Increased glomerular permeability in patients with nephropathia epidemica caused by Puumala hantavirus

Abstract

Background. Nephropathia epidemica (NE) is the Scandinavian type of haemorrhagic fever with renal syndrome. Usually heavy transient proteinuria is present at the onset of the disease. Methods. We investigated glomerular permeability in eight patients with acute NE and in eight healthy controls. Six patients were followed for 1 year. The glomerular filtration rate (GFR) was determined by inulin clearance and effective renal plasma flow (ERPF) by para-aminohippurate clearance. Results. GFR and ERPF were significantly reduced in NE patients during the acute phase compared with those in controls (P < 0.001 and P < 0.001, respectively). The filtration fraction (FF) was thus high, 0.37. The fractional clearances of albumin, IgG, and IgG4 were markedly increased. As a sign of tubular dysfunction, increased urinary excretion of α1-microglobulin was observed in all patients. After 1 year, the GFR of the patients no longer differed from that of the controls. ERPF was lower and FF higher than those in controls (P = 0.014 and P = 0.009, respectively). The fractional clearances of albumin, IgG, and IgG4 remained increased. The high-molecular fractional dextran clearances in the patients were significantly increased compared with controls during the acute phase. Computed analysis of glomerular membrane-pore structure showed that the 'shunt-flow' was increased in the patients during the acute phase compared with the controls. There was a positive correlation between the FF and the shunt (r = 0.768, P = 0.026). In addition, fractional clearances of albumin and IgG correlated significantly with the shunt (r = 0.810, P = 0.015 and r = 0.762, P = 0.028, respectively). Conclusions. Renal involvement in the acute phase of NE is characterized by a markedly decreased GFR and ERPF. Increased glomerular permeability is associated with impairment of both the size- and charge-selectivity properties of the glomerular filter.