Methods:
Retrospective case review of 79 children with DKA admitted between
2011-2014. Results: 28 children developed AKI during the hospital
stay; 20 (71.4%) recovered with hydration alone. Serum chloride at 24
hours was independently associated with AKI. Children with AKI had
prolonged acidosis, longer PICU stay, and higher mortality.
Conclusions: Majority of children with AKI and DKA recover with
hydration. Hyperchloremia at 24 hours had independent association with
AKI, although cause-effect relation could not be ascertained.
Keywords: Diabetes, Hyperchloremia, Outcome, Renal failure.
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D iabetic ketoacidosis (DKA) is a life-threatening
complication of diabetes with a reported frequency ranging from 15-70%
across different study populations. Mortality from DKA in developing
countries is still high (3.4%-13%), due to putative reasons like
cerebral edema, sepsis, venous thrombosis and dyselectrolytemias [1-3].
Although renal injury is frequently encountered in hyperglycemic
hyperosmolar state, it is not so well reported in DKA [4]. Furthermore,
renal injury can be masked in children with DKA, due to osmotic diuresis
and spurious elevations in creatinine secondary to ketonemia. We
undertook this study to evaluate the predictors and outcome of AKI in
children with DKA admitted to a Pediatric Intensive Care Unit (PICU).
Methods
Electronic medical records of children with DKA
admitted consecutively to our PICU from 2011-2014 were accessed
retrospectively after seeking ethical clearance. DKA was diagnosed using
standard definitions [5]. Rehydration was based on sum of 6.5% deficit
and maintenance over 36 hours. Additional bolus of 20 mL/kg isotonic
saline was administered in first hour to children with hypoperfusion or
hypotension. Isotonic saline was continued until the blood glucose fell
to Ł13.9 mmol/L
(250 mg/dL) after which fluid was changed to N/2 saline with 5%
Dextrose. Insulin was started after first hour at a rate of 0.05- 0.1
U/kg/hour [6]. AKI was defined by pRIFLE classification using estimated
creatinine clearance (eCCl), as urine output criterion is unreliable in
the setting of osmotic diuresis [7]. The patients were classified into
one of the three pRIFLE categories at three time points viz,
admission, 12 hours and 24 hours. Children with pRIFLE category 0-1 were
labelled as ‘No AKI’ and those with pRIFLE category 2-3 at admission
were labelled as ‘AKI at admission’. Children who progressed from ‘No
AKI’ at admission to pRIFLE 2-3 during hospital stay were labelled as
‘AKI progression’.
Univariate and multivariate analyses was done to
compare demographic and biochemical characteristics between ‘No AKI’ and
‘AKI progression’ groups. P value <0.05 was considered
significant.
Results
Of 79 children enrolled, 56 (71%) were new onset
diabetes presenting as DKA. In children with documented healthcare
contacts prior to referral (n=51), DKA was diagnosed only in 18
(35.3%), of which just 8 (44.4%) received appropriate fluids and insulin
prior to referral. Majority of the children (n=59, 75%) had
presented as severe DKA.
Twenty eight (35%) children were diagnosed with AKI;
13 (46.4%) at admission and rest within 24 hours of hospital stay. The
number (proportion) of children categorized into pRIFLE-0,1,2,3 at
admission and end of 24 hours were 35 (44.3%), 31 (39.2%), 11 (13.9%), 2
(2.5%) and 54 (68.4%), 10 (12.6%), 9 (11.4%) and 6 (7.6%), respectively.
Twenty (71.4%) children recovered with hydration alone while 8 (28.6%)
required renal replacement therapy (RRT).
None of the admission variables could predict AKI.
However on multivariable analysis, elevated chloride levels at 24 hours
had an independent association with AKI progression [Adjusted OR 1.14
(95% CI 1.04-1.27), P=0.007] (Table I and II).
Serum chloride >112 mmol/L at 24 hours had a sensitivity, specificity
and area under ROC curve of 73.3%, 82.4% and 0.835, respectively for
development of AKI (P<0.001).
