Acute kidney injury in burn patients

Overview

Acute kidney injury (AKI) is a common and severe complication of major burn injury. Depending on the cohort and definition used, AKI develops in 20-25% of patients with burns exceeding 15% total body surface area ^[1,3]. Once AKI develops after major burns, mortality exceeds 50%, and survivors face prolonged ICU stays and increased risk of chronic kidney disease ^[1,3].

Burn-associated AKI is multifactorial. In the early phase (first 48-72 hours), the dominant mechanisms are hypovolemia from inadequate or delayed resuscitation, myoglobinuria from rhabdomyolysis (especially with deep circumferential or high-voltage electrical burns), and direct inflammatory-mediated renal tubular injury. The opposite extreme is equally dangerous: over-resuscitation causes volume overload, renal venous congestion, elevated intra-abdominal pressure, and reduced renal perfusion pressure. The tension between under-resuscitation and over-resuscitation is a fundamental challenge in the first 24-48 hours. Beyond the resuscitation phase, nephrotoxin exposure (aminoglycosides, vancomycin, radiocontrast), sepsis, and repeated operative insults drive late renal injury ^[1,2,3].

Classification and Phenotypes

KDIGO Staging

AKI severity is classified by Kidney Disease Improving Global Outcomes (KDIGO) criteria ^[5]:

• Stage 1: Serum creatinine 1.5-1.9x baseline or increase of 0.3 mg/dL or more within 48 hours. Urine output less than 0.5 mL/kg/h for 6-12 hours.
• Stage 2: Serum creatinine 2.0-2.9x baseline. Urine output less than 0.5 mL/kg/h for 12 hours or more.
• Stage 3: Serum creatinine 3.0x or more baseline, or increase to 4.0 mg/dL or more, or initiation of RRT. Urine output less than 0.3 mL/kg/h for 24 hours or more, or anuria for 12 hours or more.

Creatinine interpretation is complicated in burn patients by the altered body composition, muscle catabolism, and fluid shifts inherent to major burns. Baseline creatinine is often unknown. Urine output trending is therefore essential but must be interpreted in context of resuscitation volumes and diuretic use.

Primary AKI

Primary AKI occurs within the first 7 days of burn injury and represents the most severe renal phenotype ^[3]. In a cohort of 733 burn patients with TBSA greater than 15%, 158 (21.6%) developed primary AKI, and mortality among those with primary AKI was 60.1%. Primary AKI was driven primarily by baseline patient vulnerability (dementia, chronic alcohol use, age) and burn severity (full-thickness TBSA, SAPS II score), with inhalation injury also contributing ^[3].

Secondary AKI and Acute Kidney Disease

Among primary AKI survivors, 45.7% developed further renal injury: secondary AKI alone (16.5%), acute kidney disease (AKD, dysfunction persisting beyond 7 days) alone (10.7%), or both (20.7%) ^[3]. Secondary AKI and AKD were driven by ICU complications, particularly infection, cardiovascular support requirements, digestive bleeding, and additional organ failures. Infection emerged as the dominant predictor across both secondary phenotypes ^[3].

Pediatric AKI

In a South African pediatric trauma and burn cohort, 51 of 291 patients (17.5%) developed AKI, with 51% classified as KDIGO stage 3 ^[4]. Most young children either recovered without kidney replacement therapy or died from multiorgan dysfunction. Only 9 patients (17.7%) received kidney replacement therapy, with only 1 survivor among them ^[4].

Diagnosis and Monitoring

AKI staging follows KDIGO criteria as above. Serum creatinine remains the primary biomarker, though its limitations in burn patients are significant: catabolic muscle loss lowers creatinine production, massive fluid resuscitation dilutes serum levels, and baseline values are rarely available. A "normal" creatinine in a burn patient may mask significant renal dysfunction.

Monitoring should include:

• Hourly urine output (the most immediately available renal indicator in the resuscitation phase)
• Serum creatinine every 12-24 hours during the first 72 hours, then daily
• Trending BUN/creatinine ratio (elevated ratio suggests prerenal physiology or GI bleeding)
• Serum potassium, phosphorus, and bicarbonate for metabolic consequences of renal dysfunction
• Bladder pressure measurement when intra-abdominal hypertension is suspected (target less than 20 mmHg)

Machine learning models incorporating hemodynamic and physiologic data (excluding traditional renal biomarkers) have demonstrated robust AKI prediction in burn ICU cohorts, achieving area under the ROC curve of 0.75-0.77, with median lead time exceeding 70 hours before clinical diagnosis ^[6].

