Management of severe polyuria in idiopathic Fanconi syndrome.

BACKGROUND: Polyuria is a common problem in patients with tubular diseases, especially for those with CKD and high-output Fanconi syndrome. There are currently no guidelines on how to treat debilitating polyuria, in children or adults, and vasopressin is usually not effective. CASE-DIAGNOSIS/TREATMENT: A 13-year-old female with idiopathic Fanconi syndrome and an eGFR of 69 mL/min/1.73 m2 was severely affected by polyuria of 5 L per day (voiding at least 11 times during the day and up to 8 times at night), impacting her mood (measured by the RCADS-child) and academic performance at school. In the absence of guidelines and with literature discouraging the use of indomethacin in this condition, we attempted indomethacin treatment at a dose of 2 mg/kg divided in two doses with substantial success. Urine output dropped to 2.5L and this was accompanied by a substantial decrease of her sodium wasting from 24.6 to 7.7 mmol/kg/day. Over the course of 18 months, the patient's eGFR dropped temporarily to 60 mL/min/1.73 m2 and was 68 mL/min/1.73 m2 at last follow-up. However, a sodium-23 (23Na) MRI of her thigh revealed ongoing moderate sodium decrease in her skin and substantial Na+ decrease in her muscle when compared to age-matched peers with normal kidney function. CONCLUSIONS: Indomethacin may be a safe and effective treatment option for polyuria in idiopathic Fanconi syndrome.

Evaluation of Urine NDRG1 as Noninvasive Biomarker for Bladder Cancer Diagnosis.

BACKGROUND: N-myc downstream regulated gene 1 (NDRG1) was involved in cell differentiation and was recently reported to exert various effects in tumorigenesis. The aim of this study was to assess its diagnostic value in urine as a useful marker for bladder cancer (BC). METHODS: In this study, we recruited 119 BC patients, 65 patients with non-cancerous bladder diseases, and 60 healthy volunteers as control. Their urine concentrations of NDRG1, nuclear matrix protein 22 (NMP22), and creatinine (Cr) were measured and relevant clinical information was retrieved from their medical history records. RESULTS: The expression of NDRG1/Cr and NMP22/Cr in urine were significantly higher in BC patients than those in non-cancerous bladder diseases (p = 0.009 and p = 0.023) and healthy controls (p = 0.005 and p = 0.002). The level of NDRG1/Cr was significantly associated with pathologic T stage (p < 0.001) and pathological grade (p < 0.001). The ROC of NDRG1/Cr to diagnose BC was 0.713 (95% CI, 0.630 - 0.797), with a sensitivity of 63.8% and a specificity of 73.4% at a cutoff of 76.3 ng/mg. NMP22/Cr was 0.705 (95% CI, 0.626 - 0.784), with a sensitivity of 64.2% and a specificity of 66.2% at a cutoff of 12.1 ng/mg. NDRG1/Cr in combination with NMP22/Cr shows a ROC of 0.719 (95% CI, 0.632 0.806) with a sensitivity of 64.9% and specificity of 75.9% Conclusions: Urine NDRG1 may be useful in a minimally invasive modality for determining bladder cancer. Predictive value of the two biomarkers was slightly higher than that of routine NMP22 parameter alone.

Exploration of invasive mechanisms via global ncRNA-associated virus-host crosstalk.

Viral infection is a complex pathogenesis and the underlying molecular mechanisms remain poorly understood. In this study, an integrated multiple resources analysis was performed and showed that the cellular ncRNAs and proteins targeted by viruses were primarily "hubs" and "bottlenecks" in the human ncRNA/protein-protein interaction. The common proteins targeted by both viral ncRNAs and proteins tended to skew toward higher degrees and betweenness compared with other proteins, showed significant enrichment in the cell death process. Specifically, >800 pairs of human cellular ncRNAs and viral ncRNAs that exhibited a high degree of functional homology were identified, representing potential ncRNA-mediated co-regulation patterns of viral invasion. Additionally, clustering analysis further revealed several distinct viral clusters with obvious functional divergence. Overall, this is the first attempt to systematically explore the invasive mechanism via global ncRNA-associated virus-host crosstalk. Our results provide useful information in comprehensively understanding the viral invasive mechanism.

The association of circulating irisin with metabolic risk factors in Chinese adults: a cross-sectional community-based study.

BACKGROUND: Irisin is a myokine that leads to increased energy expenditure by stimulating the browning of white adipose tissue. We aimed to investigate the association of serum irisin levels with metabolic parameters in middle aged Chinese population. METHODS: The study was based on a cross-sectional analysis of data from 524 nondiabetic subjects aged 40~65. All participants were recruited from a screening survey for Metabolic Syndrome in a community in Southwest China, including 294 subjects categorized as overweight (defined as BMI≧25 kg/m2) and 230 subjects as normal control (defined as 18.5≦BMI < 25 kg/m2). Serum irisin concentration was quantified by enzyme linked immunosorbent assay (ELISA). The relationship of irisin with metabolic factors was determined by Pearson correlation. Multivariate linear regression was used to analyze the association of irisin with insulin resistance. Logistic regression was performed to assess the association of irisin with odds of overweight. RESULTS: Serum irisin levels were significantly lower in nondiabetic overweight subjects compared with control (11.46 ± 4.11vs14.78 ± 7.03 µg/mL, p = 0.02). Circulating irisin was positively correlated with quantitative insulin sensitivity check index (QUICKI, r = 0.178, p = 0.045) and triglycerides (r = 0.149, p = 0.022); while irisin was negatively correlated with waist circumference (WC, r = - 0.185, p = 0.037), waist-to-hip ratio (WHR, r = - 0.176, p = 0.047), fasting insulin (r = - 0.2, p = 0.024), serum creatinine (r = - 0.243, p = 0.006), homeostasis model assessment for insulin resistance (HOMA-IR, r = - 0.189, p = 0.033). Multiple linear regression showed that irisin was inversely associated with HOMA-IR (ß = - 0.342 ± 0.154, p = 0.029). Higher irisin was associated with decreased odds of being overweight (OR = 0.281, ß = - 1.271, p = 0.024). CONCLUSIONS: We found that serum irisin levels were lower in overweight subjects. Moreover, serum irisin levels were inversely correlated with adverse metabolic parameters including WC, WHR, creatinine, HOMA-IR and fasting insulin, suggesting that irisin may play a role in obesity related insulin resistance.