Pediatric Nephrology

, Volume 32, Issue 1, pp 131–137 | Cite as

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

  • Johanna Stock
  • Johannes Kuenanz
  • Niklas Glonke
  • Joseph Sonntag
  • Jenny Frese
  • Burkhard Tönshoff
  • Britta Höcker
  • Bernd Hoppe
  • Markus Feldkötter
  • Lars Pape
  • Christian Lerch
  • Simone Wygoda
  • Manfred Weber
  • Gerhard-Anton Müller
  • Oliver GrossEmail author
Original Article



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.


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.


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 <60 ml/min, 67.6 % had proteinuria and 27.0 % had microalbuminuria. Therapeutic strategies included angiotensin-converting enzymer inhibitors (97.1 %), angiotensin receptor antagonists (1 patient), dual therapy (11.8 %) and statins (8.8 %). Among patients included in the prospective dataset, prevented the need for dialysis. Among new patients, no patient at risk for renal failure progressed to the next disease stage after 4 years follow-up; three patients even regressed to a lower stage during therapy.


Treatment with blockers of the renin–angiotensin–aldosterone system prevents progressive renal failure in AS patients with heterozygous mutations in the genes causing AS. Considerable numbers of aging AS patients on dialysis may have heterozygous mutations in these genes (present in 1 % of total population) as underlying disease. Hence, greater alertness towards timely diagnosis and therapy has the potential to prevent progressive renal failure in most—if not all—AS patients with heterozygous mutations in the causal genes.


Chronic kidney disease Renal insufficiency Fibrosis Collagen Alport syndrome Thin basement membrane disease Familial benign hematuria 



The authors wish to thank the patients and relatives and the German patients advocacy group (Alport Selbsthilfe e.V.) for their contributions. Original data acquisition of the European Alport Registry was supported 2006 to 2010 by the Association pour l’Information et la Recherche sur les Maladies Rénales Génétiques (AIRG). Parts of the registry data were made public in abstract form at the annual meetings of the German and the European Renal Association in 2015.

Authors’ contributions

The first and the last author JS and OG had full access to all the data in the study and take responsibility for the content of the manuscript, including the data and analysis. JS and OG contributed to the conception and design of the study, analysis and interpretation of data, drafting the article, revising the paper and final approval of the manuscript. All other authors contributed to the acquisition of data, revision of the manuscript and final approval. All authors have agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Compliance with ethical standards

Competing interests

The authors declare that they have no competing interests.

Ethics statement

The registry and data storage, in conformity with GCP guidelines, were approved by the Ethics Committee of the University Medical Center Göttingen. For ethical and data safety reasons, we only re-contacted patients from German-speaking countries and only patients who contacted us previously by email, facsimile or personally. Informed consent was obtained for all participants.

Supplementary material

467_2016_3452_MOESM1_ESM.docx (24 kb)
Supplemental Table 1 Table of all patients in our study of data, which could be statistically evaluated (DOCX 24 kb)
467_2016_3452_Fig4_ESM.gif (109 kb)
Supplemental Figure 1

Percentage of untreated patients in different stages of Alport disease 2011 versus prospective follow-up (GIF 108 kb)

467_2016_3452_MOESM2_ESM.tif (193 kb)
High resolution image (TIF 192 kb)


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Copyright information

© IPNA 2016

Authors and Affiliations

  • Johanna Stock
    • 1
  • Johannes Kuenanz
    • 1
  • Niklas Glonke
    • 1
  • Joseph Sonntag
    • 1
  • Jenny Frese
    • 1
  • Burkhard Tönshoff
    • 2
  • Britta Höcker
    • 2
  • Bernd Hoppe
    • 3
  • Markus Feldkötter
    • 3
  • Lars Pape
    • 4
  • Christian Lerch
    • 4
  • Simone Wygoda
    • 5
  • Manfred Weber
    • 6
  • Gerhard-Anton Müller
    • 1
  • Oliver Gross
    • 1
    Email author
  1. 1.Clinic for Nephrology and RheumatologyUniversity Medical Center GöttingenGöttingenGermany
  2. 2.Department of Pediatrics IUniversity Children’s HospitalHeidelbergGermany
  3. 3.Division of Pediatric NephrologyUniversity Children’s Hospital BonnBonnGermany
  4. 4.Department of Pediatric Kidney, Liver and Metabolic DiseasesHannover Medical SchoolHannoverGermany
  5. 5.Clinic for Children and AdolescentsHospital St. GeorgLeipzigGermany
  6. 6.Cologne General Hospital MerheimUniversity Witten-HerdeckeCologneGermany

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