Kidney360 Publish Ahead of Print, published on June 24, 2020 as doi:10.34067/KID.0001632020 1 Impaired Tubular Secretion of Organic Solutes in Acute Kidney Injury Frank J. O’Brien1, Robert D. Mair2,3, Natalie S. Plummer2,3, Timothy W. Meyer2,3, *Scott M. Sutherland4, *Tammy L. Sirich2,3 1The Department of Medicine, Washington University, St. Louis, MO 2The Department of Medicine, Stanford University, Palo Alto, CA 3The Department of Medicine, VA Palo Alto Healthcare System, Palo Alto, CA 4The Department of Pediatrics, Lucile Packard Children’s Hospital, Stanford University, Palo Alto, CA *SMS and TLS are Joint Senior Authors Correspondence: Tammy L. Sirich Nephrology 111R Palo Alto VAHCS 3801 Miranda Ave. Palo Alto, CA 94304
[email protected] Copyright 2020 by American Society of Nephrology. 2 Abstract Background. Impairment of kidney function is routinely assessed by measuring the accumulation of creatinine, an organic solute cleared largely by glomerular filtration. We tested whether the clearance of solutes which undergo tubular secretion is reduced in proportion to the clearance of creatinine in humans with acute kidney injury (AKI). Methods. Four endogenously produced organic solutes – phenylacetylglutamine (PAG), hippurate (HIPP), indoxyl sulfate (IS), and p-cresol sulfate (PCS) – were measured in spot urine and plasma samples from 10 AKI patients and 17 control subjects. Fractional clearance relative to creatinine was calculated to assess tubular secretion. Fractional clearance values were calculated in terms of the free, unbound levels of HIPP, IS, and PCS which bind to plasma proteins. Results. Fractional clearance values for PAG, HIPP, IS, and PCS were greater than 1.0 in AKI patients as well as control subjects, indicating that these solutes were still secreted by the tubules of the injured kidneys.