Hantavirus Disease As a Cause For Hematuria and Acute Tubular Necrosis?

CORRESPONDENCE

HANTAVIRUS DISEASE AS A CAUSE FOR HEMATURIA AND ACUTE TUBULAR NECROSIS? To the Editor: In a recent report by Duflot et aI,' the authors offered four possible explanations for the patient's macrohematuria in acute renal failure. Another strong possibility is that the patient experienced Hantavirus disease (HVD). This disease has been described worldwide; there is now evidence that the disease had existed in the United States even before the current outbreak in the four-corner's area (Utah, Colorado, Arizona, New Mexico).2 Patients with Hantaan infection have protean manifestations with 90% to 100% renal involvement, including proteinuria, microhematuria, and/or macro hematuria, oligoanuria, elevated blood urea nitrogen, and serum creatinine.3.' Other signs and symptoms include fever, myalgia, nausea and vomiting, diarrhea, abdominal pain, petechiae, conjunctival injection, neurologic abnormalities, hypotension, and shock. With supportive therapy the overall mortality has decreased from as high as 30% to 5% to 10%. The diagnosis can be confirmed by the detection of either anti-hantavirus antibodies in serum, hantavirus antigen in tissues (immunohistochemically), or viral message in tissue specimens (polymerase chain reaction amplification). Immunoglobulin G titers may be elevated for a prolonged time, sometimes exceeding 10 years. In the referred case, therefore, serologic evidence could be obtained retrospectively. In contrast to well-defined renal abnormalities during HVD, recent communications from the United States have emphasized severe pulmonary involvement, with adult respiratory distress syndrome (ARDS) leading to death in 75% of patients. 6 The reason for the absence of renal manifestations may be related to either lack of awareness in critically ill patients or differences in the virulence of US strains. In the case report, the patient's prodromal signs and symptoms, abdominal pain, renal involvement, and atypical pulmonary edema with hypoxemia are typical of HVD.' Furthermore, the histologic features on renal biopsy are consistent with most published reports. Tubulointerstitial lesions with congestion of peritubular capillaries and hemorrhage, predominantly in the medulla and corticomedulJary junction, most often predominate. 7•• In addition, medullary interstitial inflammation with acute tubular necrosis has been observed .•.9 Mild glomerular hypercelJularity and mesangial proliferation occasionally have been found,'·9 but more frequently glomeruli appear normal. Extensive immunoglobulin deposition described by Finnish investigators has not been confirmed. 7. 10 If the patient survives, complete recovery of renal function is typical; however, Hantaan infection leading to chronic renal insufficiency and/or hypertension has been reported.' '.'2 In summary, physicians should consider Hantaan virus infection in cases of unexplained acute renal failure associated 730

with hemorrhagic manifestations and/or atypical pulmonary edema. Borut tilman, MD Renal Electrolyte Division University of Pennsylvania Medical Center Philadelphia, P A

REFERENCES 1. Duflot J, Cohen AH, Adler S: Macroscopic hematuria as a presenting manifestation of oliguric acute tubular necrosis. Am J Kidney Dis 22:607-611, 1993. 2. MMWR Morb Mortal Wkly Rep 42:612-614, 1993 3. Avsic-Zupanc T, Cizman B, Gligic A, Hoafd G, van der Groen G: Evidence for hantavirus disease in Slovenia, Yugoslavia. Acta Virol 33:327-337, 1989 4. Bruno P, Hassel LH, Brown J, Tanner W, Lau A: The protean manifestations of hemorrhagic fever with renal syndrome. Ann Intern Med 113:385-392, 1990 5. Lee JS: Clinical features of hemorrhagic fever with renal syndrome in Korea. Kidney Int 35:S88-93, 1991 6. MMWR Morb Mortal Wkly Rep 42:517-519,1993 7. Van Ypersele de Strihou C, Mery JP: Hantavirus-related acute interstitial nephritis in Western Europe: Expansion of world-wide zoonosis. Q J Med 270:941-950, 1989 8. Cizman B, Ferluga D, Kaplan-PavlovCic S, Koselj M, Drinovec J, Avsic T: Renal involvement in hantavirus disease. Adv Exp Med BioI 252:173-180, 1989 9. Zeier M, Andrassy K, Waldherr R, Ritz E: Akutes Nierenversagen durch Hantavirus. Dtsch Med Wochenschr 111 :207-210,1986 10. Jokinen EJ, Lahdevirta J, Collan Y: Nephropathia Epidemica: Immunohistochemical study of pathogenesis. Clin Nephrol 9:1-10, 1978 11. Siamopoulos KC, Elisaf M, Antoniadis A, Moutsopoulos HM: Hemorrhagic fever with renal syndrome in an endemic area of Greece. Am J Nephrol 12:170-173, 1992 12. Glass GE, Watson AJ, LeDuc JW, Kelen GD, Quinn TC, Childs JE: Infection with a tat-borne hantavirus in US residents is consistently associated with hypertensive renal disease. J Infect Dis 167 :614-620, 1993

Reply: In response to Dr Cizman' s query, we sent our renal biopsy material to the Centers for Disease Control (CDC) via our state Board of Health. After considerable delay, the CDC informed us that they were unable to use the renal biopsy material in their assay, so they are unable to determine whether viral antigens were present. Unfortunately, with regard to this particular patient, we are not able to confirm or refute the diagnosis of Hantaan virus infection. There have been reports of rats in California carrying Hantaan virus, although no case of Hantaan virus involving the kidney has

American Journal of Kidney Diseases, Vol 24, No 4 (October), 1994: pp 730-731