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

• Published in: Pediatric nephrology (Berlin, West) West), 2017, Vol.32 (1), p.131-137
• Main Authors: Stock, Johanna, Kuenanz, Johannes, Glonke, Niklas, Sonntag, Joseph, Frese, Jenny, Tönshoff, Burkhard, Höcker, Britta, Hoppe, Bernd, Feldkötter, Markus, Pape, Lars, Lerch, Christian, Wygoda, Simone, Weber, Manfred, Müller, Gerhard-Anton, Gross, Oliver
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Age of Onset; Child; Child, Preschool; Chronic kidney failure; Collagen; Complications and side effects; Datasets; Diagnosis; Disease Progression; Drug therapy; Female; Follow-Up Studies; Genetic aspects; Genotype; Hematuria; Hereditary nephritis; Heterozygote; Hospitals; Humans; Infant; Infant, Newborn; Kaplan-Meier Estimate; Kidney diseases; Kidney Failure, Chronic - prevention & control; Male; Medicine; Medicine & Public Health; Middle Aged; Mutation; Nephritis, Hereditary - complications; Nephritis, Hereditary - drug therapy; Nephritis, Hereditary - genetics; Nephrology; Original Article; Patients; Pediatrics; Physiological aspects; Prospective Studies; Renal Insufficiency, Chronic - drug therapy; Renal Insufficiency, Chronic - etiology; Renal Insufficiency, Chronic - genetics; Renin-angiotensin system; Renin-Angiotensin System - drug effects; Risk factors; Treatment Outcome; Urology; Young Adult
• ISSN: 0931-041X; 1432-198X
• DOI: 10.1007/s00467-016-3452-z

Background Patients with autosomal or X-linked Alport syndrome (AS) with heterozygous mutations in type IV collagen genes have a 1–20 % risk of progressing to end-stage renal disease during their lifetime. We evaluated the long-term renal outcome of patients at risk of progressive disease (chronic kidney disease stages 1–4) with/without nephroprotective therapy. Methods This was a prospective, non-interventional, observational study which included data from a 4-year follow-up of AS patients with heterozygous mutations whose datasets had been included in an analysis of the 2010 database of the European Alport Registry. Using Kaplan–Meier estimates and logrank tests, we prospectively analyzed the updated datasets of 52 of these patients and 13 new datasets (patients added to the Registry after 2011). The effects of therapy, extrarenal symptoms and inheritance pattern on renal outcome were analyzed. Results The mean prospective follow-up was 46 ± 10 months, and the mean time on therapy was 8.4 ± 4.4 (median 7; range 2–18) years. The time from the appearance of the first symptom to diagnosis was 8.1 ± 14.2 (range 0–52) years. At the time of starting therapy, 5.4 % of patients had an estimated glomerular filtration rate of