Alport syndrome

Alport syndrome is an inherited renal disorder characterized by early haematuria, progressing to proteinuria, sensorineural hearing loss, and progressive renal failure typically in the third or fourth decade but with wide variation. It is responsible for about 1% of end-stage renal failure. Over 80% of cases are X-linked and young men are most affected, but heterozygous carriers of the abnormal gene are also at significantly increased risk of end-stage renal failure in their lifetime. Those affected by the autosomal recessive variant are phenotypically very similar. It is caused by mutations in tissue-specific isoforms of basement membrane (type IV) collagen encoded by COL4A5 (X chromosome), COL4A3, and COL4A4 (chromosome 2).

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Alport syndrome

10.1093/med/9780199592548.003.0322_update_001 ◽

2018 ◽

Author(s):

Laurence Heidet ◽

Bertrand Knebelmann ◽

Marie Claire Gubler

Keyword(s):

Renal Failure ◽

Hearing Loss ◽

Alport Syndrome ◽

Significant Risk ◽

Angiotensin Converting Enzyme Inhibitors ◽

Aortic Disease ◽

Converting Enzyme Inhibitors ◽

Ocular Abnormalities ◽

End Stage Renal Failure ◽

End Stage

This chapter describes the clinical features of Alport syndrome. The characteristic features of this familial condition are haematuria with progressive nephropathy and sensorineural hearing loss. Most cases are X-linked so this is typically seen in boys and young men, but female heterozygous (‘carriers’) of X-linked Alport syndrome are also at significant risk of renal disease in their lifetime. The average age of end-stage renal failure is in the third or fourth decade. Those with autosomal recessive disease (approximately 15%) show a similar phenotype. Hearing loss characteristically develops during teenage years or as a young adult, usually as proteinuria becomes prominent and renal function begins to be lost. Angiotensin-converting enzyme inhibitors may modify this classic description. Ocular abnormalities are less consistent and tend to occur later, often after end-stage renal failure. Retinal changes do not affect sight. Lenticonus can be treated by lens replacement. Other ocular abnormalities occur rarely. Aortic disease has been reported in occasional families.

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Alport syndrome

10.1093/med/9780199592548.003.0324 ◽

2015 ◽

Author(s):

Laurence Heidet ◽

Bertrand Knebelmann ◽

Marie Claire Gubler

Keyword(s):

Renal Failure ◽

Hearing Aids ◽

Alport Syndrome ◽

Enzyme Inhibitors ◽

Angiotensin Converting Enzyme Inhibitors ◽

Converting Enzyme Inhibitors ◽

End Stage Renal Failure ◽

Animal Data ◽

Average Survival ◽

End Stage

Management of Alport syndrome has in the past been expectant and supportive. Modern hearing aids have substantially improved the function of affected individuals. However, animal data and more recently observational data from Alport registries strongly suggest a protective effect of angiotensin-converting enzyme inhibitors. There is a suggestion that early commencement of treatment may slow progression substantially. These should now be recommended for all with proteinuria, and possibly even before then for those known to harbour mutations certain to cause end-stage renal failure. A very small minority develop the difficult post-transplant complication of Alport anti-glomerular basement membrane disease. This can rarely be treated successfully and leaves some patients on long-term dialysis. However, overall, patients with Alport syndrome have better than average survival and other outcomes than other patients with end-stage renal failure. Most are successfully transplanted. The question of risk to heterozygous carriers from donating kidneys to their affected relatives arises frequently. The risks may be felt acceptable in some circumstances. Additional therapies are under investigation.

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First-use Reactions: A Potential Hazard for Referral Centers

The International Journal of Artificial Organs ◽

10.1177/039139888901201104 ◽

1989 ◽

Vol 12 (11) ◽

pp. 688-691 ◽

Cited By ~ 5

Author(s):

R.J. Caruana

Keyword(s):

Renal Failure ◽

Tertiary Care ◽

Clinical Signs ◽

Signs And Symptoms ◽

Potential Hazard ◽

End Stage Renal Failure ◽

Increased Risk ◽

Dialysis Facility ◽

Clinical Signs And Symptoms ◽

End Stage

First-use reactions comprise a spectrum of adverse clinical signs and symptoms occurring in end-stage renal failure patients during hemodialysis treatments. This report describes four patients experiencing first-use reactions in the context of being referred to or from a tertiary care inpatient dialysis facility. Theories on the pathogenesis of first-use reactions are reviewed and recommendations for identifying patients at increased risk for this problem are proposed.

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X-linked Alport Syndrome

Journal of the American Society of Nephrology ◽

10.1681/asn.v114649 ◽

2000 ◽

Vol 11 (4) ◽

pp. 649-657 ◽

Cited By ~ 12

Author(s):

JEAN PHILIPPE JAIS ◽

BERTRAND KNEBELMANN ◽

IANNIS GIATRAS ◽

MARIO DE MARCHI ◽

GIANFRANCO RIZZONI ◽

...

