Negative Staining for COL4A5 Correlates With Worse Prognosis and More Severe Ultrastructural Alterations in Males With Alport Syndrome

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• 作者：Samar M. Said¹ ; Mary E. Fidler¹ ; Anthony M. Valeri² ; Brooke McCann¹ ; Wade Fiedler¹ ; Lynn D. Cornell¹ ; Mariam Priya Alexander¹ ; Ahmed M. Alkhunaizi³ ; Anne Sullivan⁴ ; Carl H. Cramer⁵ ; Marie C. Hogan⁶ ; Samih H. Nasr¹ ; ^{nasr.samih@mayo.edu}
• 关键词：Alport syndrome ; collagen chains staining ; electron microscopy ; hereditary nephritis ; renal biopsy
• 刊名：Kidney International Reports
• 出版年：2017
• 出版时间：January 2017
• 年：2017
• 卷：2
• 期：1
• 页码：44-52
• 全文大小：1405 K
• 卷排序：2

文摘

Alport syndrome (AS) is a genetic disorder characterized by progressive hematuric nephropathy with or without sensorineural hearing loss and ocular lesions. Previous studies on AS included mostly children.MethodsTo determine the prognostic value of loss of staining for collagen type IV alpha 5 (COL4A5) and its relationship with the ultrastructural glomerular basement membrane alterations, we performed direct immunofluorescence using a mixture of fluorescein isothiocyanate-conjugated and Texas-red conjugated antibodies against COL4A5 and COL4A2, respectively, on renal biopsies of 25 males with AS (including 16 who were diagnosed in adulthood).ResultsAll patients showed normal positive staining of glomerular basement membranes and tubular basement membranes for COL4A2. Of the 25 patients, 10 (40%) patients showed loss of staining for COL4A5 (including 89% of children and 13% of adults) and the remaining 15 (60%) had intact staining for COL4A5. Compared with patients with intact staining for COL4A5, those with loss of staining had more prominent ultrastructural glomerular basement membrane alterations and were younger at the time of biopsy. By Kaplan-Meier survival analysis and Cox regression analysis, loss of staining for COL4A5 predicted earlier progression to overt proteinuria and stage 2 chronic kidney disease or worse. By multivariate Cox regression analysis, loss of staining for COL4A5 was an independent predictor of the development of overt proteinuria and stage 2 chronic kidney disease or worse.DiscussionThus, the COL4A5 expression pattern has an important prognostic value and it correlates with the severity of ultrastructural glomerular basement membrane alterations in males with AS. Loss of COL4A5 staining is uncommon in patients with AS diagnosed in their adulthood.