Novel biomarkers associated with persistent albuminuria and progression of chronic kidney disease in sickle cell anemia

• There are no biomarkers that predict the development of persistent albuminuria in individuals with sickle cell anemia. • Urinary AGT and soluble VCAM-1 may predict the development and progression of CKD in sickle cell anemia. As chronic kidney disease (CKD) is associated with increased 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 multicenter cohort. Of 178 patients with follow-up data, new-onset PA was observed in 16.8% and up to 29% developed CKD progression. In univariate analysis, patients with new-onset PA had higher white blood cell counts (10.1 × 10 9 /L vs 8.4 × 10 9 /L, P = .023) and systolic blood pressure (SBP) (122.5 mm Hg vs 116 mm Hg, P = .022) at diagnosis than patients without PA. Patients with CKD progression had higher SBP (122 mm Hg vs 113 mm Hg, P = .001) and higher urine albumin-creatinine ratio (ACR) (116.8 mg/g vs 17.95 mg/g, P = .006) at baseline. Patients with new-onset PA had higher urinary angiotensinogen (AGT) at diagnosis than those without PA (17.6 ng/mg [interquartile range (IQR), 13.5-32.1] vs 8.99 ng/mg [IQR, 6.7-16.1]; P = .02). Urinary AGT (8.03 ng/mg [IQR, 6.04-14.5] vs 5.5 ng/mg [IQR, 3.5-9.99]; P = .015) and plasma levels of soluble VCAM-1 (1434.5 ng/mL [IQR, 1160.5-1861.6] vs 1011.2 ng/mL [IQR, 833.5-1271.5]; P < .0001) at the baseline visit were higher in patients with CKD progression, but only soluble VCAM-1 remained significantly associated with CKD progression after adjustment for baseline urine ACR and estimated glomerular filtration rate. 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. This trial was registered at www.clinicaltrials.gov as NCT03277547.