Aim: To investigate the possibility of permanent renal function impairment and other organ lesions following hemorrhagic fever with renal syndrome (HFRS).
Methods: Data on 30/37 patients infected with HFRS, treated at the Department of Infectious Diseases, Split University Hospital, in 1995 were retrospectively analyzed. The data were collected three to six years following the appearance of HFRS. In 1998, 30/37 patients presented for control checkup, when their history data were collected, along with physical examination, hematology and biochemistry tests, and urinalysis. Creatinine clearance and sodium, potassium, chlorine, phosphorus, beta 2-microglobulin and N-acetyl-beta-D glucosaminase in 24-h urine were determined. In native urine, erythrocyturia was observed, with 10 erythrocytes per field were considered pathologic result. During the 1998-2001 period, renal scintigraphy by means of technetium labeled diethylene triaminopentacetic acid (99mTC DTPA) was performed in 13/30 patients.
Results: Of subjective discomforts, 29/30 (96.7%) patients reported lumbar pain. Elevated blood pressure was found in 9/30 (30.0%), erythrocyturia in 4/30 (13.3%) and hepatic lesion in 4/30 (13.3%) patients. Decreased creatinine clearance values (< 1.2 ml/s) were found in 4 and increased values (> 2.35 ml/s) in 10 patients. Increased sodium in 24-h urine was recorded in 10/23 and increased beta 2-microglobulin in 6/23 (26%) patients. Proteinuria exceeding 150 mg/day was detected in 11/23 (47.8%) patients. Scintigraphy of the kidneys demonstrated reduced glomerular filtration (< 100 ml/min/1.72 m2) in 3/13 patients. Prolonged mean times (> 5 minutes) of radiopharmaceutical passage through the renal parenchymae were found in 7/13 (53.8%) patients.
Discussion: Studies performed in 30 patients three years after they had recovered from HFRS revealed changes suggesting a mild to moderate impairment of the renal function. Hypertension found in 9/30 patients was a significant finding, considering the fact that all subjects were soldiers, thus having undergone through examinations to prove them completely healthy prior to joining army. Hypertension results were consistent with those reported from the USA. Although erythrocyturia points to urinary tract damage, its glomerular or postglomerular origin was not examined. Decreased creatinine clearance found in 4/23 patients suggested functional renal impairment. Increased natriuresis found in 10/23 patients implied tubular damage, i.e. reduced ability of tubular cells for sodium reabsorption from primary urine. Non-selective albuminuria detected in 11/23 patients indicated permanent lesion of the glomerular basal membrane. Increased beta 2-microglobulin found in 6/23 patients indicated that the lysosomal enzyme level was elevated only in the acute stage of the disease, but may have been an indicator of permanent lesion. No description of post-HFRS scintigraphic lesion of the kidneys was found in the literature. A decreased value of glomerular filtration, found in three patients, and especially the prolonged mean time of glomerular micropharmaceutical passage in 7/13 (53.8%) patients may have suggested glomerular damage. However, the possible reason may have also been a reduced passage of glomerular filtrate through the damaged lower parts of the nephrons. Transaminase increase during the acute stage of HFRS suggested the possible liver infection, maybe even hantavirus replication in hepatocytes. Even though biopsy confirmed the histologic picture of chronic hepatitis in one patient, the question remains whether it could have been caused by hantavirus.
Conclusion: Studies performed in 30 patients with a history of HFRS revealed renal function impairment, along with hypertension and damage to the liver parenchyma in some patients. The results obtained showed that the HFRS infection in Croatia may have entailed chronic sequels. To confirm this hypothesis, additional studies including a control group of hantavirus negative persons are needed.