Abstract Background and Aims The high prevalence of CKD and its increasing awareness by primary care clinicians is posing a huge burden over health care systems, especially over Nephrology departments. While the referral of CKD stage 4 and 5 to a nephrology clinic is undisputable, the need for stage 3 patients referral is still subject to debate. Our objective was to investigate baseline characteristics of CKD stage 3 patients associated with subsequent CKD progression, in order to help determine which patients should be referred at this stage. Additionally, we investigated the association of CKD stage 3 progression with morbidity and overall mortality. Method We conducted a patient-level, retrospective, cohort analysis of all patients referred to a nephrology clinic over a 6 years period. We included CKD stage 3 patients with at least 36 months of follow-up or 24 to 36 months of follow up with more than 3 serum creatinine determinations. CKD progression was defined by one of the following: 1) an eGFR (CKD-EPI) decline superior to 5mL/min/year; 2) Serum creatinine duplication; 3) The need for chronic RRT. Baseline covariates included demographics, comorbid conditions and laboratory values. Univariate and multivariate analysis were employed to determine independent predictors of CKD progression and mortality. Results Out of the 3008 patients referred to the nephrology clinic, 1288 (42.8%) were CKD stage 3 patients and from these, 594 (19.8%) met the inclusion criteria (median age: 71.9 years; 63.8% male). Median follow-up was 4.9 years (IQR 2.2). 133 (22.4%) met the criteria for CKD progression and 110 (18.6%) died. In univariate analysis, CKD progression was associated with higher proteinuria (405.7 vs 65.5mg/gr, p<0.001), Diabetes (60.9 vs 45.3%, p=0.002), Congestive heart failure (CHF) (40.6 vs 28.7%, p=0.009), Anemia (OMS definition) (68.0 vs 44.7%, p<0.001), higher diuretic use (48.9 vs 34.1%, p=0.002) and higher mortality (40.9 vs 12.2%, p<0.001) In multivariate logistic regression analysis, albuminuria over 300 mg/gr [Odds ratio (OR) 3.57, 95% CI 2.20 - 5.80, p<0.001] and Anemia (OR 1.97, 95% CI 1.20 – 3.22, p=0.007) were associated with CKD progression. The possible association with other variables was not confirmed. The independent predictors of mortality were: CKD progression (OR 4.49, 95% CI 2.69-7.50, p=<0.001), Older age (OR per 1 year increase 1.03, 95% CI 1.01-1.05, p=0.003), presence of CHF (OR 1.75, 95% CI 1.03-2.98, p=<0.037), presence of Hyperkalemia at first consultation (OR 2.12, 95% CI 1.00 – 4.52, p=0.049) and Anemia (OR 1.93, 95% CI 1.03 - 3.62, p=0.025). Higher body mass index was associated with a lower risk of mortality (OR 0.58, 95% CI 0.35 – 0.95, p=0.033) Conclusion Our study suggests that patients with macroalbuminuria and anemia at first consultation are at increased risk for rapid CKD stage 3 progression. In this group, patients with CHF, anemia and hyperkalemia (even at first consultation) have a higher risk of mortality. This study may be useful and help us in guiding which CKD stage 3 patients should be referred to a nephrology clinic.