Mwangi, Daniel Muturi2017-10-022017-10-022008-09http://ir-library.ku.ac.ke/handle/123456789/17814A thesis submitted in partial fulfilment of the requirements for the award of the degree of Master of Science (medical biochemistry) of Kenyatta University, September, 2008Occupational exposure to silica and cigarette smoking could lead to slow and progressive renal injury. Assessment of renal injury based on the concentrations of blood urea nitrogen (BUN), serum creatinine (S.cr) or total urinary protein (V.TP) is insensitive in detecting early kidney injury. Urinary biomarkers which could be used to detect nephrotoxicity at early stages and defects on various parts of the nephron include: the proteins albumin, al-microglobulm (V.alM) and retinol binding protein (V.RBP; the enzymes leucine aminopeptidase (V.LAP), N-acetyl-p-Dglucosaminidase (V.NAG) and glutathione-S-transferase (V.GST). Animal studies have identified enzymes alkaline phosphatase (V.ALP) and y-glutamyltransferase (V.y-GT) and lactate dehydrogenase (V.LDH) as potential urinary biomarkers of renal injury. The nephrotoxic effects caused by silica exposure have been studied elsewhere but the effect of silica exposure on the urinary excretion of microalbumin (V.Malb), total protein (V.TP), alkaline phosphatase (V.ALP), y-glutamyltransferase (V.y-GT), and lactate dehydrogenase (U.LDH), aspartate aminotransferase (V.AST) and alanine aminotransferase (V.ALT) has not been studied in Kenyan human subjects. The present study investigated early signs of renal injury due to silica exposure and smoking by measuring urinary indicators of nephrotoxicity and the association of this excretion to work duration. The study subjects comprised 37 silica exposed male and 25 silica exposed female industrial workers and 46 male and 14 female referents. Both male and female subjects for the silica exposed and referents were subdivided into those with work duration of less than or more than ten years and into smokers and non-smokers. Glomerular function was studied by determining the urinary levels of microalbumin (V.Malb), while proximal tubular structural integrity was studied by determining the activities of alkaline phosphatase (V.ALP), 't: glutamyltransferase (V.y-GT), lactate dehydrogenase (V.LDH), aspartate aminotransferase (V.ALT) and alanine aminotransferase (V.AST). In addition, the levels of urinary silicon (V.Si) and creatinine (V.cr) were also measured. Compared with the: referent non-smoking males, non-smoking silica exposed males excreted significantly increased levels ofU.TP, U.Malb, U.ALP, U.y-GT and U.LDH; referent smoking males, smoking silica exposed males excreted significantly increased levels of U.TP, U.Malb, and U.LDH. Silica exposed males with work duration of less than ten years had significantly reduced U.y-GT compared to those with work duration of more than ten years. Compared with the: referent non-smoking females, non-smoking silica exposed females excreted significantly increased U.Malb and non-significantly increased U.ALP and significantly decreased U.Si. Silica exposed females with work duration of less than ten years had a significantly reduced U.TP, U.Malb, UALP, U.y-GT, and U.LDH compared to those with work duration of more than ten years. Among the silica exposed males with work duration of less than ten years, U.TP was negatively correlated. The present study confirms: that silica exposure may lead to nephrotoxicity; that smoking has also a nephrotoxic effect on the kidney and is synergistic to nephrotoxicity of silica exposure; that the elevation of some of the measured urinary parameters in silica exposed male workers is not associated with work duration; that urinary excretion ofU.TP, U.Malb, U.ALP, U.y-GT and U.LDH could be useful biomarkers for glomerular function and proximal tubular injury; and that U.AST and U.ALT may not be relevant in the diagnosis of renal injuryenNephrotoxicologySilicaSmokingThesis