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• Previous studies showed that urinary levels of some miRNA targets are significantly altered in IgA nephropathy. • The persent study used healthy subjects and patients with biopsy-proved hypertensive nephrosclerosis as controls, so as to eliminate the confounding effect of kidney scarring. • The result showed that urinary miR-106a has good sensitivity but limited specificity in detecting IgA nephropathy. • Our result indicates that urinary miRNA level may be used for screening of IgA nephropathy. Urinary micro-RNA (miRNA) level may serve as non-invasive disease markers for immunoglobulin A nephropathy (IgAN), but urinary miRNA targets identified in previous studies may represent kidney scarring rather than being specific for IgAN. We aim to identify urinary miRNA targets for the diagnosis of IgAN by including hypertensive nephrosclerosis (HTN) as a control group. Methods In the development cohort, we performed complete miRNA profiling of urinary sediment in 33 patients with IgAN, 9 with HTN, and 9 healthy controls (CTL). Potential miRNA targets were quantified by a separate validation cohort of 72 IgAN, 34 HTN, and 20 healthy controls. Results In the development cohort, we identified 6 miRNA targets with urinary levels significantly increased in IgAN as compared to both HTN and CTL. In the validation study, all 6 miRNA targets remained increased than the other groups, although the result of miR-345 did not reach statistical significance. The area-under-curve of the receiver operating characteristic (ROC) curve for urinary mi-106a level for the diagnosis of IgAN was 0.742 (p < 0.0001), and the diagnostic performance was not further improved by having additional miRNA targets. At the cut-off ≥ 800 copy per 1000 copies of housekeeping gene, urinary miR-106a has 100% sensitivity and 14.8% specificity in detecting IgA nephropathy. Conclusions We identified 6 miRNA targets whose urinary levels are significantly elevated in IgAN, and urinary miR-106a level has an excellent sensitivity for the identification of IgAN. Further validation studies are needed to confirm its role in disease screening. [ABSTRACT FROM AUTHOR]

An improved HPLC method has been established for the measurement of harderoporphyrin (HP) in the harderian gland of rats and mice. Groups of female Wistar rats were given a single oral dose of sodium arsenite at 0, 0.5 or 5.0 mg As(III)/kg body weight, or a slurry of arsenic-contaminated soil at equivalent dose rates and the animals were sacrificed 96 h after dosing. A group of C57BL/6J female mice were chronically exposed to drinking water containing 500 μg As(V)/l of sodium arsenate ad libitum for over 2 years. Porphyrins were measured in the harderian glands of rats and mice. Our results suggest that HP and the alteration of the porphyrin profile in the harderian glands of rodents is a highly sensitive biomarker for both single sub-lethal and chronic arsenic exposure. [Copyright &y& Elsevier]

Highlights: [•] We examined arsenic and two biomarkers in subjects post the water intervention. [•] Urinary arsenic levels were significantly higher in villagers from the endemic area. [•] Urinary porphyrins and malondialdehyde were elevated when arsenic was high. [•] Skin lesions were observed in 51 out of 178 surveyed people in the As-endemic area. [•] Four out of nine young villagers born after the intervention exhibited As-related skin lesions. [Copyright &y& Elsevier]

Arsenic interferes with the function of enzymes responsible for haem biosynthesis leading to alteration in the porphyrin profile. In this study, young female C57Bl/6J mice were given drinking water containing 0, 100, 250 and 500 μg AsV/L as sodium arsenate ad libitum for 24 months. 24 h pooled urine samples were collected bimonthly for urinary arsenic methylation and porphyrin analyses by HPLC-ICP-MS and HPLC respectively. The levels of total arsenic were significantly dose related except for the 2nd month interval. No significant differences in the urinary arsenic methylation pattern between control and test groups were observed. Coproporphyrin I (Copro I) showed a significant dose–response relationship after 12, 14 and 20 months of exposure. Significant differences in the levels of coproporphyrin III (Copro III) were observed in the 8th month in 250 and 500 μg/L treatment groups and the dose–response pattern was maintained after 10 and 12 months. Our results suggest that urinary arsenic is a useful biomarker for internal dose, and that urinary coproporphyrin can be used as an early warning biomarker of effects before the onset of cancer. [Copyright &y& Elsevier]

Arsenic has been classified as a human carcinogen based on epidemiological data however the mechanism of its carcinogenicity is still unclear. Urinary biomarkers for chronic arsenic exposure would be valuable as an early warning indicator for timely interventions. In this study, young female C57Bl/6J mice were given drinking water containing 0, 100, 250 and 500μg Asv/L as sodium arsenate ad libitum for 12 months. Urine was collected bimonthly for urinary arsenic methylation assay and porphyrin analysis. All detectable arsenic species showed strong linear correlation with administered dosage and the arsenic methylation patterns were similar in all three treatment groups. No significant changes of methylation patterns were observed over time for either the control or test groups. Urinary coproporphyrin III was significantly increased in the 8th month in 250 and 500μg/L groups and remained significantly dose-related after 10 and 12 months. Coproporphyrin I also showed a significant dose-response relationship after 12 months. Our results confirm that urinary arsenic is a useful biomarker for internal dose. The alteration of porphyrin profile suggests that arsenic can affect the heme metabolism and this may occur prior to the onset of arsenic induced carcinogenesis. [Copyright &y& Elsevier]