title: The Urine Preservative Acetic Acid Degrades Urine Protein: Implications for Urine Biorepositories and the AASK Cohort Study.
abstract: Patients enrolled in the African American Study of Kidney Disease and Hypertension (AASK) Cohort Study who exhibited overt proteinuria have been reported to show high nonalbumin proteinuria (NAP), which is characteristic of a tubulopathy. To determine whether African American Study of Kidney Disease and Hypertension nephropathy (AASK-N) is a tubulopathy, we obtained urine samples of 37 patients with AASK-N, with 24-hour protein-to-creatinine ratios (milligrams per milligram) ranging from 0.2 to 1.0, from the National Institute of Diabetes and Digestive Kidney Diseases repository and tested for seven markers of tubular proteinuria. By protocol, each sample had been collected in acetic acid (0.5%; mean final concentration). Compared with samples from patients with lupus nephritis or healthy black controls, AASK-N samples had lower amounts of six markers. Four markers (albumin,β-2-microglobulin, cystatin C, and osteopontin) were undetectable in most AASK-N samples. Examination by SDS-PAGE followed by protein staining revealed protein profiles indicative of severe protein degradation in 34 of 37 AASK-N urine samples. Treatment of lupus nephritis urine samples with 0.5% acetic acid produced the same protein degradation profile as that of AASK-N urine. We conclude that the increased NAP in AASK-N is an artifact of acetic acid-mediated degradation of albumin. The AASK-N repository urine samples have been compromised by the acetic acid preservative.
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Davis Heart and Lung Research Institute, Ohio State University Medical Center, Columbus, Ohio.
authors.forename: Salem
authors.initials: S
authors.lastname: Almaani
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Davis Heart and Lung Research Institute, Ohio State University Medical Center, Columbus, Ohio.
authors.forename: Lee A
authors.initials: LA
authors.lastname: Hebert
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Davis Heart and Lung Research Institute, Ohio State University Medical Center, Columbus, Ohio.
authors.forename: Brad H
authors.initials: BH
authors.lastname: Rovin
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Davis Heart and Lung Research Institute, Ohio State University Medical Center, Columbus, Ohio dan.birmingham@osumc.edu.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Birmingham
mesh_terms: D019342:Acetic Acid / Q000494:pharmacology*; D001741:Black or African American; D018070:Biological Specimen Banks; D015331:Cohort Studies; D006801:Humans; D011310:Preservatives, Pharmaceutical / Q000494:pharmacology*; D011507:Proteinuria; D059748:Proteolysis / Q000187:drug effects*; D013997:Time Factors; D014556:Urine
chemical_list: D011310:Preservatives, Pharmaceutical; D019342:Acetic Acid
keywords: AASK (African American Study of Kidney Disease and Hypertension); albuminuria; urine preservation