Glomerular Proteinuria Predicts the Severity of Acute Kidney Injury in Puumala Hantavirus-Induced Tubulointerstitial Nephritis

Abstract

Background:Puumala virus (PUUV)-induced hemorrhagic fever with renal syndrome is common in many European countries. The typical renal histologic lesion is acute tubulointerstitial nephritis. We examined the type and kinetics of urine protein excretion and prognostic significance of proteinuria for the severity of acute kidney injury (AKI) in acute PUUV infection. Methods: The amount of dipstick albuminuria at hospital admission was analyzed in 205 patients with acute PUUV infection. Dipstick albuminuria at admission was graded into 3 categories: 0-1+, 2+, and 3+. In 70 patients, 24-h urinary excretion of protein, overnight urinary excretion of albumin, immunoglobulin (Ig) G, and α1-microglobulin also were measured over 3 consecutive days during the hospital stay. Results: Maximum median daily proteinuria, overnight albuminuria, and IgG excretion were observed over 5 days, while that of creatinine values was observed 9 days after the onset of the disease. The medians of maximum plasma creatinine levels during hospital stay were different in the 3 categories of dipstick albuminuria: 0-1+: 98 µmol/L (58-1,499), 2+: 139 µmol/L (71-829), and 3+: 363 µmol/L (51-1,285; p < 0.001). Dipstick albuminuria ≥2+ at admission could be detected in 89% of the patients who subsequently developed severe AKI. Glomerular proteinuria, but not tubular proteinuria (α1-microglobulin), correlated with the severity of the emerging AKI. Conclusion: In acute PUUV infection, maximum median proteinuria values preceded the most severe phase of AKI by a few days. A highly useful finding for clinical work was that a quick and simple albuminuria dipstick test at hospital admission predicted the severity of the upcoming AKI.

Proteinuria and the Clinical Course of Dobrava-Belgrade Hantavirus Infection

“…Glomerular proteinuria is used as a predictive marker for Puumala hantavirus-induced interstitial nephritis [ 23 ]; a dipstick albumin assessment was performed on 205 patients with acute PUUV infection upon hospitalization, and the amounts of albumin, IgG, creatinine, and α 1 -microglobulin were determined for 3 consecutive days. In acute PUUV infection, maximum median proteinuria values preceded the most severe phase of AKI by a few days [ 23 ]. Therefore, simple dipstick albumin testing was able to predict upcoming AKI.…”

Clinical Characteristics of Ratborne Seoul Hantavirus Disease

“…Epidemics of a then ill-defined fever called epidemic hemorrhagic fever, which was later proven serologically to be a wild rat–induced HFRS ( 7 ), was present principally in the back alleys of Osaka, Japan, and characterized by marked but transient proteinuria that peaked in 32 case-patients on day 6 postonset of symptoms and disappeared completely on day 7 in mild cases and on approximately day 12 in those with severe AKI ( 8 ). Moreover, severity of proteinuria was found to be predictive of overall epidemic hemorrhagic fever clinical severity, as confirmed 53 years later in 70 case-patients infected with Puumala orthohantavirus; proteinuria (30% of nephrotic range), which peaked on day 5 postonset of symptoms, decreased almost completely on day 11, whereas serum creatinine levels peaked on day 9 ( 6 ). …”

“…Proteinuria and microhematuria, although transient, are considered severity indicators for HFRS ( 5 , 6 ). The rapidity of increasing/decreasing proteinuria is virtually pathognomonic for HFRS and was noted as early as 1964.…”

Flash-Like Albuminuria in Acute Kidney Injury Caused by Puumala Hantavirus Infection

“…In our previous study of 70 patients with acute PUUV infection, albuminuria peaked around the fifth day after the beginning of the fever, i.e., 4-5 days before the maximum values of plasma creatinine [6]. There was a clear decline in urine albumin excretion during the hospital stay, but the disappearance of albuminuria was not systemically studied in these patients.…”