RESUMO
Approximately 500 monogenic causes of chronic kidney disease (CKD) have been identified, mainly in pediatric populations. The frequency of monogenic causes among adults with CKD has been less extensively studied. To determine the likelihood of detecting monogenic causes of CKD in adults presenting to nephrology services in Ireland, we conducted whole exome sequencing (WES) in a multi-centre cohort of 114 families including 138 affected individuals with CKD. Affected adults were recruited from 78 families with a positive family history, 16 families with extra-renal features, and 20 families with neither a family history nor extra-renal features. We detected a pathogenic mutation in a known CKD gene in 42 of 114 families (37%). A monogenic cause was identified in 36% of affected families with a positive family history of CKD, 69% of those with extra-renal features, and only 15% of those without a family history or extra-renal features. There was no difference in the rate of genetic diagnosis in individuals with childhood versus adult onset CKD. Among the 42 families in whom a monogenic cause was identified, WES confirmed the clinical diagnosis in 17 (40%), corrected the clinical diagnosis in 9 (22%), and established a diagnosis for the first time in 16 families referred with CKD of unknown etiology (38%). In this multi-centre study of adults with CKD, a molecular genetic diagnosis was established in over one-third of families. In the evolving era of precision medicine, WES may be an important tool to identify the cause of CKD in adults.
Assuntos
Sequenciamento do Exoma , Predisposição Genética para Doença , Testes Genéticos/métodos , Insuficiência Renal Crônica/genética , Adolescente , Adulto , Idade de Início , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Exoma/genética , Feminino , Humanos , Irlanda , Rim , Masculino , Anamnese , Pessoa de Meia-Idade , Mutação , Linhagem , Medicina de Precisão , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/terapia , Adulto JovemRESUMO
The many manifestations of atheroembolism are apparent in all specialties. However, with increasing intervention in older patients with atherosclerotic disease, it has become an important renal clinical problem. Atheroembolic disease is widely recognized as a cause of acute catastrophic renal dysfunction and recent important data have suggested that effective management protocols can improve outcome. It is probable that the clinical course is insidious in the majority of patients with severe atherosclerotic aortic disease. The management of these patients is less clear and at present rests on small anecdotal reports.
