Background: First-line treatment of PCNSL consists in a polychemotherapy based on high-dose MTX with hyperhydratation until MTX elimination. Renal toxicity remains frequent with pejorative impact on renal function and patient survival. Our objective was to determine urinary predictive factors of MTX elimination delay. Methods: Patients with PCNSL followed in our institution were prospectively recruited from December 2020 to May 2021. Daily serum and urinary creatinine and ionogram were collected from the day before MTX administration until elimination. Patients characteristics, biological data and MTX concentration were recorded. Normal elimination time was defined by MTX ≤ 0.05 at 72 hours. Results: We collected data from 64 MTX cycles corresponding to 20 patients. Median age was 71 years (range, 33 - 86) and median Karnofsky Performance Status (KPS) was 70. Forty-four percent of cycles were full dose (3500 mg/m²). Median urinary osmolarities one day before, the day and 24 hours after MTX administration were 325 mOsm (range, 62 - 542), 316 mOsm (range, 58 - 671) and 291 mOsm (range, 56 - 554), respectively. Median time for MTX elimination was 94.7 hours (range, 47 - 205). Only one patient needed to receive MTX antidote (glucarpidase). The factors significantly associated with MTX elimination time were age (p < 0.001), KPS (p < 0.001) and urinary K+ concentration at 24 hours post MTX administration (u-K+) (p = 0.008). Using ROC curve analyses, we determine optimal cutoffs for age (80 years, p < 0.001, AUC = 0.825), KPS (70, p < 0.001, AUC = 0.808) and u-K+ (17.2 mmol/L, p = 0.008 AUC = 0.712). This u-K+ cutoff presented with a specificity of 81% and a sensibility of 60%. Focusing on patients aged < 80 years (52 cycles / 64), we confirmed that both KPS (p = 0.022) and u-K+ (p = 0.027) were significantly correlated with MTX elimination time by multivariate analysis. Then, we derived a 3-factors score including 5 subgroups: 1) aged ≥ 80 (N = 12); 2) age < 80, KPS < 70 and high u-K+ (N = 11); 3) age < 80, KPS < 70 and low u-K+ (N = 6); 4) age < 80, KPS ≥ 70 and high u-K+ (N = 8); 5) age < 80, KPS≥70 and low u-K+ (N = 21). The median times for MTX elimination were 112, 96, 95, 82 and 72 hours respectively. The normal elimination rates in each subgroup were 17%, 0%, 17%, 37% and 71% respectively. Conclusions: Age, KPS and u-K+ were correlated with MTX elimination time. We derived a predictive score based on these items that could be used in routine to anticipate MTX elimination delay and to potentially prevent the risk of renal toxicity. These results need to be prospectively confirmed in a larger cohort.