Urinary N tau-methylimidazole acetic acid excretion in respiratory disease

Abstract

N tau-methylimidazole acetic acid (N tau-MIAA) is the principal urinary metabolite of histamine. The basal urinary excretion rate of N tau-MIAA was determined as 0.117 +/- 0.008 (SE) mg/h, with a renal clearance for N tau-MIAA of 273 +/- 27 ml/min implying active secretion. After subpharmacological infusion of histamine (50 ng.kg-1.min-1 over 2 h) in five volunteers that increased plasma histamine from 0.28 +/- 0.04 to 0.71 +/- 0.15 ng/ml, urinary excretion of N tau-MIAA over 8 h was increased by less than 17% compared with a control saline infusion. Urinary N tau-MIAA excretion in normal controls (273 +/- 14 micrograms/mmol creatinine) was similar to that observed in patients with severe acute asthma (253 +/- 22 micrograms/mmol), antigen-induced bronchoconstriction (269 +/- 21 micrograms/mmol), seasonal allergic rhinitis (304 +/- 31 micrograms/mmol), and clinically stable bronchiectasis (270 +/- 22 micrograms/mmol). In contrast, large increases in metabolite excretion (greater than 7,000 micrograms/mmol creatinine) were observed in a patient with systemic mastocytosis where very high plasma histamine levels were recorded (greater than 500 ng/ml) and marked systemic hemodynamic effects occurred. We conclude that urinary N tau-MIAA will only be increased in pathologies where sustained hyperhistaminemia occurs and that increased local histamine production in the lung or the upper airway does not cause a measurable change in the basal urinary excretion of this metabolite.

Wastewater-Based Analysis of Antihistamines to Investigate Pollinosis Symptom Burden at Population-Scale

“…Inclusion of additional contextual factors like short-acting β2 adrenergic receptor agonists (such as salbutamol) [39] and endogenous histamine urine metabolites (for instance, 1,4-methylimidazole acetic acid) [40] could provide further insights into the relationship with asthmatic symptoms and histamine-mediated conditions. However, the quantification of histamine metabolites presents notable analytical challenges [41], and their potential as biomarkers is presumably limited to systemic mastocytosis rather than allergen exposure [42].…”

Frontiers in the Development of New Medicines in Relation to Clinical Pharmacology

“…One important limitation of biochemical methods is the problem of detection when the wanted signal is localised and may be swamped by the physiological background. For example, there is good evidence that histamine is released in large amounts locally in the nasal and airway mucosa during allergen challenge of an atopic individual but the background excretion of histamine metabolites is so large that even large local differences in production cannot be measured using histamine metabolites in urine as the index (Taylor et al 1990).…”

Population diet and stress estimates using wastewater based epidemiology

“…Histamine is a vasodilator that mediates allergic and inflammatory reactions in humans (409). Most physiological histamine is stored in mast cells and basophils which, upon activation through immunoglobulin E cross-linkage, release histamine and other cytokines (410). Many of the symptoms associated with allergies (flushing, itch, nasal congestion, headache etc.)…”

“…MIAA is an indicator of histamine turnover and mastocytosis (419)(420)(421) . Its excretion also reflects blood histamine levels to a limited degree (410), and is increased during mastocytosis, urticaria, atopic dermatitis, allergic rhinitis and other conditions involving high histamine turnover (420,(422)(423)(424)(425). A more extensive summary of conditions implicating MIAA is provided in Table S4.1.…”