🧪 LDH (Lactate Dehydrogenase) Test
🧪 LDH (Lactate Dehydrogenase) Test: A Complete Clinical Guide
One of the most sensitive markers for tissue damage, hemolysis, and tumor activity
Lactate Dehydrogenase (LDH) is an intracellular enzyme present in almost every tissue of the human body. When cells are damaged, LDH is released into the bloodstream, making it a highly sensitive—but nonspecific—marker of cellular injury.
LDH levels rise in conditions involving organ damage, hypoxia, hemolysis, inflammation, and malignancies with high tumor turnover. This article provides an updated, evidence-based overview of its applications in modern clinical practice.
1. 🧬 What Is LDH?
LDH catalyzes the interconversion of lactate and pyruvate in cellular metabolism:
Lactate ⇄ Pyruvate
LDH consists of five isoenzymes (LDH1–LDH5), each predominant in specific organs:
| Isoenzyme | Major Locations |
|---|---|
| LDH1 | Heart, red blood cells |
| LDH2 | Reticuloendothelial system |
| LDH3 | Lungs |
| LDH4 | Liver, skeletal muscle |
| LDH5 | Liver, skeletal muscle |
💡 Total LDH elevation indicates cellular injury, while isoenzyme patterns may help identify the damaged tissue.
2. 🎯 Clinical Indications for the LDH Test
✔ 1) Assessing Tissue Damage
Useful when evaluating:
- Hepatic injury
- Pulmonary diseases
- Renal infarction
- Muscle injury
- Inflammatory conditions
Often elevated early, serving as a sensitive first clue.
✔ 2) Evaluation of Hemolytic Anemia
Red blood cells contain abundant LDH, especially LDH1.
Hemolysis triad:
- ↑ LDH
- ↓ Haptoglobin
- ↑ Indirect bilirubin
Microangiopathic hemolytic anemia (TTP, HUS, DIC) shows marked LDH elevation.
✔ 3) Tumor Marker for Malignancies
LDH correlates with tumor burden and cell turnover in:
- Non-Hodgkin and Hodgkin lymphoma
- Leukemia (AML, ALL)
- Testicular cancer (especially seminoma)
- Advanced solid tumors
Higher LDH → poorer prognosis.
✔ 4) Liver, Kidney, and Muscle Disorders
- Liver: rises in hepatitis, cirrhosis, drug-induced injury
- Muscle: elevated in rhabdomyolysis, myositis
- Kidneys: elevated in renal infarction, glomerulonephritis
✔ 5) Pulmonary Conditions
LDH increases in:
- Pulmonary embolism (PE)
- Pneumonia
- Interstitial lung disease
3. 🔬 Test Method: UV Kinetic Assay (Standard Technique)
Most hospital laboratories use the UV kinetic method, based on measuring NADH absorbance at 340 nm.
✔ Principle
LDH catalyzes:
Pyruvate + NADH → Lactate + NAD⁺
- NADH strongly absorbs light at 340 nm
- As LDH converts NADH to NAD⁺, absorbance decreases
- Rate of absorbance decline = LDH activity
✔ Advantages
- Rapid and accurate
- Fully automated (cobas, Architect, AU analyzers)
- Good inter-lab reproducibility
4. 📊 Reference Ranges
Typical reference range (may vary by laboratory):
| Group | LDH Reference Range |
|---|---|
| Adults | 119–229 U/L |
| Children | Slightly higher normal values |
| Isoenzymes | Lab-specific ranges |
Pregnancy, recent exercise, or mild hemolysis may cause minor elevation.
5. 🩺 Clinical Interpretation of LDH Levels
🔺 LDH Elevation (Clinically Significant Conditions)
1) Hemolytic Anemia
- Marked elevation of LDH1 & LDH2
- Strong rise in microangiopathic hemolysis (TTP, HUS, DIC)
2) Liver Injury
- Viral hepatitis
- Cirrhosis
- Drug-induced liver injury
- Often accompanied by ALT/AST elevation
- LDH5 predominance may be noted
3) Myocardial Infarction (Historical Use)
Not routinely used today (troponin is preferred).
However:
LDH1 > LDH2 (“LDH flip”) → classic pattern in myocardial infarction.
4) Malignancies / High Tumor Burden
- Lymphoma
- Leukemia
- Testicular tumors (seminoma)
- Metastatic cancers
- Indicator of poor prognosis
5) Pulmonary Disease
- Pulmonary embolism
- Pneumonia
- ILD
6) Renal Disorders
- Renal infarction
- Glomerulonephritis
7) Muscle Injury
- Rhabdomyolysis
- Myositis
8) Severe Hypoxia, Shock, Sepsis
Global tissue hypoxia → LDH spike.
🔻 LDH Decrease (Rare and Less Clinically Relevant)
Possible causes include:
- High-dose vitamin C
- Rare hereditary LDH deficiency
- Severe, end-stage hepatic failure (enzyme production reduced)
6. 🩻 Important Pitfalls in LDH Interpretation
⚠ 1) Hemolysis of the Sample (Most Common Cause of False Elevation)
Even slight hemolysis during collection, transport, or centrifugation increases LDH significantly.
Always check hemolysis index (HI).
⚠ 2) Recent Strenuous Exercise
Can temporarily elevate LDH for 24–48 hours.
⚠ 3) Isolated LDH Elevation in NASH
Occasionally LDH rises even when ALT/AST are normal.
⚠ 4) ESRD (End-Stage Kidney Disease)
Reduced clearance → Mild LDH elevation possible.
⚠ 5) Tumor Evaluation Requires Additional Markers
LDH must be interpreted alongside:
- CRP
- Ferritin
- β-hCG
- AFP
- Imaging
7. 📚 References
- Bishop ML, Fody EP, Schoeff LE. Clinical Chemistry: Principles, Techniques, and Correlations.
- Burtis CA, Ashwood ER. Tietz Textbook of Clinical Chemistry and Molecular Diagnostics.
- Lacher DA et al. “Laboratory Reference Intervals for LDH.” Clin Biochem.
- Henry JB. Clinical Diagnosis and Management by Laboratory Methods.
- AACC Guidelines on LDH Utilization.
- Hoffbrand AV. Postgraduate Haematology.