Pediatric Nephrology

, Volume 28, Issue 7, pp 1025–1036 | Cite as

An update on the pathomechanisms and future therapies of Alport syndrome

  • Damien Noone
  • Christoph LichtEmail author


Alport Syndrome (AS) is an inherited progressive disease that is caused by mutations of the genes encoding the key collagen chains, α3, α4, and α5, which are necessary for the composition of collagen type IV to form a robust glomerular basement membrane (GBM), capable of withstanding the significant biomechanical strain to which the glomerulus is subjected. Progressive loss of the filtration barrier allows excessive proteinuria, which ultimately leads to end-stage kidney disease (ESKD). The evidence for a beneficial renoprotective effect of renin-angiotensin-aldosterone system (RAAS) blockade by angiotensin-converting enzyme (ACE) inhibition and/or angiotensin receptor blockers (ARBs) is well established in AS and recent evidence has shown that it can significantly delay the time to onset of renal replacement therapy and ESKD. Future potential treatments of AS disease progression are evaluated in this review.


Alport syndrome Proteinuria Glomerular basement membrane Proximal tubular epithelial cells Tubulointerstitium Inflammation Fibrosis 



Angiotensin-converting enzyme


Alternative pathway of complement activation


Angiotensin receptor I blocker


Alport syndrome


Bone morphogenetic protein 7


Bone marrow transplant


Chemokine (C-C Motif) ligand 2 (MCP-1)


Chemokine (C-C Motif) ligand 5


β Chemokine receptor


Connective tissue growth factor


Chronic kidney disease


α Chemokine receptor


Discoidin domain receptor


Diabetic nephropathy


Extracellular matrix


Epidermal growth factor receptor


Epithelial-to-mesenchymal transformation


Extracellular regulated kinase


End-stage kidney disease


Glomerular basement membrane


Glomerular filtration rate


3-Hydroxy-3-methylglutaryl CoA


Membrane attack complex


Monocyte chemotactic protein-1 (CCL-2)


Matrix metalloproteinase


Mesenchymal stromal cell


Peroxisome proliferator-activated receptor γ


Proximal tubular epithelial cell


Renin–angiotensin–aldosterone system


Regulated upon activation, normal T-cell expressed, and secreted (CCL5)


Transforming growth factor - β1


Tumor necrosis factor-α


X-linked Alport syndrome


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Copyright information

© IPNA 2012

Authors and Affiliations

  1. 1.Division of Nephrology, Department of PaediatricsThe Hospital for Sick ChildrenTorontoCanada
  2. 2.Program in Cell BiologyThe Hospital for Sick ChildrenTorontoCanada
  3. 3.Department of PaediatricsUniversity of TorontoTorontoCanada

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