Aim: Clinical interpretation of B-Type Natriuretic Peptide (BNP) levels in hemodialysis patients (HD) for fluid management remains elusive. Method: We conducted a retrospective observational monocentric study. We built a mathematical model to predict BNP levels, using multiple linear regressions. Fifteen clinical/biological associated with BNP variation were selected. A first cohort of 150 prevalent HD (from September 2015 to march 2016) was used to build several models. The best model proposed was internally validated in an independent cohort of 62 incidents HD (from March 2016 to September 2017). Results: In cohort 1, mean BNP Level was 630±717 ng/ml. Cardiac disease (CD = Stable Coronary Artery Disease and/or Atrial Fibrillation) was present in 45% of patient. The final model includes: Age, systolic Blood Pressure (sBP), Albumin, CD, Normo-hydrated Weight (NHW) and the Fluid Overload (FO) assessed by bio-impedancemetry. The correlation between the measured and the predicted log-BNP was 0.567 and 0.543 in cohort-1 and 2 respectively. Age (β=3.175e-2, p<0.00), CD (β=5.243e-1, p<0.001) and FO (β=1.227e-1, p<0.001) contribute the most significantly to the BNP level, respectively, but within a certain range. We observed a logistic relationship between BNP and age between 30 to 60 years, after which this relationship was lost. BNP level was inversely correlated with NHW independently of CD. Finally, our model allows us to predict the BNP level according to the FO. Conclusion: We developed a mathematical model capable of predicting the BNP level in HD. Our results show the complex contribution of age, CD and FO on BNP level.