TABLE I Comparison of ‘No AKI’ and ‘AKI Progression’ – Univariate Analysis
Variable |
No AKI (n=51) Mean (SD) |
AKI progression (n=15) Mean (SD) |
P value |
Age (years) |
7.3 (3.6) |
8.2 (3.6) |
0.37 |
PRISM III Score |
23 (7) |
27 (8) |
0.07 |
At admission |
- Blood glucose (mmol/L) |
25.3 (6.8) |
23.7 (9.2) |
0.44 |
- Blood urea nitrogen (mmol/L) |
2.6 (1.2) |
3 (1) |
0.19 |
- Serum creatinine (µmol/L) |
53 (26.5) |
75 (26.5) |
0.01 |
- Corrected serum sodium (mmol/L) |
139 (6) |
142 (12) |
0.53 |
- Serum Chloride (mmol/L) |
101 (8) |
107 (13) |
0.09 |
- Blood bicarbonate (mmol/L) |
6 (3) |
5 (2) |
0.18 |
- Blood pH |
7.05 (0.12) |
6.99 (0.13) |
0.14 |
- Serum effective osmolality (mmol/kg) |
293.3 (12.4) |
296.3 (23.5) |
0.64 |
At 24 hours |
- Blood glucose (mmol/L) |
11.3 (4.4) |
13.8 (4.4) |
0.01 |
- Blood urea nitrogen (mmol/L)* |
3.5 (2.1) |
8.1 (5.2) |
<0.001 |
- Serum creatinine (µmol/L)# |
41 (18) |
124 (86) |
<0.001 |
- Corrected serum sodium (mmol/L) |
138.7 (5.9) |
145.7 (10.5) |
0.001 |
- Serum chloride (mmol/L) |
106.6 (7.2) |
118.6 (10.3) |
0.001 |
- Blood bicarbonate (mmol/L) |
15.8 (3.4) |
10.9 (4.8) |
<0.001 |
- Blood pH |
7.25 (0.14) |
7.13 (0.13) |
0.003 |
- Serum effective osmolality (mmol/kg) |
285.5 (12.5) |
301 (21.1) |
0.001 |
*24 hours Blood urea nitrogen (mmol/L) expressed as Median
(IQR) among No AKI vs. AKI progression: 2.8 (2,4.8) vs. 6
(5,9.3); P<0.001; #Median (IQR) 24 hours creatinine
(µmol/L) No AKI vs AKI progression: 35 (27,49) vs. 97 (57,124);
P<0.001. |
TABLE II Comparison of ‘No AKI’ and ‘AKI Progression’ – Multivariate analysis
Characteristics |
Adjusted OR (95% CI) |
P value |
PRISM III Score |
1.07 (0.96, 1.2) |
0.20 |
24 hours serum corrected sodium (mmol/L) |
0.70 (0.39, 1.26) |
0.24 |
24 hours serum effective osmolality (mmol/kg) |
1.19 (0.89, 1.57) |
0.23 |
24 hours serum chloride (mmol/L) |
1.20 (1.05, 1.37) |
0.008 |
AKI: acute kidney injury. |
Time to resolution of acidosis was significantly
longer in those with AKI than those without [Median (IQR) 31 (24, 77)
vs 26 (20, 35) hours, P=0.006]. Children with AKI had higher
odds for needing vasoactive drugs and ventilation, and developing
cerebral edema. Those with AKI had prolonged PICU stay [Median (IQR) 3
(2, 5) vs 2 (1, 2) days, P<0.001] and lesser likelihood to
survive to hospital discharge
(Table III).
TABLE III PICU Needs, Complications and Outcome of children with DKA and AKI
Characteristics |
Odds ratio |
P value |
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(95% CI) |
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Vasoactive requirement |
5.1 (1.5-17) |
0.005 |
Mechanical ventilation requirement |
7.6 (1.8-31) |
0.002 |
Cerebral edema |
7.6 (1.8-31) |
0.002 |
Mortality in PICU |
13.6 (1.5-120) |
0.004 |
Survival to hospital |
0.07 (0.01-0.6) |
0.004 |
Discussion
One-third of our patients with DKA had AKI at some
point during their PICU stay, with nearly half of them having AKI at
presentation. Majority of the children were new-onset DKA, who remained
undiagnosed prior to referral and tended to present as severe DKA . This
trend was similar to our previous observations [1,2] and in sharp
contrast to the data from the developed world [8]. Those with missed
diagnosis had more likelihood of complications like cerebral edema (CE)
and AKI, possibly related to uncorrected hypovolemia [2]. The small
proportion in whom AKI did not revert with fluids, needed RRT,
indicating that factors other than hypovolemia could have contributed to
AKI.
Although children with ‘AKI progression’ had higher
PRISM III and admission chloride levels, only the 24 hours serum
chloride was independently associated with ‘AKI progression’.
Independent association of 24 hour serum chloride rather than admission
value leads one to believe that hyperchloremia could have been an
iatrogenic element caused by the type of intravenous fluids received.
Though the current guidelines favour isotonic saline as the initial
fluid in DKA, the recommended duration of infusion is not clear. Since
half normal saline without dextrose was not easily available in our
setup, children continued to receive isotonic saline till blood glucose
fell to 250 mg/dL.
Hyperchloremia, in many clinical settings has been
hypothesised to cause renal hypoperfusion and AKI by virtue of its renal
vascular smooth muscle constrictor effect [9,10]. Hursh, et al.
[1] reported AKI in a high proportion of children with DKA (64.2%) using
Kidney Disease/Improving Global Outcomes criteria, but none in
association with hyperchloremia. Although studies from developing world
have reported about 4-11% incidence of renal injury in children with DKA
[12,13] neither standard definitions were used nor association with
hyperchloremia was reported. The disparity in incidence of AKI between
studies is largely related to use of different definitions. Though we
demonstrated a significant association between hyperchloremia at 24 hrs
and AKI in our study, a causal link cannot be ascertained due to the
retrospective nature of our data. Use of balanced crystalloids with
lower chloride content have been studied in adults with DKA [14,15], but
mostly in relation to hyperchloremia induced normal anion gap acidosis.
There is, thus, a need for for future prospective
studies on risk factors of AKI, cause-effect relationship between AKI
and type of fluid, and role of balanced salt solutions in preventing AKI
in children with DKA.
Contributors: MB: study conceptualization,
data collection, statistical analysis, drafting the manuscript; MJ:
study conceptualization, supervised data collection and statistical
analysis, critical review of the manuscript; KN, SS, AB: data analysis,
critical review of the manuscript, drafted the manuscript. All authors
approved the final version of the manuscript.
Funding: None; Competing Interest:
None stated.
What This Study Adds?
• 24-hour serum chloride was an independent
predictor of acute kidney injury in children with diabetic
ketoacidosis.
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