薛澄;周晨辰;梅长林;
XUE Cheng;ZHOU Chen-chen;MEI Chang-lin;Department of Nephrology,Changzheng Hospital,the Second Military Medical University;

• 1:第二军医大学上海长征医院肾内科解放军肾脏病研究所

摘要(Abstract)：

常染色体显性多囊肾病(autosomal dominant polycystic kidney disease,ADPKD)患病率为1‰~2‰,属于罕见病,临床主要表现为双侧肾囊肿且逐渐发展,肾脏体积进行性增大,肾功能逐步降低。PKD1基因突变约占81%,PKD2基因突变约占10.5%~22%。血管加压素(arginine vasopressin,AVP)和环磷酸腺苷(cyclic adenosine monophosphate,c AMP)信号通路在ADPKD囊肿发展过程中发挥重要作用。近年来发表的梅奥风险评估模型和PROPKD(predicting renal outcome in polycystic kidney disease)评分是ADPKD较好的预后评估模型,已成为临床医生决策的重要依据。通过拮抗AVP受体,抑制c AMP通路的托伐普坦已成为ADPKD首个特异治疗药物,可有效抑制总肾脏体积的增长和保护肾功能。药物的长期安全性仍需进一步研究。
The prevalence of autosomal dominant polycystic kidney disease(ADPKD) is 1‰ to 2‰,belonging to rare diseases. ADPKD is mainly manifested as gradually developing bilateral renal cysts,progressively increasing renal size,and gradually reduced renal function. PKD1 mutation accounts for about 81%; PKD2 mutation accounts for about 10. 5% to 22%. Vasopressin and cyclic adenosine monophosphate(c AMP) signaling pathways play an important role in the development of ADPKD cysts. In recent years,the Mayo risk assessment model and predicting renal outcome in polycystic kidney disease(PROPKD) score,which are good prognostic models for ADPKD,have become important evidences for clinical decision-making. Tolvaptan,which inhibits c AMP pathway by antagonizing vasopressin receptor,has become the first specific treatment for ADPKD. Tolvaptan could effectively inhibit the growth of total renal size,and protect renal function. Long-term safety of the drug still needs further study.

关键词(KeyWords)： 多囊肾病;常染色体显性;预后评估;治疗
polycystic kidney disease;autosomal dominant;prognostic evaluation;treatment

Abstract:

Keywords:

基金项目(Foundation): 国家重点研发计划(2016YFC0901500);; 国家自然科学基金面上项目(81670612);; 上海地区慢性肾脏病早发现和诊疗体系建设与示范(GWIV-18)

作者(Author): 薛澄;周晨辰;梅长林;
XUE Cheng;ZHOU Chen-chen;MEI Chang-lin;Department of Nephrology,Changzheng Hospital,the Second Military Medical University;

Email:

DOI:

