Risk factors for renal outcomes in children with antineutrophil cytoplasmic antibody-associated vasculitis:a nationwide retrospective study in China

Background Pediatric antineutrophil cytoplasmic antibody-associated vasculitis(AAV)is a life-threatening systemic vasculitis featured by liability to renal involvement.However,there are few studies on the risk factors and predictive models for renal outcomes of AAV in children.Methods Data from 179 AAV children in multiple centers between January 2012 and March 2020 were collected retrospectively.The risk factors and predictive model of end-stage renal disease(ESRD)in AAV were explored.Results Renal involvement was the most typical manifestation(95.5%),and the crescent was the predominant pathological lesion(84.9%).The estimated glomerular filtration rate(eGFR)was evaluated in 114 patients,of whom 59.6%developed ESRD,and the median time to ESRD was 3.20 months.The eGFR[P=0.006,odds ratio(OR)=0.955,95%confidence interval(CI)=0.924–0.987]and the percentages of global glomerulosclerosis(pGGS;P=0.018,OR=1.060,95%CI=1.010–1.112)were independent risk factors for ESRD of renal biopsy.Based on the pGGS and eGFR at renal biopsy,we developed three risk grades of ESRD and one predictive model.The Kaplan‒Meier curve indicated that renal outcomes were significantly different in different risk grades(P<0.001).Compared with serum creatinine at baseline,the predictive model had higher accuracy(0.86 versus 0.58,P<0.001)and a lower coefficient of variation(0.07 versus 0.92)in external validation.Conclusions Renal involvement is the most common manifestation of pediatric AAV in China,of which more than half deteriorates into ESRD.The predictive model based on eGFR at renal biopsy and the pGGS may be stable and accurate in speculating the risk of ESRD in AAV children.

Overexpression of IQGAP1 in human pancreatic cancer

BACKGROUND:Pancreatic cancer is a highly aggressive malignant tumor with the lowest survival rate.A better understanding of the molecular mechanisms which contribute to pancreatic cancer occurrence and progression will aid in the development of new approaches to the early diagnosis,prevention,and treatment of this deadly disease.The scaffold protein IQGAP1 shows elevated levels in a variety of cancer types.Currently,we investigated whether or not IQGAP1 is also overexpressed in pancreatic cancer.METHODS:IQGAP1 expression was examined in pancreatic cancer and normal tissues adjacent to cancerous tissues(adjacent tissues)by Western blotting and real-time RT-PCR as well as in paraffin sections of tissue microarray by immunohistochemistry.The correlations between IQGAP1 expression and various clinicopathological characteristics were analyzed.RESULTS:Western blotting and real-time RT-PCR revealed that the levels of IQGAP1 protein and mRNA expression in pancreatic cancer tissues were significantly increased compared with adjacent tissues.Immunohistochemistry analysis on tissue microarray showed that IQGAP1 protein expression was significantly higher in pancreatic cancer(80.0%,48/60)compared with adjacent tissues(18.3%,11/60)(P【0.001).Moreover,overexpression of IQGAP1 was shown to be associated with the grades of tumor differentiation(P【0.05).CONCLUSION:The overexpression of IQGAP1 may play an important role in pancreatic cancer occurrence and progression,and IQGAP1 may serve as a novel molecular target for the diagnosis and treatment of pancreatic cancer.