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Increased secretion of urinary kidney injury molecule-1 in patients with hemorrhagic fever with renal syndrome caused by Puumala virus

Kidney injury molecule-1 (Kim-1) is a transmembrane receptor from the T cell immunoglobulin and mucin domain family, whose members have critical roles in various immune responses like allergy, autoimmunity, viral infections as well as kidney injuries including diabetic and chronic kidney disease or acute kidney injury. In patients with hemorrhagic fever with renal syndrome (HFRS), kidneys are severely affected, sometimes with complete renal failure. KIM-1 has been identified as a modulator of the immune response in the kidney and protects the tissue from further trauma. In addition, it is secreted and elevated in urine of various diseases, affecting physiological kidney functions and acting as an early biomarker for kidney injury. We aimed to detect potential secretion of urinary KIM-1 in HFRS patients infected with Puumala virus (PUUV) and asses KIM-1 as a non-invasive biomarker of kidney injury. Paired urine samples of 61 male HFRS patients with confirmed PUUV infection, have been collected at hospitalization and before discharge. Patients were hospitalized at the University Hospital of Infectious Diseases in Zagreb and clinical and laboratory data were collected retrospectively from the patients history. Urine samples of HFRS patients and 20 age matched male healthy controls have been tested for the presence of KIM-1 according to the manufacturer’s protocol. Nonparametric statistical analysis was used for analysis. The levels of secreted KIM-1 were significantly (p value: <0.001) increased in urine of HFRS patients, in both time points, compared to healthy controls. In the convalescent urine samples, the overall KIM-1 excretion was significantly (p value: <0.001) lower then during the acute phase of disease. Due to a majority of mild cases (76 %), with no or only moderately increased serum creatinine (mean: 123 µmol/L, range 72 – 893 µmol/L) and urea values (mean: 6, 05 mmol/L, range: 2 – 47, 5 mmol/L), no signifacant correlation between KIM-1 and these traditional markers of kidney function have been observed. Our study also indicate that KIM-1 could be more sensitive biomarker of kidney injury in HFRS than urea and creatinine.

KIM-1, TIM-1, urine, biomarker, kidney injury

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