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Homogentisic acid is not only eliminated by glomerular filtration and tubular secretion but also produced in the kidney in alkaptonuria.
- Source :
-
Journal of inherited metabolic disease [J Inherit Metab Dis] 2020 Jul; Vol. 43 (4), pp. 737-747. Date of Electronic Publication: 2020 Feb 05. - Publication Year :
- 2020
-
Abstract
- The clinical effects of alkaptonuria (AKU) are delayed and ageing influences disease progression. Morbidity of AKU is secondary to high circulating homogentisic acid (HGA) and ochronosis. It is not known whether HGA is produced by or processed in the kidney in AKU. Data from AKU patients from four studies were merged to form a single AKU group. A control group of non-AKU subjects was generated by merging data from two non-AKU studies. Data were used to derive renal clearance and fractional excretion (FE) ratios for creatinine, HGA, phenylalanine (PHE) and tyrosine (TYR) using standard calculations, for comparison between the AKU and the control groups. There were 225 AKU patients in the AKU group and 52 in the non-AKU control group. Circulating HGA increased with age (P < 0.001), and was significantly associated with decreased HGA clearance (CL <subscript>HGA</subscript> ) (P < 0.001) and FE <subscript>HGA</subscript> (P < 0.001). CL <subscript>HGA</subscript> and FE <subscript>HGA</subscript> were increased beyond the theoretical maximum renal plasma flow, confirming renal production and emphasising the greater contribution of net tubular secretion than glomerular filtration to renal elimination of HGA. The kidneys are crucial to elimination of HGA. Elimination of HGA is impaired with age resulting in worsening disease over time. The kidney is an important site for production of HGA. Tubular secretion of HGA contributes more to elimination of HGA in AKU than glomerular filtration.<br /> (© 2019 SSIEM.)
- Subjects :
- Adult
Alkaptonuria physiopathology
Case-Control Studies
Creatinine metabolism
Female
Humans
Linear Models
Male
Middle Aged
Ochronosis physiopathology
Phenylalanine metabolism
Sex Factors
Tyrosine metabolism
Alkaptonuria metabolism
Glomerular Filtration Rate
Homogentisic Acid metabolism
Kidney metabolism
Ochronosis etiology
Subjects
Details
- Language :
- English
- ISSN :
- 1573-2665
- Volume :
- 43
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Journal of inherited metabolic disease
- Publication Type :
- Academic Journal
- Accession number :
- 31609457
- Full Text :
- https://doi.org/10.1002/jimd.12181