Journal Club: Silica Exposure and CKD

Persisting with the theme of environmental exposures being associated with CKD - an interesting study linking silica exposure to kidney disease was published recently by Suma Vupputuri of Kaiser Permanente Georgia in Atlanta, GA, USA and colleagues published in Renal Failure (it's available open access). [I suspect that the reason this paper didn't get published in a higher impact journal is that the association between silica and CKD is already known, however this study was larger and better designed].

Approximately 3 million people are exposed to silica for variable periods of time. Silica in commercial use is obtained by processing (such as crushing or milling) from naturally occurring sources and can be found in abrasive cleaners, toothpaste, scouring powder, and metal polish. At least 10% of these workers may have dangerously high exposures (at least 2-10 times the recommended exposure limit).Occupations that are at risk of exposure include, agricultural (e.g. sweet potato transplanting in North Carolina) and industrial workers (e.g., miners, sandblasters, glassmakers, brick and grain workers)

Prior studies have shown that men  exposed to silica, particularly in foundries, brick making or sandblasting, are more likely to have ESRD compared to those who were not exposed and that individuals had increase risk of ESRD with increasing levels of silica exposure.

Overall Design
This was a case control study. Cases were hospital patients with newly diagnosed CKD and community controls were selected using random digit dialing and frequency matched by age, gender, race and proximity to the hospital. The study population consisted of hospital patients and community controls, age 30-79 years residing in North Carolina between 1980 and 1982. The four North Carolina medical centers (Duke University Medical Center, North Carolina Memorial Hospital, Charlotte Memorial Hospital and North Carolina Baptist Hospital) with newly diagnosed CKD, identified by review of kidney-related ICD-9 discharge diagnoses. 

Silica exposure estimates were assigned by industrial hygiene review of lifetime job history data and weighted for certainty and intensity. Conditional logistic regression was used to estimate the odds ratios (ORs) for CKD conditioned on demographic, lifestyle and clinical variables.

Sample
Six hundred and seven of 709 case patients could be contacted for interview, 554 of whom (91%) participated in the study (78% overall response rate for cases). Among the control participants, 608 of 717 could be contacted and 520 (86%) were interviewed (73% overall response rate for controls). 

Key findings

• Occupational exposure to silica was associated with a 37% increased risk of CKD and appeared to be specifically related to unclassified renal insufficiency, representing earlier stages of diagnosed CKD. 
• Cases, however, were more likely than controls to have fewer years of education, have higher BMI, have histories of hypertension and diabetes, use analgesic medications daily, and have proxy respondents. 
• Among those with silica exposure, the median duration of silica exposure after weighting for both certainty and intensity was higher in cases than in controls (22.5 vs. 13.0 years).
• The prevalence of occupational exposure to silica was high and more frequent among cases than controls (48.8% vs. 40.3%, respectively).
• Assessment of duration of occupational exposures showed trends of increasing CKD risk with increased duration of silica exposure.

Limitations

• Self reporting of exposure could have introduced bias (recall and information bias).
• Misclassification bias because the exposure was relatively remote.
• The use of proxies (e.g., spouse or caregiver).

Bottom-line

Silica exposure is associated with an increased of CKD. Specific occupations are at high risk. The dose and the duration of silica exposure, as one would expect, are important risk factors