Renal handling of free sialic acid in normal humans and patients with Salla disease or renal disease.
The renal handling of free sialic acid, a negatively charged sugar, was investigated in normal humans and in patients with impaired sialic acid metabolism or impaired renal function. A sensitive assay for sialic acid, based upon the specific degradation of free sialic acid by N-acetylneuraminic acid aldolase, was developed to measure small amounts of sialic acid in human plasma. Using this assay on plasma from patients with disorders of sialic acid metabolism, we determined that the fractional excretion of sialic acid was maintained at approximately 98% over a wide range of filtered loads, i.e., from 40 to 2617 nmoles/minute. In other patients with different degrees of renal insufficiency, free sialic acid clearance varied directly with creatinine clearance, indicating filtration of this sugar by renal glomeruli. In patients with renal Fanconi syndrome, the urinary excretion of free sialic acid was independent of the severity of the generalized tubular defect, indicating that sialic acid was not reabsorbed by renal tubular cells. These findings indicate that sialic acid is filtered but not reabsorbed by the human kidney, in contrast with the handling of other sugars known to be reabsorbed by renal tubular cells. In addition, three of eight patients with Salla disease, a storage disorder due to impaired lysosomal transport of free sialic acid, were found to have reduced creatinine clearances, but all Salla disease patients had entirely normal renal tubular function.
Seppala
R
R
Section on Human Biochemical Genetics, National Institute of Child Health and Human Development, Bethesda, Maryland.
Renlund
M
M
Bernardini
I
I
Tietze
F
F
Gahl
W A
WA
D002239:Carbohydrate Metabolism, Inborn Errors / Q000378:metabolism*; D002940:Circadian Rhythm; D005198:Fanconi Syndrome / Q000378:metabolism; D006801:Humans; D007668:Kidney / Q000378:metabolism*; D007674:Kidney Diseases / Q000378:metabolism*; D019158:N-Acetylneuraminic Acid; D012794:Sialic Acids / Q000097:blood / Q000378:metabolism* / Q000652:urine
D012794:Sialic Acids; D019158:N-Acetylneuraminic Acid