Prospective study on the potential of RAAS blockade to halt renal disease in Alport syndrome patients with heterozygous mutations

Stock, Johanna; Kuenanz, Johannes; Glonke, Niklas; Sonntag, Joseph; Frese, Jenny; Tönshoff, Burkhard; Höcker, Britta; Höppe, Bernd; Feldkötter, Markus; Pape, Lars; Lerch, Christian; Wygoda, Simone; Weber, Manfred; Müller, Gerhard-Anton; Groß, Oliver

doi:10.1007/s00467-016-3452-z

Cited by 31 publications

(19 citation statements)

References 29 publications

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“…Therefore, with the help of registry data, the further positive effect of ramipril already can be predicted with great certainty in children with early stages of AS. 8,14,15,27 Baseline albuminuria was almost 2 times lower in the placebo (23 mg/gCrea) versus the ramipril (39.4 mg/gCrea) group. Therefore, more children in the placebo group needed a tripling of albuminuria to reach the primary efficacy Progression of renal disease in the randomized arm.…”

Section: Discussionmentioning

confidence: 96%

A multicenter, randomized, placebo-controlled, double-blind phase 3 trial with open-arm comparison indicates safety and efficacy of nephroprotective therapy with ramipril in children with Alport’s syndrome

Groß

Tönshoff

Weber

et al. 2020

Kidney International

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110

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Section: Discussionmentioning

confidence: 96%

A multicenter, randomized, placebo-controlled, double-blind phase 3 trial with open-arm comparison indicates safety and efficacy of nephroprotective therapy with ramipril in children with Alport’s syndrome

Groß

Tönshoff

Weber

et al. 2020

Kidney International

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110

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“…Both had histology consistent with TBMN. Though this gene has typically been associated with recessive Alport syndrome, multiple reports (Marcocci et al 2009;Hines et al 2018;Longo et al 2002) have demonstrated that patients with heterozygous COL4A4 or COL4A3 variants can develop significant renal disease and can benefit from early initiation of renin-angiotensinaldosterone system blockade (Stock et al 2017).…”

Section: Discussionmentioning

confidence: 99%

Diagnostic utility of genetic testing in patients undergoing renal biopsy

Benson

Murray

Doyle

et al. 2020

Cold Spring Harb Mol Case Stud

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High-throughput DNA testing is becoming established as a standard diagnostic test in the renal clinic. Previously published studies on cohorts of patients with unexplained chronic kidney disease of a suspected genetic aetiology have suggested a diagnostic yield for genomic sequencing of up to 18%. Here we determine the yield of targeted gene panel in a clinically unscreened cohort of patients referred for percutaneous native renal biopsy. Patients who underwent renal biopsy for investigation of chronic kidney disease were sequenced using a genomic sequencing panel covering 227 genes in which variation is known to be associated with monogenic chronic kidney disease (CKD). Candidate disease-causing variants were assessed for pathogenicity using guidelines from the American College for Medical Genetics and Genomics. Fifty CKD patients were recruited and sequenced. A molecular diagnosis was obtained for two patients (4%). A molecular diagnosis is possible using genomic testing in ∼4% of clinically unscreened patients undergoing renal biopsy. Genetic screening may be useful for diagnosis in a subset of CKD patients but is most valuable when applied to patients with suspected heritable forms of kidney disease.

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“…Patients cannot be cured, but like in other forms of glomerular disease, will benefit from timely initiated general supportive care including blood pressure control and anti-proteinuric medication [25]. More specifically, evidence is increasing that early treatment with angiotensin converting enzyme inhibitors or angiotensinogen receptor blocking agents considerably delays the progressive decline in renal function in patients with Alport syndrome [26][27][28][29][30][31][32]. Therefore, both from a counseling and a therapeutic point of view, it is important to identify patients early in life.…”

Section: Discussionmentioning

confidence: 99%

Diagnosing Alport Syndrome: Lessons from the Pediatric Ward

Vos

Zietse

Geel

et al. 2018

Nephron

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Background: Alport syndrome is a rare inheritable kidney disease frequently leading to end-stage kidney disease in young adults. Patients could benefit from early recognition of the disease. In several children with Alport syndrome, a parent was noticed to have renal symptoms attributed to another renal disease. Aim: To review the renal history of the closest family members of a cohort of pediatric patients with genetically proven Alport syndrome. Methods: The medical records of all children with genetically proven Alport syndrome identified at our pediatric nephrology department in the last 20 years were reviewed, with focus on the medical history of affected parents. Results: Twenty-three children with Alport syndrome from 21 different families were identified. Eight of 21 probands had family member(s) with renal symptoms attributed to other diseases. In these, a type IV collagen mutation was determined only after the manifestation of Alport syndrome in their child. One proband presented atypically with acute membrano-proliferative glomerulo-nephritis. Only 3 out of 8 probands with a known family history of Alport syndrome had been intentionally screened for this disease. A COL4A5 mutation was found in 18 probands, COL4A3 in 2, and COL4A4 in 1. Each family showed private mutations; 17 out of 21 mutations were novel. Conclusions: Atypical presentation of Alport syndrome was quite common in mothers of our pediatric patients. To enable earlier diagnosis of Alport syndrome, nephrologists should look for a positive diagnosis in any patient with persistent renal symptoms, especially if there is a positive family history of (any) renal disease.

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Prospective study on the potential of RAAS blockade to halt renal disease in Alport syndrome patients with heterozygous mutations

Cited by 31 publications

References 29 publications

A multicenter, randomized, placebo-controlled, double-blind phase 3 trial with open-arm comparison indicates safety and efficacy of nephroprotective therapy with ramipril in children with Alport’s syndrome

A multicenter, randomized, placebo-controlled, double-blind phase 3 trial with open-arm comparison indicates safety and efficacy of nephroprotective therapy with ramipril in children with Alport’s syndrome

Diagnostic utility of genetic testing in patients undergoing renal biopsy

Diagnosing Alport Syndrome: Lessons from the Pediatric Ward

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