Revisiting acute kidney injury outcomes in traumatic brain injury

Abstract

Acute kidney injury in traumatic brain injury is a major concern, affecting up to 10% of the patients in intensive care unit due to multifaceted mechanisms, including hemorrhagic shock, rhabdomyolysis, and brain-kidney cross-talk, compounded by hyperosmolar therapies. A significant challenge is that serum creatinine is considered a late and nonspecific marker, often missing the critical early insult phase. Future strategies for early prediction and prevention must focus on emerging factors, such as preventing hyperchloremia and utilizing novel biomarkers, such as neutrophil gelatinase-associated lipocalin and kidney injury molecule 1, which detect subclinical injury and predict the need for renal replacement therapy. Composite risk stratification tools (e.g., renal angina index) are vital for personalized management. Although over 90% of patients recover renal function, prevention of collateral damage to the kidney must be recognized as a critical priority in traumatic brain injury care.

Key Words: Trauma-related acute kidney injury; Traumatic brain injury; Brain-kidney crosstalk; Neutrophil gelatinase-associated lipocalin; Biomarkers; Renal replacement therapy; Hyperchloremia; Risk-stratification

Core Tip: Trauma-related acute kidney injury is a critical concern in traumatic brain injury care, affecting up to 10% of intensive care unit patients. Since creatinine is a late marker, early prediction is vital. Strategies must focus on preventing hyperchloremia using novel biomarkers (e.g., neutrophil gelatinase-associated lipocalin/kidney injury molecule 1) and risk stratification tools to detect subclinical injury and prevent collateral kidney damage.

TO THE EDITOR

We read with great enthusiasm the retrospective cohort study by Wankhade et al[1], in which the authors delved into the incidence, risk factors, and predictors of acute kidney injury (AKI) in patients with traumatic brain injury (TBI). Although this is a single-center retrospective cohort study, it adds a plethora of information to the existing literature, especially because of the demographic profile of the patients being from the apex trauma center of the United Arab Emirates, without additional burden of significant chronic diseases. Additionally, the inclusion criteria quite rightfully included low Glasgow Coma Scale ≤ 11, which underscores the fact that this patient population is also at the highest risk of AKI. Additionally, by examining the related neurosurgical factors, this study offers a fresh clinical viewpoint.

CURRENT SITUATION AND CHALLENGES FOR ASSESSING AKI OUTCOMES IN TBI

The burden of AKI in TBI appears to be enormous, particularly in light of the fact that approximately 10% of the patients with TBI admitted to the intensive care unit (ICU) develop AKI, and 2% require renal replacement therapy (RRT)[2,3]. To this end, trauma-related AKI (TRAKI) remains a distinct pathophysiological entity, occurring due to multiple competing mechanisms, such as hemorrhagic shock, rhabdomyolysis, ischemia-reperfusion injury, abdominal compartment syndrome, contrast nephrotoxicity, and brain-kidney crosstalk[4,5]. Agents used to treat increased intracranial pressure, such as mannitol and hypertonic saline, are themselves associated with an increased risk of AKI[6]. As Robba et al[7] showed from the results of the Collaborative European Neurotrauma Effectiveness Research in Traumatic Brain Injury study, the peak incidence of TRAKI is within the first 2 days of admission to the ICU[7]. In this context, serum creatinine lacks specificity and is a late indicator, typically taking 48-72 hours to increase after a renal insult.

FUTURE DIRECTIONS FOR EARLY PREDICTION OF AKI OUTCOMES IN TBI

Because preventing hyperchloremia-induced kidney impairment has become a viable preventive approach for patients with TRAKI, serum levels of chloride, a neglected ion, appear to be a crucial determinant[8]. The rates of solute clearance and subsequent osmolar clearance are essential for preventing AKI in TBI patients on RRT. The exact optimization targets for cerebral perfusion pressure and its simultaneous effects on the perfusion pressure of the kidney remain unclear. A combination of risk factors, such as advanced age, preexisting chronic kidney disease, exposure to nephrotoxic agents, use of hyperosmolar therapy, combined use of vasoactive drugs, and perfusion pressure in the kidney, is necessary to predict AKI outcomes in TBI. Several existing and novel biomarkers are available for evaluating the effects of these and other risk factors. Biomarkers such as neutrophil gelatinase-associated lipocalin, kidney injury molecule 1, and liver-type fatty acid-binding protein detect subclinical TRAKI and predict the need of RRT (Table 1)[9,10]. Composite scores and risk stratification tools such as the renal angina index, McMahon score, and Haines model help tailor personalized management strategies for AKI in this subset of critically ill patients (Table 2)[11]. These tools have limited direct validation in patient with TBI. To assess the precise trajectory of outcomes in TRAKI, large prospective randomized controlled trials with homogeneous patient populations, using the Kidney Disease: Improving Global Outcomes criteria for AKI, are essential.

Table 1 Common biomarkers for acute kidney injury in traumatic brain injury.

Biomarker	Specimen sample	Remarks
Neutrophil gelatinase-associated lipocalin	Plasma and urine	Released from damaged tubular epithelial cells
Kidney injury molecule 1	Urine	Transmembrane glycoprotein released from damaged tubular epithelial cells
Liver-type fatty acid-binding protein	Plasma and urine	14 kDa cytoplasmic transporter for free fatty acids in proximal tubular epithelial cells
Interleukin-18	Urine	Pro-inflammatory cytokine released from stressed proximal tubular epithelial cells
Tissue inhibitor of metalloproteinases-2; insulin-like growth factor-binding protein 7 (NephroCheck™)	Urine	Metalloproteinases released from stressed tubular epithelial cells during cell cycle arrest

Table 2 Risk-stratification tools for acute kidney injury in traumatic brain injury.

Risk-stratification tool	Components	Cut-off/range	Remarks
Haines model	Key variables: First serum creatinine (around ICU admission), first phosphate (around ICU admission), units of blood transfused in the first 24 hours, age, Charlson comorbidity index	Range: 0-31	This model was developed specifically for trauma patients admitted to critical care
RAI	RAI = risk score × injury score. Risk score (patient context/risk strata), point values are assigned to various risk factors, such as: Admission to an ICU, solid organ or stem cell transplantation, use of mechanical ventilation, use of inotropes or vasopressors, other severe comorbidities (in modified adult versions). Injury score (early signs of loss of function). It usually incorporates the worse of two parameters: Change in serum creatinine and extent of fluid overload	Cut-off ≥ 8: Renal angina positive. Range: 1-40	The RAI is designed for pediatric critically ill patients. The modified RAI is used for critically ill adults
McMahon score	Key variables at admission: Age (years), sex, initial creatinine (mg/dL), initial calcium (mg/dL), initial creatine kinase (U/L), initial phosphate (mg/dL), initial bicarbonate (mEq/L), etiology (rhabdomyolysis secondary to seizure, syncope, exercise, statin, or myositis)	Cut-off ≥ 6: Indicates a higher risk of serious adverse outcomes, including AKI requiring RRT	This score is to predict the risk of severe AKI requiring RRT or mortality in patients with rhabdomyolysis

AKI: Acute kidney injury; ICU: Intensive care unit; RAI: Renal angina index; RRT: Renal replacement therapy.

CONCLUSION

A positive aspect for patients with TRAKI is that more than 90% of patients affected recover their renal function[7]. Although the guiding principle of TBI management is to prevent secondary brain damage, it is important to recognize and prevent collateral damage to the kidney.