SS Nephrology ASOU san Luigi, Orbassano, Torino, Italy.
BMC Nephrol. 2012 Feb 21;13:9. doi: 10.1186/1471-2369-13-9.
MELAS syndrome (MIM ID#540000), an acronym for Mitochondrial Encephalopathy, Lactic Acidosis and Stroke-like episodes, is a genetically heterogeneous mitochondrial disorder with protean manifestations and occasional kidney involvement. Interest in the latter is rising due to the identification of cases with predominant kidney involvement and to the hypothesis of a link between mitochondrial DNA and kidney neoplasia.
We report the case of a 41-year-old male with full blown MELAS syndrome, with lactic acidosis and neurological impairment, affected by the "classic" 3243A > G mutation of mitochondrial DNA, with kidney cancer. After unilateral nephrectomy, he rapidly developed severe kidney functional impairment, with nephrotic proteinuria. Analysis of the kidney tissue at a distance from the two tumor lesions, sampled at the time of nephrectomy was performed in the context of normal blood pressure, recent onset of diabetes and before the appearance of proteinuria. The morphological examination revealed a widespread interstitial fibrosis with dense inflammatory infiltrate and tubular atrophy, mostly with thyroidization pattern. Vascular lesions were prominent: large vessels displayed marked intimal fibrosis and arterioles had hyaline deposits typical of hyaline arteriolosclerosis. These severe vascular lesions explained the different glomerular alterations including ischemic and obsolescent glomeruli, as is commonly observed in the so-called "benign" arteriolonephrosclerosis. Some rare glomeruli showed focal segmental glomerulosclerosis; as the patient subsequently developed nephrotic syndrome, these lesions suggest that silent ischemic changes may result in the development of focal segmental glomerulosclerosis secondary to nephron loss.
Nephron loss may trigger glomerular sclerosis, at least in some cases of MELAS-related nephropathy. Thus the incidence of kidney disease in the "survivors" of MELAS syndrome may increase as the support therapy of these patients improves.
MELAS 综合征（MIM ID#540000），是线粒体脑肌病伴高乳酸血症和卒中样发作的缩写，是一种具有多种表现形式且偶尔累及肾脏的遗传异质性线粒体疾病。由于发现了主要累及肾脏的病例以及线粒体 DNA 与肾脏肿瘤之间存在关联的假说，人们对后者的兴趣日益增加。
我们报告了一例 41 岁男性，患有典型的 MELAS 综合征，伴有乳酸酸中毒和神经功能障碍，受线粒体 DNA 的“经典”3243A>G 突变影响，同时患有肾癌。单侧肾切除术后，他迅速出现严重的肾功能损害，伴有肾病性蛋白尿。在血压正常、近期发生糖尿病且蛋白尿尚未出现的情况下，对肾切除时取自两个肿瘤病变远处的肾脏组织进行了分析。形态学检查显示广泛的间质纤维化，伴有密集的炎症浸润和肾小管萎缩，主要呈甲状腺化模式。血管病变明显：大血管显示明显的内膜纤维化，小动脉有典型的玻璃样动脉血管硬化的透明沉积物。这些严重的血管病变解释了不同的肾小球改变，包括缺血性和废用性肾小球，这在所谓的“良性”小动脉血管肾硬化症中很常见。一些罕见的肾小球显示局灶节段性肾小球硬化；由于患者随后出现肾病综合征，这些病变表明，沉默性缺血变化可能导致局灶节段性肾小球硬化，继发于肾单位丢失。
肾单位丢失可能引发肾小球硬化，至少在某些 MELAS 相关肾病病例中是这样。因此，随着这些患者的支持治疗得到改善，MELAS 综合征“幸存者”中肾脏疾病的发生率可能会增加。
