Homogentisic acid is not only eliminated by glomerular filtration and tubular secretion but also produced in the kidney in alkaptonuria.

Autor: Ranganath LR; Department of Clinical Biochemistry and Metabolic Medicine, Royal Liverpool University Hospital, Liverpool, UK.; Department of Musculoskeletal Biology, University of Liverpool, Liverpool, UK., Milan AM; Department of Clinical Biochemistry and Metabolic Medicine, Royal Liverpool University Hospital, Liverpool, UK.; Department of Musculoskeletal Biology, University of Liverpool, Liverpool, UK., Hughes AT; Department of Clinical Biochemistry and Metabolic Medicine, Royal Liverpool University Hospital, Liverpool, UK.; Department of Musculoskeletal Biology, University of Liverpool, Liverpool, UK., Khedr M; Department of Clinical Biochemistry and Metabolic Medicine, Royal Liverpool University Hospital, Liverpool, UK., Davison AS; Department of Clinical Biochemistry and Metabolic Medicine, Royal Liverpool University Hospital, Liverpool, UK.; Department of Musculoskeletal Biology, University of Liverpool, Liverpool, UK., Shweihdi E; Department of Clinical Biochemistry and Metabolic Medicine, Royal Liverpool University Hospital, Liverpool, UK., Norman BP; Department of Musculoskeletal Biology, University of Liverpool, Liverpool, UK., Hughes JH; Department of Musculoskeletal Biology, University of Liverpool, Liverpool, UK., Bygott H; Department of Clinical Biochemistry and Metabolic Medicine, Royal Liverpool University Hospital, Liverpool, UK., Luangrath E; Department of Clinical Biochemistry and Metabolic Medicine, Royal Liverpool University Hospital, Liverpool, UK., Fitzgerald R; Clinical Pharmacology, Royal Liverpool University Hospital, Liverpool, UK., Psarelli EE; Liverpool Cancer Trials Unit, University of Liverpool, Liverpool, UK., van Kan C; PSR group B.V, Hoofddorp, Netherlands., Laan D; PSR group B.V, Hoofddorp, Netherlands., Olsson B; Swedish Orphan Biovitrum AB (publ), Stockholm, Sweden., Rudebeck M; Swedish Orphan Biovitrum AB (publ), Stockholm, Sweden., Mankowitz L; Swedish Orphan Biovitrum AB (publ), Stockholm, Sweden., Sireau N; AKU Society, Cambridge, UK., Arnoux JB; Hôpital Necker-Enfants Malades, APHP, Paris Descartes University, Paris, France., Le Quan Sang KH; Hôpital Necker-Enfants Malades, APHP, Paris Descartes University, Paris, France., Jarvis JC; School of Sport and Exercise Science, Liverpool John Moores University, Liverpool, UK., Genovese F; Nordic Bioscience, Herlev, Denmark., Braconi D; Dipartimento di Biotecnologie, Chimica e Farmacia, Università degli Studi di Siena, Siena, Italy., Santucci A; Dipartimento di Biotecnologie, Chimica e Farmacia, Università degli Studi di Siena, Siena, Italy., Zatkova A; Biomedical Research Center, Slovak Academy of Sciences, Bratislava, Slovakia., Glasova H; Biomedical Research Center, Slovak Academy of Sciences, Bratislava, Slovakia., Stančík R; National Institute of Rheumatic Diseases, Piešťany, Slovakia., Imrich R; Biomedical Research Center, Slovak Academy of Sciences, Bratislava, Slovakia., Rhodes NP; Department of Musculoskeletal Biology, University of Liverpool, Liverpool, UK., Gallagher JA; Department of Musculoskeletal Biology, University of Liverpool, Liverpool, UK.
Jazyk: angličtina
Zdroj: Journal of inherited metabolic disease [J Inherit Metab Dis] 2020 Jul; Vol. 43 (4), pp. 737-747. Date of Electronic Publication: 2020 Feb 05.
DOI: 10.1002/jimd.12181
Abstrakt: 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 HGA ) (P < 0.001) and FE HGA (P < 0.001). CL HGA and FE HGA 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.
(© 2019 SSIEM.)
Databáze: MEDLINE
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