Background and objectives: The Consortium for Radiologic Imaging Studies of Polycystic Kidney Disease (CRISP) was created to identify markers of disease progression in patients with autosomal dominant polycystic kidney disease (ADPKD). Design, setting, participants, & measurements: Linear mixed models were utilized to model effects of baseline parameters on changes in natural-log (ln)-transformed total kidney volume (TKV) and iothalamate clearance (GFR) across time in CRISP participants (creatinine clearance at entry >70 ml/min). Stepwise selection was used to obtain a final main effect model. Results: TKV increased from year to year, whereas GFR uncorrected for body surface area (BSA) decreased only at year 6. Higher lnTKV and urine sodium excretion (U NaV), lower serum HDL-cholesterol, and younger age at baseline associated with greater lnTKV growth from baseline to year 3 and to year 6. Higher lnTKV at baseline associated with greater GFR decline from year 1 to year 3 and to year 6. Higher BSA and 24-hour urine osmolality at baseline associated with greater GFR decline from year 1 to year 6. Higher UNaV and lower serum HDL-cholesterol at baseline associated with greater GFR decline from year 1 to year 6 by univariate analysis only. Associations seen during year 1 to year 6 (not seen during year 1 to year 3) reflect the time lag between structural and functional disease progression. Conclusions: Serum HDL-cholesterol, UNaV, and 24-hour urine osmolality likely affect ADPKD progression. To what extent their modification may influence the clinical course of ADPKD remains to be determined. Copyright © 2011 by the American Society of Nephrology.