Sexual Health
Hemolytic associated acute renal injury: Distal renal tubules present hemoglobin tubular type
A 43 year old African American woman developed a high fever, weakness, and difficulty walking. The patient has been healthy in the past, currently has a large menstrual volume, is anemic, and has a hemoglobin of 5 g/dL, with a negative direct agglutination reaction. Physical examination revealed deep venous thrombosis in the right lower limb (confirmed by imaging examination). Left pulmonary embolism. The gynecological examination revealed a huge uterine fibroid. Normal renal function.
The patient inputs 2 units of concentrated red blood cells, and the hemoglobin rises to 7 g/dL. Colonoscopy, esophageal, gastric, and duodenal endoscopy were normal. Negative for HCV, HBV, HIV, and Mycoplasma pneumoniae. Anti nuclear antibodies were positive with a titer of 1:160, but anti double stranded DNA, anti Sm, anti SSA, and anti SSB antibodies were negative. The complement is normal. Flow cytometry showed the presence of neutrophils CD55 and CD59 in peripheral blood, excluding paroxysmal nocturnal hemoglobinuria.
The patient was implanted with an inferior vena cava filter and treated with prednisone, resulting in relief of symptoms. She was discharged 11 days after onset.
Later, the patient was hospitalized due to high fever and Hb<6g/dL. Within 2 days, 4 units of concentrated red blood cells were administered, followed by shortness of breath, deepening of urine color, and acute renal injury. Blood creatinine: 3mg/dL, eGFR: 22mL/min/1.73m2. Urinary protein 2+, red blood cell 3+, 5-10 RBCs/high power visual field.
Renal biopsy
A renal biopsy showed 43 glomeruli, with one ischemic lesion. The proximal tubules show diffuse disappearance of brush like margins, cytoplasmic detachment, nuclear atypia, and occasional mitosis. A large number of spherical and granular tubular patterns are seen in the lumen of the distal renal tubules.
No obvious interstitial fibrosis and tubular atrophy were observed. Immunohistochemistry showed that myoglobin tube type was negative and hemoglobin A tube type was strongly positive. Prussian blue staining showed a negative deposition of hemosiderin.
Immunofluorescence showed no IgG, IgA, IgM, C3, C1q κ Light chain λ Light chain, fibronectin, albumin. Some protein tubular staining can be seen in IgA κ Light chain λ Light chain. The ultrastructure of glomerulus is not abnormal. Significant deposition of electron dense material can be seen in the distal renal tubular lumen. No hemosiderin particles were found in renal tubular epithelial cells.
Visible deposition of electron dense material in the distal renal tubule
Diagnosis
Acute tubular necrosis with diffuse intravascular hemoglobin tubular patterns suggests acute renal injury caused by intravascular hemolysis.
Clinical follow-up
Binding globin<20mg/dL, lactate dehydrogenase 2557U/L (reference value 116-245), direct agglutination reaction positive. Antibody screening was negative. Positive anti Cw antibody, which has been present in neonatal hemolysis, but has not been found to be associated with severe hemolytic transfusion reactions.
Although it is inferred from time that the hemolysis may be caused by blood transfusion, the exact reason is unclear. S protein, C protein, and prothrombin III were normal. There is no resistance to activated protein C, and the prothrombin G20210A mutation is negative. Lupus anticoagulant negative.
Discussion
The damaging effects of heme containing proteins such as hemoglobin and myoglobin include intrarenal vasoconstriction, tubular formation, and direct cytotoxicity. Intravascular hemolysis causes excessive hemoglobin to filter through the glomerulus and enter the distal nephron, forming an intratubular type. Tubular obstruction of the lumen aggravates renal injury.
Reports of intravascular hemoglobinuria are rare. Most previous reports have been of deposition of hemosiderin in the proximal renal tubular epithelium, which is characterized by persistent or recurrent episodes of hemoglobinuria. There was no deposition of hemosiderin in this case. Immunohistochemical staining showed no myoglobin, but hemoglobin A staining was strongly positive. The absence of hemosiderin may be due to the sudden onset of hemolysis and early biopsy.
Differential diagnosis
1. Renal injury associated with rhabdomyolysis: The patient has muscle pain, elevated creatine kinase, eosinophilic granular or globular tubular distal nephron seen by HE staining, and myoglobin seen by immunohistochemistry.
Biliary nephropathy: Total bilirubin increases, often greater than 20 mg/dL. HE staining showed a yellow-green granular tubular pattern of the distal nephron, as well as eosinophilic. Hall staining showed bile.
3. Acute renal tubular necrosis: Cell necrosis, cytoplasmic detachment, and single necrotic tubular cell detachment from the basement membrane can be seen. No staining for myoglobin or hemoglobin.
4. Light chain tubular nephropathy: There is a history of plasma cell cachexia, and monotypic light chains can be seen on serum or urine protein electrophoresis. It is commonly found in the distal nephron, with fissures in the tubular type and cellular reactions around it. Immunofluorescence showed light chain restriction.
Acute intravascular hemolysis can cause acute tubular injury. In such cases, special care should be taken if the immunohistochemical staining for hemoglobin A is not typical or if the deposition of hemosiderin in the cytoplasm is not evident.