Novel Biomarkers Associated with Persistent Albuminuria and Progression of Chronic Kidney Disease in Sickle Cell Anemia Open Access

1. There are no biomarkers that predict the development and progression of chronic kidney disease in individuals with sickle cell anemia.

2. Urinary angiotensinogen and soluble VCAM-1 may predict the development and progression of chronic kidney disease in sickle cell anemia

As chronic kidney disease (CKD) is associated with an increased risk of mortality in sickle cell disease (SCD), biomarkers that predict its development and progression are needed. We evaluated the association of select biomarkers with the development of persistent albuminuria (PA) and CKD progression in adults with SCD in a longitudinal, multicenter cohort. Of 178 subjects with follow-up data, new-onset PA was observed in 16.8% and up to 29% developed CKD progression. In univariate analysis, subjects with new-onset PA had higher WBC counts (10.1x10⁹/L vs. 8.4x10⁹/L, p=0.023) and systolic blood pressure (SBP) (122.5 mmHg vs. 116 mmHg, p=0.022) at diagnosis vs. no PA. Subjects with CKD progression had higher SBP (122 mmHg vs. 113 mmHg, p=0.001) and higher urine albumin-creatinine ratio (ACR) (116.8 mg/g vs. 17.95 mg/g, p=0.006) at baseline. Subjects with new-onset PA had higher urinary angiotensinogen (AGT) at diagnosis vs. those without PA (17.6 ng/mg [IQR: 13.5, 32.1] vs. 8.99 ng/mg [IQR: 6.7, 16.1], p=0.02). Urinary AGT (8.03 ng/mg [IQR: 6.04, 14.5] vs. 5.5 ng/mg [IQR: 3.5, 9.99], p=0.015) and plasma levels of soluble vascular cell adhesion molecule-1 (VCAM-1) (1434.5 ng/mL [IQR: 1160.5, 1861.6] vs. 1011.2 ng/mL [IQR: 833.5, 1271.5], p<0.0001) at the baseline visit were higher in subjects with CKD progression, but only soluble VCAM-1 remained significantly associated with CKD progression following adjustment for baseline urine ACR and estimated GFR. More studies are required to evaluate the predictive capacity of urinary AGT and soluble VCAM-1 for the development of PA and CKD progression in SCD. (Clinicaltrials.gov Identifier: NCT03277547)