What are the potential causes of chest pain in a patient with multiple myeloma, impaired renal function, and hyperkalemia?

Chest Pain in Multiple Myeloma with Elevated Creatinine and Potassium

Direct Answer

In a multiple myeloma patient presenting with chest pain, elevated creatinine, and hyperkalemia, the most critical immediate concern is life-threatening hyperkalemia causing cardiac arrhythmias, followed by uremic pericarditis from acute kidney injury secondary to light chain cast nephropathy, and cardiovascular complications from myeloma treatments or disease-related factors.

Life-Threatening Cardiac Causes (Immediate Priority)

Hyperkalemia-Induced Cardiac Toxicity

• Severe hyperkalemia can cause fatal cardiac arrhythmias including ventricular fibrillation and asystole, manifesting as chest pain or discomfort 1
• The combination of renal failure (creatinine >2 mg/dL) and hyperkalemia in MM patients creates immediate cardiac risk requiring urgent ECG evaluation 1
• Hyperkalemia is a direct consequence of acute kidney injury, which occurs in 16-31% of MM patients at diagnosis 1

Uremic Pericarditis

• Acute kidney injury with significantly elevated creatinine can cause uremic pericarditis, presenting as chest pain that worsens with inspiration and improves when leaning forward 1
• Renal impairment (defined as creatinine >2 mg/dL or eGFR <40 mL/min) is one of the CRAB criteria defining active myeloma requiring treatment 1, 2
• Approximately 20% of MM patients have creatinine ≥2.0 mg/dL at diagnosis, with light chain cast nephropathy being the primary cause 1

Myeloma-Specific Renal and Metabolic Causes

Light Chain Cast Nephropathy (LCCN)

• LCCN is the most common cause of acute kidney injury in MM, occurring when monoclonal free light chains interact with Tamm-Horsfall protein to form obstructing casts in renal tubules 1
• The resulting acute renal failure leads to electrolyte imbalances including hyperkalemia, which directly threatens cardiac function 1
• Serum free light chain concentrations >80-200 mg/dL significantly increase AKI risk 1
• Recovery of renal function requires rapid reduction of involved serum free light chain by at least 50-60% 1

Hypercalcemia-Related Complications

• Hypercalcemia (calcium >11.5 mg/dL or >0.25 mmol/L above upper limit of normal) is a CRAB criterion that can cause chest discomfort and contributes to renal failure 1, 2
• Hypercalcemia and dehydration are the two major causes of compromised renal function in MM, creating a vicious cycle 1
• Prompt treatment of hypercalcemia with aggressive hydration (>3 L/24h) and bisphosphonates (zoledronic acid or pamidronate) is crucial 1, 3

Treatment-Related Cardiovascular Complications

Cardiotoxicity from Myeloma Therapies

• Immunomodulators (thalidomide, lenalidomide) and proteasome inhibitors used in MM treatment are associated with cardiovascular adverse events including thromboembolism and cardiac dysfunction 4
• Thalidomide combined with dexamethasone requires monitoring for thromboembolic complications and prophylaxis against deep vein thrombosis 1
• Newer MM agents have dramatically improved survival but introduced cardiovascular events not previously observed regularly 4

Pulmonary Embolism

• Patients receiving thalidomide-based regimens have increased risk of venous thromboembolism, which can present as chest pain with dyspnea 1, 5
• Prophylaxis against deep vein thrombosis should be provided to patients on thalidomide combined with dexamethasone or chemotherapy 1

Disease-Related Cardiovascular Pathology

Cardiac Amyloidosis

• MM can cause cardiomyopathy and heart failure from cardiac amyloid light chain deposition, presenting with chest pain, dyspnea, and heart failure symptoms 4
• Amyloid deposition may also contribute to renal failure, creating overlapping complications 1

Anemia-Related Cardiac Strain

• Severe anemia (hemoglobin <10 g/dL, a CRAB criterion) causes high-output cardiac strain and angina-like chest pain 1, 2, 6
• Approximately 73% of MM patients have anemia at presentation 6
• Erythropoietic-stimulating agents may be initiated for persistent symptomatic anemia after excluding other causes 1

Pulmonary Hypertension

• Echocardiography-diagnosed pulmonary hypertension is relatively common in MM patients and associated with increased mortality and chest pain symptoms 5
• PH in MM is usually multifactorial, involving disease-specific factors, comorbidities, and treatment-related adverse effects 5

Skeletal Complications

Pathologic Rib Fractures

• Lytic bone lesions occur in approximately 79% of MM patients, with ribs being a frequent site; pathologic rib fractures cause pleuritic chest pain 1, 6
• Bone disease is one of the CRAB criteria and requires treatment with bisphosphonates (zoledronic acid 4 mg IV over 15 minutes or pamidronate 90 mg IV over 2 hours every 3-4 weeks) 1

Critical Management Algorithm

Immediate Assessment (First 30 Minutes)

1. Obtain urgent ECG to evaluate for hyperkalemia-induced changes (peaked T waves, widened QRS, sine wave pattern) 1
2. Check serum potassium, calcium, creatinine, and cardiac biomarkers immediately 1
3. If hyperkalemia confirmed, initiate emergent treatment with calcium gluconate (cardiac membrane stabilization), insulin/glucose, and consider dialysis 1

Diagnostic Workup (First 24 Hours)

1. Measure serum free light chains with kappa/lambda ratio to assess LCCN severity 1, 2
2. Obtain chest imaging (CT preferred over plain radiography) to evaluate for rib fractures, pulmonary embolism, pericardial effusion, and pulmonary infiltrates 1
3. Perform echocardiography to assess for pericardial effusion, cardiac function, and pulmonary hypertension 4, 5
4. Consider renal biopsy if diagnosis of LCCN versus other causes of AKI is uncertain 1

Definitive Treatment

1. For LCCN with AKI: Initiate bortezomib-based regimen immediately as it is the standard of care and can be safely administered without dose adjustment in renal impairment 1, 3
2. Maintain high urine output (>3 L/day) with aggressive IV hydration to prevent further renal damage 1, 3
3. Consider plasma exchange for rapidly progressive renal failure to remove monoclonal light chains, which may restore renal function in >50% of patients 1
4. Initiate bisphosphonates for hypercalcemia and bone disease once renal function is stabilized 1, 3

Common Pitfalls to Avoid

• Do not delay treatment while awaiting renal biopsy if clinical presentation strongly suggests LCCN; early treatment initiation is critical for renal recovery 1
• Avoid NSAIDs in patients with renal impairment as they worsen kidney function 3
• Do not use contrast media without ensuring adequate hydration, though risk of contrast-induced nephropathy is <1% when dehydration is avoided 1
• Bisphosphonate infusion times must not be shortened: pamidronate requires ≥2 hours, zoledronic acid requires ≥15 minutes to prevent renal toxicity 1
• Monitor for albuminuria (>500 mg/24h) and azotemia every 3-4 weeks in patients on chronic bisphosphonates; discontinue if these develop 1
• Do not attribute all chest pain to musculoskeletal causes; cardiac and pulmonary etiologies must be excluded first given the high mortality risk 4, 5