Division of Nephrology, Spedali Civili of Brescia, Brescia, Italy.
1] Division of Nephrology and Dialysis, Department of Medical and Surgical Specialties, Radiological Sciences, and Public Health, University of Brescia and Montichiari Hospital, Brescia, Italy [2] Prenatal Diagnosis Unit, Department of Obstetrics and Gynecology, University of Brescia, Brescia, Italy.
Kidney Int. 2015 Jun;87(6):1223-9. doi: 10.1038/ki.2014.389. Epub 2015 Jan 7.
Apolipoprotein A-I is the main protein of high-density lipoprotein particles, and is encoded by the APOA1 gene. Several APOA1 mutations have been found, either affecting the lecithin:cholesterol acyltransferase activity, determining familial HDL deficiency, or resulting in amyloid formation with prevalent deposits in the kidney and liver. Evaluation of familial tubulointerstitial nephritis in patients with the Leu75Pro APOA-I amyloidosis mutation resulted in the identification of 253 carriers belonging to 50 families from Brescia, Italy. A total of 219 mutation carriers underwent clinical, laboratory, and instrumental tests. Of these, 62% had renal, hepatic, and testicular disease; 38% were asymptomatic. The disease showed an age-dependent penetrance. Tubulointerstitial nephritis was diagnosed in 49% of the carriers, 13% of whom progressed to kidney failure requiring dialysis. Hepatic involvement with elevation of cholestasis indices was diagnosed in 30% of the carriers, 38% of whom developed portal hypertension. Impaired spermatogenesis and hypogonadism was found in 68% of male carriers. The cholesterol levels were lower than normal in 80% of the mutation carriers. Thus, tubulointerstitial nephritis was highly prevalent in this large series of patients with Leu75Pro apoA-I amyloidosis. Persistent elevation of alkaline phosphatase, reduced HDL cholesterol plasma levels, and hypogonadism in men are key diagnostic features of this form of amyloidosis.
载脂蛋白 A-I 是高密度脂蛋白颗粒的主要蛋白，由 APOA1 基因编码。已经发现了几种 APOA1 突变，要么影响卵磷脂：胆固醇酰基转移酶活性，导致家族性 HDL 缺乏，要么导致淀粉样物质形成，在肾脏和肝脏中普遍存在沉积物。对具有 Leu75Pro APOA-I 淀粉样变性突变的患者进行家族性肾小管间质性肾炎的评估，导致在意大利布雷西亚的 50 个家庭中鉴定出 253 名携带者。共有 219 名突变携带者接受了临床、实验室和仪器检查。其中，62%有肾脏、肝脏和睾丸疾病；38%无症状。该疾病表现出年龄相关的外显率。在 49%的携带者中诊断出肾小管间质性肾炎，其中 13%进展为需要透析的肾衰竭。在 30%的携带者中诊断出肝受累伴胆汁淤积指数升高，其中 38%发展为门静脉高压。68%的男性携带者出现精子生成受损和性腺功能减退。胆固醇水平低于正常水平的携带者占 80%。因此，在这个患有 Leu75Pro apoA-I 淀粉样变性的大型患者系列中，肾小管间质性肾炎的患病率很高。碱性磷酸酶持续升高、高密度脂蛋白胆固醇血浆水平降低和男性性腺功能减退是这种淀粉样变性的关键诊断特征。
