Polymorphisms of PAI-1 and platelet GP Ia may associate with impairment of renal function and thrombocytopenia in Puumala hantavirus infection

Abstract

Introduction Puumala virus (PUUV) infection is a viral hemorrhagic fever with renal syndrome (HFRS) characterized by thrombocytopenia and acute impairment of renal function. We aimed to assess whether genetic polymorphisms of platelet antigens together with those of von Willebrand factor (VWF) and plasminogen activator inhibitor (PAI-1) correlate with disease severity. Patients and methods 172 consecutive hospital-treated patients with serologically confirmed acute PUUV infection were included. Platelet glycoprotein (GP) IIIa T>C (rs5918), GP Ia T>C (rs1126643), GP Ib C>T (rs6065), GP VI T>C (rs1613662), VWF A>G (rs1063856) and PAI-1 A>G (rs2227631) were genotyped. The associations of the rarer alleles with variables reflecting the severity of the disease were analyzed. Results PAI-1 G-carriers had higher maximum creatinine level compared with the non-carriers (median 213 μmol/l, range 60–1499 μmol/l vs. median 122 μmol/l, range 51–1156 μmol/l, p=0.01). The GG-genotypes had higher creatinine levels than GA- and AA-genotypes (medians 249 μmol/l, 204 μmol/l and 122 μmol/l, respectively, p=0.03). Polymorphisms of GP VI and VWF associated with lower creatinine levels during PUUV infection. The minor C-allele of GP Ia associated with lower platelet counts (median 44×109/l, range 20–90×109/l vs median 64×109/l, range 3–238×109/l; p=0.02). Conclusions Polymorphism of PAI-1, a major regulator of fibrinolysis, has an adverse impact on the outcome of kidney function in PUUV-HFRS. Platelet collagen receptor GP Ia polymorphism associates with lower platelet count.

Community Acquired Severe Acute Kidney Injury Caused by Hantavirus-Induced Hemorrhagic Fever with Renal Syndrome Has a Favorable Outcome

“…In patients with HFRS caused by the more severe Asian prototype hantavirus species, Hantaan virus, trombocytopenia has also predicted severe AKI [51]. On the other hand, PUUV-infected carriers of plasminogen activator inhibitor-1 G-allele have more severe AKI and coincidently less severe thrombocytopenia [19]. Thus, the association between renal impairment and thrombocytopenia in hantavirus infections remains obscure.…”

“…The study cohort consisted of 556 PUUV-infected patients, who had participated in our previous clinical studies [12,17,18,19,24,25,26,27,28,29,30,31,32,33,34,37,38,39,40,41]. The diagnosis of acute PUUV infection was serologically confirmed in all cases.…”

“…The patients commonly suffer from sudden high fever, headache, abdominal pain, nausea, backache, and visual disturbances [12,13,14,15,16]. The clinical picture has also been shown to be influenced by host genetics [17,18,19]. …”

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

“…The patients also participated in our previous studies [17,22,[24][25][26][27][28][29][30][31][32][33] . All patients were examined during the acute phase of the disease, and the diagnosis of acute PUUV infection was serologically confirmed [34][35][36][37] .…”

Smoking Is a Risk Factor for Severe Acute Kidney Injury in Hantavirus-Induced Nephropathia Epidemica

“…Hantavirus fever caused by PUUV can differ in disease severity from mild-form NE to severe kidney injury and some fatal rare cases [29], and the host influences the clinical picture [10,30,31,32]. Recently, Tervo et al [26 ]demonstrated that smoking is a risk factor associated with severity of AKI in patients with acute PUUV infection.…”