What are the next steps in management for a 17‑year‑old male with a normal renal‑bladder ultrasound, proteinuria, markedly elevated creatine kinase (CK), markedly elevated alanine aminotransferase (ALT), and normal serum creatinine?

Immediate Evaluation for Rhabdomyolysis and Muscular Dystrophy

This 17-year-old male with a markedly elevated CK of 85,385 U/L, elevated ALT of 548 U/L, proteinuria, and normal creatinine requires urgent evaluation for rhabdomyolysis and underlying neuromuscular disease—specifically, stop any nephrotoxic medications immediately, ensure aggressive intravenous hydration to prevent acute kidney injury, and obtain a comprehensive metabolic panel with urine myoglobin to assess for evolving renal dysfunction. 1

Understanding the Clinical Picture

The constellation of findings points to severe muscle injury rather than primary kidney disease:

• CK elevation of 85,385 U/L is >850-fold above the upper limit of normal and indicates massive muscle breakdown (rhabdomyolysis), which releases myoglobin that can cause acute tubular necrosis despite currently normal creatinine 1, 2

• ALT elevation (548 U/L) in the context of extreme CK elevation reflects muscle-derived transaminases rather than primary hepatic injury, as skeletal muscle contains high concentrations of ALT 1

• Proteinuria with normal renal ultrasound and normal creatinine suggests either myoglobinuria (which tests positive on urine dipstick as "protein") or early glomerular injury from myoglobin toxicity 1, 3

Immediate Management Steps (Within 24 Hours)

Rule Out Acute Rhabdomyolysis Complications

• Check urine myoglobin and urine color immediately—visible myoglobinuria (tea- or cola-colored urine) indicates high risk for acute kidney injury and requires hospitalization 1

• Obtain comprehensive metabolic panel including serum potassium, phosphate, calcium, and uric acid—hyperkalemia, hyperphosphatemia, hypocalcemia, and hyperuricemia are life-threatening complications of rhabdomyolysis 1

• Monitor urine output closely—target >200 mL/hour (or 3 mL/kg/hour) with aggressive intravenous normal saline to prevent myoglobin precipitation in renal tubules 1

• Repeat serum creatinine within 24–48 hours—normal creatinine at presentation does not exclude evolving acute kidney injury, as CK peaks before creatinine rises 1, 2

Discontinue Potential Causative Agents

• Stop all statins, fibrates, or other lipid-lowering drugs immediately if the patient is taking them, as these are common causes of drug-induced rhabdomyolysis 1

• Review medication list for other myotoxic agents including antipsychotics (especially olanzapine), colchicine, and antiretrovirals 4

• Inquire about recent illicit drug use (cocaine, amphetamines, MDMA) or alcohol intoxication, which are frequent causes of rhabdomyolysis in adolescents 1

Diagnostic Workup for Underlying Neuromuscular Disease

History and Physical Examination Focused on Muscle Disease

• Ask specifically about exercise tolerance, muscle weakness, muscle cramps, dark urine after exercise, and family history of muscular dystrophy or metabolic myopathy—these features suggest inherited muscle disease rather than acquired rhabdomyolysis 2

• Examine for proximal muscle weakness (difficulty rising from a chair, climbing stairs, lifting arms overhead) and calf pseudohypertrophy, which are hallmarks of Duchenne or Becker muscular dystrophy 1

• Document any recent viral illness, trauma, or extreme exertion—these are common triggers for rhabdomyolysis in patients with underlying metabolic myopathies 2

Laboratory Evaluation for Muscular Dystrophy

• Order serum creatine kinase-MB (CK-MB) and CK-MB:total CK ratio—a ratio <3% confirms skeletal muscle origin rather than cardiac injury 2, 4

• Obtain baseline aldolase and lactate dehydrogenase (LDH)—these muscle enzymes are elevated in muscular dystrophy and help differentiate chronic myopathy from acute rhabdomyolysis 1

• Send genetic testing for Duchenne/Becker muscular dystrophy (dystrophin gene deletion/duplication analysis) if clinical suspicion is high, as CK levels >10,000 U/L in an asymptomatic adolescent male strongly suggest dystrophinopathy 1

• Consider metabolic myopathy screening including carnitine palmitoyltransferase II (CPT II) deficiency and myophosphorylase deficiency (McArdle disease) if recurrent episodes or exercise intolerance 1

Nephrology Referral Criteria

When to Refer Urgently (Within 1 Week)

• Refer immediately if serum creatinine rises >20% from baseline or if urine output falls below 0.5 mL/kg/hour despite adequate hydration, as these indicate evolving acute kidney injury requiring specialist management 1

• Refer if proteinuria persists after CK normalizes—persistent proteinuria (>1 g/day or protein-to-creatinine ratio >1000 mg/g) after resolution of rhabdomyolysis suggests primary glomerular disease and warrants kidney biopsy 1, 5

• Do not delay referral for patients with nephrotic-range proteinuria (>3.5 g/day) and hematuria, as this combination mandates renal biopsy to exclude rapidly progressive glomerulonephritis 6, 7

When Outpatient Nephrology Follow-Up is Appropriate

• Schedule outpatient nephrology consultation within 4–6 weeks if creatinine remains normal and proteinuria is <1 g/day after CK normalizes, to evaluate for chronic kidney disease 1, 5

Monitoring and Follow-Up

Short-Term Monitoring (First 2 Weeks)

• Recheck CK, creatinine, and electrolytes every 2–3 days until CK falls below 1000 U/L—CK should decline by approximately 40% per day once muscle injury stops 1, 2

• Quantify proteinuria with spot urine protein-to-creatinine ratio once CK normalizes to determine if proteinuria was due to myoglobinuria or represents true glomerular disease 5

• Avoid nephrotoxic medications (NSAIDs, aminoglycosides, contrast agents) until CK and creatinine normalize 1

Long-Term Management if Muscular Dystrophy is Confirmed

• Refer to neuromuscular specialist for definitive diagnosis, genetic counseling, and multidisciplinary care including cardiology (for cardiomyopathy screening) and pulmonology (for respiratory muscle weakness) 1

• Educate patient to avoid triggers including strenuous exercise, fasting, extreme heat, and certain medications (statins, general anesthetics) that precipitate rhabdomyolysis in metabolic myopathies 2

Common Pitfalls to Avoid

• Do not assume normal creatinine excludes significant rhabdomyolysis—acute kidney injury may develop 24–72 hours after presentation, especially with CK >15,000 U/L 1, 2

• Do not attribute elevated ALT to liver disease without checking CK—in the setting of extreme CK elevation, ALT originates from skeletal muscle and does not indicate hepatotoxicity 1

• Do not order 24-hour urine protein collection in acute rhabdomyolysis—spot protein-to-creatinine ratio is sufficient and avoids delay in diagnosis 5

• Do not initiate ACE inhibitors or ARBs for proteinuria until rhabdomyolysis resolves—these agents can worsen acute kidney injury in the setting of volume depletion and myoglobinuria 5