RAAS inhibition and the course of Alport syndrome
Pierides, Alkis M.
Constantinou-Deltas, Constantinos D.
Google Scholar check
MetadataShow full item record
Alport syndrome (AS) is a hereditary progressive glomerulonephritis with a high life-time risk for end-stage renal disease (ESRD). Most patients will reach ESRD before the age of 30 years, while a subset of them with milder mutations will do so at older ages, even after 50 years. Frequent extrarenal manifestations are hearing loss and ocular abnormalities. AS is a genetically heterogeneous collagen IV nephropathy, with 85% of the cases caused by mutations in the X-linked COL4A5 gene and the rest by homozygous or compound heterozygous mutations in either the COL4A3 or the COL4A4 gene on chromosome 2q36-37. There is no radical cure for the disease and attempts to use various stem cell therapies in animal models have been met with ambiguous success. However, effective treatment has been accomplished with pharmacological intervention at the renin-angiotensin-aldosterone system (RAAS), first in animal models of AS and more recently in humans. Angiotensin converting enzyme inhibitors (ACEis) and angiotensin receptor blockers (ARBs) have been shown to significantly delay the progression of chronic kidney disease and the onset of ESRD. Also, renin inhibitors and aldosterone blockade were used with positive results, while the combination of ACEis and ARBs was met with mixed success. An important study, the EARLY-PROTECT, aims at evaluating the efficacy of ACEis when administered very early on in children with AS. Novel therapies are also tested experimentally or are under design in animal models by several groups, including the use of amniotic fluid stem cells and synthetic chaperones.
Showing items related by title, author, creator and subject.
Angiotensin inhibition enhances drug delivery and potentiates chemotherapy by decompressing tumour blood vessels Chauhan, V. P.; Martin, J. D.; Liu, H.; Lacorre, D. A.; Jain, S. R.; Kozin, S. V.; Stylianopoulos, T.; Mousa, A. S.; Han, X.; Adstamongkonkul, P.; Popovic, Z.; Huang, P.; Bawendi, M. G.; Boucher, Y.; Jain, R. K. (2013)Cancer and stromal cells actively exert physical forces (solid stress) to compress tumour blood vessels, thus reducing vascular perfusion. Tumour interstitial matrix also contributes to solid stress, with hyaluronan ...
Alport syndrome from bench to bedside: The potential of current treatment beyond RAAS blockade and the horizon of future therapies Gross, O.; Perin, L.; Constantinou-Deltas, Constantinos D. (2014)The hereditary type IV collagen disease Alport syndrome (AS) always leads to end-stage renal failure. Yesterday, for the past 90 years, this course was described as 'inevitable'. Today, RAAS blockade has changed the ...
On 'Incidence of renal failure and nephroprotection by RAAS inhibition in heterozygous carriers of X-chromosomal and autosomal recessive Alport mutations' Voskarides, Konstantinos; Pierides, Alkis M.; Constantinou-Deltas, Constantinos D. (2013)