Background <p>Few studies have analyzed the quality-of-life trajectories of CKD patients not receiving kidney replacement therapy, and the results are inconsistent. This study aimed to identify subgroups of long-term trajectories of the physical (PCS) and mental components summary (MCS) of the KDQOL-36 in patients with CKD stages 3–5 and to describe their associations with patient characteristics.</p> Methods <p>We used a joint latent class–mixed model to identify the PCS and MCS trajectories of 2716 patients with CKD stages 3–5 enrolled in the CKD–Renal Epidemiology and Information Network (CKD–REIN) cohort study. Quality-of-life was assessed annually using the Kidney Disease Quality-of-life-36. All the participants had scores for at least one-time point.</p> Results <p>During a median follow-up of 5.56 (4.77–6.16) years, 664 participants started KRT, and 465 died before KRT. We identified three profiles of PCS: a “High and declining PCS trajectory” which included 5.89% of patients, characterized by a higher initial score and a decline of more than 10 points over three years; a “High and stable PCS trajectory” in 50.96%, characterized by a higher initial score that remained stable; and a “Low and stable PCS trajectory” in 43.15%, characterized by a lower initial score that remained stable. For MCS, we identified a single, stable mean trajectory over time. A decline in eGFR was faster in participants with a “High and declining PCS trajectory” (-4.30 mL/min per years). Patients in the high and stable trajectory had a more favorable clinical and biological profile at baseline. The evolution of the specific dimensions of CKD within each PCS trajectory followed a pattern similar to that of the PCS itself.</p> Conclusions <p>The study highlights substantial heterogeneity in PCS evolution in patients with CKD, which contrasts with the stability of that for MCS.</p>