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Background: Although cancer management in dialysis patients has become a commonly encountered issue, known as “onco-nephrology”, few evidence-based clinical recommendations have been proposed. Here, we examined the variation in referral behaviors adopted by dialysis physicians on encountering dialysis patients with signs/symptoms suggestive of cancer. Methods: We conducted a vignette-based study in August 2015. We sent a 14-page questionnaire to 191 dialysis physicians, including the representative dialysis facilities participating in a Japanese dialysis cohort (the Japan Dialysis Outcomes and Practice Patterns Study). Using vignette scenarios for respiratory, digestive, and urological areas, we assessed the referral behaviors (expert referral or not) adopted by dialysis physicians on encountering dialysis patients with symptoms suggestive of cancer. Each scenario contained three patient functional factors: age (60 or 75 years), performance status (PS 0 or 1), and cognitive dysfunction (absence or presence). We examined the association between physician factors, patient factors, and referral behaviors. Results: We obtained 94 replies (response rate: 49.2%). For the respiratory scenarios, 38.3% and 51.9% of physicians reported watchful waiting when encountering bilateral and unilateral pleural effusion, respectively. In digestive and urologic scenarios, most physicians (>85%) selected expert referral. We detected differences in referral behaviors between scenarios with different cancer biological factors. However, we found consistency in referral behaviors within the same scenario, even with different patient functional factors (intra-class correlation coefficients within each scenario all >0.7). Conclusions: Physicians’ referral behaviors for dialysis patients suspected of having cancer vary for different cancer biological factors (probability of having cancer). However, the referral behaviors are similar for different patient functional factors (age, PS, and cognitive dysfunction). [ABSTRACT FROM AUTHOR]

We assessed the utility of two forms of osteopontin (OPN), OPN full and its cleaved form (OPN N-half), in plasma and urine as markers of disease activity in lupus nephritis (LN). Samples were collected from patients with systemic lupus erythematosus (SLE) (LN: N = 29, non-LN: N = 27), IgA nephropathy (IgAN) (N = 14), minimal change nephrotic syndrome (MCNS) (N = 5), diabetic nephropathy (DN) (N = 14) and healthy volunteers (HC) (N = 17). While there was no significant difference in urine OPN full concentration between groups, urine OPN N-half concentration was significantly higher in patients with LN than HC (p < 0.05). Moreover, urine OPN N-half was higher in LN patients with overt proteinuria (urine protein/creatinine ratio: P/C > 0.5) than LN patients with minimal proteinuria (P/C < 0.5, p < 0.0001), and also higher than in DN patients with overt proteinuria (P/C > 0.5, p < 0.01). Urine thrombin activity correlated with urine OPN N-half concentration (p < 0.0001), but not with urine OPN full concentration. These results suggest that urine OPN N-half concentration reflects renal inflammation. Thus, urine OPN N-half may be a novel disease activity marker for LN. [ABSTRACT FROM AUTHOR]

Supernumerary teeth and tooth agenesis are common morphological anomalies in humans. We previously obtained evidence that supernumerary maxillary incisors form as a result of the successive development of the rudimentary maxillary incisor tooth germ in Usag-1 null mice. The development of tooth germs is arrested in Runx2 null mice, and such mice also exhibit lingual epithelial buds associated with the upper molars and incisors. The aim of this study is to investigate the potential crosstalk between Usag-1 and Runx2 during tooth development. In the present study, three interesting phenomena were observed in double null Usag-1-/-/Runx2-/- mice: the prevalence of supernumerary teeth was lower than in Usag-1 null mice; tooth development progressed further compared than in Runx2 null mice; and the frequency of molar lingual buds was lower than in Runx2 null mice. Therefore, we suggest that RUNX2 and USAG-1 act in an antagonistic manner. The lingual bud was completely filled with odontogenic epithelial Sox2-positive cells in the Usag-1+/+/Runx2-/- mice, whereas almost no odontogenic epithelial Sox2-positive cells contributed to supernumerary tooth formation in the rudimentary maxillary incisors of the Usag-1-/-/Runx2+/+ mice. Our findings suggest that RUNX2 directly or indirectly prevents the differentiation and/or proliferation of odontogenic epithelial Sox2-positive cells. We hypothesize that RUNX2 inhibits the bone morphogenetic protein (BMP) and/or Wnt signaling pathways regulated by USAG-1, whereas RUNX2 expression is induced by BMP signaling independently of USAG-1. [ABSTRACT FROM AUTHOR]

Nephrin is a critical component of glomerular filtration barrier, which is important to maintain glomerular structure and avoid proteinuria. Downregulation of nephrin expression is commonly observed at early stage of glomerular disorders, suggesting that methods to increase nephrin expression in podocytes may have therapeutic utility. Here, we generated a knockin mouse line carrying single copy of 5.5 kb nephrin promoter controlling expression of enhanced green fluorescent protein (EGFP) at Rosa26 genomic locus (Nephrin-EGFP mouse). In these mice, EGFP was specifically expressed in podocytes. Next, we isolated and cultivated glomeruli from these mice, and developed a protocol to automatically quantitate EGFP expression in cultured glomeruli. EGFP signal was markedly reduced after 5 days of culture but reduction was inhibited by vitamin D treatment. We confirmed that vitamin D increased mRNA and protein expression of endogenous nephrin in cultivated glomeruli. Thus, we generated a mouse line converting nephrin promoter activity into fluorescence, which can be used to screen compounds having activity to enhance nephrin gene expression. [ABSTRACT FROM AUTHOR]

Tacrolimus is widely used as an immunosuppressant in liver transplantation, and tacrolimus-induced acute kidney injury (AKI) is a serious complication of liver transplantation. For early detection of AKI, various urinary biomarkers such as monocyte chemotactic protein-1, liver-type fatty acid-binding protein, interleukin-18, osteopontin, cystatin C, clusterin and neutrophil gelatinase-associated lipocalin (NGAL) have been identified. Here, we attempt to identify urinary biomarkers for the early detection of tacrolimus-induced AKI in liver transplant patients. Urine samples were collected from 31 patients after living-donor liver transplantation (LDLT). Twenty recipients developed tacrolimus-induced AKI. After the initiation of tacrolimus therapy, urine samples were collected on postoperative days 7, 14, and 21. In patients who experienced AKI during postoperative day 21, additional spot urine samples were collected on postoperative days 28, 35, 42, 49, and 58. The 8 healthy volunteers, whose renal and liver functions were normal, were asked to collect their blood and spot urine samples. The urinary levels of NGAL, monocyte chemotactic protein-1 and liver-type fatty acid-binding protein were significantly higher in patients with AKI than in those without, while those of interleukin-18, osteopontin, cystatin C and clusterin did not differ between the 2 groups. The area under the receiver operating characteristics curve of urinary NGAL was 0.876 (95% confidence interval, 0.800–0.951; P<0.0001), which was better than those of the other six urinary biomarkers. In addition, the urinary levels of NGAL at postoperative day 1 (p = 0.0446) and day 7 (p = 0.0006) can be a good predictive marker for tacrolimus-induced AKI within next 6 days, respectively. In conclusion, urinary NGAL is a sensitive biomarker for tacrolimus-induced AKI, and may help predict renal event caused by tacrolimus therapy in liver transplant patients. [ABSTRACT FROM AUTHOR]