Chapman Arlene B
Emory University School of Medicine, 1639 Pierce Drive, Atlanta, GA 30322, USA.
J Am Soc Nephrol. 2007 May;18(5):1399-407. doi: 10.1681/ASN.2007020155. Epub 2007 Apr 11.
Diagnosis and treatment of autosomal dominant polycystic kidney disease (ADPKD) is rapidly changing. Cellular pathways that involve the polycystins are being mapped and involve the primary cilium, intracellular calcium and cAMP regulation, and the mammalian target of rapamycin (mTOR) pathway. With the use of new imaging approaches, earlier diagnosis of hepatic cystic disease is possible, and measurement of kidney and cystic growth as well as kidney blood flow is possible over relatively short periods. PKD gene type, gender, proteinuria, and the presence of hypertension relate to the rate of kidney growth in ADPKD. On the basis of risk factors for progression to ESRD and the pathogenic roles that intracellular cAMP and mTOR play in cystogenesis, novel therapies are now being tested, including maximal inhibition of the renin-angiotensin system, inhibition of renal intracellular cAMP using vasopressin V2 receptor antagonists, and somatostatin analogues, as well as inhibitors of mTOR. This review addresses the current understanding of the pathogenesis and the natural history of ADPKD; accuracy and reliability of diagnostic approaches in utero, childhood, and adulthood; the value of reliable magnetic resonance imaging to measure disease progression early in the course of ADPKD; and novel therapeutic approaches that are being evaluated in ADPKD.
常染色体显性多囊肾病（ADPKD）的诊断和治疗正在迅速变化。涉及多囊蛋白的细胞途径正在被绘制，包括初级纤毛、细胞内钙和环磷酸腺苷（cAMP）调节以及雷帕霉素靶蛋白（mTOR）途径。通过使用新的成像方法，可以更早地诊断肝囊性疾病，并且在相对较短的时间内可以测量肾脏和囊肿的生长以及肾脏血流。PKD基因类型、性别、蛋白尿和高血压的存在与ADPKD中肾脏生长速率有关。基于进展至终末期肾病（ESRD）的危险因素以及细胞内cAMP和mTOR在囊肿形成中的致病作用，目前正在测试新的治疗方法，包括最大程度抑制肾素-血管紧张素系统、使用血管加压素V2受体拮抗剂抑制肾脏细胞内cAMP、生长抑素类似物以及mTOR抑制剂。本综述阐述了目前对ADPKD发病机制和自然病史的理解；宫内、儿童期和成年期诊断方法的准确性和可靠性；可靠的磁共振成像在ADPKD病程早期测量疾病进展的价值；以及正在ADPKD中评估的新治疗方法。
