AbstractChronic kidney disease (CKD) is a complex health condition characterized by the gradual loss of renal function, often leading to end-stage renal disease (ESRD). It results from a combination of medical, environmental, and genetic factors. Predicting the rate of renal function decline and effectively managing the progression to ESRD is challenging in clinical practice. CKD assessment involves various indicators, including estimated glomerular filtration rate (eGFR), albuminuria levels, serum creatinine, and others. This study aimed to explore the predictive potential of specific blood cell indexes in forecasting further renal function decline and the transition from CKD stage 3–4 to ESRD. We assessed the following blood cell indexes in 377 CKD stage 3–4 patients: absolute neutrophil count (ANC), neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), derived NLR (dNLR), mean platelet volume (MPV), aggregate index of systemic inflammation (AISI), and systemic inflammation index (SII). ANC, MPV, NLR, PLR, dNLR, and SII were found to independently predict a rapid decline in eGFR. Notably, NLR and dNLR demonstrated the highest sensitivity and specificity with cut-off values of 3.36 and 2.45, respectively (NLR: 88.6 and 81.7%; dNLR: 85.2 and 75.8%). The corresponding area under the ROC curve values were 0.877 (95% CI 0.837–0.918, p < 0.001) for NLR and 0.849 (95% CI 0.805–0.892, p < 0.001) for dNLR. However, none of the blood cell indexes independently predicted the transition to ESRD. The NLR and the dNLR exhibited the highest predictive capacity towards a rapid decline in renal function in CKD. No blood cell index, however, independently predicted the transition into ERSD.