Pro-B amino-terminal natriuretic peptide (NT-proBNP) is a diagnostic marker for heart failure (HF), a severe complication of chronic kidney disease (CKD). However, its significance in CKD is not clear, as other factors, such as renal function, may also have an impact. Recent studies have shown that ghrelin treatment is effective in HF in the general population, but the impact of ghrelin on cardiac function in CKD patients is still unknown. Our study aimed to investigate the factors associated with NT-proBNP in pre-dialysis CKD patients and to evaluate the correlation between NT-proBNP and ghrelin and acyl-ghrelin, molecules determined using ELISA methods. In a cross-sectional observational study, we included 80 patients with pre-dialysis CKD, with a mean age of 68 years and 50% men. The median values for NT-proBNP were 351.8 pg/mL, for acyl ghrelin 16.39 pg/mL, and for ghrelin 543.32 pg/mL. NT-proBNP was correlated with ghrelin ( = 0.034, r = 0.24), acyl-ghrelin ( = 0.033, r = -0.24), estimated glomerular filtration rate ( = 0.027, r = -0.25), serum urea ( = 0.006, r = 0.31), and ferritin ( = 0.041, r = 0.28). In multivariate analysis, ghrelin ( = 0.040) and blood urea ( = 0.040) remained significant predictors for NT-proBNP levels. NT-proBNP was a significant predictor for acyl-ghrelin ( = 0.036). In conclusion, in pre-dialysis CKD patients, a high value of NT-proBNP was associated with a high value of total ghrelin and a low value of acyl-ghrelin.