Environmental risk factors for ANCA glomerulonephritis

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Small vessel vasculitis results in significant organ damage, most often involving the kidney and lungs. ANCA glomerulonephritis (ANCA-GN) is a form of small vessel vasculitis with renal involvement, with or without involvement of the lungs of other organs. ANCA GN is a serious with a short-term (< 3 mortality of 5-10% and a clinical course that often includes periods of remission and relapse that frequently progresses to chronic dialysis. Exposure to silica dust has been associated with a 4-fold increase in risk of ANA GN in three case-control studies. Deficiencies in these studies include small sample size and limited exposure assessment techniques. Smoking may also play a role in the involvement and progression of vasculitis, especially in the upper airways, lungs and kidney, but has never been examined as a risk factor. The purpose of this study is to evaluate the role of environmental exposures, specifically silica and smoking, in the development and progression of ANCA-GN. The proposed study is population-based case control study using a detailed telephone interview to evaluate the intensity and duration of silica and smoking exposures. The study will include 200 patients diagnosed with ANCA GN and 400 controls. ANCA GN cases will be identified through Nephropathology services in NC, SC and Southern Virginia by renal biopsy diagnosis and positive ANCA evaluation. Cases will be contacted with their nephrologist and will be followed prospectively to evaluate the role of silica and smoking on clinical outcomes. Controls will be identified by random digit telephone dialing for those age 18 to 64, and by Health Care Financing Administration database records for those age 65. Controls will be frequency matched on gender, and age group. Exposure to silica dust will be assessed by and experienced Industrial Hygienist. Given the sample size in this study statistical power of 0.80 and a two-sided alpha-0.05, the minimum detectable odds ratio is 1.7 and 1.8 for the relatively common exposures will be 3.4 for high silica exposure and 2.6 for moderate silica exposure. In summary, this study will expand the knowledge of the role of silica dust and smoking in ANCA-GN. This is an aggressive disease for which little is known about etiology. Exposure to silica dust and smoking are modifiable exposures, therefore understanding their role in ANCA-GN may lead to interventions to improve patient outcomes.