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Background: Renal glycogen synthase kinase-3 beta (GSK3β) overactivity has been associated with a diverse range of kidney diseases. GSK3β activity in urinary exfoliated cells was reported to predict the progression of diabetic kidney disease (DKD). We compared the prognostic value of urinary and intrarenal GSK3β levels in DKD and nondiabetic chronic kidney disease (CKD). Methods: We recruited 118 consecutive biopsy-proved DKD patients and 115 nondiabetic CKD patients. Their urinary and intrarenal GSK3β levels were measured. They were then followed for dialysis-free survival and rate of renal function decline. Results: DKD group had higher intrarenal and urinary GSK3β levels than nondiabetic CKD (p < 0.0001 for both), but their urinary GSK3β mRNA levels were similar. Urinary p-GSK3β level is statistically significantly correlated with the baseline estimated glomerular filtration rate (eGFR), but urinary GSK3β level by ELISA, its mRNA level, the p-GSK3β level, or the p-GSK3β/GSK3β ratio had no association with dialysis-free survival or the slope of eGFR decline. In contrast, the intrarenal pY216-GSK3β/total GSK3β ratio significantly correlated with the slope of eGFR decline (r = −0.335, p = 0.006) and remained an independent predictor after adjusting for other clinical factors. Conclusion: Intrarenal and urinary GSK3β levels were increased in DKD. The intrarenal pY216-GSK3β/total GSK3β ratio was associated with the rate of progression of DKD. The pathophysiological roles of GSK3β in kidney diseases deserve further studies. [ABSTRACT FROM AUTHOR]

• 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]

Background Relapsing and recurrent peritonitis episodes are major causes of technique failure in peritoneal dialysis (PD). We examined the efficacy of extended antibiotic therapy for the prevention of relapsing and recurrent peritonitis. Methods From February 2016 to November 2018 we recruited 254 PD patients who fulfilled the diagnostic criteria for PD peritonitis. They were randomized to a standard group, with the duration of intraperitoneal (IP) antibiotic treatment following the International Society for Peritoneal Dialysis (ISPD) guideline according to the causative microorganisms, and an extended group, with 1 extra week of IP antibiotics. The primary endpoint was relapsing, recurrent or repeat peritonitis episodes within 6 months. Results The primary endpoint developed in 36 and 29 patients of the extended and standard groups, respectively (28.3% versus 22.8%; P = 0.34). The rate of complete cure, without relapsing, recurrent or repeat peritonitis within 6 months, was 63.8 and 69.3% for the extended and standard groups, respectively (P = 0.35). Repeat peritonitis episodes were more common in the extended than the standard group (15.0% versus 5.5%; P = 0.013). Conclusions In patients with PD-related peritonitis, extending the antibiotic therapy for 1 extra week beyond the ISPD protocol should not be recommended. Extending the treatment does not reduce the risk of relapsing or recurrent peritonitis episodes but rather is associated with a higher risk of repeat peritonitis episodes. [ABSTRACT FROM AUTHOR]

Abstract: Coal is widely used in PR China. Unfortunately, coal from some areas in Guizhou Province contains elevated levels of arsenic. This has caused arsenicosis in individuals who use arsenic-contaminated coal for the purposes of heating, cooking and drying of food in poorly ventilated dwellings. The population at risk has been estimated to be approximately 200,000 people. Clinical symptoms of arsenicosis may include changes of skin pigmentation, hyperkeratosis of hand and feet, skin cancers, liver damage, persistent cough and chronic bronchitis. We analyzed the porphyrin excretion profile using a HPLC method in urine samples collected from 113 villagers who lived in Xing Ren district, a coal-borne arsenicosis endemic area and from 30 villagers from Xing Yi where arsenicosis is not prevalent. Urinary porphyrins were higher in the arsenic exposed group than those in the control group. The correlation between urinary arsenic and porphyrin concentrations demonstrated the effect of arsenic on heme biosynthesis resulting in increased porphyrin excretion. Both uroporphyrin and coproporphyrin III showed significant increases in the excretion profile of the younger age (&#60;20 years) arsenic-exposed group, suggesting that porphyrins could be used as early warning biomarkers of chronic arsenic exposure in humans. Greater increases of urinary arsenic and porphyrins in women, children and older age groups who spend much of their time indoors suggest that they might be at a higher risk. Whether elevated porphyrins could predict adverse health effects associated with both cancer and non-cancer end-points in chronically arsenic-exposed populations need further investigation. [Copyright &y& Elsevier]

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]

Background: Emerging evidence suggests that long non-coding RNA (lncRNA) plays important roles in the regulation of gene expression. We determine the role of using urinary lncRNA as a non-invasive biomarker for lupus nephritis. Method: We studied three cohorts of lupus nephritis patients (31, 78, and 12 patients, respectively) and controls (6, 7, and 24 subjects, respectively). The urinary sediment levels of specific lncRNA targets were studied using real-time quantitative polymerase chain reactions. Results: The severity of proteinuria inversely correlated with urinary maternally expressed gene 3 (MEG3) (r = −0.423, p = 0.018) and ANRIL levels (r = −0.483, p = 0.008). Urinary MEG3 level also inversely correlated with the SLEDAI score (r = −0.383, p = 0.034). Urinary cancer susceptibility candidate 2 (CASC2) levels were significantly different between histological classes of nephritis (p = 0.026) and patients with pure class V nephritis probably had the highest levels, while urinary metastasis-associated lung carcinoma transcript 1 (MALAT1) level significantly correlated with the histological activity index (r = −0.321, p = 0.004). Urinary taurine-upregulated gene 1 (TUG1) level was significantly lower in pure class V lupus nephritis than primary membranous nephropathy (p = 0.003) and minimal change nephropathy (p = 0.04), and urinary TUG1 level correlated with eGFR in class V lupus nephritis (r = 0.706, p = 0.01). Conclusions: We identified certain urinary lncRNA targets that may help the identification of lupus nephritis and predict the histological class of nephritis. Our findings indicate that urinary lncRNA levels may be developed as biomarkers for lupus nephritis. [ABSTRACT FROM AUTHOR]

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]

Abstract: Arsenicals are proven carcinogens in humans and it imposes significant health impacts on both humans and animals. Recently monomethylarsonous acid (MMAIII), the toxic metabolite of arsenic has been identified in human urine and believed to be more acutely toxic than arsenite and arsenate. Arsenic also affects the activity of a number of haem biosynthesis enzymes. As a part of 2-year arsenic carcinogenicity study, young female C57BL/6J mice were given drinking water containing 0, 100, 250 and 500 μg/L arsenic as MMAIII ad libitum. 24 h urine samples were collected at 0, 1, 2, 4, 8 weeks and every 8 weeks for up to 104 weeks. Urinary arsenic speciation and porphyrins were measured using HPLC-ICP-MS and HPLC with fluorescence detection respectively. DMAV was a major urinary metabolite detected. Significant dose–response relationship was observed between control and treatment groups after 1, 4, 24, 32, 48, 56, 88, 96 and 104 weeks. The level of uroporphyrin in 250 and 500 μg As/L group is significantly different from the control group after 4, 8, 16, 32, 56, 72, 80, 96 and 104 weeks. Coproporphyrin I level in 500 μAs/L group is significantly different from control group after 8, 24, 32, 40, 56, 72, 80, 88 and 104 weeks. After 4 weeks the level of coproporphyrin III concentration significantly increased in all the treatment groups compared to the control except week 16 and 48. Our results show urinary DMAV and porphyrin profile can be used as an early warning biomarker for chronic MMAIII exposure before the onset of cancer. [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]