参考文献(References)：

• [1]Neumann HP,Jilg C,Bacher J,et al.Epidemiology of autosomal-dominant polycystic kidney disease:an in-depth clinical study for south-western Germany[J].Nephrol Dial Transplant,2013,28:1472-1487.
• [2]Xue C,Zhou CC,Wu M,et al.The clinical manifestation and management of autosomal dominant polycystic kidney disease in China[J].Kidney Dis(Basel),2016,2:111-119.
• [3]Ong AC,Devuyst O,Knebelmann B,et al.Autosomal dominant polycystic kidney disease:the changing face of clinical management[J].Lancet,2015,385:1993-2002.
• [4]Sommerer C,Zeier M.Clinical manifestation and management of ADPKD in western countries[J].Kidney Dis(Basel),2016,2:120-127.
• [5]Steinman TI.Polycystic kidney disease:a 2011 update[J].Curr Opin Nephrol Hypertens,2012,21:189-194.
• [6]Mao Z,Chong J,Ong AC.Autosomal dominant polycystic kidney disease:recent advances in clinical management[J].F1000Res,2016,5:2029.
• [7]Chen L,Zhou X,Fan LX,et al.Macrophage migration inhibitory factor promotes cyst growth in polycystic kidney disease[J].J Clin Invest,2015,125:2399-2412.
• [8]Ong AC,Harris PC.Molecular pathogenesis of ADPKD:the polycystin complex gets complex[J].Kidney Int,2005,67:1234-1247.
• [9]Porath B,Gainullin VG,Cornec-Le Gall E,et al.Mutations in GANAB,encoding the glucosidaseⅡαsubunit,cause autosomal-dominant polycystic kidney and liver disease[J].Am J Hum Genet,2016,98:1193-1207.
• [10]Audrezet MP,Cornec-Le Gall E,Chen JM,et al.Autosomal dominant polycystic kidney disease:comprehensive mutation analysis of PKD1 and PKD2 in 700 unrelated patients[J].Hum Mutat,2012,33:1239-1250.
• [11]Ong AC,Harris PC.A polycystin-centric view of cyst formation and disease:the polycystins revisited[J].Kidney Int,2015,88:699-710.
• [12]Harris PC,Torres VE.Genetic mechanisms and signaling pathways in autosomal dominant polycystic kidney disease[J].J Clin Invest,2014,124:2315-2324.
• [13]Grantham JJ,Torres VE,Chapman AB,et al.Volume progression in polycystic kidney disease[J].N Engl J Med,2006,354:2122-2130.
• [14]Chapman AB,Bost JE,Torres VE,et al.Kidney volume and functional outcomes in autosomal dominant polycystic kidney disease[J].Clin J Am Soc Nephrol,2012,7:479-486.
• [15]Bhutani H,Smith V,Rahbari-Oskoui F,et al.A comparison of ultrasound and magnetic resonance imaging shows that kidney length predicts chronic kidney disease in autosomal dominant polycystic kidney disease[J].Kidney Int,2015,88:146-151.
• [16]Pei Y,Obaji J,Dupuis A,et al.Unified criteria for ultrasonographic diagnosis of ADPKD[J].J Am Soc Nephrol,2009,20:205-212.
• [17]Simms RJ,Travis DL,Durkie M,et al.Genetic testing in the assessment of living related kidney donors at risk of autosomal dominant polycystic kidney disease[J].Transplantation,2015,99:1023-1029.
• [18]Zong C,Lu S,Chapman AR,et al.Genome-wide detection of single-nucleotide and copy-number variations of a single human cell[J].Science,2012,338:1622-1626.
• [19]Chapman AB,Devuyst O,Eckardt KU,et al.Autosomaldominant polycystic kidney disease(ADPKD):executive summary from a Kidney Disease:Improving Global Outcomes(KDIGO)Controversies Conference[J].Kidney Int,2015,88:17-27.
• [20]Schrier RW,Brosnahan G,Cadnapaphornchai MA,et al.Predictors of autosomal dominant polycystic kidney disease progression[J].J Am Soc Nephrol,2014,25:2399-2418.
• [21]Cornec-Le Gall E,Audrezet MP,Rousseau A,et al.The PROPKD score:a new algorithm to predict renal survival in autosomal dominant polycystic kidney disease[J].J Am Soc Nephrol,2016,27:942-951.
• [22]Irazabal MV,Rangel LJ,Bergstralh EJ,et al.Imaging classification of autosomal dominant polycystic kidney disease:a simple model for selecting patients for clinical trials[J].J Am Soc Nephrol,2015,26:160-172.
• [23]Xue C,Zhou C,Dai B,et al.Antihypertensive treatments in adult autosomal dominant polycystic kidney disease:network meta-analysis of the randomized controlled trials[J].Oncotarget,2015,6:42515-42529.
• [24]Torres VE,Abebe KZ,Chapman AB,et al.Angiotensin blockade in late autosomal dominant polycystic kidney disease[J].N Engl J Med,2014,371:2267-2276.
• [25]Walz G,Budde K,Mannaa M,et al.Everolimus in patients with autosomal dominant polycystic kidney disease[J].N Engl J Med,2010,363:830-840.
• [26]Serra AL,Poster D,Kistler AD,et al.Sirolimus and kidney growth in autosomal dominant polycystic kidney disease[J].N Engl J Med,2010,363:820-829.
• [27]Caroli A,Perico N,Perna A,et al.Effect of longacting somatostatin analogue on kidney and cyst growth in autosomal dominant polycystic kidney disease(ALADIN):a randomised,placebo-controlled,multicentre trial[J].Lancet,2013,382:1485-1495.
• [28]Torres VE,Chapman AB,Devuyst O,et al.Tolvaptan in patients with autosomal dominant polycystic kidney disease[J].N Engl J Med,2012,367:2407-2418.
• [29]Torres VE,Chapman AB,Devuyst O,et al.Multicenter,open-label,extension trial to evaluate the long-term efficacy and safety of early versus delayed treatment with tolvaptan in autosomal dominant polycystic kidney disease:the TEMPO 4:4 Trial[J].Nephrol Dial Transplant,2017.doi:10.1093/ndt/gfx043.[Epub ahead of print].
• [30]Torres VE,Higashihara E,Devuyst O,et al.Effect of tolvaptan in autosomal dominant polycystic kidney disease by CKD stage:results from the TEMPO 3:4 trial[J].Clin J Am Soc Nephrol,2016,11:803-811.