Lifelong effect of therapy in young patients with the COL4A5 Alport missense variant p.(Gly624Asp) : a prospective cohort study
© The Author(s) 2022. Published by Oxford University Press on behalf of the ERA..
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 m2] 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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:37 |
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| Enthalten in: |
Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association - 37(2022), 12 vom: 23. Nov., Seite 2496-2504 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Boeckhaus, Jan [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 30.11.2022 Date Revised 29.12.2022 published: Print Citation Status MEDLINE |
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| doi: |
10.1093/ndt/gfac006 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM335576753 |
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| 100 | 1 | |a Boeckhaus, Jan |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Lifelong effect of therapy in young patients with the COL4A5 Alport missense variant p.(Gly624Asp) |b a prospective cohort study |
| 264 | 1 | |c 2022 | |
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| 500 | |a Date Completed 30.11.2022 | ||
| 500 | |a Date Revised 29.12.2022 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © The Author(s) 2022. Published by Oxford University Press on behalf of the ERA. | ||
| 520 | |a 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) | ||
| 520 | |a 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 | ||
| 520 | |a 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 m2] 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 | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Observational Study | |
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Alport syndrome | |
| 650 | 4 | |a chronic renal failure | |
| 650 | 4 | |a nephroprotective therapy | |
| 650 | 4 | |a renin–angiotensin system | |
| 650 | 4 | |a type IV collagen disease | |
| 650 | 7 | |a COL4A5 protein, human |2 NLM | |
| 650 | 7 | |a Collagen Type IV |2 NLM | |
| 700 | 1 | |a Hoefele, Julia |e verfasserin |4 aut | |
| 700 | 1 | |a Riedhammer, Korbinian M |e verfasserin |4 aut | |
| 700 | 1 | |a Nagel, Mato |e verfasserin |4 aut | |
| 700 | 1 | |a Beck, Bodo B |e verfasserin |4 aut | |
| 700 | 1 | |a Choi, Mira |e verfasserin |4 aut | |
| 700 | 1 | |a Gollasch, Maik |e verfasserin |4 aut | |
| 700 | 1 | |a Bergmann, Carsten |e verfasserin |4 aut | |
| 700 | 1 | |a Sonntag, Joseph E |e verfasserin |4 aut | |
| 700 | 1 | |a Troesch, Victoria |e verfasserin |4 aut | |
| 700 | 1 | |a Stock, Johanna |e verfasserin |4 aut | |
| 700 | 1 | |a Gross, Oliver |e verfasserin |4 aut | |
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