Parietal epithelia cells in the urine as a marker of disease activity in glomerular diseases
Parietal epithelia cells in the urine as a marker of disease activity in glomerular diseases
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DOI：
10.1093/ndt/gfn235
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发表时间：
2008-10-01
影响因子：
6.1
通讯作者：
Schiffer, Mario
中科院分区：
文献类型：
--
作者：
Achenbach, Johannes;Mengel, Michael;Schiffer, Mario
背景蛋白尿疾病患者尿液中活足细胞的检测已被描述为监测疾病活动的非侵入性方法。大多数已发表的研究使用足细胞标记蛋白（PDX）作为足细胞特异性标记物。我们检测了经活检证实的局灶节段性肾小球硬化症（FSGS）、膜性肾病（MGN）或膜增生性肾小球肾炎（MPGN）患者的随机点尿中活PDX阳性细胞的排泄，并对排泄的细胞进行足细胞和壁上皮标记物以及增殖活性的表征。我们发现，未经治疗的活动性疾病患者在尿液中排出大量的PDX阳性细胞。与此相反，我们不能检测到大量的PDX阳性细胞在尿液中的患者与活动性微小病变疾病（MCD）和患者FSGS或MGN完全缓解。当我们进一步表征细胞时，我们很少在PDX阳性细胞中检测到足细胞特异性标志物的表达，但至少50%的PDX阳性细胞对细胞角蛋白（CK 8 -18）呈双阳性。免疫组化显示足细胞和壁细胞PDX染色阳性率为100%。半定量分析显示45%的壁细胞和100%的近端小管细胞CK 8 -18阳性。肾小球上皮细胞CK 8 - 18均为阴性。PDX阳性细胞在需要足细胞再生的疾病状态下在尿液中丢失，并且是肾小球疾病活动的有用的非侵入性标记物。这些细胞可能来源于壁上皮层。
Background. The detection of viable podocytes in the urine of patients with proteinuric diseases has been described as a non-invasive method to monitor disease activity. Most of the published studies use podocalyxin (PDX) as a podocyte specific marker.Methods. We examined the excretion of viable PDX-positive cells in a random set of spot urine from patients with biopsy-proven focal segmental glomerulosclerosis (FSGS), membranous nephropathy (MGN) or membranoproliferative glomerulonephritis (MPGN) and characterized the excreted cells for podocyte and parietal epithelia markers as well as for proliferation activity.Results. We found that untreated patients with active disease excrete high numbers of PDX-positive cells in their urine. In contrast to that we were not able to detect significant amounts of PDX-positive cells in the urine of patients with active minimal change disease (MCD) and patients with FSGS or MGN in full remission. When we further characterized the cells we rarely detected expression of podocyte specific markers in the PDX-positive cells, but at least 50% of the PDX-positive cells were double positive for cytokeratin (CK8-18). Immunohistochemistry of the corresponding renal biopsies showed that 100% of podocytes and parietal cells stained positive for PDX. Semiquantitative analysis revealed that 45% of parietal cells were positive for CK8-18 and 100% of proximal tubular cells. No cells of the glomerular epithelial layer stained positive for CK8-18.Conclusions. PDX-positive cells are lost in the urine in disease states that require podocyte regeneration and are a useful non-invasive marker for glomerular disease activity. These cells are possibly derived from the parietal epithelial layer.