Abstract
Changes in urinary porphyrin excretion may be the result of hereditary causes and/or from environmental or occupational exposure. The objective of this study was to measure the amount of some porphyrins in spot urine samples obtained from volunteers randomly selected from a healthy adult population of São Paulo with a sensitive HPLC method and to estimate normal ranges for a non-exposed population. Spot urine samples were collected from 126 subjects (both genders, 18 to 65 years old) not occupationally exposed to porphyrinogenic agents. Porphyrin fractions were separated on RP-18 HPLC column eluted with a methanol/ammonium acetate buffer gradient, pH 4.0, and measured fluorometrically (excitation 405 nm/emission 620 nm). The amount of porphyrins was corrected for urinary creatinine excretion. Only 8-carboxyl (uro) and 4-carboxyl (copro) porphyrins were quantified as microg/g creatinine. Data regarding age, gender, occupational activities, smoking and drinking habits were analyzed by Mann-Whitney and Kruskal-Wallis tests. Uroporphyrin results did not differ significantly between the subgroups studied. Copro and uro + copro porphyrins were significantly different for smokers (P = 0.008) and occupational activities (P = 0.004). With respect to alcohol consumption, only men drinking >20 g/week showed significant differences in the levels of copro (P = 0.022) and uro + copro porphyrins (P = 0.012). The 2.5-97.5th percentile limit values, excluding those for subjects with an alcohol drinking habit >20 g/week, were 0-20.8, 11.7-93.1, and 15.9-102.9 microg/g creatinine for uro, copro and uro + copro porphyrins, respectively. These percentile limit values can be proposed as a first attempt to provide urinary porphyrin reference values for our population, serving for an early diagnosis of porphyrinopathies or as biomarkers of exposure to porphyrinogenic agents.
Highlights
Porphyrins are intermediates of the heme biosynthesis pathway, ranging from eight to four carboxyl groups known as uroporphyrin (8-carboxyl), hepta, hexa, penta, and coproporphyrin (4-carboxyl), respectively [1]
Fifteen volunteers were excluded from the study for the following reasons: one for hereditary hemoglobinopathy, which is a known cause of secondary coproporphyrinuria [1]; two for presenting urinary creatinine below 0.3 g/L, considered too diluted for proper analysis [24], and the remaining 12 volunteers for abnormal urinalysis results according to NCCLS standards [23]
The aim of the present investigation was to determine the characteristic profile of urinary porphyrins in spot urine samples from a normal population in order to establish reference values and, to provide tools for an early diagnosis of porphyrinopathies and to allow the use of these values as biomarkers of exposure to porphyrinogenic agents
Summary
Porphyrins are intermediates of the heme biosynthesis pathway, ranging from eight to four carboxyl groups known as uroporphyrin (8-carboxyl), hepta, hexa, penta, and coproporphyrin (4-carboxyl), respectively [1]. The predominant porphyrin in urine of healthy individuals is coproporphyrin (copro), followed by uroporphyrin (uro) at minor concentrations [2]. Porphyrias are inherited or acquired metabolic disorders whose clinical cutaneous, neurologic or visceral manifestations are related to characteristic patterns of overproduction of specific heme precursors. There are eight known enzymes involved in heme biosynthesis and enzymatic defects in any subsequent step lead to an excessive excretion of porphyrins and/or their precursors [3]. In some cases even when latent or in clinical remission, porphyrias induce high levels of heme precursors in blood, urine, and/or stool [1].
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