Management

Prevention and Fluid Optimization

The best treatment for burn-associated AKI is prevention. Key principles:

• Resuscitation targeting: Use Parkland formula as a starting point but titrate to urine output of 0.5-1.0 mL/kg/h. Avoid the reflex to chase urine output above 1.0 mL/kg/h, which drives fluid creep and its own renal consequences.
• Nephrotoxin avoidance: Minimize aminoglycoside exposure. Use vancomycin with trough-guided or AUC-based dosing. Avoid iodinated contrast when possible; if unavoidable, ensure adequate hydration and minimize contrast volume. Review medication lists daily for nephrotoxic agents.
• Myoglobin clearance: For patients with rhabdomyolysis (CK greater than 5,000 U/L, dark urine), maintain urine output above 1-2 mL/kg/h with crystalloid. The role of urine alkalinization remains controversial.
• Abdominal compartment surveillance: Monitor bladder pressures in patients receiving large-volume resuscitation (more than 250 mL/kg in 24 hours). Elevated intra-abdominal pressure (greater than 20 mmHg) directly compresses renal vasculature and impairs filtration. Decompressive laparotomy may be required.
• Sepsis control: Early wound excision and infection source control are renal protection strategies. Sepsis is the dominant driver of late AKI ^[3].

Renal Replacement Therapy

When AKI progresses to require RRT, standard indications apply: refractory hyperkalemia, severe metabolic acidosis, volume overload unresponsive to diuretics, and uremic symptoms. There is no benefit to starting RRT early (before these indications develop) in critically ill patients. The STARRT-AKI trial randomized 2,927 critically ill patients with severe AKI and found no difference in 90-day mortality between accelerated and standard RRT initiation strategies ^[7]. A secondary analysis of STARRT-AKI demonstrated that intermittent hemodialysis was associated with significantly higher rates of hemodynamic adverse events compared to CRRT (HR 1.74 for IHD, HR 2.73 for SLED vs CRRT), supporting the preference for continuous modalities in hemodynamically unstable patients ^[8].

CRRT is the preferred modality in the burn ICU for practical and physiologic reasons: hemodynamic stability during treatment, continuous solute and fluid removal matching the ongoing resuscitation and nutrition demands of burn patients, and better temperature control.

Pharmacokinetic considerations during CRRT are important for burn patients requiring antimicrobial therapy. CRRT, augmented renal clearance (common in the hypermetabolic burn state), and the expanded volume of distribution in burns create complex dosing challenges for beta-lactams and other antibiotics. Pharmacy involvement in dose optimization is essential ^[9].

Prognosis and Outcomes

Early AKI predicts progressive renal dysfunction and higher mortality in severely burned adults. Mosier et al. demonstrated that AKI developing within the first week of burn injury was an independent predictor of death, and that early AKI predicted progression to more severe renal dysfunction later in the course ^[1]. Steinvall et al. confirmed that AKI substantially increases mortality in burn patients and identified TBSA, age, and inhalation injury as the primary risk factors for its development ^[2].

Long-term renal outcomes after burn-associated AKI are poorly characterized, but general critical care literature suggests survivors of severe AKI carry increased risk of CKD progression over years. Follow-up renal function testing after discharge is warranted.

Controversies and Evidence Gaps

The optimal balance between adequate resuscitation and renal protection from volume overload remains the fundamental unresolved tension in early burn management. Whether novel renal biomarkers (NGAL, KIM-1, cystatin C) add clinically meaningful value to creatinine-based staging in burn patients requires prospective validation. The STARRT-AKI trial included predominantly medical and nonsurgical patients, and burn-specific data on RRT timing are lacking. The role of AI-based prediction models in clinical workflow implementation is promising but early. The threshold for decompressive laparotomy in the setting of AKI with intra-abdominal hypertension is not standardized.

References

[1] Mosier MJ et al. "Early acute kidney injury predicts progressive renal dysfunction and higher mortality in severely burned adults." J Burn Care Res 2010;31(1):83-92. PMID: 20061841 [2] Steinvall I et al. "Acute kidney injury is common, parallels organ dysfunction or failure, and carries appreciable mortality in patients with major burns: a prospective exploratory cohort study." Crit Care 2008;12(5):R124. PMID: 18847465 [3] Boutin L et al. "Kidney failure trajectories and sub phenotypes in severe burn patients." Anaesth Crit Care Pain Med 2025;45(4):101696. PMID: 41242388 [4] Moodley K et al. "Acute kidney injury and kidney replacement therapy in pediatric severe trauma and burns patients, a single-center review from a middle-income country." Clin Nephrol 2026;105(4):283-290. PMID: 41508887 [5] KDIGO Work Group. "KDIGO Clinical Practice Guideline for Acute Kidney Injury." Kidney Int Suppl 2012;2(1):1-138. DOI: 10.1038/kisup.2012.1 [6] Boutin L et al. "From haemodynamics to kidney risk: AI-based early prediction validated in general and burn ICU populations." Eur Heart J Digit Health 2026;7(1):ztaf150. PMID: 41574040 [7] Bagshaw SM et al. "Timing of Initiation of Renal-Replacement Therapy in Acute Kidney Injury." N Engl J Med 2020;383(3):240-251. PMID: 32668114 [8] Kelly YP et al. "Factors associated with adverse haemodynamic events during the STARRT-AKI trial: a post-hoc secondary analysis." Crit Care 2025;29(1):534. PMID: 41466322 [9] Gatti M, Pea F. "Pharmacokinetics-pharmacodynamics perspective to optimizing therapy with beta-lactams in critically ill patients: an update." Expert Rev Anti Infect Ther 2025;23(12):1215-1233. PMID: 41437777