Background <p>Kidney volume, reflecting cumulative effects of many cysts, is an important prognostic biomarker for autosomal dominant polycystic kidney disease (ADPKD) but fails in many patients. Tracking individual cysts may more directly assess disease progression.</p> Methods <p>Individual cysts (<i>n</i> = 299) from 37 subjects were evaluated retrospectively over ≥ 8 years by serial MRI (mean follow-up = 11 years). Cysts were labeled on every available MRI scan, totaling 1654 contours (median timepoints per cyst = 5). Effects of cyst location, morphology, and growth pattern on kidney function decline were evaluated by univariate and multivariate analyses.</p> Results <p>Simple, T2-bright cysts follow logistic growth (median cyst growth rate = 11%/year). A subset (94/222, 42%) transitions over time to shrinking, to complex solid-fluid/fluid-fluid cysts, then to homogeneously T1-bright cysts and finally disappearing. By contrast, T1-bright complex cysts have no volume change (median cyst growth rate = 0%/year; <i>p</i> &lt; 0.001). On multivariate analysis, faster kidney function decline is associated with simple cyst diameter &gt; 2 cm on index scan (<i>p</i> = 0.007) and simple cyst transitions (<i>p</i> = 0.02). There is a trend towards faster kidney function decline with higher simple cyst growth rate (<i>p</i> = 0.16).</p> Conclusions <p>Profiling individual cysts on serial MRI to identify transitions as well as size and growth rate may improve predictions of ADPKD progression and treatment response.</p>