Mycophenolic acid, the active metabolite for mycophenolate mofetil and mycophenolic sodium, is a strong, noncompetitive, reversible inhibitor of inosine monophosphate dehydrogenase, the key enzyme in de novo synthesis...Mycophenolic acid, the active metabolite for mycophenolate mofetil and mycophenolic sodium, is a strong, noncompetitive, reversible inhibitor of inosine monophosphate dehydrogenase, the key enzyme in de novo synthesis of guanosine nucleotides leading to selective inhibition of lymphocyte proliferation. Mycophenolic acid has been evaluated as induction and remission maintenance agent in the treatment of antineutrophil cytoplasmic antibody-associated vasculitis (AAV). Since the course of disease of AAV usually requires long term immunosuppression, mycophenolate has been explored as a less toxic agent compared to cyclophosphamide and azathioprine. Mycophenolate is a potent immunosuppressive agent in the therapy of AAV, non-inferior to other available drugs with comparable side effect profile. Therefore, it could be a valuable alternative in cases of toxicity with life threatening side effects or intolerance to cyclophosphamide or azathioprine, in cases with high cumulative dose of cyclophosphamide, but also in cases with insufficient response. Several studies have shown a higher relapse rate following discontinuation of mycophenolate or in mycophenolate treated subjects that raises concerns about its usefulness in the treatment of AAV. This review describes the efficacy of mycophenolate in AAV as remission induction agent, as remission maintenance agent, and as therapeutic option in relapsing AAV disease, the relapse rate following discontinuation of mycophenolate, and the adverse events related to mycophenolate treatment.展开更多
Antineutrophil cytoplasmic antibodies(ANCA) are well known to be associated with several types of vasculitis, including pauci-immune crescentic glomerulonephritis, a form of rapid progressive glomerular nephritis(RPGN...Antineutrophil cytoplasmic antibodies(ANCA) are well known to be associated with several types of vasculitis, including pauci-immune crescentic glomerulonephritis, a form of rapid progressive glomerular nephritis(RPGN). ANCA vasculitis has also been reported after administration of propylthiouracil, hydralazine, cocaine(adulterated with levimasole), allopurinol, penicillamine and few other drugs. All previously reported cases of drug-associated ANCA glomerulonephritis were in native kidneys. Sofosbuvir is a new and effective drug for hepatitis C virus infection. Here, we report a case of ANCA vasculitis and RPGN following sofosbuvir administration in a kidney transplant recipient. It also represents the first case of drug-associated ANCA vasculitis in a transplanted kidney. Further drug monitoring is necessary to elucidate the degree of association and possible causal effect of sofosbuvir and perinuclear ANCA vasculitis.展开更多
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...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.展开更多
Renal involvement with rapidly progressive glomeru-lonephritis is a common manifestation of antineutrophil cytoplasmic antibody(ANCA) associated vasculitides, which is characterized by end-stage renal disease and high...Renal involvement with rapidly progressive glomeru-lonephritis is a common manifestation of antineutrophil cytoplasmic antibody(ANCA) associated vasculitides, which is characterized by end-stage renal disease and high mortality rates in untreated and/or late referral patients. The long-term renal survival has improved dramatically since the addition of cyclophosphamide(CYC) and recently of rituximab(RTX) in association with corticosteroids in the remission induction thera-peutic regimens. However, renal prognosis remains unfavorable for many patients and the mortality rate is still significantly high. In this review, we analyze the open challenges to be addressed to optimize the induction remission therapy, principally in patients with advanced kidney failure. This concern the first-line therapy(CYC or RTX) based on different parameters(estimated glomerular filtration rate at baseline, new or relapsed disease, ANCA specificity, tissue injury, safety), the role of plasma exchange and the role of new therapies. Indeed, we discuss future perspectives in induction remission therapy by reporting recent advances in new targeted therapies with particular reference to avacopan, an orally administered selective C5a receptor inhibitor.展开更多
Olfactory dysfunction(OD)has been described in patients with antineutrophil cytoplasmic antibody-associated vasculitides(AAV),but the underlying mechanisms are not completely understood.The causes of altered smell fun...Olfactory dysfunction(OD)has been described in patients with antineutrophil cytoplasmic antibody-associated vasculitides(AAV),but the underlying mechanisms are not completely understood.The causes of altered smell function can generally be divided into conductive,sensorineural or others.To date no specific treatment is available for AAV-related OD and the efficacy of currently available options has not been explored.The aim of this review is to provide an overview of the causes that may lead to OD in patients with AAV.Current available treatments for OD and possible options in patients with AAV presenting with smell impairment are also mentioned.展开更多
