Universität zu Köln

Boeckhaus, Jan, Hoefele, Julia ORCID: 0000-0002-7917-7129, Riedhammer, Korbinian M., Nagel, Mato, Beck, Bodo B., Choi, Mira, Gollasch, Maik, Bergmann, Carsten, Sonntag, Joseph E., Troesch, Victoria, Stock, Johanna and Gross, Oliver ORCID: 0000-0002-8390-8852 (2022). Lifelong effect of therapy in young patients with the COL4A5 Alport missense variant p.(Gly624Asp): a prospective cohort study. Nephrol. Dial. Transplant., 37 (12). S. 2496 - 2505. OXFORD: OXFORD UNIV PRESS. ISSN 1460-2385

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Abstract

Background Angiotensin-converting enzyme inhibitors (ACEis) have evolved as a first-line therapy for delaying end-stage renal failure (ESRF) in Alport syndrome (AS). The present study tested the hypothesis of a superior nephroprotective potential of an early ACEi intervention, examining a cohort with the COL4A5 missense variant p.(Gly624Asp). Methods In this observational cohort study (NCT02378805), 114 individuals with the identical gene variant were explored for age at ESRF and life expectancy in correlation with treatment as endpoints. Results All 13 untreated hemizygous patients developed ESRF (mean age 48.9 +/- 13.7 years), as did 3 very late treated hemizygotes (51.7 +/- 4.2 years), with a mean life expectancy of 59.2 +/- 9.6 years. All 28 earlier-treated [estimated glomerular filtration rate (eGFR) >= 60 mL/min/1.73 m(2)] hemizygous patients were still alive and still had not reached ESRF. Therapy minimized the annual loss of their GFR, similar to the annual loss in healthy individuals. Of 65 heterozygotes, 4 untreated individuals developed ESRF at an age of 53.3 +/- 20.7 years. None of the treated heterozygous females developed ESRF. Conclusions For the first time, this study shows that in AS, early therapy in individuals with missense variants might have the potential to delay renal failure for their lifetime and thus to improve life expectancy and quality of life without the need for renal replacement therapy. Some treated patients have reached their retirement age with still-functioning kidneys, whereas their untreated relatives have reached ESRF at the same or a younger age. Thus, in children with glomerular haematuria, early testing for Alport-related gene variants could lead to timely nephroprotective intervention.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Boeckhaus, Jan UNSPECIFIED UNSPECIFIED UNSPECIFIED Hoefele, Julia UNSPECIFIED orcid.org/0000-0002-7917-7129 UNSPECIFIED Riedhammer, Korbinian M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Nagel, Mato UNSPECIFIED UNSPECIFIED UNSPECIFIED Beck, Bodo B. UNSPECIFIED UNSPECIFIED UNSPECIFIED Choi, Mira UNSPECIFIED UNSPECIFIED UNSPECIFIED Gollasch, Maik UNSPECIFIED UNSPECIFIED UNSPECIFIED Bergmann, Carsten UNSPECIFIED UNSPECIFIED UNSPECIFIED Sonntag, Joseph E. UNSPECIFIED UNSPECIFIED UNSPECIFIED Troesch, Victoria UNSPECIFIED UNSPECIFIED UNSPECIFIED Stock, Johanna UNSPECIFIED UNSPECIFIED UNSPECIFIED Gross, Oliver UNSPECIFIED orcid.org/0000-0002-8390-8852 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-689268
DOI:	10.1093/ndt/gfac006
Journal or Publication Title:	Nephrol. Dial. Transplant.
Volume:	37
Number:	12
Page Range:	S. 2496 - 2505
Date:	2022
Publisher:	OXFORD UNIV PRESS
Place of Publication:	OXFORD
ISSN:	1460-2385
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language GENOTYPE-PHENOTYPE CORRELATIONS; DELAYS RENAL-FAILURE; NATURAL-HISTORY; 195 FAMILIES; INHIBITION; RAMIPRIL Multiple languages Transplantation; Urology & Nephrology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/68926