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• W2980406477 abstract "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 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." @default.
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• W2980406477 date "2020-02-05" @default.
• W2980406477 modified "2023-09-30" @default.
• W2980406477 title "Homogentisic acid is not only eliminated by glomerular filtration and tubular secretion but also produced in the kidney in alkaptonuria" @default.
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• W2980406477 doi "https://doi.org/10.1002/jimd.12181" @default.
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