Kidney hyperfiltration with augmented renal clearance is frequently observed in patients with traumatic brain injury. The aim of this study is to report preliminary findings about the relationship between brain autoregulation impairment, estimated kidney glomerular filtration rate and outcome in critically ill patients after severe traumatic brain injury. Data collected from a cohort of 18 consecutive patients with severe traumatic brain injury managed with ICP monitoring in a Neurocritical Care Unit, were retrospectively analyzed. Early morning blood tests were performed for routine chemistry assessments and we analyzed creatinine and estimated creatinine clearance, osmolarity, and sodium. Daily norepinephrine dose, protein intake, and water balance were documented. Time average of brain monitoring data (intracranial pressure, cerebral perfusion pressure, and cerebrovascular reactivity pressure index--PRx) were calculated for 6 h before blood sample tests. Patient outcome was evaluated using Glasgow outcome scale at 6-month follow-up, considering nonfatal outcome if GOS ≥ 3 and fatal outcome if GOS < 3. Multiple linear regression models were used to study the crude and adjusted effects of the above variables on PRx throughout time. A total of 199 complete daily observations from 18 adult consecutive multiple trauma patients with severe traumatic brain injury were analyzed. At hospital admission, the median post-resuscitation Glasgow coma score was 6 (range 3-12), mean SAPSII score was 44.65 with predicted mortality of 36 %. Hospital mortality rate was 27 % and median GOS at 6 month after discharge was 3. Creatinine clearance (CrCl) was found to have a negative correlation with PRx (Pearson correlation--0.82), with statistically significant crude (p < 0.001) and adjusted (p = 0.001) effects. For each increase of 10 ml/min in CrCl (estimated either by the Cockcroft-Gault or by Modification of Diet in Renal Disease Study equations) a mean decrease in PRx of approximately 0.01 was expected. Amongst possible confounders only norepinephrine was shown to have a significant effect. Mean PRx value for outcome fatal status was greater than mean PRx for nonfatal status (p < 0.05), regardless of the model used for the CrCl estimation. Better cerebral autoregulation evaluated with cerebrovascular PRx is significantly correlated with augmented renal clearance in TBI patients and associates with better outcome.