What is the significance of elevated lactate dehydrogenase (LDH) levels in patients with Acute Kidney Injury (AKI)?

Elevated LDH in AKI: A Prognostic Marker of Mortality and Tissue Damage

Elevated lactate dehydrogenase (LDH) levels in patients with acute kidney injury serve as an independent predictor of in-hospital mortality and indicate the severity of cellular injury, with higher levels correlating directly with worse outcomes. 1

Prognostic Significance

LDH functions as a mortality predictor in AKI patients, particularly in critical care settings:

• LDH independently predicts in-hospital mortality with an odds ratio of 1.56 (95% CI 1.39-1.73) in critically ill AKI patients, and this relationship remains stable across different patient subgroups 1

• The relationship between LDH and mortality is nearly linear, meaning progressively higher LDH levels correspond to incrementally higher death rates 1

• When combined with severity scores (such as SAPSII), LDH increases predictive accuracy for in-hospital mortality to an AUC of 0.83, demonstrating its value as an adjunctive prognostic tool 1

The LDH-to-Albumin Ratio (LAR)

Recent evidence suggests that the ratio of LDH to albumin provides even more refined prognostic information:

• Elevated LAR at admission independently predicts 28-day mortality in sepsis-associated AKI, with hazard ratios of 1.20 for moderate elevation and 1.61 for high elevation compared to low LAR 2

• LAR demonstrates a non-linear relationship with mortality, and this association remains significant across various patient subclasses 3

• Higher LAR correlates with increased mortality at all AKI stages (stages 1,2, and 3), making it useful for risk stratification regardless of AKI severity 3

Pathophysiologic Significance

LDH elevation reflects specific pathologic processes in AKI:

• LDH indicates cellular damage and tissue necrosis, particularly in conditions like rhabdomyolysis-induced AKI where muscle breakdown releases intracellular enzymes 4

• Altered lactate metabolism occurs during AKI, with disrupted glycolysis and gluconeogenesis in the kidneys significantly disturbing lactate metabolic balance, which impacts AKI severity and prognosis 5

• LDH serves as a marker of acute tubular necrosis, as cellular injury releases this cytoplasmic enzyme into circulation 4

Clinical Application Algorithm

When encountering elevated LDH in an AKI patient, follow this approach:

Step 1: Risk Stratification

• Calculate the LDH-to-albumin ratio for more precise prognostic information, as LAR outperforms LDH alone 3, 2
• Recognize that LAR ≥14.66 IU/g indicates highest mortality risk (approximately 60% increased hazard) 2

Step 2: Identify Underlying Cause

• Screen for rhabdomyolysis when LDH is markedly elevated, as this represents a three-fold increase in AKI risk and requires urgent intervention 4
• Consider drug-induced rhabdomyolysis as the most common cause in emergency settings 4

Step 3: Prognostic Counseling

• Use LDH/LAR to inform discussions about mortality risk with patients and families, particularly in ICU settings where baseline mortality is already elevated 1, 2
• Recognize that mortality rates increase progressively across LDH tertiles, with the highest tertile showing significantly worse survival on Kaplan-Meier analysis 2

Step 4: Monitoring Strategy

• Serial LDH measurements can track disease trajectory, as persistently elevated or rising levels suggest ongoing cellular injury 1
• Combine LDH with standard AKI staging criteria (KDIGO stages 1-3) for comprehensive risk assessment 6, 3

Critical Pitfalls to Avoid

• Do not dismiss modest LDH elevations, as even small increases correlate with mortality, similar to how creatinine increases ≥0.3 mg/dL independently increase mortality approximately four-fold 7, 1

• Do not use LDH in isolation—always calculate LAR when albumin is available, as the ratio provides superior prognostic discrimination 3, 2

• Do not overlook rhabdomyolysis when LDH is disproportionately elevated relative to creatinine, as delayed diagnosis carries mortality risk 4

• Do not assume LDH elevation is non-specific—in the AKI context, it specifically indicates cellular injury severity and has been validated across multiple large cohorts totaling over 20,000 patients 1, 3, 2

Practical Value

LDH is easily assessed, cost-effective, and widely available, making it an ideal prognostic biomarker that can be immediately incorporated into clinical decision-making without additional resource burden 1, 4