Clinical Images in Nephrology and Dialysis
A 15-year-old woman presented to a hospital with malaise and visible pallor that had lasted for 2 weeks. The patient was treated with ferrous iron and discharged home. Following discharge, the patient’s symptoms did not improve and she subsequently developed dark urine. As a result, the family decided to seek care at a larger center. When the patient arrived to our center, urinalysis was obtained in view of the reported symptoms. Dipstick urinalysis revealed pH 7.0, specific gravity 1.015, protein 3+, hemoglobin 3+, urobilinogen excess, and bilirubin 1+. Examination of the spun urine sediment revealed numerous renal tubular epithelial cells (RTECs) (>50/high power field), red blood cells (1–2/high power field), granular casts (5–6/lower power field) and RTEC casts (1–2/lower power field). On admission, serum chemistry revealed a serum creatinine of 1.31 mg/dl and the complete blood count was notable for hemoglobin 7.4g/dl, hematocrit 25%, and platelets 252,000/μl. Review of the patient’s medication list uncovered recent use of cephalexin for the past 4 weeks to treat a finger infection. The spun urine sediment was prepared and stained with May–Grünwald–Giemsa stain. Numerous iron deposits (hemosiderin granules) were clearly seen within the casts (Figure 1, A and C) and RTECs (Figure 1B), which was diagnostic of heme pigment–related kidney injury.
Due to concern for drug-induced hemolytic anemia with pigment-related AKI, prednisone 40 mg (morning) and 20 mg (afternoon) was prescribed. Over the next 12 days, the patient’s symptoms improved and the serum creatinine returned to baseline (0.69 mg/dl).
In this case, hemolytic anemia was caused by cephalexin. This drug has been described to cause both hemolytic anemia and acute tubular injury (1,2). Intravascular erythrocyte destruction leads to excessive release of hemoglobin/heme into the circulation, with subsequent filtration of some of this protein into the renal tubules. The heme group present in the molecules of hemoglobin causes cell injury and death. Cell death by regulated necrosis causes tremendous tissue damage in a wide variety of diseases, including myocardial infarction, stroke, sepsis, and ischemia-reperfusion injury upon solid organ transplantation (3).
Hemolytic anemia can cause AKI by promoting heme pigment–related cellular injury and cell death. Basic tests such as urinalysis and complete blood cell count supplemented with urine-sediment examination can lead to the correct diagnosis and treatment.
- Dark urine can be a sign of urinary pigment due to rhabdomyolysis, hyperbilirubinuria, or hemolytic anemia (as described in this case).
- These clinical conditions can lead to acute tubular injury due to the toxicity of myoglobin (rhabdomyolysis), direct bilirubin (hyperbilirubinuria) and hemoglobin (hemolytic anemia) or their metabolites to tubular epithelial cells.
- Urine sediment will provide the clue to suspect acute tubular injury with increased numbers of RTECs, pigmented granular casts, and RTEC casts.
- Acute tubular injury that develops in patients with hemolytic anemia can be mediated by iron deposits within RTECs.
F. Hickmann and J. Poloni have nothing to disclose.
J. Poloni wrote the original draft; F. Hickmann reviewed and edited the writing; and J. Poloni and F. Hickmann conceptualized the study.
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