PKD1 Mutation Is a Biomarker for Autosomal Dominant Polycystic Kidney Disease

Abstract

Background: Autosomal dominant polycystic kidney disease (ADPKD) occurs in 1 in 500-4000 people worldwide. Genetic mutation is a biomarker for predicting renal dysfunction in patients with ADPKD. In this study, we performed a genetic analysis of Japanese patients with ADPKD to investigate the prognostic utility of genetic mutations in predicting renal function outcomes.

Methods: Patients clinically diagnosed with ADPKD underwent a panel genetic test for germline mutations in PKD1 and PKD2. This study was conducted with the approval of the Ethics Committee of Juntendo University (no. 2019107).

Results: Of 436 patients, 366 (83.9%) had genetic mutations. Notably, patients with PKD1 mutation had a significantly decreased ΔeGFR/year compared to patients with PKD2 mutation, indicating a progression of renal dysfunction (-3.50 vs. -2.04 mL/min/1.73 m²/year, p = 0.066). Furthermore, PKD1 truncated mutations had a significantly decreased ΔeGFR/year compared to PKD1 non-truncated mutations in the population aged over 65 years (-6.56 vs. -2.16 mL/min/1.73 m²/year, p = 0.049). Multivariate analysis showed that PKD1 mutation was a more significant risk factor than PKD2 mutation (odds ratio, 1.81; 95% confidence interval, 1.11-3.16; p = 0.020).

Conclusions: The analysis of germline mutations can predict renal prognosis in Japanese patients with ADPKD, and PKD1 mutation is a biomarker of ADPKD.

Keywords: ADPKD; PKD1 mutation; analysis of germline mutations; biomarkers; predicting renal prognosis.

Figure 1

Flow chart of patients with ADPKD. ADPKD: autosomal dominant polycystic kidney disease.

Figure 2

Mann−Whitney analysis of the clinically important factors related to the rate of change in ΔeGFR performed in the subgroup analysis and comparison of ΔeGFR between patients with PKD1 and PKD2 (A), HtTKV (B), Mayo 1A and 1B and 1C, 1D, and 1E (C), PKD1 truncated or non-truncated mutations (D), and PKD1 truncated or non-truncated mutations in the population aged ≥65 years (E). HtTKV: height-adjusted total kidney volume (mL/m), eGFR: estimated glomerular filtration rate, ΔeGFR/year: represents the 1-year change in eGFR calculated using the least-squares method based on the change in eGFR values before tolvaptan treatment, aged ≥65 years: population aged ≥65 years.

Figure 3

Kaplan–Meier kidney survival plot of the group of patients with a PKD1 mutation and the group of patients with a PKD2 mutation (A), PKD1 truncated or non-truncated mutations (B).