Konieczny Andrzej, Czyżewska-Buczyńska Agnieszka, Ryba Monika, Rukasz Dagna, Krajewska Magdalena, Witkiewicz Wojciech, Hruby Zbigniew
Am J Nephrol. 2015;42(1):35-41. doi: 10.1159/000438930.
BACKGROUND/AIMS: A link between the number of podocytes excreted in the urine and activity of glomerular disease has been established. The aim of this study was to investigate possible correlations between urinary cells' phenotype and the progression of focal segmental glomerulosclerosis (FSGS).
Forty patients with newly diagnosed FSGS were included. Cells were isolated from urine by adherence to collagen-coated cover slips and assessed for the expression of podocalyxin (PDX), CD68 and Ki67 antigens by indirect immunofluorescence. In addition, double-staining procedures were performed in combinations of the above antigens plus cytokeratin, WT1 and CD-105. Twenty-two patients in whom urinary protein to creatinine ratio exceeded 2.0 at diagnosis were followed for 36 months, with assessments of renal function and proteinuria every 3 months. During observation, patients were subjected to standard therapy.
Significantly higher numbers of Ki67 positive cells at the onset of the study were observed in patients who have doubled serum creatinine (SCr) in follow-up, than in those who have not (p = 0.0149). By logistic regression analysis, both CD68 and Ki67, but not anti-PDX positive cell numbers at diagnosis were found to be predictors of doubling SCr concentration in 36 months' follow-up. Results of double staining indicate that PDX positive cells could be identified as podocytes or their precursors and parietal epithelial cells.
Urinary sediment PDX positive cell numbers do not predict the progression of FSGS, whereas CD68 and Ki67 phenotype of urinary podocytic lineage clearly has a prognostic significance in 36 months' observation of primary FSGS.
背景/目的:尿中排泄的足细胞数量与肾小球疾病活动之间的联系已被确立。本研究的目的是调查尿细胞表型与局灶节段性肾小球硬化(FSGS)进展之间可能的相关性。
纳入40例新诊断的FSGS患者。通过贴附于胶原包被的盖玻片从尿中分离细胞,并通过间接免疫荧光评估足细胞标记蛋白(PDX)、CD68和Ki67抗原的表达。此外,将上述抗原与细胞角蛋白、WT1和CD - 105组合进行双重染色。对22例诊断时尿蛋白与肌酐比值超过2.0的患者进行36个月的随访,每3个月评估一次肾功能和蛋白尿。在观察期间,患者接受标准治疗。
随访期间血清肌酐(SCr)翻倍的患者在研究开始时Ki67阳性细胞数量显著高于未翻倍的患者(p = 0.0149)。通过逻辑回归分析,发现诊断时CD68和Ki67阳性细胞数量,而非抗PDX阳性细胞数量,是36个月随访中SCr浓度翻倍的预测指标。双重染色结果表明,PDX阳性细胞可被鉴定为足细胞或其前体以及壁层上皮细胞。
尿沉渣中PDX阳性细胞数量不能预测FSGS的进展,而尿足细胞谱系的CD68和Ki67表型在原发性FSGS的36个月观察中显然具有预后意义。