非布索坦治疗肾移植术后合并高尿酸血症的临床研究
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摘要
目的探讨肾移植术后合并高尿酸血症(hyperuricemia,HUA)患者应用非布索坦的安全性和有效性。方法回顾性分析2016年1月—2017年12月在本院规律随访的肾移植受者的临床资料,接受传统降尿酸治疗〔生活方式干预、碱化尿液、别嘌醇(0.1～0.2 g/d)或苯溴马隆(50 mg/d)〕至少4周,血尿酸(serum uric acid,SUA)水平仍可诊断为HUA的共104例患者,在停用别嘌醇或苯溴马隆基础上转为口服非布索坦,随访12周,比较非布索坦治疗前后SUA水平变化及不良反应。同时观察免疫抑制剂药物浓度等指标。结果非布索坦治疗前SUA水平为(497.88±47.37)μmol/L,治疗后第十二周SUA水平明显下降至(348.05±49.88)μmol/L (P <0.001)。观察治疗前后丙氨酸转氨酶、血白细胞计数、血肌酐及免疫抑制剂药物浓度,均无显著性差异。观察过程中无心血管事件发生,用药后有2例出现痛风急性发作,对症处理后均好转。结论肾移植术后HUA应用传统综合治疗效果不佳时,转换为非布索坦治疗效果确切,且安全性高。
Objective To investigate the safety and efficacy of febuxostat in the treatment of patients with hyperuricemia after renal transplantation.Methods The clinical data of renal transplant recipients who were regularly followed up in Shanghai Changzheng Hospital from January 2016 to December 2017,were analyzed retrospectively.They were received traditional uric acid reduction therapy[lifestyle intervention,alkalized urine,allopurinol(0.1～0.2 g/d)or phenyl bromide Malone(50 mg/d)]for at least 4 weeks,a total of 104 patients with hyperuricemia were diagnosed with hyperuricemia,these patients were switched to oral febuxostat on the basis of discontinuation of allopurinol or benzbromarone with follow-up of 12 weeks,the changes of blood uric acid level and adverse reactions before and after treatment with febuxostat were compared,and the concentrations of immunosuppressive drugs were observed.Results The serum uric acid level before treatment with febuxostat was(497.88±47.37)μmol/L,andthe blood uric acid level decreased significantly to(348.05±49.88)μmol/L at the 12th week after treatment(P<0.001).There were no significant differences in white blood cell,serum creatinine,and immunosuppressive drug concentration levels.No cardiovascular events occurred during the observation,and 2 patients with acute gout after the medication were cured.Conclusion When the traditional comprehensive treatment of hyperuricemia after renal transplantation is not effective,the conversion to febuxostat is effective and safe.
Objective To investigate the safety and efficacy of febuxostat in the treatment of patients with hyperuricemia after renal transplantation.Methods The clinical data of renal transplant recipients who were regularly followed up in Shanghai Changzheng Hospital from January 2016 to December 2017,were analyzed retrospectively.They were received traditional uric acid reduction therapy[lifestyle intervention,alkalized urine,allopurinol(0.1～0.2 g/d)or phenyl bromide Malone(50 mg/d)]for at least 4 weeks,a total of 104 patients with hyperuricemia were diagnosed with hyperuricemia,these patients were switched to oral febuxostat on the basis of discontinuation of allopurinol or benzbromarone with follow-up of 12 weeks,the changes of blood uric acid level and adverse reactions before and after treatment with febuxostat were compared,and the concentrations of immunosuppressive drugs were observed.Results The serum uric acid level before treatment with febuxostat was(497.88±47.37)μmol/L,andthe blood uric acid level decreased significantly to(348.05±49.88)μmol/L at the 12th week after treatment(P<0.001).There were no significant differences in white blood cell,serum creatinine,and immunosuppressive drug concentration levels.No cardiovascular events occurred during the observation,and 2 patients with acute gout after the medication were cured.Conclusion When the traditional comprehensive treatment of hyperuricemia after renal transplantation is not effective,the conversion to febuxostat is effective and safe.
引文
[1]Clive DM.Renal transplant-associated hyperuricemia and gout[J].Am Soc Nephrol,2000,11(5):974-979.
[2]Bellomo G.Asymptomatic hyperuricemia following renal transplantation[J].World J Nephrol,2015,4(3):324-329.
[3]Malheiro J,Almeida M,Fonseca I,et al.Hyperuricemia in adult renal allograft recipients:prevalence and predictors[J].Transplant Proc,2012,44(8):2369-2372.
[4]中华医学会器官移植学分会.中国肾移植术后高尿酸血症诊疗技术规范(2019版)[J].器官移植杂,2019,10(1):10-15.
[5]Richette P,Doherty M,Pascual E,et al.2016 updated EULA Revidence-based recommendations for the management of gout[J].Ann Rheum Dis,2017,76(1):29-42.
[6]Huang Y,Li YL,Huang H,et al.Effects of hyperuricemia on renal function of renal transplant recipients:a systematic review and meta-analysis of cohort studies[J].PLoS One,2012,7(6):e39457.
[7]Hong Q,Qi K,Feng Z,et al.Hyperuricemia induces endothelial dysfunction via mitochondrial Na+/Ca2+exchanger-mediated mitochondrial calcium overload[J].Cell Calcium,2012,51(5):402-410.
[8]Kanellis J,Watanabe S,Li JH,et al.Uric acid stimulates monocyte chemoattractant protein-1 production in vascular smooth muscle cells via mitogen-activated protein kinase and cyclooxygenase-2[J].Hypertension,2003,41(6):1287-1293.
