A 57-year-old man arrives at the hospital with nausea, dark urine, and decreased urine output for 2 days. For the past week, the patient has had generalized fatigue, muscle pain, and weakness. He reports no recent fever, chills, sore throat, skin infection, or abdominal pain. Medical history is significant for coronary artery disease with stenting to the right coronary artery, hypertension, gout, and obstructive sleep apnea. Current medications include aspirin, ticagrelor, simvastatin, metoprolol, lisinopril, and colchicine. The patient does not use alcohol, tobacco, or illicit drugs. Temperature is 37 C (98.6 F), blood pressure is 140/90 mm Hg, pulse is 88/min, and respirations are 18/min. There is no orthostasis. Skin turgor is normal. Oropharynx is clear. Cardiopulmonary examination shows no abnormalities. The abdomen is soft, nontender, and without bruit; there are no masses felt. There is no peripheral edema. The right great toe is slightly inflamed. Laboratory studies reveal the following: Baseline laboratory studies conducted a month ago were normal. Which of the following is most helpful to establish a diagnosis?

Question

A 57-year-old man arrives at the hospital with nausea, dark urine, and decreased urine output for 2 days.  For the past week, the patient has had generalized fatigue, muscle pain, and weakness.  He reports no recent fever, chills, sore throat, skin infection, or abdominal pain.  Medical history is significant for coronary artery disease with stenting to the right coronary artery, hypertension, gout, and obstructive sleep apnea.  Current medications include aspirin, ticagrelor, simvastatin, metoprolol, lisinopril, and colchicine.  The patient does not use alcohol, tobacco, or illicit drugs.  Temperature is 37 C (98.6 F), blood pressure is 140/90 mm Hg, pulse is 88/min, and respirations are 18/min.  There is no orthostasis.  Skin turgor is normal.  Oropharynx is clear.  Cardiopulmonary examination shows no abnormalities.  The abdomen is soft, nontender, and without bruit; there are no masses felt.  There is no peripheral edema.  The right great toe is slightly inflamed.  Laboratory studies reveal the following:  Baseline laboratory studies conducted a month ago were normal.  Which of the following is most helpful to establish a diagnosis?

Quizplus · Accepted Answer

11ec25c8_d20e_9287_bc81_2559ee015aa4_MD0003_00 This patient's presentation-muscle weakness, dark urine, decreased urine output, elevated creatinine, and blood on urinalysis without a significant number of red blood cells (RBCs) on urine microscopy-is consistent with rhabdomyolysis. Rhabdomyolysis is commonly due to trauma (eg, crush injury, immobilization) or extreme exertion (eg, exercise in the heat), not seen in this patient. However, both statins (eg, simvastatin) and colchicine are direct myotoxins and may trigger rhabdomyolysis, especially when used in combination. Statins can cause many adverse effects on skeletal muscle (eg, asymptomatic inflammation, myopathy, rhabdomyolysis), possibly by impairing regulatory proteins (eg, coenzyme Q). Colchicine inhibits microtubule function, leading to myocyte waste product accumulation. Synergistic toxicity can lead to widespread skeletal muscle necrosis. Myoglobin (containing heme) is released into the bloodstream and delivers heme pigments to the kidneys, where they create dark urine (pigmenturia) and can cause tubular toxicity and oliguric acute kidney injury (AKI). The heme pigments are detected as blood on urinalysis; however, because true hematuria is absent, no RBCs are present on urine microscopy (ie, discordant blood findings on urine testing). Potassium and phosphate release into the bloodstream can lead to hyperkalemia and hyperphosphatemia. Creatine phosphokinase is a marker of skeletal muscle damage, and serum elevation >1,000 U/L confirms the diagnosis in the appropriate clinical setting. (Choice A) 24-hour urine protein measurement is used to evaluate for nephrotic syndrome. However, nephrotic syndrome typically causes foamy (rather than dark) urine, rarely causes profound AKI, and is extremely unlikely given the absence of proteinuria. (Choice B) Renal ultrasonography can detect hydronephrosis, which suggests urinary tract obstruction as a cause of AKI. However, severe hydronephrosis is less likely in the absence of palpable abdominal masses and would not explain blood on urinalysis in the absence of RBCs. (Choice C) Renal vascular imaging (Doppler ultrasonography) can evaluate for renal artery stenosis (RAS) which, if bilateral, can cause severe AKI in patients on an ACE inhibitor (eg, lisinopril). However, marked hypertension is expected, and RAS would not account for discordant blood findings on urine testing. (Choice D) Low serum complement (C3 and C4) levels help diagnose certain types of glomerulonephritis (eg, lupus nephritis, poststreptococcal), but true hematuria is expected with blood on urinalysis and RBCs on urine microscopy. Educational objective: Some drugs (eg, statins, colchicine) are directly myotoxic and may cause rhabdomyolysis, especially when used in combination. Rhabdomyolysis is suggested by dark urine, blood on urinalysis in the absence of red blood cells on urine microscopy, and acute kidney injury. References: Cytoskeletal myotoxicity from simvastatin and colchicine. (http://www.ncbi.nlm.nih.gov/pubmed/15389652)

A 57-Year-Old Man Arrives at the Hospital with Nausea, Dark