文摘Mycophenolic acid, the active metabolite for mycophenolate mofetil and mycophenolic sodium, is a strong, noncompetitive, reversible inhibitor of inosine monophosphate dehydrogenase, the key enzyme in de novo synthesis of guanosine nucleotides leading to selective inhibition of lymphocyte proliferation. Mycophenolic acid has been evaluated as induction and remission maintenance agent in the treatment of antineutrophil cytoplasmic antibody-associated vasculitis (AAV). Since the course of disease of AAV usually requires long term immunosuppression, mycophenolate has been explored as a less toxic agent compared to cyclophosphamide and azathioprine. Mycophenolate is a potent immunosuppressive agent in the therapy of AAV, non-inferior to other available drugs with comparable side effect profile. Therefore, it could be a valuable alternative in cases of toxicity with life threatening side effects or intolerance to cyclophosphamide or azathioprine, in cases with high cumulative dose of cyclophosphamide, but also in cases with insufficient response. Several studies have shown a higher relapse rate following discontinuation of mycophenolate or in mycophenolate treated subjects that raises concerns about its usefulness in the treatment of AAV. This review describes the efficacy of mycophenolate in AAV as remission induction agent, as remission maintenance agent, and as therapeutic option in relapsing AAV disease, the relapse rate following discontinuation of mycophenolate, and the adverse events related to mycophenolate treatment.
文摘Antineutrophil cytoplasmic antibodies(ANCA) are well known to be associated with several types of vasculitis, including pauci-immune crescentic glomerulonephritis, a form of rapid progressive glomerular nephritis(RPGN). ANCA vasculitis has also been reported after administration of propylthiouracil, hydralazine, cocaine(adulterated with levimasole), allopurinol, penicillamine and few other drugs. All previously reported cases of drug-associated ANCA glomerulonephritis were in native kidneys. Sofosbuvir is a new and effective drug for hepatitis C virus infection. Here, we report a case of ANCA vasculitis and RPGN following sofosbuvir administration in a kidney transplant recipient. It also represents the first case of drug-associated ANCA vasculitis in a transplanted kidney. Further drug monitoring is necessary to elucidate the degree of association and possible causal effect of sofosbuvir and perinuclear ANCA vasculitis.
基金approved by the Ethics Committee of the Children’s Hospital of Chongqing Medical University(approval Number:149/2022)other enrolled centers.This study was registered at the Chinese Clinical Trial Registry(registered number:ChiCTR2000034203).
文摘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.
文摘Renal involvement with rapidly progressive glomeru-lonephritis is a common manifestation of antineutrophil cytoplasmic antibody(ANCA) associated vasculitides, which is characterized by end-stage renal disease and high mortality rates in untreated and/or late referral patients. The long-term renal survival has improved dramatically since the addition of cyclophosphamide(CYC) and recently of rituximab(RTX) in association with corticosteroids in the remission induction thera-peutic regimens. However, renal prognosis remains unfavorable for many patients and the mortality rate is still significantly high. In this review, we analyze the open challenges to be addressed to optimize the induction remission therapy, principally in patients with advanced kidney failure. This concern the first-line therapy(CYC or RTX) based on different parameters(estimated glomerular filtration rate at baseline, new or relapsed disease, ANCA specificity, tissue injury, safety), the role of plasma exchange and the role of new therapies. Indeed, we discuss future perspectives in induction remission therapy by reporting recent advances in new targeted therapies with particular reference to avacopan, an orally administered selective C5a receptor inhibitor.
文摘Olfactory dysfunction(OD)has been described in patients with antineutrophil cytoplasmic antibody-associated vasculitides(AAV),but the underlying mechanisms are not completely understood.The causes of altered smell function can generally be divided into conductive,sensorineural or others.To date no specific treatment is available for AAV-related OD and the efficacy of currently available options has not been explored.The aim of this review is to provide an overview of the causes that may lead to OD in patients with AAV.Current available treatments for OD and possible options in patients with AAV presenting with smell impairment are also mentioned.
