Subclinical nephrotoxicity caused by occupational silica exposure and smoking among Kenyan industrial workers
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Date
2008-09
Authors
Mwangi, Daniel Muturi
Journal Title
Journal ISSN
Volume Title
Publisher
Kenyatta University
Abstract
Occupational 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 injury
Description
A thesis submitted in partial fulfilment of the requirements for the award of the degree of Master of Science (medical biochemistry) of Kenyatta University, September, 2008
Keywords
Nephrotoxicology, Silica, Smoking