Keyword(s):

Renal Failure ◽

Hearing Loss ◽

Alport Syndrome ◽

Hereditary Disease ◽

Missense Mutations ◽

Site Mutation ◽

Dominant Form ◽

End Stage Renal Failure ◽

Male Patients ◽

End Stage

Abstract. Alport syndrome (AS) is a type IV collagen hereditary disease characterized by the association of progressive hematuric nephritis, hearing loss, and, frequently, ocular changes. Mutations in the COL4A5 collagen gene are responsible for the more common X-linked dominant form of the disease. Considerable allelic heterogeneity has been observed. A “European Community Alport Syndrome Concerted Action” has been established to delineate accurately the AS phenotype and to determine genotype-phenotype correlations in a large number of families. Data concerning 329 families, 250 of them with an X-linked transmission, were collected. Characteristics of the 401 male patients belonging to the 195 families with COL4A5 mutation are presented. All male patients were hematuric, and the rate of progression to end-stage renal failure and deafness was mutation-dependent. Large deletions, nonsense mutations, or small mutations changing the reading frame conferred to affected male patients a 90% probability of developing end-stage renal failure before 30 yr of age, whereas the same risk was of 50 and 70%, respectively, in patients with missense or splice site mutation. The risk of developing hearing loss before 30 yr of age was approximately 60% in patients with missense mutations, contrary to 90% for the other types of mutations. The natural history of X-linked AS and correlations with COL4A5 mutations have been established in a large cohort of male patients. These data could be used for further evaluation of therapeutic approaches.

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Nephrotic syndrome

InnovAiT Education and inspiration for general practice ◽

10.1177/1755738019895050 ◽

2020 ◽

Vol 13 (3) ◽

pp. 159-163

Author(s):

Thuvaraka Ware

Keyword(s):

Primary Care ◽

Renal Failure ◽

Renal Function ◽

Nephrotic Syndrome ◽

Diagnostic Process ◽

Risk Of Infection ◽

Rare Presentation ◽

End Stage Renal Failure ◽

Increased Risk ◽

End Stage

Nephrotic syndrome is characterised by proteinuria, hypoalbuminaemia and oedema. The renal function is often normal and symptoms may mimic other common pathologies presenting in the community. The underlying aetiology is more heterogenous in adults compared with children, further confounding the diagnostic process and leading to delays in recognition. It is a relatively rare presentation in primary care, but the consequences of nephrotic syndrome can be significant. Complications include hyperlipidaemia, hypercoaguability, increased risk of infection and end-stage renal failure. It is, therefore, important to diagnose, investigate and manage nephrotic syndrome appropriately.

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Childhood kidney disease is associated with increased risk of end-stage renal failure in adulthood

Archives of Disease in Childhood - Education and Practice ◽

10.1136/archdischild-2018-315332 ◽

2018 ◽

Vol 104 (1) ◽

pp. 55-56 ◽

Cited By ~ 1

Author(s):

Amanda Louise Newnham ◽

Amanda Jane Friend

Keyword(s):

Renal Failure ◽

Kidney Disease ◽

End Stage Renal Failure ◽

Increased Risk ◽

End Stage

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SGLT2 inhibitors – a potential treatment for Alport syndrome

Clinical Science ◽

10.1042/cs20191276 ◽

2020 ◽

Vol 134 (4) ◽

pp. 379-388 ◽

Cited By ~ 1

Author(s):

Holly Mabillard ◽

John A. Sayer

Keyword(s):

Chronic Kidney Disease ◽

Kidney Disease ◽

Alport Syndrome ◽

Sglt2 Inhibitors ◽

Potential Candidate ◽

Potential Treatment ◽

Type Iv ◽

Patients With Diabetes ◽

Membrane Type ◽

End Stage

Abstract Alport syndrome is a rare genetic disease that results in disordered basement membrane type IV collagen resulting in occular and auditory defects as well of progressive kidney disease. Although no ‘cure’ currently exists, therapeutic blockade of the renin–angiotensin–aldosterone system can slow the progression to end-stage kidney disease (ESKD). Clinical trials for treatments in preventing chronic kidney disease have largely been negative over the last two decades until recent trials have shown positive cardiovascular and renal outcomes of sodium–glucose co-transporter-2 (SGLT2) inhibitors in patients with diabetes mellitus. Although marketed as medications for Type 2 diabetes, SGLT2 inhibitors have been found to have additional properties that are nephroprotective which makes them a potential candidate for treatment for those with other forms of progressive kidney disease. This review discusses the evidence for the use of SGLT2 inhibitors as a potential treatment in Alport syndrome that may slow the progression of chronic kidney disease and prevent patients reaching ESKD.

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