A 42-year-old African American woman with a history of sickle cell trait (SCT) was admitted to the hospital for painless gross hematuria with the passage of clots for 3 weeks. She also complained of fatigue, dizziness, and general malaise. She denied abdominal pain, dysuria, or fever. She had a remote history of similar presentation 20 years ago that resulted in right-sided partial nephrectomy. It was performed in an outside hospital and medical records were not available. She reported no other significant medical history and was not taking any medications at home. Family and social history was unremarkable.
On physical examination, the patient had stable vital signs with a blood pressure of 120/70 mm Hg, heart rate 90/min, and temperature of 98.4 F. She appeared comfortable but with marked pallor. Her abdomen was soft, non-tender, non-distended, and revealed no costovertebral angle tenderness. The rest of the physical examination was unremarkable.
Laboratory data revealed hemoglobin of 5.7 g/dl, hematocrit 17.2%, platelets 317 K/microl, INR 0.93., and creatinine of 0.9 mg/dl. Other pertinent laboratory values showed bilirubin of 1.1, LDH of 139 U/L, and haptoglobin of 90 mg/dl. Hemoglobin electrophoresis demonstrated Hb A 74.7%, Hb A2 2.9%, Hb F 0.4%, and Hb S 22%, but it was drawn after transfusion. Urinalysis showed numerous red blood cells (RBCs), 2+ protein, and 2-5 WBC/HPF. Peripheral smear, vasculitis work up, or urine culture were not performed. Initial CT scan of abdomen and pelvis revealed hyper dense material in collecting system of right kidney extending into renal pelvis but no aneurysm or calculus was demonstrated. Later patient underwent renal angiography, which demonstrated normal arterial anatomy. She also underwent CT urography that revealed a filling defect within the pyramid of the lower pole of the right kidney representing papillary necrosis as demonstrated in Fig. 1.
The patient was managed conservatively during the hospital course. She was transfused with 3 units of blood and blood counts remained stable after transfusion. In the beginning, our differential diagnosis was broad, including renal papillary necrosis, IgA nephropathy, bladder cancer, and renal medullary carcinoma. But the diagnosis was narrowed down to renal papillary necrosis after CT urography was performed. Patient was started on sodium bicarbonate infusion along with aggressive hydration and diuretics. After 3 days of treatment, her hematuria had completely resolved and she was discharged home in stable condition.
SCT is a carrier state of sickle cell disease with one copy of normal beta globulin gene and one copy of sickle variant gene-producing heterozygous HbAS. SCT is estimated to have prevalence of 300 million worldwide, mostly concentrated in Africa, Middle East, and Mediterranean region. In the United States, the prevalence of SCT is around 8-10% in African American population. Although SCT is considered a benign condition with no increased mortality in individuals, it has been associated with several complications.
A number of abnormalities have been reported in SCT, including renal medullary carcinoma, papillary necrosis, thromboembolic events, and hyposthenuria. Renal complications are listed in Table 1 . Our discussion will be limited to renal papillary necrosis.
Renal papillary necrosis is frequently associated with sickle cell disease, but it is not uncommon in SCT as well. It has been usually associated with diabetes, analgesic nephropathy, chronic pyelonephritis, and renal tuberculosis. Renal papillary necrosis is usually precipitated by some factors such as intense exercise, dehydration, and taking NSAIDs. In our patient, none of these factors were present. To date no comparative data exist with regard to the distribution and frequency of occurrence of renal papillary necrosis among persons with SCT, hemoglobin SC, and thalassemias; however, there have been case reports on hemoglobin SC but none to date on thalassemia unless associated with a sickling hemoglobin (Sbeta+).
Papillary necrosis results from obstruction of the vasa recta producing ischemia and micro infarction of medullary region of the kidneys. Polymerization of the RBCs in the vasa recta of the renal medulla is the main trigger for renal papillary necrosis. Numerous factors are involved in initiating the sickling of RBCs including hypoxia, hypertonicity, and acidosis. Once sickling starts it leads to increased blood viscosity and decreased blood flow to medulla, which ultimately results in micro infarction of vasa recta causing papillary necrosis. The extent of polymerization of RBCs depends upon the concentration of HbS.
The clinical presentation varies from painless gross hematuria to acute condition with pain, fever, and obstructive urinary symptoms. Hematuria is by far the most important clinical feature. It usually manifests in the age group between 30-40 years and there seems to be no sex predominance. Any patient with SCT, who presents with hematuria, needs a thorough clinical investigation especially in young patients because renal medullary carcinoma can also presents in a similar fashion. Renal medullary carcinoma is a rare, aggressive fatal tumor, which presents in young patients with SCT. Because renal medullary cancer is very rare, there is no epidemiological data available, but according to one report in 2003, there are 55 cases of renal medullary cancer that were reported in literature.