ps1 17 lupus nephritis severely reduced urinary dnase i levels reflect loss of renal dnase i disease progression and may reduce the need for renal biopsies

Loss of renal DNase I leads to progression of lupus nephritis. Therefore, we determined if loss of renal DNase I reflects a concurrent loss of urinary DNase I, and whether absence of urinary DNase I predicts disease progression, which thus may reduce the need for renal biopsies. Here, mouse renal DNase I mRNA was determined by qPCR, whereas mouse and human DNase I protein and DNase I endonuclease activity levels were determined by Western blots, and gel and radial zymography assays, respectively, during different stages of the murine and human forms of the disease. Cellular localization of DNase I was analysed by immunohistochemistry, immunofluorescence, confocal microscopy and immune electron microscopy. We further compared DNase I levels in human native and transplanted kidneys to determine if the disease depended on autologous renal genes, or whether the nephritic process proceeded also in transplanted kidneys. We also analysed if DNase I levels in urine samples reflected expression levels in the kidneys, and if the mouse data were translatable to humans. The data indicates that silencing of the renal DNase I gene expression level relates to serious progression of lupus nephritis in murine, human native, and transplanted kidneys. Notably, silencing of renal DNase I correlates with loss of DNase I protein and endonuclease activity in the urine samples. Thus, urinary DNase I levels reflects the renal DNase I expression and activity levels, and may therefore be used as a marker of lupus nephritis disease progression and reduce the need for renal biopsies

Vitamin D intake in mid-pregnancy and child allergic disease – a prospective study in 44,825 Danish mother-child pairs

Background: Past studies suggest that maternal vitamin D intake during pregnancy may protect against child wheeze but studies on asthma are limited. Our objective was to examine the relation between intake of vitamin D in mid-pregnancy and child asthma and allergic rhinitis at 18 months and 7 years. Methods: We examined data from 44,825 women enrolled during pregnancy in the longitudinal Danish National Birth Cohort (1996–2002). We estimated vitamin D intake from diet and supplements based on information from a validated food frequency questionnaire completed in gestational week 25. At 18 months, we evaluated child asthma using data from phone interviews. We assessed asthma and allergic rhinitis by self-report at age 7 and asthma by using records from national registries. Current asthma at age 7 was defined as lifetime asthma diagnosis and wheeze in the past 12 months. We calculated multivariable risk ratios with 95% CIs comparing highest vs. lowest quintile of vitamin D intake in relation to child allergic disease outcomes. Results: The median (5%-95%ile) intake of total vitamin D was 11.7(3.0-19.4) μg/day (68% from supplements). In multivariable analysis, mothers in the highest (vs. lowest) quintile of total vitamin D intake were less likely to have children classified with current asthma at 7 years (Q5 vs. Q1: 0.74, 95% CI: 0.56, 0.96, P = 0.02) and they were less likely to have children admitted to the hospital due to asthma (Q5 vs. Q1: 0.80, 95% CI: 0.64, 1.00, P = 0.05). We found no associations with child asthma at 18 months or with allergic rhinitis at 7 years. Conclusions: Our findings suggest a weak inverse relationship between high total vitamin D and asthma outcomes in later, but not early, childhood. The data did not suggest a clear threshold of vitamin D intake above which risk of asthma was reduced