Acute Kidney Injury during Pediatric Vaso-Occlusive Crisis

Several potential risk factors are being evaluated for their impact on the development of chronic kidney disease (CKD) in patients with Sickle Cell Disease (SCD). Recent studies in animals, children and adults without SCD, have established that acute kidney injury (AKI) can lead to CKD, yet the risk of repeated AKI events during vaso-occlusive crisis (VOC) has not been defined in SCD. During VOC events, patients may be at risk for developing AKI due to the use of nephrotoxic pain medications, dehydration (poor concentrating ability), hemolysis, or inflammatory responses. Multiple gaps in our understanding of AKI in SCD patients need to be addressed.

Methods: In order to improve our understanding of the incidence, risk factors, and outcomes associated with AKI, we conducted a two year IRB approved retrospective review of 234 episodes of ICD-10 defined VOC admitted from Children's of Alabama Pediatric Emergency Department (ED). AKI was defined by KDIGO definition of an increase in serum creatinine (SCr) by ≥ 0.3 mg/dl or 50% increase in serum creatinine from baseline. Baseline labs were defined as the most recent outpatient laboratory value and within 12 months from admission. Thirty seven admissions were excluded as their baseline SCr could not be established. Variables analyzed included age, gender, SCD genotype, baseline and admission CBC (hemoglobin (Hb) value, white blood cell count (WBC), absolute neutrophil count (ANC), platelet count, and absolute reticulocyte count (ARC)), length of stay (LOS), and SCD modifying therapy. Generalized mixed effects model for binary outcome with random intercept, to accommodate repeated hospitalizations for the same subject, was fitted to assess the associations between clinical variables and AKI for all patients and severe phenotypes. Similarly, a generalized mixed Poisson effects model with random intercept was fitted to determine if AKI was independently associated with hospital length of stay.

Results: Among 197 admissions for VOC, 33 (17%) were identified with AKI. Seventeen (52%) of the thirty three AKI events were first diagnosed in the ED. Compared to children without AKI, patients with AKI had a larger drop in hemoglobin from baseline at admission (0.5 vs. 1.21g/dL, p=0.005). For every 1 unit drop in Hb from baseline to admission, the odds of AKI increased by 49% (OR= 1.49, 95% CI 1.1-2.0). We identified no differences in AKI vs. no AKI by age, gender, SCD genotype, or SCD modifying therapy, change in WBC, ANC, Platelets or absolute reticulocyte count. In multivariate analysis accounting for age, gender, change in blood counts, SCD genotype or therapy, a drop in Hb remained the only significant variable (OR= 1.48, 95% CI 1.05-2.1). Patients with AKI admitted for vaso-occlusive crisis required significantly longer length of stay. The average LOS for those with AKI was 32% longer than the without AKI (OR 1.32, 95% CI 1.10-1.58).

Conclusion: Seventeen percent of SCD patients with pain admitted to the hospital can present with or develop AKI. An acute drop in hemoglobin is a major risk factor for developing AKI. Patients that develop AKI require longer hospitalizations for their pain crisis, independent of potential confounders. Research should focus on pathophysiology of kidney injury in patients with SCD, the impact of nephrotoxic medications, and the role by which AKI leads to CKD in this population.