An 18-year-old African American man comes to the office due to several months of excessive urination. The patient voids every few hours during the day and wakes 2 or 3 times per night to urinate despite restricting his evening fluid intake. He says that his urine appears clear and has no visible blood. Medical history is significant for seasonal allergies, for which he frequently takes an antihistamine. He takes no other medications and does not use tobacco, alcohol, or illicit drugs. The patient is sexually active and does not use condoms. He was adopted at a young age; records indicate that his birth mother had sickle cell disease and died from a stroke at age 32. The patient is afebrile and normotensive. Hematocrit is 41% and serum sodium is 138 mEq/L. Urinalysis of a first-morning specimen reveals the following:
| Specific gravity | 1.001 | (normal: 1.010-1.030) |
| pH | 6.6 | (normal: 4.5-8) |
| Protein | none | |
| Blood | negative | |
| Glucose | negative | |
| Ketones | negative | |
| Leukocyte esterase | negative | |
| Nitrites | negative |
This patient's polyuria is most likely caused by which of the following?
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 has a low urine specific gravity consistent with hyposthenuria, the inability of the kidneys to concentrate urine. His family history is significant for early-onset stroke, which can be a severe complication of sickle cell disease (SCD) due to cerebrovascular occlusion from sickling; however, he has a normal hematocrit level and no other symptoms. Therefore, sickle cell trait (SCT) is the most likely cause of this patient's hyposthenuria.
Hyposthenuria is common in patients with SCD and may also develop in those with SCT. In response to hypoxic, hyperosmolar conditions of the renal medulla, red blood cells sickle in the vasa recta, impairing free water reabsorption and countercurrent exchange. Patients typically have polyuria and nocturia despite fluid restriction. Urine osmolality is low; however, normal serum sodium is maintained due to intact antidiuretic hormone (ADH). Urinary diluting capacity is also intact as it is a function of the superficial loop of Henle, which is not supplied by the vasa recta.
Typically, mild hyposthenuria due to SCT requires no treatment. In patients with SCD, red blood cell transfusions often improve urine-concentrating ability and provide relief of symptoms.
(Choice A) Central diabetes insipidus causes polyuria and hyposthenuria due to insufficient ADH production. However, thirst mechanism is impaired and serum sodium is elevated in patients with central diabetes insipidus.
(Choice B) Chlamydia infection in men can cause dysuria and urethral discharge. Impaired urine-concentrating ability is not associated with chlamydia infection, and urinalysis would likely be positive for leukocyte esterase.
(Choice D) Antihistamines (eg, diphenhydramine) treat allergic rhinitis and can cause anticholinergic adverse effects such as dry mouth, tachycardia, and urinary retention, none of which is consistent with this patient's presentation.
(Choice E) Primary (psychogenic) polydipsia causes hyposthenuria due to excessive water intake. However, serum sodium is typically low, and this condition is unlikely in a patient restricting evening fluid intake.
(Choices F and G) Diabetes mellitus is characterized by elevated serum glucose due to lack of insulin (type 1) or insulin resistance (type 2). When serum glucose exceeds the capacity of kidney resorption, glucose draws water into the collecting system, causing polyuria and glucosuria. Negative urine glucose makes this diagnosis unlikely.
Educational objective:
Hyposthenuria is the inability of the kidneys to concentrate urine and can occur in patients with sickle cell disease and sickle cell trait. Patients have polyuria, low urine specific gravity, and normal serum sodium.