Alport Syndrome Classification and Management
Alport syndrome affects up to 60,000 people in the United States. The proposed reclassification of thin basement membrane nephropathy and some cases of focal segmental glomerulosclerosis as Alport syndrome could substantially increase the affected population. The reclassification scheme categorizes...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2020-09-01
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| Series: | Kidney Medicine |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2590059520301606 |
| _version_ | 1818515266208792576 |
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| author | Bradley A. Warady Rajiv Agarwal Sripal Bangalore Arlene Chapman Adeera Levin Peter Stenvinkel Robert D. Toto Glenn M. Chertow |
| author_facet | Bradley A. Warady Rajiv Agarwal Sripal Bangalore Arlene Chapman Adeera Levin Peter Stenvinkel Robert D. Toto Glenn M. Chertow |
| author_sort | Bradley A. Warady |
| collection | DOAJ |
| description | Alport syndrome affects up to 60,000 people in the United States. The proposed reclassification of thin basement membrane nephropathy and some cases of focal segmental glomerulosclerosis as Alport syndrome could substantially increase the affected population. The reclassification scheme categorizes Alport syndrome as 3 distinct diseases of type IV collagen α3/4/5 based on a genetic evaluation: X-linked, autosomal, and digenic. This approach has the advantage of identifying patients at risk for progressive loss of kidney function. Furthermore, the shared molecular cause of Alport syndrome and thin basement membrane nephropathy arises from mutations in the COL4A3, COL4A4, and COL4A5 genes, which contribute to downstream pathophysiologic consequences, including chronic kidney inflammation. Recent evidence indicates that chronic inflammation and its regulation through anti-inflammatory nuclear factor erythroid 2–related factor 2 (Nrf2) and proinflammatory nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) transcription factors plays a central role in renal tubular and glomerular cell responses to injury. Crosstalk between the Nrf2 and NF-κB pathways is important in the regulation of inflammation in patients with chronic kidney disease; moreover, there is evidence that an insufficient Nrf2 response to inflammation contributes to disease progression. Given the association between type IV collagen abnormalities and chronic inflammation, there is renewed interest in targeted anti-inflammatory therapies in Alport syndrome and other forms of progressive chronic kidney disease. |
| first_indexed | 2024-12-11T00:26:46Z |
| format | Article |
| id | doaj.art-2c5fd47a1b1c4ef5b389452b3235db65 |
| institution | Directory Open Access Journal |
| issn | 2590-0595 |
| language | English |
| last_indexed | 2024-12-11T00:26:46Z |
| publishDate | 2020-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Kidney Medicine |
| spelling | doaj.art-2c5fd47a1b1c4ef5b389452b3235db652022-12-22T01:27:31ZengElsevierKidney Medicine2590-05952020-09-0125639649Alport Syndrome Classification and ManagementBradley A. Warady0Rajiv Agarwal1Sripal Bangalore2Arlene Chapman3Adeera Levin4Peter Stenvinkel5Robert D. Toto6Glenn M. Chertow7Division of Pediatric Nephrology, Children’s Mercy Kansas City, Kansas City, MO; Address for Correspondence: Bradley A. Warady, MD, Division of Pediatric Nephrology, Children’s Mercy Kansas City; Department of Pediatrics, University of Missouri-Kansas City School of Medicine, 2401 Gillham Rd, Kansas City, MO 64108.Division of Nephrology, Indiana University, Indianapolis, INDivision of Cardiology, New York University, New York, NYDivision of Nephrology, University of Chicago, Chicago, ILDivision of Nephrology, University of British Columbia, Vancouver, BC, CanadaKarolinska Institute, Stockholm, SwedenDivision of Nephrology, University of Texas Southwestern Medical Center, Dallas, TXDivision of Nephrology, Stanford University, Stanford, CAAlport syndrome affects up to 60,000 people in the United States. The proposed reclassification of thin basement membrane nephropathy and some cases of focal segmental glomerulosclerosis as Alport syndrome could substantially increase the affected population. The reclassification scheme categorizes Alport syndrome as 3 distinct diseases of type IV collagen α3/4/5 based on a genetic evaluation: X-linked, autosomal, and digenic. This approach has the advantage of identifying patients at risk for progressive loss of kidney function. Furthermore, the shared molecular cause of Alport syndrome and thin basement membrane nephropathy arises from mutations in the COL4A3, COL4A4, and COL4A5 genes, which contribute to downstream pathophysiologic consequences, including chronic kidney inflammation. Recent evidence indicates that chronic inflammation and its regulation through anti-inflammatory nuclear factor erythroid 2–related factor 2 (Nrf2) and proinflammatory nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) transcription factors plays a central role in renal tubular and glomerular cell responses to injury. Crosstalk between the Nrf2 and NF-κB pathways is important in the regulation of inflammation in patients with chronic kidney disease; moreover, there is evidence that an insufficient Nrf2 response to inflammation contributes to disease progression. Given the association between type IV collagen abnormalities and chronic inflammation, there is renewed interest in targeted anti-inflammatory therapies in Alport syndrome and other forms of progressive chronic kidney disease.http://www.sciencedirect.com/science/article/pii/S2590059520301606Alport syndromechronic kidney diseasechronic inflammationCOL4A3COL4A4COL4A5 |
| spellingShingle | Bradley A. Warady Rajiv Agarwal Sripal Bangalore Arlene Chapman Adeera Levin Peter Stenvinkel Robert D. Toto Glenn M. Chertow Alport Syndrome Classification and Management Kidney Medicine Alport syndrome chronic kidney disease chronic inflammation COL4A3 COL4A4 COL4A5 |
| title | Alport Syndrome Classification and Management |
| title_full | Alport Syndrome Classification and Management |
| title_fullStr | Alport Syndrome Classification and Management |
| title_full_unstemmed | Alport Syndrome Classification and Management |
| title_short | Alport Syndrome Classification and Management |
| title_sort | alport syndrome classification and management |
| topic | Alport syndrome chronic kidney disease chronic inflammation COL4A3 COL4A4 COL4A5 |
| url | http://www.sciencedirect.com/science/article/pii/S2590059520301606 |
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