Association of Acute Kidney Injury During Diabetic Ketoacidosis With Risk of Microalbuminuria in Children With Type 1 Diabetes

Abstract

IMPORTANCE Diabetic kidney disease is among the most important causes of end-stage kidney disease worldwide. Risk factors for diabetic kidney disease remain incompletely defined. Recent studies document a high frequency of acute kidney injury (AKI) during diabetic ketoacidosis (DKA) in children, raising the question of whether these AKI episodes might contribute to future risk of diabetic kidney disease. OBJECTIVE To determine whether episodes of AKI occurring during DKA in children are associated with increased risk of development of microalbuminuria. DESIGN, SETTING, AND PARTICIPANTS This retrospective review of medical records included children with type 1 diabetes with 1 or more urine albumin levels measured during routine diabetes care from 2 university-affiliated urban tertiary children's hospitals in the United States from January 2006 to December 2019. Age at diagnosis of diabetes, hemoglobin A 1c levels, episodes of DKA, pH and creatinine levels during DKA, and urine albumin and creatinine measurements were analyzed. Cox proportional hazards regression models were used to identify variables affecting the hazard rate for microalbuminuria development. Analyses began January 2021 and ended May 2021.EXPOSURES Episodes of DKA and episodes of AKI occurring during DKA MAIN OUTCOMES AND MEASURES AKI occurrence and AKI stage were determined from serum creatinine measurements during DKA using Kidney Disease: Improving Global Outcomes criteria. Microalbuminuria was defined as urine albumin-to-creatinine ratio of 30 mg/g or more or excretion of 30 mg or more of albumin in 24 hours. RESULTSOf 2345 children, the mean (SD) age at diagnosis was 9.4 (4.4) years. One or more episodes of DKA occurred in 963 children (41%), and AKI occurred during DKA in 560 episodes (47%). In multivariable models adjusting for the associations of age at diagnosis and mean hemoglobin A 1c level since diagnosis, each episode of AKI during DKA was associated with a hazard ratio of 1.56 (95% CI, 1.3-1.87) for development of microalbuminuria. Four or more episodes increased the hazard rate by more than 5-fold. DKA episodes without AKI did not significantly increase the hazard rate for microalbuminuria development after adjusting for other covariates.CONCLUSIONS AND RELEVANCE These data demonstrate that episodes of AKI occurring during DKA in children with type 1 diabetes are significantly associated with risk of developing microalbuminuria. Greater efforts are necessary to reduce the frequency of DKA.

Association of Neighborhood Resources and Race and Ethnicity With Readmissions for Diabetic Ketoacidosis at US Children’s Hospitals

“…We also found that diabetes-related AKI was associated with race and ethnicity but not COI category. Although studies among adults with T1D have demonstrated racial differences in AKI 60 , 61 , 62 and recent work among children has highlighted the frequency of AKI in children with DKA, 19 , 20 , 21 , 22 no studies to our knowledge have explicitly studied the association between race and ethnicity and diabetes-related AKI risk in the pediatric population. Thus, our finding that race and ethnicity constituted a significant factor associated with AKI across all levels of COI is novel, and future research should focus on racial and ethnic disparities in AKI among children with DKA.…”

“…Secondary outcomes included the proportion of encounters with codes for AKI ( ICD-9 : 584.5-584.9 and 586; ICD-10 : N17.0-N17.2, N17.8, N17.9, and N19) or CE ( ICD-9 : 348.5; ICD-10 : G93.6) at the index visit. Acute kidney injury and CE were selected as secondary outcomes given the commonality of AKI 19 , 20 , 21 , 22 and the mortality associated with CE. 17 , 23 , 24 , 25 …”

Diagnostic Performance of Height-Estimated Baseline Creatinine in Diagnosing Acute Kidney Injury in Children with Type 1 Diabetes Mellitus Onset

“…The identification of T1DM patients who have developed an AKI episode is relevant for the planning of an accurate follow-up for renal function, microalbuminuria and blood pressure. For example, patients who developed an AKI at T1DM onset presented an increased risk of developing microalbuminuria during the follow-up [ 26 ].…”

SARS-CoV-2 infection and Diabetes: Pathophysiological Mechanism of Multi-System Organ Failure

“…A retrospective study in 2345 children having both type-1 diabetes and albuminuria demonstrated that the development of acute kidney injury is positively associated with the episodes of DKA [93]. A study that included 658 hospitalized patients with confirmed COVID-19…”