Soluble LR11 as a Novel Biomarker in Acute Kawasaki Disease.

BACKGROUND: Intimal smooth muscle cells (SMCs) play an important role in the vasculitis caused by Kawasaki disease (KD). Lipoprotein receptor 11 (LR11) is a member of the low-density lipoprotein receptor family, which is expressed markedly in intimal vascular SMCs and secreted in a soluble form (sLR11). sLR11 has been recently identified as a potential vascular lesion biomarker. sLR11 is reportedly elevated in patients with coronary artery lesions long after KD, but there is no description of sLR11 in acute KD. Our aim was to determine the sLR11 dynamics in acute KD and to assess its usefulness as a biomarker.Methods and Results: 106 acute KD patients and 18 age-matched afebrile controls were enrolled. KD patients were classified into the following subgroups: intravenous immunoglobulin (IVIG) responders (n=85) and non-responders (n=21). Serum sLR11 levels before IVIG therapy were higher in non-responders (median, 19.6 ng/mL; interquartile range [IQR], 13.0-24.9 ng/mL) than in controls (11.9 ng/mL, 10.4-14.9 ng/mL, P<0.01) or responders (14.3 ng/mL, 11.7-16.5 ng/mL, P<0.01). Using a cutoff of >17.5 ng/mL, non-responders to initial IVIG therapy were identified with 66.7% sensitivity and 78.8% specificity. CONCLUSIONS: sLR11 can reflect the state of acute KD and might be a biomarker for patient response to IVIG therapy.

Hyponatremia due to an excess of arginine vasopressin is common in children with febrile disease.

Hypotonic fluids are commonly used for treating hospitalized children. However, an excess of arginine vasopressin (AVP) with impaired free water excretion is thought to contribute to the development of hyponatremia in febrile children. The aim of this two-part study was to define the clinical relationship between hyponatremia and excess AVP. In a retrospective study carried out between 2001 and 2005, we found that approximately 17% of the hospitalized patients had hyponatremia [serum sodium (Na) < 135 mEq/l] upon admission and that the ratio of patients with hyponatremia was significantly higher among febrile patients than among afebrile patients. In a subsequent prospective study, we examined 73 hospitalized patients who presented with acute febrile diseases accompanied by hyponatremia (serum Na <134 mEq/l). Almost all of these patients demonstrated excess AVP, defined as high plasma AVP levels (>1 pg/ml). There were no significant relationships between the levels of AVP and other laboratory variables, including serum sodium, serum osmolality, atrial natriuretic peptide, and brain natriuretic peptide. About 30% (22/73) of the patients fulfilled the criteria of the syndrome of inappropriate secretion of antidiuretic hormone. These findings suggest that fever and other nonosmotic stimuli lead directly to excess AVP and hyponatremia. We therefore recommend that isotonic fluids should be used for patients with prolonged fever and hyponatremia.