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 impacting evidence based guidelines. We performed a natural history study of the development of pediatric albuminuria.We identified participants with HbSS/HbSB0 thalassemia ≥ 5 years with albumin/creatinine ratio (ACR) measurements performed at a steady-state clinic visit. Participants were characterized with 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 SS/SB0 thalassemia participants 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 prior to 10 years of age. A single ACR measurement ≥100 mg/g was associated with a 55.5 times (95% CI:12.3-527) higher odds of having persistent albuminuria. Among participants with ACR ≥100 mg/g, we identified significant variability in repeated measures. The median ACR at the initial and next measurements were 175.8 mg/g (IQR:135-242) and 117.3 (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 prior to 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.