Investigators Explore Role of Sickle Cell in Risk of Acute Kidney Injuries

Kabir O. Olaniran, MD

For African Americans, both sickle cell trait (SCT) and sickle cell disease (SCD) are independent risk factors for a decline in estimated glomerular filtration rate (eGFR). However, the understanding on how these risk factors impact the risk of acute kidney injuries (AKI), as well as the role of AKI in eGFR decline in patients with sickle cell trait or disease is limited.

A team of researchers, led by Kabir O. Olaniran, MD, Massachusetts General Hospital, described the relative risk for acute kidney injuries in sickle cell trait and disease, as well as the effect of AKI on eGFR decline in the disorders in data presented during the American Society of Nephrology’s Kidney Week 2020.

In the multi-center observational study, the investigators examined adult African American patients with a baseline eGFR of at least 15 ml/min and at least 1 year of follow-up between 2005-2018. The researchers determined the presence of SCT/SCD exposure and normal hemoglobin phenotype reference using hemoglobin electrophoresis.

The investigators sought main outcomes of incident all AKI measured by Kidney Disease: Improving Global Outcome Criteria, incident severe AKI measured by doubling of baseline creatinine, and incident sustained AKI measured by AKI persisting for ≥72 hours]. These measures were adjudicated by chart review and evaluated by Cox regression.

The team used only first AKI events in the study and investigated the effect of all AKI on eGFR decline using mixed linear models.

The models were also adjusted for predictors of AKI.

Overall, there were 8968 identified references, 1279 of which involved sickle cell traits and 254 involved sickle cell disease. There was a median follow-up of 7.6 years and a mean serum creatinine of 0.8 mg/dl. Sickle cell trait was linked to sustained AKI (AHR, 1.42; 95% CI, 1.08-1.88) compared to the reference.

On the other hand, sickle cell disease was associated with all AKI (aHR, 3.13; 95% CI, 2.33-4.21), severe AKI (aHR, 3.04; 95% CI, 1.90-4.87), and sustained AKI (aHR, 2.10; 95% CI, 1.24-3.53) compared to the reference.

“The risk for AKI is increased in both SCT (Sustained) and SCD (all forms) and may contribute to faster eGFR decline in SCT/D,” the authors wrote. “Further studies are needed to understand the mechanisms of AKI in SCT/D. Such studies will inform best practices that will help attenuate the burden of kidney disease in SCT/D.”

Recently, investigators found using a combination of strategies—through clinics, affiliated sites, community events, and/or phone calls—can be useful to ensuring adequate patient participation in sickle cell clinical trials.

Several barriers — ranging from distrust of research to transportation challenges—pose challenges for the recruitment process, and so adopting multiple strategies can allow the strengths of one to compensate for the weakness of another.

The study, “AKI Among African Americans with Sickle Cell Trait and Disease,” was published online by ASN 2020.