Renal Prognostic Identification in Patients With Autosomal Dominant Polycystic Kidney Disease by Whole Genome Sequencing: A Prospective, Observational Study.

RATIONALE &

OBJECTIVE

The association between autosomal dominant polycystic kidney disease (ADPKD) genetic variants and renal prognosis remains unclear. We conducted whole genome sequencing to identify the factors contributing to disease severity.

STUDY

DESIGN

Prospective, observational study.

SETTING & POPULATION: Using data collected from a 2-year prospective cohort of 200 patients with ADPKD, gene mutations were identified using whole genome sequencing.

EXPOSURE: None.

OUTCOMES: The primary endpoint was the rate of increase in total kidney volume. The secondary endpoints were composite renal endpoints (induction of dialysis, kidney transplantation, or a decrease in the estimated glomerular filtration rate of ≥25%).

ANALYTICAL APPROACH: Logistic regression analyses were performed to determine the factors associated with the outcomes.

RESULTS

Among 169 patients for whom genetic diagnosis was performed, genetic mutations were identified in 144 cases, with 109 (75.7%) PKD1, 34 (23.6%) PKD2, and 1 (0.7%) GANAB variants identified. The median annual increase in total kidney volume was 5.9%. Among the patients who were followed, 60 patients (33.5%) achieved the composite renal endpoint. The independent risk factors for reaching the renal composite endpoint were estimated glomerular filtration rate at enrollment (OR, 0.93; 95% CI, 0.91-0.96) and PKD1 truncation (OR, 3.05; 95% CI, 1.11-8.40). Hypertension and overweight exacerbated disease severity, particularly in patients with PKD1 truncation. The annual rate of kidney function deterioration was higher in the order of PKD1 truncating, PKD1 non-truncating, PKD2 truncating, and PKD2 non-truncating variants. The rate of Mayo imaging classification 1C-1E was highest in the same order.

LIMITATIONS: Owing to the various PKD variants, the sample size for each variant was insufficient for comprehensive evaluation of kidney function.

CONCLUSIONS

PKD1 truncation is a sensitive severity marker in patients with ADPKD, and PKD2 non-truncation is the least severe. Genetic diagnosis is useful for predicting renal prognosis.