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Homogentisic acid is not only eliminated by glomerular filtration and tubular secretion but also produced in the kidney in alkaptonuria
Author(s) -
Ranganath Lakshminarayan R.,
Milan Anna M.,
Hughes Andrew T.,
Khedr Milad,
Davison Andrew S.,
Shweihdi Ella,
Norman Brendan P.,
Hughes Juliette H.,
Bygott Helen,
Luangrath Emily,
Fitzgerald Richard,
Psarelli Eftychia E.,
Kan Christa,
Laan Dinny,
Olsson Birgitta,
Rudebeck Mattias,
Mankowitz Louise,
Sireau Nicolas,
Arnoux JeanBaptiste,
Le Quan Sang KimHanh,
Jarvis Jonathan C.,
Genovese Federica,
Braconi Daniela,
Santucci Annalisa,
Zatkova Andrea,
Glasova Helena,
Stančík Roman,
Imrich Richard,
Rhodes Nicholas P.,
Gallagher James A.
Publication year - 2020
Publication title -
journal of inherited metabolic disease
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.462
H-Index - 102
eISSN - 1573-2665
pISSN - 0141-8955
DOI - 10.1002/jimd.12181
Subject(s) - homogentisic acid , alkaptonuria , renal function , ochronosis , kidney , medicine , endocrinology , chemistry , kidney disease , biochemistry , surgery
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.