Characterization of Monogenic Kidney Disease in Older Patients With CKD

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11110%2F25%3A10501979" target="_blank" >RIV/00216208:11110/25:10501979 - isvavai.cz</a>

Výsledek na webu

<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=V2NBI2Wfi3" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=V2NBI2Wfi3</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.ekir.2025.04.017" target="_blank" >10.1016/j.ekir.2025.04.017</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Characterization of Monogenic Kidney Disease in Older Patients With CKD

Popis výsledku v původním jazyce

Introduction: Although 10% of adults with chronic kidney disease (CKD) have a monogenic cause, the characteristics of monogenic CKD in older adults (aged &gt;= 60 years) are less characterized. We aimed to assess the clinical and genetic spectrum of older adults with CKD and the clinical utility of genetic findings. Methods: The diagnostic yield of clinically validated disease-causing variants and their type (&quot;typical&quot; vs. &quot;later-onset&quot; phenotypes) were analyzed in older patients with suspected monogenic CKD who were referred to an Irish registry according to predetermined criteria. Independent genetic diagnosis and kidney survival time predictors were analyzed using marginal logistic and Cox regression analyses. Results: Two hundred sixty-five adults (from 202 families) were aged &gt;= 60 years at the time of genetic testing, of which 74.3% (197/265) progressed to kidney failure. Diagnostic variants were found in 60.4% (122/202) families, including 39% of noncystic kidney disease families. Variants causing &quot;later-onset&quot; phenotypes were more prevalent in patients with disease-onset &gt;= 60 years (56% vs. 8.3%; P &lt;= 0.001), which include genetic variants in: IFT140, ALG5, ALG9, DNAJB11, COL4A5 in females, monoallelic COL4A3, and the UMOD p.Thr62Pro variant, associated with delayed onset of kidney failure compared with &quot;typical&quot; variants (hazard ratio: 0.52; 95% confidence interval: 0.27-0.98; P = 0.043). A family history of CKD and a priori cystic kidney disease diagnosis independently predicted genetic diagnosis (P &lt;= 0.05). In 24% of older adults with positive results, the treatment plan was modified. Conclusion: In older patients with CKD, genetic testing revealed enriched variants associated with less-penetrant phenotypes, often with a family history of CKD, which affects clinical management.

Název v anglickém jazyce

Characterization of Monogenic Kidney Disease in Older Patients With CKD

Popis výsledku anglicky

Introduction: Although 10% of adults with chronic kidney disease (CKD) have a monogenic cause, the characteristics of monogenic CKD in older adults (aged &gt;= 60 years) are less characterized. We aimed to assess the clinical and genetic spectrum of older adults with CKD and the clinical utility of genetic findings. Methods: The diagnostic yield of clinically validated disease-causing variants and their type (&quot;typical&quot; vs. &quot;later-onset&quot; phenotypes) were analyzed in older patients with suspected monogenic CKD who were referred to an Irish registry according to predetermined criteria. Independent genetic diagnosis and kidney survival time predictors were analyzed using marginal logistic and Cox regression analyses. Results: Two hundred sixty-five adults (from 202 families) were aged &gt;= 60 years at the time of genetic testing, of which 74.3% (197/265) progressed to kidney failure. Diagnostic variants were found in 60.4% (122/202) families, including 39% of noncystic kidney disease families. Variants causing &quot;later-onset&quot; phenotypes were more prevalent in patients with disease-onset &gt;= 60 years (56% vs. 8.3%; P &lt;= 0.001), which include genetic variants in: IFT140, ALG5, ALG9, DNAJB11, COL4A5 in females, monoallelic COL4A3, and the UMOD p.Thr62Pro variant, associated with delayed onset of kidney failure compared with &quot;typical&quot; variants (hazard ratio: 0.52; 95% confidence interval: 0.27-0.98; P = 0.043). A family history of CKD and a priori cystic kidney disease diagnosis independently predicted genetic diagnosis (P &lt;= 0.05). In 24% of older adults with positive results, the treatment plan was modified. Conclusion: In older patients with CKD, genetic testing revealed enriched variants associated with less-penetrant phenotypes, often with a family history of CKD, which affects clinical management.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30101 - Human genetics

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2025

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Kidney International Reports

ISSN

2468-0249

e-ISSN

2468-0249

Svazek periodika

10

Číslo periodika v rámci svazku

7

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

13

Strana od-do

2140-2152

Kód UT WoS článku

001546446800004

EID výsledku v databázi Scopus

2-s2.0-105004801657