Verlaufskontrolle einer prospektiven Beobachtungsstudie bezüglich des Therapieerfolges bei Patienten mit Alport Syndrom

Follow-up of a prospective observational study on treatment success in patients with Alport syndrome

by Anna Lena Dierkes
Doctoral thesis
Date of Examination:2024-08-07
Date of issue:2024-07-26
Advisor:Prof. Dr. Oliver Gross
Referee:Prof. Dr. Oliver Gross
Referee:Prof. Dr. Nicolas Feltgen
Persistent Address: http://dx.doi.org/10.53846/goediss-10643

 

 

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Abstract

English

Alport Syndrome (AS) is the second most common hereditary kidney disorder globally. It is induced by a pathological collagen IV network caused by variants in the COL4A3, COL4A4, and COL4A5 genes, leading to renal dysfunction manifesting as hematuria, microalbuminuria, or significant proteinuria. Without treatment, AS often progresses to end-stage renal disease (ESRD) and reduces life expectancy, pointing out the need for early and effective intervention. This study evaluates the therapeutic efficacy of a Renin-Angiotensin-Aldosterone System (RAAS) blockade using data from the European Alport Therapy Registry. Previous studies have demonstrated that ACE inhibitors significantly delay ESRD and extend survival, though no curative treatment exists to date. The study compares two cohorts: classical and heterozygous AS patients. Aligning with literature it includes 80% COL4A5 and 20% COL4A3/COL4A4 patients. Genotype-phenotype correlations are evident: In general hemizygous XLAS patients exhibiting the shortest renal survival (average 35 years). The RAAS blockade treatment demonstrates a noticeably therapeutic effect. Treated classical AS patients experienced a 17-year delay of ESRD compared to untreated patients. Also in heterozygous patients ESRD was prolonged over 10 years. Early initiation of RAAS blockade was significantly delaying ESRD in classical AS patients: over 24 years for early-treated, over 21 years for late-treated and over 3 years for very late-treated patients compared to untreated patients. Moreover, the RAAS blockade treatment extended average life expectancy by over five years in general; classical AS patients show an increase of over eight years. In conclusion, RAAS blockade significantly delays renal function decline and extends life expectancy in AS patients. These findings advocate for the early implementation of ACE inhibitors in AS treatment. Despite this progress, the pursuit of a curative therapy remains a pivotal goal for future research.
Keywords: alport syndrome; chronic kidney disease; fibrosis; pediatric nephrology; nephroprotection
 
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