Achenbach Johannes, Mengel Michael, Tossidou Irini, Peters Imke, Park Joon-Keun, Haubitz Marion, Ehrich Jochen H, Haller Hermann, Schiffer Mario
Mario Schiffer, Division of Nephrology, Department of Medicine, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany.
Nephrol Dial Transplant. 2008 Oct;23(10):3138-45. doi: 10.1093/ndt/gfn235. Epub 2008 May 5.
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.
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.
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.
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.
蛋白尿性疾病患者尿液中存活足细胞的检测已被描述为一种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志物。
我们检测了经活检证实为局灶节段性肾小球硬化(FSGS)、膜性肾病(MGN)或膜增生性肾小球肾炎(MPGN)患者的随机晨尿样本中存活的PDX阳性细胞的排泄情况,并对排泄细胞的足细胞和壁层上皮标志物以及增殖活性进行了表征。
我们发现,患有活动性疾病的未治疗患者尿液中排泄大量PDX阳性细胞。相比之下,我们在活动性微小病变病(MCD)患者以及完全缓解的FSGS或MGN患者的尿液中未能检测到大量PDX阳性细胞。当我们进一步对细胞进行表征时,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阳性细胞细胞角蛋白(CK8-18)呈双阳性。相应肾活检的免疫组织化学显示,100%的足细胞和壁层细胞PDX染色呈阳性。半定量分析显示,45%的壁层细胞CK8-18呈阳性,100%的近端肾小管细胞呈阳性。肾小球上皮层细胞CK8-18染色均为阴性。
在需要足细胞再生的疾病状态下,PDX阳性细胞会从尿液中丢失,并且是肾小球疾病活动的一种有用的非侵入性标志物。这些细胞可能来源于壁层上皮层。