Quantitative and qualitative evaluation of plasma and urine α1-microglobulin in healthy donors and patients with different haemolytic disorders and haemochromatosis

Background: The haem-binding protein alpha(1)-microglobulin (alpha(1)m) is involved in protection against oxidative damage induced by extracellular haem/haemoglobin. A carboxy-terminally truncated form of alpha(1)m (t-alpha(1)m), formed by reactions with haemoglobin, degrades haem into a yellow-brown chromophore linked to the protein. The aim of this work was to investigate if t-alpha(1) in is present in urine from a large cohort and if urinary and plasma alpha(1)m/t-alpha(1)m concentrations are changed in patients with haemolytic disorders and haemochromatosis. Methods: Urine and blood from patients (n = 20) and a control group (n = 22) were investigated for alpha(1) in and t-alpha(1)m by gel electrophoresis, Western blotting and radioimmunoassay. Data were compared to clinical chemistry data and medical records. Results: Two thirds of all studied subjects displayed t-alpha(1)m in urine but the t-alpha(1)m/alpha(1)m ratio was not increased in patients. Instead, significantly elevated ratios were found in females compared to males. Patients with intravascular or extravascular haemolysis showed higher alpha(1)m, albumin and beta(2)-microglobulin/creatinine ratios in urine indicating glomerulo-tubular dysfunction. Conclusions: The demonstration of t-alpha(1)m in urine of this cohort may be of importance in quantitative clinical chemistry. Whilst impaired kidney function due to intravascular haemolysis is well-known to occur, it is an unexpected finding in a group of patients with extravascular haemolysis. (C) 2007 Elsevier B.V. All rights reserved.