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Ranganath, LR, Milan, AM, Hughes, AT, Khedr, M, Davison, AS, Shweihdi, E, Norman, BP, Hughes, JH, Bygott, H, Luangrath, E, Fitzgerald, R, Psarelli, EE, van Kan, C, Laan, D, Olsson, B, Rudebeck, M, Mankowitz, L, Sireau, N, Arnoux, J-B, Le Quan Sang, K-H , Jarvis, JC, Genovese, F, Braconi, D, Santucci, A, Zatkova, A, Glasova, H, Stančík, R, Imrich, R, Rhodes, NP and Gallagher, JA (2019) Homogentisic acid is not only eliminated by glomerular filtration and tubular secretion but also produced in the kidney in alkaptonuria. Journal of Inherited Metabolic Disease. ISSN 0141-8955
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Homogentisic acid is not only eliminated by glomerular filtration and tubular secretion but also produced in the kidney in alkaptonuria..pdf - Accepted Version Download (1MB) | Preview |
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 (CLHGA ) (P < 0.001) and FEHGA (P < 0.001). CLHGA and FEHGA 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.
| Item Type: | Article |
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| Additional Information: | This is the peer reviewed version of the following article: Ranganath, LR, Milan, AM, Hughes, AT, et al. Homogentisic acid is not only eliminated by glomerular filtration and tubular secretion but also produced in the kidney in alkaptonuria. J Inherit Metab Dis. 2020; 1– 11., which has been published in final form at http://dx.doi.org/10.1002/jimd.12181. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions |
| Uncontrolled Keywords: | 1103 Clinical Sciences |
| Subjects: | R Medicine > RC Internal medicine > RC1200 Sports Medicine |
| Divisions: | Sport & Exercise Sciences |
| Publisher: | Wiley |
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| Date Deposited: | 07 Apr 2020 11:12 |
| Last Modified: | 04 Sep 2021 07:30 |
| DOI or ID number: | 10.1002/jimd.12181 |
| URI: | https://researchonline.ljmu.ac.uk/id/eprint/12668 |
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