More dissimilarities than affinities between DNAJB11-PKD and ADPKD

Area of Science:

• Nephrology
• Genetics
• Chronic Kidney Disease Research

Background:

• Polycystic kidney diseases (PKD) are a significant cause of chronic kidney disease (CKD).
• Autosomal dominant polycystic kidney disease (ADPKD) is the most common form, typically caused by PKD1 or PKD2 mutations.
• Atypical ADPKD can arise from mutations in other genes, including a recently described form linked to DNAJB11 mutations (DNAJB11-PKD).

Purpose of the Study:

• To characterize the distinct clinical and renal phenotypes of DNAJB11-PKD.
• To compare the natural history and extrarenal manifestations of DNAJB11-PKD with typical ADPKD.
• To determine if DNAJB11-PKD should be classified separately from ADPKD.

Main Methods:

• Retrospective recruitment of 27 patients with a specific DNAJB11 mutation (c.100C>T, p.Arg34*) from six families.
• Comparison of the DNAJB11-PKD cohort with a cohort of 42 patients diagnosed with typical ADPKD.
• Analysis of renal imaging (ultrasound, CT/MRI), clinical data, and prevalence of comorbidities.

Main Results:

• DNAJB11-PKD kidneys are small/normal-sized with smaller cysts and slower progression to end-stage kidney disease (ESKD) compared to ADPKD.
• Renal cysts were not always detected by ultrasound in DNAJB11-PKD patients but were visible on CT/MRI.
• DNAJB11-PKD patients exhibited proteinuria, were older, and had higher rates of type 2 diabetes and kidney stones, but fewer cardiac valvular defects than ADPKD patients.

Conclusions:

• DNAJB11-PKD exhibits a unique renal and extrarenal phenotype, clinical presentation, and natural history.
• The clinical features of DNAJB11-PKD are generally more subtle than those of ADPKD.
• These findings support the classification of DNAJB11-PKD as a distinct genetic kidney disease separate from ADPKD.