Renal markers for assessment of renal tubular and glomerular dysfunction

*Corresponding author: Dr. Dejan Spasovski, Department of Rheumatology, University Clinical Centre, Skopje, Republic of Macedonia. Email: [email protected] There are approximately 40 different enzymes in the urine with different origin. They originate from the kidneys, urinary tract epithelium and urinary tract glands, plasma and blood cells (1). Subcellular locations of these enzymes are: 1. Membranous (Alanine Amino Peptidase; AAP, γ-glutamyl transferase; γ-GT) 2. Lysosomal (N-acetyl-β-(D)-glucosaminidase activity; NAG) 3. Mitochondrial (Malate dehydrogenase: MDH) 4. Cytoplasmic (LDH) However, proximal tubules of the kidneys have a dominant role in their excretion. Examination of the brush border epithelium (BBE) of the proximal tubules confirms that alanine amino peptidase (AAP ) (90%), alkaline phosphatase, ALP (70%) and γ-glutamyl transferase, γ-GT (50%), constitute the largest part of the total activity of these enzymes in the kidney (1). Because BBE is very sensitive to insults, these and other enzymes can be used as markers for secondary renal damage in the setting of different diseases, medicines and toxins (2). Increased enzymatic activity can be a reflection of disease activity and of the residual functional capacity of the kidney. Elevation of the urinary enzymes may indicate renal tubular damage. Urinary enzymes such as microsomal AAP and γ-GT can be used to detect early acute renal tubular damage which may be provoked by immunosuppressive medications, contrast media, antibiotics and chronic inflammatory disorders such as rheumatoid arthritis. Renal tubular damage could be a visceral manifestation of systemic diseases too (3). The standard routine parameters which are used for assessment of glomerular filtration rate (GFR); have a relatively low sensitivity due to the large functional renal reserve (4). Up to 50% of renal functional capacity would be lost before any increase in blood urea nitrogen and appearance of proteinuria. Renal function and integrity can be determined by many methods such as immune, radiologic, cytological analyses, but an important modality is biochemical analyses, as non-invasive methods which have a major role in the early detection of some pathological conditions. The regulation of activity of enzymes and their isoenzymes in urine is very important because their activity in serum has small diagnostic value. Pathogenic mechanisms leading to the destruction of epithelial cells of proximal tubules that are responsible for the appearance of enzymuria are; immune mechanism, complement, lysosomal enzymes and tubular obstruction by cell debris, protein cylinders, toxic noxes, medicaments or proteinuria. Each of them, to a different degree, in a direct or indirect way, contributes to the release of biochemical markers in urine.