Progression of albuminuria in patients with sickle cell anemia: a multicenter, longitudinal study

• Type of Material: Article
• Authors: Omar Niss, University of Cincinnati; Adam Lane, University of Cincinnati; Monika R. Asnani, University of the West Indies; Marianne Yee, Emory University; Ashok Raj, University of Louisville; Susan Creary, Nationwide Children's Hospital; Courtney Fitzhugh, National Heart, Lung, and Blood Institute; Prasad Bodas, Akron Childrens Hosp; Santosh L. Saraf, University of Illinois; Sharada Sarnaik, Children's Hospital of Michigan; Prasad Devarajan, University of Cincinnati; Punam Malik, University of Cincinnati
• Language: English
• Date: 2020-04-14
• Publisher: American Society of Hematology
• Publication Version: Final Published Version
• Copyright Statement: © 2020 American Society of Hematology. All rights reserved.
• Final Published Version (URL): http://dx.doi.org/10.1182/bloodadvances.2019001378
• Title of Journal or Parent Work: Blood Advances
• Volume: 4
• Issue: 7
• Start Page: 1501
• End Page: 1511
• Grant/Funding Information: This work was supported by National Institutes of Health, National Heart, Lung, and Blood Institute grants R34 HL 108752 and 1UO1 HL117709-01 (P.M.).; O.N. was the recipient of a Translational Research Scholar Award (U01HL117709).
• Keywords: Nephrotic syndrome; Function decline; Chronic kidney disease; Risk factors; Hemoglobin SS; Science & Technology; Hematology; Glomerular filtration rate; United States; Life Sciences & Biomedicine; Pulmonary hypertension; Hydroxyurea treatment; Renal failure
• Research Categories: Health Sciences, Medicine and Surgery; Health Sciences, Human Development; Biology, Cell; Health Sciences, Oncology

Abstract

Sickle cell nephropathy results in chronic kidney disease (CKD), which is associated with significant morbidity and mortality in sickle cell anemia (SCA). Albuminuria is an early manifestation of sickle nephropathy; however, little is known about progression of albuminuria or its correlation with glomerular filtration rate (GFR) decline or CKD. We studied nephropathy progression in 303 SCA participants in a prospective, multicenter, longitudinal study. We collected steady-state urine and serum samples yearly and assessed albumin/creatinine ratio (ACR), estimated GFR (eGFR), and SCA and nephropathy biomarkers. Participants with albuminuria (ACR $30 mg/g) for $2 annual measurements were classified as having persistent albuminuria (PA). At baseline (mean age, 21 years; range, 2-64 years), 32% had albuminuria. In longitudinal multivariate analysis, ACR was associated with sex, anemia, older age, and higher bilirubin and kidney injury molecule-1 levels. Albuminuria increased with age by 3.5 mg/g per year (P , .0001). Of 175 participants with $3 annual samples, 81% with baseline albuminuria $100 mg/g developed PA. Decreased eGFR and adult CKD were associated with PA (P 5 .002 and P 5 .02, respectively), but not with baseline albuminuria. Rate of eGFR decline was steeper among adults (but not children) with albuminuria, compared with those without (P 5 .02). Participants with PA were more likely to have rapid eGFR decline compared with those without (P 5 .03). In this longitudinal study, albuminuria progressed with age, and adults with albuminuria had worse eGFR decline than those without. Albuminuria $100 mg/g predicted PA, which was associated with rapid eGFR decline and CKD development in adults with SCA. This trial was registered at www.clinicaltrials.gov as #NCT02239016.