Progression of autosomal dominant polycystic kidney disease (ADPKD) is highly variable. On average, protein-truncating mutations are associated with the most severe kidney disease among all mutation classes. Here, we report that patients with protein-truncating mutations may also have mild kidney disease, a finding not previously well recognized.

From the extended Toronto Genetic Epidemiologic Study of Polycystic Kidney Disease, 487 patients had and 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.

Among 174 study patients with typical imaging patterns and protein-truncating mutations, 32 (18%) were found to have mild disease on the basis of imaging results (., 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 mutations and Mayo Clinic Imaging class 1A-1B. Most of these mildly affected patients with protein-truncating mutations reported a positive family history of ADPKD in preceding generations and displayed significant intrafamilial disease variability.

Despite having the most severe mutation class, 18% of patients with protein-truncating mutations had mild disease on the basis of clinical and imaging assessment.

This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2021_02_18_CJN11100720_final.mp3.