In a dialysis patient with new‑onset flank pain, hypertension, and a relatively normal urinalysis, what does a markedly elevated lactate dehydrogenase (LDH) indicate?

What is LDH in the Context of a Dialysis Patient with Flank Pain and Hypertension?

LDH (lactate dehydrogenase) is an intracellular enzyme that catalyzes the reversible conversion of lactate to pyruvate during glucose metabolism, and a markedly elevated level in your dialysis patient with flank pain suggests acute tissue injury—most likely renal infarction, hemolysis, or occult malignancy. 1

Biochemical Definition

LDH is an oxidoreductase enzyme present in the cytoplasm of virtually all cells that participates in anaerobic glycolysis by converting pyruvate to lactate (and vice versa) using NAD⁺/NADH as a coenzyme. 2, 3 The enzyme exists as five isoforms (LDH-1 through LDH-5) composed of two subunit types (H and M), with different tissues expressing characteristic isoenzyme patterns. 2, 4

• High concentrations exist in heart, liver, skeletal muscle, kidney, and erythrocytes, making LDH a nonspecific marker of cellular injury when released into serum. 4
• The enzyme is predominantly cytoplasmic but has multi-organellar locations within cells. 2

Clinical Significance in Your Dialysis Patient

Marked Elevation Indicates Severe Pathology

Very high isolated LDH (≥800 IU/L) is associated with 26.6% in-hospital mortality and serves as an independent predictor of death in admitted medical patients. 5 In your dialysis patient presenting with new flank pain and hypertension, this degree of elevation demands urgent investigation for:

• Renal infarction: Acute arterial occlusion in the native kidney releases massive amounts of LDH from ischemic renal tubular cells, often with minimal urinalysis findings because the infarcted tissue cannot excrete cellular contents into urine. 1
• Hemolysis: Erythrocytes contain extremely high LDH concentrations; intravascular hemolysis (from dialysis catheter trauma, thrombotic microangiopathy, or mechanical shear) releases LDH into plasma. 1, 4
• Occult malignancy: Very high LDH identifies metastatic cancer (14% liver metastases) or hematologic malignancy (5% of cases) in hospitalized patients. 5

Diagnostic Algorithm for Your Patient

First, exclude hemolysis by inspecting the serum for pink discoloration and checking haptoglobin, indirect bilirubin, and peripheral smear. 1 If hemolysis is present, investigate dialysis-related mechanical causes or thrombotic microangiopathy.

Second, if hemolysis is absent, obtain urgent CT angiography of the abdomen to evaluate for renal artery occlusion or renal vein thrombosis, which are vascular catastrophes in dialysis patients that present with flank pain, hypertension (from renin release), and markedly elevated LDH without significant hematuria or proteinuria. 1

Third, if vascular imaging is negative, pursue malignancy evaluation with CT chest/abdomen/pelvis and consider bone marrow biopsy if lymphoma or leukemia is suspected, because very high isolated LDH identifies cancer in 27% of hospitalized patients versus 4% of controls. 5

Prognostic Implications

The presence of very high isolated LDH (≥800 IU/L) predicts longer hospitalization (9.3 vs 4.1 days), more major complications, and six-fold higher mortality (26.6% vs 4.3%) compared to patients without LDH elevation. 5 This finding is an independent mortality predictor even after adjusting for other clinical variables. 5

Common Pitfalls to Avoid

• Do not dismiss markedly elevated LDH as "nonspecific"—levels ≥800 IU/L warrant aggressive investigation for life-threatening conditions. 5
• Repeat the LDH measurement if the blood sample appears hemolyzed, because in-vitro hemolysis from traumatic phlebotomy can falsely elevate LDH values. 1
• Do not rely on urinalysis to exclude renal infarction; infarcted kidney tissue cannot excrete cellular contents, so urine may appear relatively normal despite massive parenchymal injury. 1
• Assess hepatic function (ALT, AST, alkaline phosphatase, bilirubin) to identify liver disease, which can elevate LDH but typically shows a different clinical picture than isolated flank pain. 1

Additional Diagnostic Considerations

In males with unexplained LDH >1.5× upper limit of normal, include serum AFP and β-hCG testing because LDH carries prognostic significance for germ-cell tumors. 1 However, in your dialysis patient with flank pain, renal vascular catastrophe remains the most urgent consideration.

Measure baseline LDH before any red-cell transfusion if malignancy workup is planned, as the baseline value has established prognostic significance. 1