A prospective study of the effects of erythropoietin and early sustained hypothermia on renal function and renal biomarkers in patients with traumatic brain injury

Acute Kidney Injury (AKI) is the consensus term developed and validated in the last 10 years encompassing all classes or stages of kidney injury; it refers to a continuum of injury. AKI is common in critically ill patients and is associated with adverse outcomes such as mortality and progression to Chronic Kidney Disease. Research into therapies for AKI has been largely unsuccessful, which is partly due to the inadequacy of conventional methods to detect AKI early enough for therapies to be implemented effectively. As a result, the investigation of novel markers for the early detection of AKI and new therapies for AKI have become a research priority. Two treatments were to be given to patients with traumatic brain injury in clinical trials commencing in 2010, to investigate their benefit for neurological function. The treatments: erythropoietin and early, sustained hypothermia, had also been shown to protect the kidney and hasten renal recovery in animal studies. However, few human studies had been undertaken. In this thesis we took the opportunity that the EPO-TBI and POLAR trials presented to investigate whether erythropoietin and hypothermia (respectively) reduce the occurrence, severity, and duration of AKI. Furthermore, in nested cohorts from each trial several promising new biomarkers for AKI were evaluated as predictors of AKI and in their response to therapy. Results of this thesis are embargoed until both the 'parent' trials are published.