Natural history and variability in albuminuria in pediatric and murine sickle cell anemia

It is critical to characterize the natural history of albuminuria in patients with sickle cell anemia (SCA); however, these data are currently lacking and affecting evidence-based guidelines. We performed a natural history study of the development of pediatric albuminuria. We identified participants with hemoglobin SS/SB0 thalassemia ≥5 years with albumin to creatinine ratio (ACR) measurements performed at a steady-state clinic visit. Participants were characterized as either persistent, intermittent, or never albuminuria. We determined the prevalence of persistent albuminuria, use of ACR ≥100 mg/g as a predictor, and variation in ACR measurements. We mirrored this study to determine the variation in albuminuria measurements in the SCA murine model. Among 355 participants with HbSS/SB0 thalassemia with 1728 ACR measurements, we identified 17% with persistent and 13% with intermittent albuminuria. Thirteen percent of participants with persistent albuminuria developed an abnormal ACR before 10 years of age. A single ACR measurement ≥100 mg/g was associated with 55.5 times (95% confidence interval, 12.3-527) higher odds of having persistent albuminuria. Among participants with ACR ≥100 mg/g, we identified significant variability in the results of repeated measurements. The median ACR at the initial and next measurements were 175.8 mg/g (interquartile range [IQR], 135-242) and 117.3 mg/g (IQR, 64-292). The human variability in ACR was mirrored by ∼20% variability in albuminuria in murine model. This evidence suggests adopting standards for repeating ACR measurements, consider screening for ACR before 10 years of age, and using an ACR >100 mg/g as a risk factor for progression. Pediatric and murine renoprotective clinical trials need to consider the high variability in repeated ACR measurements.