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Diabetic Ketoacidosis Increases Risk of Acute Renal Failure in Pediatric Patients with Type 1 Diabetes

Condition often under-recognized, yet preventable and treatable.

Diabetic ketoacidosis (DKA) is a syndrome presenting in people with diabetes when insulin utilization is markedly diminished, whether via sudden increases in insulin requirements (most often due to acute illness) or sharp decreases in exogenous insulin administration (sudden cessation, for example).  DKA is manifested as severe hyperglycemia, systemic acidosis, and severe dehydration due to rapidly increasing osmotic diuresis.  This condition is especially worrisome in the pediatric diabetic population, as the resulting risk of renal injury often goes unrecognized at presentation.

In 2014, the results of the SEARCH for Diabetes in Youth Study suggested that approximately 30% of pediatric (<18 y.o.) type 1 diabetes patients presented with DKA at initial diagnosis.  Other studies have looked at the treatment of DKA in the pediatric population, and its effects on morbidity and mortality, but until now, none have attempted to correlate DKA and acute renal failure. The current issue of JAMA Pediatric presents a study looking at the incidence of acute kidney injury in pediatric patients hospitalized for DKA and attempts to show a correlation between the two events.  This retrospective review collected data on pediatric T1D patients admitted to the British Columbia Children’s Hospital with DKA between September 2008 and December 2013.  Patients with the above mentioned conditions and complete medical records during that period were included.  The primary objective was to determine the proportion of eligible subjects who developed acute kidney injury (AKI).

During the prescribed time frame, 211 children were hospitalized at BCCH with DKA. Of these, 165 admissions met criteria for the study. Demographically, 53.9% were female, and the median age was 10.6 years (5.1-13.8 y.o.). Approximately 25% required ICU stays, and about 75% were newly diagnosed with T1D during their hospitalization. During admission, 64.2% (n=106) of the patients developed acute kidney injury, with staging as defined by the Kidney Disease/Improving Global Outcomes (KDIGO) serum creatinine criteria.  The occurrence of maximum presentation stage of AKI was 37 (34.9%) stage 1, 48 (45.3%) stage 2, and 21 (19.8%) stage 3.  Of note, it was reported that 105 (99.1%) of the patients developed AKI in the first 24 hours of hospitalization. 54 patients (50.9%) had documented resolution of AKI by 72 hours from admission, and an additional 4 (3.8%) had resolution at 96 hours.

Markers of DKA (dehydration, acidosis, and corrected serum sodium) were analyzed using a multinomial logistic regression model. Unadjusted and adjusted odds ratios were calculated looking at the degree of dehydration and level of fluid resuscitation, acidosis, heart rate, and other laboratory values across the stages of AKI. All variables were significantly different over the range of no AKI to severe AKI, with the exception of age and gender. Of special importance, lower serum bicarbonate, defined as < 10 mEq/L, had a 5-fold increase in the odds of developing severe AKI (adjusted OR 5.2, 95% CI 1.35-20.22), where elevations in heart rate by 5 beats/min showed a 22% increase in the odds of severe AKI (aOR 1.22, 95% CI 1.07-1.39).  Last, the presence of initial corrected sodium at least 145 mEq/L carried a 3-fold increase in developing mild AKI (aOR 3.29, 95% CI 1.25-8.66).

The authors conclude a direct correlation between DKA and AKI exists in the pediatric T1D population. They show an association between severity of acidosis and dehydration, and the risk for severe AKI.  Regarding dehydration, there is concern that aggressive fluid repletion can lead to cerebral edema. However, multiple studies have since discounted this concern, and the benefits of fluid replacement outweigh the small risk of cerebral edema. The retrospective nature of the study contributes to a lack of complete data, and larger prospective studies would likely provide more complete information. Also of note, in the presentation of statistics is the fairly wide distribution within the odds-ratio confidence intervals, weakening the significance of these findings. In spite of these limitations, the importance of sufficient fluid replacement along with correction of acidosis certainly requires attention to decrease risk of developing AKI in this patient group.

Practice Pearls:

  • A large number of children hospitalized with DKA go on to develop acute kidney injury.
  • There is a high degree of association between worsening dehydration and acidosis, and severe AKI.
  • Because of the risk for chronic kidney disease in the pediatric diabetic population, prospective studies to determine risk factors for AKI and its long-term effects in these patients are needed.

References:

Hursh BE, Ronsley R, Islam N, Mammen C, Panagiotopoulos C. Acute Kidney Injury in Children With Type 1 Diabetes Hospitalized for Diabetic Ketoacidosis. JAMA Pediatr. 2017:e170020. Epub 2017/03/13. doi: 10.1001/jamapediatrics.2017.0020. PubMed PMID: 28288246.

Dabelea D, Rewers A, Stafford JM, et al. Trends in the prevalence of ketoacidosis at diabetes diagnosis: the SEARCH for diabetes in youth study. Pediatrics. 2014;133(4):e938-45. Epub 2014/03/31. doi: 10.1542/peds.2013-2795. PubMed PMID: 24685959; PubMed Central PMCID: PMCPMC4074618.
Mark T. Lawrence, RPh,PharmD Candidate, University of Colorado-Denver, School of Pharmacy NTPD