Silica exposure has been associated with kidney disease and rheumatoid arth
ritis; an autoimmune mechanism has been proposed. Approximately 2 million p
eople are occupationally exposed to silica in the United States, 100,000 at
more than twice the National Institute for Occupational Safety and Health
recommended exposure limit of 0.05 mg/m(3). We examined renal disease morbi
dity and mortality, as well as arthritis mortality, in a cohort of 4,626 si
lica-exposed workers in the industrial sand industry (an industry previousl
y unstudied). We compared the cohort with the U.S. population and also cond
ucted internal exposure-response analyses using a job-exposure matrix based
on more than 4,000 industrial hygiene samples. We found excess mortality f
rom acute renal disease [standardized mortality ratio (SMR) = 2.61, 95% con
fidence intervals (95% Cls) = 1.49-4.24; 16 deaths], chronic renal disease
(SMR = 1.61, 95% CI = 1.13-2.22; 36 deaths), and arthritis (SMR = 4.36, 95%
CI = 2.76-6.54; 23 deaths) on the basis of multiple cause mortality data,
which considered any mention of disease on a death certificate. Linking the
cohort with the U.S. registry of end-stage renal disease for the years 197
7-1996, we found an excess of end-stage renal disease incidence (standardiz
ed incidence ratio = 1.97, 95% CI = 1.25-2.96; 23 cases), which was highest
fur glomerulonephritis (standardized incidence ratio = 3.85, 95% CI = 1.55
-7.93; 7 cases). We found increasing end-stage renal disease incidence with
increasing cumulative exposure; standardized rate ratios by quartile of cu
mulative exposure were 1.00, 3.09, 5.22, and 7.79. A positive exposure-resp
onse trend was also observed for rheumatoid arthritis on the basis of death
certificate data. These data represent the largest number of kidney diseas
e cases analyzed to date in a cohort with well-defined silica exposure and
suggest a causal link between silica and kidney disease. Excess risk of end
-stage renal disease due to a lifetime of occupational exposure at currentl
y recommended limits is estimated to be 14%, above a background end-stage r
enal disease risk of 2%.