الفهرس 
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Abstract
Diabetic ketoacidosis (DKA) is a relatively common acute complication in children with type 1 diabetes mellitus (T1DM). Recent data show that DKA is the leading cause for death in children with T1DM diagnosed less than 15 years of age (Wolfsdorf et al. 2018).
Cerebral edema is the major cause for DKA related morbidity and mortality. However, other complications as hypoglycemia, hypokalemia, cardiac arrhythmia, hyperchloremic acidosis, other central nervous system complications (including cerebral vascular thrombosis, intracranial hemorrhage and cerebral infarction), pulmonary embolism, pulmonary edema, sepsis, acute pancreatitis and acute kidney injury (AKI) may also contribute to DKA related morbidity and mortality (Poovazhagi 2014).
AKI, previously known as acute renal failure, is a common complication in hospitalized children and characterized by sudden worsening of the renal function. The clinical manifestations of AKI range from mild increase in serum creatinine to anuria requiring dialysis. The most common risk factor for pediatric AKI is pre-renal disease or volume-responsive AKI, which is caused by hypovolemia and reduced renal perfusion. If a pre-renal insult is severe or prolonged, the injury can result in acute tubular necrosis (Hursh et al. 2017).
DKA is characterized by severe depletion of water and electrolytes from both the intra- and extracellular fluid (ECF) compartments. Despite their dehydration, patients generally continue to maintain normal blood pressure possibly due to elevated plasma catecholamine concentrations, increased release of antidiuretic hormone (ADH) in response to hyperosmolality and increased osmotic pressure from marked hyperglycemia. Considerable urine output persists because of glucosuria until extreme volume depletion leads to a critical decrease in renal blood flow and glomerular filtration and this might precipitate AKI (Orban et al. 2014).
Moreover, recent guidelines of DKA management recommend conservative fluid administration with the use of slow rehydration with iso-osmotic fluids with continuous intravenous insulin infusion. Although this approach may decrease the incidence of some DKA complications as cerebral edema, it carries the risk of increasing the incidence of AKI.
This study aimed to assess the incidence of AKI and to identify risk factors associated with its development in children admitted with DKA at Sohag University Hospital.
The study included 265 DKA episodes in 240 participants (25 participants presented with 2 DKA episodes during the study period). The median age for the study participants was 10 years with interquartile range (IQR) from 6 months to 12 years. One hundred forty three participants were females (54%). One hundred and fourteen participants (43%) presented with DKA as their first manifestation of diabetes mellitus.
One hundred and ten participants (41.5%) had AKI during hospital admission for DKA episodes. One hundred participants (37.7%) had AKI at hospital admission. At 24 hours after admission, 53 participants (20.0%) had AKI. At 48 hours after admission, 21 participants (7.9%) had AKI. Ten participants (3.8%) had no AKI at hospital admission but developed AKI later during their hospital stay.
There were no significant differences between both group as regards increased polyuria, polydipsia, abdominal pain or vomiting. However, rapid breathing and disturbed conscious level were significantly more frequent among participants with AKI (p <0.001).
At hospital admission, participants with AKI had significantly lower pH and serum bicarbonate levels (p<0.001). They also had significantly higher serum potassium , serum chloride, blood glucose levels and serum creatinine compared to participants without AKI.
At 12 hours, participants with AKI still had significantly lower pH and serum bicarbonate levels as well as significantly higher corrected serum sodium, serum potassium, serum chloride, blood glucose levels and calculated effective serum osmolality in comparison to participants without AKI.
At 24 hours, participants with AKI had significantly lower pH and serum bicarbonate levels as well as significantly higher corrected serum sodium, serum chloride, blood glucose levels, calculated effective serum osmolality and serum creatinine in comparison to participants without AKI.
At 48 hours, participants with AKI had significantly lower pH and serum bicarbonate levels as well as significantly higher corrected serum sodium, serum chloride, calculated effective serum osmolality and serum creatinine in comparison to participants without AKI.
The current study found that participants with AKI had significantly younger age compared to participants without AKI. Moreover, Participants with severe AKI had significantly younger age compared to those with mild AKI. Multivariate regression analyses revealed children younger than age 6 years of age had 2-fold increase in the odds of development of AKI and a 2-fold increase in the odds for development of severe AKI.
The current study did not find a statistically significant difference in the frequency of AKI among participants with new-onset diabetes mellitus and those with established diabetes mellitus. However, the study found that all participants with grade-III AKI were newly diagnosed with diabetes mellitus. Delayed diagnosis of new-onset diabetes mellitus and delayed medical consultation might result in hospital admission with severe degrees of dehydration and acidosis with subsequent development of AKI.
We found that clinical markers of volume depletion at hospital admission were significantly associated with development of AKI. Participants with AKI had significantly higher pulse rate and respiratory rates and significantly lower systolic and diastolic blood pressure at hospital admission. Moreover, severe dehydration at hospital admission was significantly more frequent among participants with AKI. These findings confirmed the results of previous studies that reported more frequent AKI among patients with severe volume depletion.
The strength of this study is that it was a prospective study designed to assess the incidence of AKI and the risk factors for its development among children with DKA. All previous studies were retrospective ones. Moreover, the study included a large sample size. However, the study had some limitations. First it was a single center study. Therefore, the findings might be affected by the current clinical practice used in our hospital. Further multicenter studies are required to confirm these findings. Second, the study depended on serum creatinine as a marker for AKI detection. The measurements of serum creatinine in patients with DKA might be inaccurate and falsely elevated due to the presence of acetoacetate and hyperglycemia which produce higher serum creatinine levels that decrease when blood glucose and acetone return to normal after treatment. Further studies using other biochemical markers are required to assess AKI more accurately. Finally, the study did not assess the long-term effects of AKI on the development and the progression of diabetic nephropathy. Further longitudinal follow-up studies are required.
Conclusion
Acute kidney injury among children with diabetic ketoacidosis is common. Several risk factors were associated with the development of AKI. Hyperchloremia developed during management of DKA was associated with development of AKI. Children younger than 6 years of age and children presented with GCS less than 14 at hospital admission for DKA episodes were also at an increased risk for development of AKI. Development of AKI among children with DKA was associated with increased duration of PICU stay and increased duration of hospitalization.