[9]Nakagawa T,Mazzali M,Kang DH,et al.Hyperuricemia causes glomerular hypertrophy in the rat[J].Am J Nephrol,2003,23(1):2-7.
[10]Clarson LE,Hider SL,Belcher J,et al.Increased risk of vascular disease associated with gout:a retrospective,matched cohort study in the UK clinical practice research datalink[J].Ann Rheum Dis,2015,74:642-647.
[11]Okamoto K,NishinoI T.Crystal structures of mammalian xanthine oxidoreductase bound with various inhibitors:allopurinol,febuxostat,and FYX-051[J].Nippon Med Sch,2008,75(1):2-3.
[12]严婷婷,沈洁,史向辉,等.非布司他与别嘌醇治疗痛风伴肾功能不全患者疗效观察[J].中国药物与临床,2017,17(5):695-697.
[13]Ryu ES,Kim MJ,Shin HS,et al.Uric acid-induced phenotypie transition of renal tubular cells as a novel mechanism of chronic kidney disease[J].Am J Physiol Renal Physiol,2013,304(5):F471-F480.
[14]林章梅,张荣山,范晨雪,等.非布司他对高尿酸血症大鼠肾小管上皮间质转化及血清IL-6、转化生长因子β1的影响[J].中华内科杂志,2017,56(5):363-367.
[15]Malik UZ,Hundley NJ,Romero G,et al.Febuxostat inhibition of endothelial-bound XO:implications for targeting vascular ROSproduction[J].Free Radical Biology and Med,2011,51(1):179-184.
[16]Gray CL,Walters-Smith NE.Febuxostat for treatment of chronic gout[J].Am J Health Syst Pharm,2011,68(5):389-398.
[17]Hair PI,McCormack PL,Keating GM.Febuxostat[J].Drugs,2008,68(13):1865-1874.
[18]Tojimbara T,Nakajima I,Yashima J,et al.Efficacy and safety of febuxostat,a novel nonpurine selective inhibitor of xanthine oxidase for the treatment of hyperuricemia in kidney transplant recipients[J].Transplant Proc,2014,46(2):511-513.
[2]Bellomo G.Asymptomatic hyperuricemia following renal transplantation[J].World J Nephrol,2015,4(3):324-329.
[3]Malheiro J,Almeida M,Fonseca I,et al.Hyperuricemia in adult renal allograft recipients:prevalence and predictors[J].Transplant Proc,2012,44(8):2369-2372.
[4]中华医学会器官移植学分会.中国肾移植术后高尿酸血症诊疗技术规范(2019版)[J].器官移植杂,2019,10(1):10-15.
[5]Richette P,Doherty M,Pascual E,et al.2016 updated EULA Revidence-based recommendations for the management of gout[J].Ann Rheum Dis,2017,76(1):29-42.
[6]Huang Y,Li YL,Huang H,et al.Effects of hyperuricemia on renal function of renal transplant recipients:a systematic review and meta-analysis of cohort studies[J].PLoS One,2012,7(6):e39457.
[7]Hong Q,Qi K,Feng Z,et al.Hyperuricemia induces endothelial dysfunction via mitochondrial Na+/Ca2+exchanger-mediated mitochondrial calcium overload[J].Cell Calcium,2012,51(5):402-410.
[8]Kanellis J,Watanabe S,Li JH,et al.Uric acid stimulates monocyte chemoattractant protein-1 production in vascular smooth muscle cells via mitogen-activated protein kinase and cyclooxygenase-2[J].Hypertension,2003,41(6):1287-1293.
[9]Nakagawa T,Mazzali M,Kang DH,et al.Hyperuricemia causes glomerular hypertrophy in the rat[J].Am J Nephrol,2003,23(1):2-7.
[10]Clarson LE,Hider SL,Belcher J,et al.Increased risk of vascular disease associated with gout:a retrospective,matched cohort study in the UK clinical practice research datalink[J].Ann Rheum Dis,2015,74:642-647.
[11]Okamoto K,NishinoI T.Crystal structures of mammalian xanthine oxidoreductase bound with various inhibitors:allopurinol,febuxostat,and FYX-051[J].Nippon Med Sch,2008,75(1):2-3.
[12]严婷婷,沈洁,史向辉,等.非布司他与别嘌醇治疗痛风伴肾功能不全患者疗效观察[J].中国药物与临床,2017,17(5):695-697.
[13]Ryu ES,Kim MJ,Shin HS,et al.Uric acid-induced phenotypie transition of renal tubular cells as a novel mechanism of chronic kidney disease[J].Am J Physiol Renal Physiol,2013,304(5):F471-F480.
[14]林章梅,张荣山,范晨雪,等.非布司他对高尿酸血症大鼠肾小管上皮间质转化及血清IL-6、转化生长因子β1的影响[J].中华内科杂志,2017,56(5):363-367.
[15]Malik UZ,Hundley NJ,Romero G,et al.Febuxostat inhibition of endothelial-bound XO:implications for targeting vascular ROSproduction[J].Free Radical Biology and Med,2011,51(1):179-184.
[16]Gray CL,Walters-Smith NE.Febuxostat for treatment of chronic gout[J].Am J Health Syst Pharm,2011,68(5):389-398.
[17]Hair PI,McCormack PL,Keating GM.Febuxostat[J].Drugs,2008,68(13):1865-1874.
[18]Tojimbara T,Nakajima I,Yashima J,et al.Efficacy and safety of febuxostat,a novel nonpurine selective inhibitor of xanthine oxidase for the treatment of hyperuricemia in kidney transplant recipients[J].Transplant Proc,2014,46(2):511-513.