Biomarkers of Kidney Disease Progression in ADPKD

Abstract

Autosomal dominant polycystic kidney disease (ADPKD) is the most common monogenic kidney disorder and the fourth leading cause of kidney failure (KF) in adults. Characterized by a reduction in glomerular filtration rate (GFR) and increased kidney size, ADPKD exhibits significant variability in progression, highlighting the urgent need for reliable and predictive biomarkers to optimize management and treatment approaches. This review explores the roles of diverse biomarkers—including clinical, genetic, molecular, and imaging biomarkers—in evaluating disease progression and customizing treatments for ADPKD. Clinical biomarkers such as biological sex, the predicting renal outcome in polycystic kidney disease (PROPKD) score, and body mass index are shown to correlate with disease severity and progression. Genetic profiling, particularly distinguishing between truncating and non-truncating pathogenic variants in the PKD1 gene, refines risk assessment and prognostic precision. Advancements in imaging significantly enhance our ability to assess disease severity. Height-adjusted total kidney volume (htTKV) and the Mayo imaging classification (MIC) are foundational, whereas newer imaging biomarkers, including texture analysis, total cyst number (TCN), cyst-parenchyma surface area (CPSA), total cyst volume (TCV), and cystic index, focus on detailed cyst characteristics to offer deeper insights. Molecular biomarkers (including serum and urinary markers) shed light on potential therapeutic targets that could predict disease trajectory. Despite these advancements, there is a pressing need for the development of response biomarkers in both the adult and pediatric populations, which can evaluate the biological efficacy of treatments. The holistic evaluation of these biomarkers not only deepens our understanding of kidney disease progression in ADPKD, but it also paves the way for personalized treatment strategies aiming to significantly improve patient outcomes.