Alport Syndrome: No Evidence of Improved Prognosis in Modern Era

Kelly, YP; Wallis, Lila A.; Patil, Anish; Murray, S; Kant, Sarina G.; Kaballo, M; Casserly, Liam F.; Doyle, Brian B.; Dorman, Tomasz; O’Kelly, Patrick; Conlon, PJ

doi:10.23937/2572-3286.1510036

Cited by 2 publications

(3 citation statements)

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“…The prevalence of Alport syndrome is estimated at approximately 1 in 50,000 live births. 12 Alport syndrome affects an estimated 30,000 to 60,000 persons in the United States. 13 Based on the current classification scheme, Alport syndrome accounts for an estimated 3% of CKD in children and 0.2% of adults with end-stage kidney disease (ESKD) in the United States.…”

Section: Update On the Genetics And Prevalence Of Alport Syndromementioning

confidence: 99%

Alport Syndrome Classification and Management

et al. 2020

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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.

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Section: Update On the Genetics And Prevalence Of Alport Syndromementioning

confidence: 99%

Alport Syndrome Classification and Management

et al. 2020

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“…Alport syndrome (AS) is one of the most common human fatal hereditary renal diseases. Its prevalence is reported as 1 in 5000–50 000 live births 1 2. A deficiency of type IV collagen chains α3, α4 or α5 in the basement membranes of renal glomerulus, eyes and ears is caused by mutations in COL4A3 , COL4A4 or COL4A5 , respectively 2.…”

Section: Introductionmentioning

confidence: 99%

“…Its prevalence is reported as 1 in 5000–50 000 live births. 1 2 A deficiency of type IV collagen chains α3, α4 or α5 in the basement membranes of renal glomerulus, eyes and ears is caused by mutations in COL4A3 , COL4A4 or COL4A5 , respectively. 2 Therefore, AS is characterised by haematuria, albuminuria and a progressive decline of renal function, 3 as well as sensorineural hearing loss 4 and ocular abnormalities.…”

Section: Introductionmentioning

confidence: 99%

Human umbilical cord mesenchymal stem cell therapy for renal dysfunction in Alport syndrome: protocol for an open-label, single-arm trial in China

Huang,

Zou,

Zhang

et al. 2024

BMJ Open

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IntroductionAlport syndrome (AS) is one of the most common fatal hereditary renal diseases in human, with a high risk of progressing to end-stage renal disease without effective treatments. Mesenchymal stem cells (MSCs) have recently emerged as a promising therapeutic strategy for chronic kidney disease. However, the safety and therapeutic potential of MSC transfusion for patients with AS are still need to be confirmed. Therefore, we have designed a clinical trial to evaluate the hypothesis that intravenous infusion of human umbilical cord-derived MSC (hUC-MSC) is safe, feasible, and well-tolerated in children with AS.Methods and analysisWe report the protocol of the first prospective, open-label, single-arm clinical trial to evaluate the safety and preliminary efficacy of hUC-MSC transfusion in children with early-stage AS. Paediatric patients diagnosed with AS who have persistent albuminuria will be candidates for screening. Twelve eligible patients are planned to recruit and will receive hUC-MSC infusions under close safety monitoring, and complete the efficacy assessments at scheduled follow-up visits. The primary endpoints include the occurrence of adverse events to assess safety and the albuminuria level for efficacy evaluation. Secondary endpoint assessments are based on haematuria and glomerular filtration measurements. Each patient’s efficacy endpoints will be evaluated against their baseline levels. Additionally, the underlying mechanism of hUC-MSC therapy will be explored through transcriptomic and proteomic analysis of blood and urine samples.Ethics and disseminationThe protocol (V.1.0, date 17 January 2015) was approved by the institutional review board of the Affiliated Taihe Hospital of Hubei University of Medicine (ethical approval 03 March 2015). Written informed consent will be obtained from the patient and/or guardians before study specific process. In addition to publication in a peer-reviewed scientific journal, a lay summary of study will be available for participants and the public on the Chinese Organization for Rare Disorders website (http://www.cord.org.cn/).Trial registration numberISRCTN62094626.

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Alport Syndrome: No Evidence of Improved Prognosis in Modern Era

Cited by 2 publications

References 0 publications

Alport Syndrome Classification and Management

Alport Syndrome Classification and Management

Human umbilical cord mesenchymal stem cell therapy for renal dysfunction in Alport syndrome: protocol for an open-label, single-arm trial in China

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