Dataset Information
Patients with Protein-Truncating PKD1 Mutations and Mild ADPKD.
Ontology highlight
ABSTRACT: Background and objectives
Progression of autosomal dominant polycystic kidney disease (ADPKD) is highly variable. On average, protein-truncating PKD1 mutations are associated with the most severe kidney disease among all mutation classes. Here, we report that patients with protein-truncating PKD1 mutations may also have mild kidney disease, a finding not previously well recognized.Design, setting, participants, & measurements
From the extended Toronto Genetic Epidemiologic Study of Polycystic Kidney Disease, 487 patients had PKD1 and PKD2 sequencing and typical ADPKD imaging patterns by magnetic resonance imaging or computed tomography. Mayo Clinic Imaging Classification on the basis of age- and height-adjusted total kidney volume was used to assess their cystic disease severity; classes 1A or 1B were used as a proxy to define mild disease. Multivariable linear regression was performed to test the effects of age, sex, and mutation classes on log-transformed height-adjusted total kidney volume and eGFR.Results
Among 174 study patients with typical imaging patterns and protein-truncating PKD1 mutations, 32 (18%) were found to have mild disease on the basis of imaging results (i.e., Mayo Clinic Imaging class 1A-1B), with their mutations spanning the entire gene. By multivariable analyses of age, sex, and mutation class, they displayed mild disease similar to patients with PKD2 mutations and Mayo Clinic Imaging class 1A-1B. Most of these mildly affected patients with protein-truncating PKD1 mutations reported a positive family history of ADPKD in preceding generations and displayed significant intrafamilial disease variability.Conclusions
Despite having the most severe mutation class, 18% of patients with protein-truncating PKD1 mutations had mild disease on the basis of clinical and imaging assessment.Podcast
This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2021_02_18_CJN11100720_final.mp3.
SUBMITTER: Lanktree MB
PROVIDER: S-EPMC8011025 | biostudies-literature | 2021 Mar
REPOSITORIES: biostudies-literature
Publications
Patients with Protein-Truncating <i>PKD1</i> Mutations and Mild ADPKD.
Clinical journal of the American Society of Nephrology : CJASN 20210218 3
<h4>Background and objectives</h4>Progression of autosomal dominant polycystic kidney disease (ADPKD) is highly variable. On average, protein-truncating <i>PKD1</i> mutations are associated with the most severe kidney disease among all mutation classes. Here, we report that patients with protein-truncating <i>PKD1</i> mutations may also have mild kidney disease, a finding not previously well recognized.<h4>Design, setting, participants, & measurements</h4>From the extended Toronto Genetic Epidem ...[more]