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.

中文翻译：

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Homogentisic acid 不仅通过肾小球滤过和肾小管分泌消除，而且在碱酸尿症时在肾脏中产生。

碱酸尿症 (AKU) 的临床效应会延迟，衰老会影响疾病的进展。AKU 的发病率继发于高循环尿黑酸 (HGA) 和黄斑变性。尚不清楚 AKU 中 HGA 是否由肾脏产生或在肾脏中加工。来自四项研究的 AKU 患者的数据合并为一个 AKU 组。通过合并来自两个非 AKU 研究的数据生成非 AKU 受试者的对照组。数据用于使用标准计算得出肌酐、HGA、苯丙氨酸 (PHE) 和酪氨酸 (TYR) 的肾脏清除率和排泄分数 (FE) 比率，用于比较 AKU 和对照组。AKU 组有 225 名 AKU 患者，非 AKU 对照组有 52 名患者。循环 HGA 随年龄增长而增加（P < 0.001)，并且与 HGA 清除率降低 (CL _HGA ) ( P  < 0.001) 和 FE _HGA ( P  < 0.001)显着相关。CL _HGA和 FE _HGA的增加超过了理论最大肾脏血浆流量，证实了肾脏产生并强调了净肾小管分泌比肾小球滤过对 HGA 肾脏消除的更大贡献。肾脏对于消除 HGA 至关重要。随着年龄的增长，HGA 的消除会受到损害，导致疾病随着时间的推移而恶化。肾脏是产生 HGA 的重要场所。HGA 的肾小管分泌比肾小球滤过更有助于消除 AKU 中的 HGA。