Hemorrhagic Fever With Renal Failure Syndrome Workup

Updated: Oct 31, 2023
  • Author: Rajendra Bhimma, MBChB, MD, PhD, DCH (SA), FCP(Paeds)(SA), MMed(Natal); Chief Editor: Craig B Langman, MD  more...
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Laboratory Studies

The geographic distribution of hemorrhagic fever with renal failure syndrome (HFRS), an exposure to rodents, the patient's clinical picture, and the laboratory data suggest the diagnosis.

  • Enzyme-linked immunosorbent assay (ELISA) is useful in detecting antihantaviral-specific immunoglobulin M (IgM) early in the course of the illness.

  • Antihantaviral immunoglobulin G (IgG) titers may be elevated for prolonged periods (as long as 10 y).

  • Blood findings usually reveals clinically significant leukocytosis, an elevated or normal hematocrit level, and thrombocytopenia.

  • Elevated levels of liver enzymes, BUN, and serum creatinine can be observed.

  • Hyponatremia, hyperphosphatemia, and hyperkalemia may occur during the oliguric phase.

  • Complement (C3) levels may be decreased; therefore, hemorrhagic fever with renal failure syndrome should be included in the differential diagnosis of hypocomplementemic acute nephritic syndrome.

  • The coagulation profile can be altered with a prolonged prothrombin time (PT), activated partial thromboplastin time (aPTT), or bleeding time. levels of fibrin-degradation products may also be elevated.

  • Urinalysis consistently shows hematuria and proteinuria. [14] Proteinuria may last for few years after the attack.

  • Increased levels of nitric oxide (NO) during the acute phase of the hemorrhagic fever with renal failure syndrome illness are correlated with disease activity.

  • Elevated serum amylase and lipase levels, in combination with severe abdominal pain, suggests acute pancreatitis. This can be confirmed on CT scan of the pancreas that shows edema of the pancreas and peripancreatic tissues.


Imaging Studies

Advances in cross-sectional imaging have allowed early diagnosis of the sequelae of HFRS. In the kidneys, MRI T1-weighted imaging shows a well-defined zone of low-signal intensity (blood product deposition) in the subcortical medulla in 33% of cases, and, in 80% of cases, T2-weighted images correlated with renal histopathological findings of HFRS.

Corticomedullary differentiation is apparent on both T1- and T2-weighted MRIs. These characteristic MRI findings allow for differentiation of HFRS from other causes of acute kidney injury.

In cases of acute kidney injury due to other causes, cortical blood product deposition results in a diminution of corticomedullary differentiation on T1-weighted MRIs and an enhancement of corticomedullary margin on T2-weighted MRIs. Intracranial hemorrhage fortunately is rare and occurs in less than 1% of cases, but can be fatal. Hemorrhage and necrosis of the anterior lobe of the pituitary are common findings in fatal cases of HFRS. Survivors of pituitary hemorrhage and necrosis may develop panhypopituitarism.

Radiographs of the abdomen may show ascites (74%), paralytic ileus with intestinal wall thickening (69%), retroperitoneal edema (obscured psoas shadow [68%] and obscured renal shadow [53%]), and kidney enlargement (23%). In patients with pulmonary involvement, chest radiography findings include interstitial edema (14-44%), subsegmental atelectasis (38%), pleural effusion (6-32%), and cardiomegaly (6-21%).


Other Tests

Hantavirus antigen can be detected in various tissues, predominately in the microvasculature, by using immunohistochemical (IHC) methods (eg, immunohistochemistry analysis for the Hantavirus antigen in lung and tubular cells). Polymerase chain reaction is also indicated to assess for Hantavirus.



Performing a kidney biopsy is not essential for diagnosis. As discussed above, the diagnosis of hemorrhagic fever with renal failure syndrome is based on a history of exposure to infected rodents, clinical symptoms and signs, and laboratory findings. If the diagnosis cannot be clearly made during the course of the illness and if the patient's hemodynamic and coagulation status is stable, a renal biopsy is indicated.


Histologic Findings

Upon histologic evaluation, renal alterations in hemorrhagic fever with renal failure syndrome include features of acute interstitial nephritis, such as acute tubular necrosis with evidence of glomerular and endothelial damage. Hemorrhagic necrosis has been identified in the renal medulla. Hemorrhage is observed in different organs, especially the right atrium of the heart, the anterior pituitary gland, the pancreas, and the skin.

Pulmonary infiltrates may be observed, and, pulmonary edema is occasionally present. Infiltration of large, atypical mononuclear cells in the spleen, lymph node, and hepatic portal triad has been reported.