Negative Staining for COL4A5 Correlates With Worse Prognosis and More Severe Ultrastructural Alterations in Males With Alport Syndrome
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. Methods: To determine the prognostic value of loss of staining for collagen type IV alpha 5 (C...
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| Format: | Article |
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Elsevier
2017-01-01
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| Series: | Kidney International Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2468024916301358 |
| _version_ | 1819012091566096384 |
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| author | Samar M. Said Mary E. Fidler Anthony M. Valeri Brooke McCann Wade Fiedler Lynn D. Cornell Mariam Priya Alexander Ahmed M. Alkhunaizi Anne Sullivan Carl H. Cramer Marie C. Hogan Samih H. Nasr |
| author_facet | Samar M. Said Mary E. Fidler Anthony M. Valeri Brooke McCann Wade Fiedler Lynn D. Cornell Mariam Priya Alexander Ahmed M. Alkhunaizi Anne Sullivan Carl H. Cramer Marie C. Hogan Samih H. Nasr |
| author_sort | Samar M. Said |
| collection | DOAJ |
| description | 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.
Methods: To 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).
Results: All 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.
Discussion: Thus, 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. |
| first_indexed | 2024-12-21T01:38:32Z |
| format | Article |
| id | doaj.art-77bb12782c4b462ab2328ee13dd79917 |
| institution | Directory Open Access Journal |
| issn | 2468-0249 |
| language | English |
| last_indexed | 2024-12-21T01:38:32Z |
| publishDate | 2017-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Kidney International Reports |
| spelling | doaj.art-77bb12782c4b462ab2328ee13dd799172022-12-21T19:20:13ZengElsevierKidney International Reports2468-02492017-01-0121445210.1016/j.ekir.2016.09.056Negative Staining for COL4A5 Correlates With Worse Prognosis and More Severe Ultrastructural Alterations in Males With Alport SyndromeSamar M. Said0Mary E. Fidler1Anthony M. Valeri2Brooke McCann3Wade Fiedler4Lynn D. Cornell5Mariam Priya Alexander6Ahmed M. Alkhunaizi7Anne Sullivan8Carl H. Cramer9Marie C. Hogan10Samih H. Nasr11Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USADepartment of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USADivision of Nephrology, Columbia University, College of Physicians and Surgeons, New York, New York, USADepartment of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USADepartment of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USADepartment of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USADepartment of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USANephrology Section, Johns Hopkins Aramco Healthcare, Dhahran, Saudi ArabiaPermanente Medical Group, Oakland, California, USADivision of Pediatric Nephrology, Mayo Clinic, Rochester, Minnesota, USADivision of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota, USADepartment of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USAAlport 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. Methods: To 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). Results: All 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. Discussion: Thus, 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.http://www.sciencedirect.com/science/article/pii/S2468024916301358Alport syndromecollagen chains stainingelectron microscopyhereditary nephritisrenal biopsy |
| spellingShingle | Samar M. Said Mary E. Fidler Anthony M. Valeri Brooke McCann Wade Fiedler Lynn D. Cornell Mariam Priya Alexander Ahmed M. Alkhunaizi Anne Sullivan Carl H. Cramer Marie C. Hogan Samih H. Nasr Negative Staining for COL4A5 Correlates With Worse Prognosis and More Severe Ultrastructural Alterations in Males With Alport Syndrome Kidney International Reports Alport syndrome collagen chains staining electron microscopy hereditary nephritis renal biopsy |
| title | Negative Staining for COL4A5 Correlates With Worse Prognosis and More Severe Ultrastructural Alterations in Males With Alport Syndrome |
| title_full | Negative Staining for COL4A5 Correlates With Worse Prognosis and More Severe Ultrastructural Alterations in Males With Alport Syndrome |
| title_fullStr | Negative Staining for COL4A5 Correlates With Worse Prognosis and More Severe Ultrastructural Alterations in Males With Alport Syndrome |
| title_full_unstemmed | Negative Staining for COL4A5 Correlates With Worse Prognosis and More Severe Ultrastructural Alterations in Males With Alport Syndrome |
| title_short | Negative Staining for COL4A5 Correlates With Worse Prognosis and More Severe Ultrastructural Alterations in Males With Alport Syndrome |
| title_sort | negative staining for col4a5 correlates with worse prognosis and more severe ultrastructural alterations in males with alport syndrome |
| topic | Alport syndrome collagen chains staining electron microscopy hereditary nephritis renal biopsy |
| url | http://www.sciencedirect.com/science/article/pii/S2468024916301358 |
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