Organic Solvent Exposure and Risk for End-stage Renal Disease:

MAA3-O-02 Introduction: The role of organic solvents in the progression of chronic kidney disease has been hypothesized but had never been tested using a cohort design. The objective of this study was to assess the effect of solvent exposure on the progression to end-stage renal disease (ESRD) in patients with chronic glomerulonephritis. Methods: We included 337 patients with biopsy-proven primary glomerulonephritis and baseline glomerular filtration rate greater than 15 ml/min/1.73 m2 who were diagnosed between 1994 and 2001 and followed until 2004. Three histological types were considered: IgA nephropathy (IgA N; n = 193); membranous nephropathy (MN; n = 75); and focal and segmental glomerulosclerosis (FSG; n = 69). Patients were interviewed on their lifelong occupational exposure to solvents. To minimize information bias, 2 methods were used to evaluate retrospective exposure: an expert assessment of job histories and a job exposure matrix. ESRD was the study outcome defined as either a glomerular filtration rate less than 15 ml/min/1.73 m2 or dialysis. We used a Cox model to estimate the hazard ratios (HRs) of ESRD associated with the level and duration of exposure before the disease onset as well as its persistence after diagnosis, by histologic type and adjusted for main risk factors for progression to ESRD. Results: The mean age of the cohort was 42 ± 16 years. Patients reported a mean of 3 job periods (range, 1–9). The experts classified 15% of the patients as exposed before the diagnosis at a low level and 14% at a high level; 55% of them remained exposed after disease onset. The percentages were 26%, 25%, and 45% with the job exposure matrix, respectively. Twenty-two patients with FSG reached ESRD 42 with IgA N and 12 with MN. Based on the expert assessment, solvent exposure was associated with a higher risk of ESRD in both MN and IgA N, but not in FSG (HR = 3.1; 95% CI = 0.5 – 20.0) for low exposure level and 5.5 (1.3–23.9) for high levels in MN, HR = 2.0 (0.8–4.8) and 1.8 (0.8–3.9) in IgA N, respectively. Moreover, for IgA N, HR increased with the duration of exposure: 1.2 (0.4–3.5) below 10 years and 2.8 (1.1–7.1) above. The HR tended to be higher when exposure was continued after the diagnosis. Similar trends were observed using the job exposure matrix. Conclusion: Our study shows that solvent exposure is strongly associated with the progression to ESRD, involving important implications for the monitoring of chronic kidney disease in exposed workers.