A 22-year-old man comes to the emergency department after an episode of gross hematuria and right flank pain that resolved spontaneously. The episode occurred while he was hiking in the mountains in summer heat. The patient has no dysuria, urgency, frequency, or fever. He smokes cigarettes occasionally but does not use illicit drugs or alcohol. Temperature is 36.7 C (98 F), blood pressure is 120/70 mm Hg, pulse is 70/min, and respirations are 14/min. Physical examination shows no abnormalities. Laboratory results are as follows:
| Complete blood count | ||
| Hemoglobin | 10.4 g/dL | |
| Reticulocytes | 6% | |
| Platelets | 200,000/mm3 | |
| Leukocytes | 7,500/mm3 | |
| Serum chemistry | ||
| Blood urea nitrogen | 10 mg/dL | |
| Creatinine | 0.8 mg/dL | |
| Urinalysis | ||
| pH | 5.8 | |
| Protein | none | |
| Blood | 3+ | |
| Glucose | negative | |
| Bacteria | none | |
| Red blood cells | 20-30/hpf | |
| White blood cells | 1-2/hpf | |
| Casts | none | |
Urine microscopic examination reveals numerous intact red blood cells but no other abnormal findings. Renal ultrasound demonstrates increased echogenicity of the renal medulla, but there is no hydronephrosis. Which of the following is the most likely cause of this patient's hematuria?
Sickle cell trait | |
Clinical features |
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Laboratory findings |
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Complications |
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Hb A = hemoglobin A; Hb S = hemoglobin S; RBC = red blood cell. | |
This patient's gross hematuria with normal red blood cells (RBCs) and no casts on urine microscopy reflects an extraglomerular cause of hematuria. Several features of his presentation suggest renal papillary necrosis (RPN) likely due to sickle cell trait (SCT), a carrier mutation (resulting in production of hemoglobin AS) present in up to 5% of the world's population. Although typically associated with analgesic overuse, RPN may be the initial manifestation of SCT.
SCT is most common in individuals with African, Middle Eastern, or Mediterranean ancestry. Patients may be unaware of their carrier status as they usually do not develop clinical symptoms of sickle cell disease and have a normal hemoglobin concentration and reticulocyte count. However, sickling can occur in the setting of physiologic stress, particularly with low oxygen tension (eg, hiking in the mountains), dehydration (eg, in summer heat), and acidosis.
Acute sickling can result in anemia with an appropriate reticulocytosis. The kidneys are preferentially affected, as the relatively low oxygen concentration and acidic pH of the medulla promotes sickling. This leads to ischemic injury and RPN, with increased renal medullary echogenicity seen on ultrasound. Painless hematuria is common; however, renal papilla sloughing can result in acute flank pain. Another SCT renal complication possibly seen in this patient (urine pH 5.8) is renal tubular acidosis (tubular damage with impaired H+ secretion).
(Choice A) Acute glomerulonephritis presents with hematuria, but hypertension, proteinuria, dysmorphic RBCs, and RBC casts are also expected. In addition, glomerulonephritis would not typically cause acute flank pain.
(Choice B) Nephrolithiasis causes acute flank pain and hematuria but would not explain this patient's hematologic abnormalities or the medullary echogenicity seen on ultrasound.
(Choice D) Pyelonephritis can present with flank pain and hematuria; however, urinalysis would show many white blood cells and bacteria in addition to positive nitrite and leukocyte esterase. Dysuria and fever are typical.
(Choice E) Rhabdomyolysis also occurs more frequently in patients with SCT, particularly during strenuous activity. However, myoglobinuria is expected, with urinalysis positive for blood but not RBCs. Muscle pain and weakness are also common.
Educational objective:
Patients with sickle cell trait, a carrier mutation, do not typically have specific symptoms of sickle cell disease; however, sickling can occur in the setting of physiologic stress (eg, low oxygen tension, dehydration, acidosis), leading to renal papillary necrosis with hematuria and possibly flank pain.