**5. Proteins degrading extracellular matrix (ECM)**

**Adenosine deaminase binding protein (ABP)** is a glycoprotein (120-kDa) present in lungs, liver, placenta and brush border of renal proximal tubules. Increased expression in the urinary ABP is considered an early indicator of acute renal injury (AKI). Increase in urinary ABP was reported in patients with ischemia - without sepsis, after kidney transplantation, after toxic renal tubules damage, and in newborn with sepsis. Recently published opinion suggested that ABP to be the best marker of acute renal damage, better than β2-M or α1-M (Bagshaw, 2007). As ABP excretion was higher among kidney transplants recipients than in people with normal renal function, ABP is considered as a good indicator for detection of renal graft failure (Iglesias

**β2-microglobulin (β2M)** is a membrane protein of major histocompatibility complex HLA. β2M excretion is used for evaluation of nephrotoxic renal damage (aminoglycoside antibiotics, heavy metal salts) (Guder, 2008). It should be noted that determination β2M for evaluation function of transplanted kidney may be ambiguous because of coexistence of many factors influencing its plasma and urinary concentration (e.g. toxic drugs action, ischemia reperfusion complications or renal graft rejection). Measurement of urinary β2M may be helpful in evaluation of the condition of transplanted kidney, however the interpretation of result should be careful because of the plurality of factors influencing β2M plasma concentration, renal

**4. Markers of inflammatory reaction connected with acute renal failure**

**Neutrophil gelatinase-associated lipocalin (NGAL)** is a glycoprotein expressed and secreted by immune cells, trachea, stomach, colon, and injured kidney epithelial cells as an monomer (22 kDa), dimer or trimer. NGAL may complex with collagenase type IV of human neutrophils named gelatinase B or metalloproteinase 9 (MMP-9) creating heterodimer (125 kDa) (Flower, 1996). NGAL binds and transports small lipophilic molecules e.g. free fatty acids, retinoids, arachidonic acid, and steroids (Mishra et al., 2003). NGAL is considered as provider iron to proximal renal tubules. Iron stimulates oxygenase synthesis which protects renal tubules cells. NGAL may be applied as a predictor of ischemic or toxic renal damage, before development of a full symptomatic renal insufficiency. Increase in urinary NGAL concentration is early, sensitive and non-invasive marker of renal damage correlating with intensity and time of ischemia and preceding increase in other markers such as hexosaminidase or β2-microglobu‐ lin. A strict correlation between NGAL concentration and degree of proteinuria was demon‐ strated (Flower, 1996). NGAL activated formation of nephrons in early step of renal development demonstrates a protective action in kidney (Mori & Nakao, 2007). Low molecular weight, resistant to degradation NGAL is easily excreted by cells of thick ascending arm of Henry loops and collective tubules into urine both free and in complex with MMP-9. Increase in urinary excretion of NGAL is observed several hours after stimuli of nephrotoxic factor. As concentration of urinary NGAL correlates with plasma NGAL concentration, NGAL may be an useful marker in diagnostics of renal diseases (Nickolas et al., 2008). There is an opinion that NGAL is the most promising biomarker for diagnosis of acute renal injury (AKI) in acute

filtration ability and tubular function (Kuźniar et al., 2006).

66 Current Issues and Future Direction in Kidney Transplantation

renal graft dysfunction (Halawa, 2011; Ting et al., 2012; Hollmen, 2011).

& Richard, 1994).

**Urokinase-type plasminogen activator (uPA)** and its specific receptor (uPAR) regulate renal allograft function. Allogenic renal graft uPAR deficiency, strongly attenuates ischemia reperfusion injury and acute kidney allograft rejection. Deficiency of uPAR in renal graft diminished generation of reactive oxygen species and renal cells apoptosis (Gueler et al., 2008). Therefore serum and urinary uPA may be treated as an early marker of the acute kidney transplant rejection (Alachkar, 2012).

**Matrix metalloproteinases (MMPs)** are extracellular proteases which depend on bound Ca2+ and Zn2+ for activity. Urinary panel of metalloproteinases was proposed for the early diagnosis of renal allograft rejection (Metzger et al., 2011; Sánchez-Escuredo et al., 2010; Hu et al., 2010).

**Tissue inhibitors of metalloproteinases (TIMP)** are extracellular inhibitors protease-specific, which bind tightly to the activated protease, blocking its activity. Presently 2% to 4% of renal allografts are rejected one year after from transplantation, because of chronic allograft injury. Mazanowska et al. (Mazanowska et al., 2011) suggest that determination of TIMP in urine may confirm the process of an active rejection of the transplanted kidney.
