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1.  Association of Silica Exposure with Anti-Neutrophil Cytoplasmic Autoantibody Small-Vessel Vasculitis: A Population-Based, Case-Control Study 
Anti-neutrophil cytoplasmic autoantibodies (ANCA) are associated with a category of small-vessel vasculitis (SVV) with frequent glomerulonephritis. The goal of this study was to evaluate the association of lifetime silica exposure with development of ANCA-SVV, with particular attention to exposure dosage, intensity, and time since last exposure. A southeastern United States, population-based, case-control study was conducted. Case patients had ANCA-SVV with pauci-immune crescentic glomerulonephritis. Population-based control subjects were frequency-matched to case patients by age, gender, and state. Jobs were assessed in a telephone interview. Silica exposure scores incorporated exposure duration, intensity, and probability for each job and then were categorized as none, low/medium, or high lifetime exposure. Logistic regression models were used to estimate adjusted odds ratios (OR) and 95% confidence intervals (CI). Silica exposure was found in 78 (60%) of 129 case patients and in 49 (45%) of 109 control subjects. There was no increased risk for disease from low/medium exposure relative to no exposure (OR 1.0; 95% CI 0.4 to 2.2) but increased risk with high exposure (OR 1.9; 95% CI 1.0 to 3.5; P = 0.05). Crop harvesting was associated with elevated risk (OR 2.5; 95% CI 1.1 to 5.4; P = 0.03). However, both agricultural and traditional occupational sources contributed to the cumulative silica exposure scores; therefore, the overall effect could not be attributed to agricultural exposures alone. There was no evidence of decreasing by duration of time since last exposure. High lifetime silica exposure was associated with ANCA-SVV. Exposure to silica from specific farming tasks related to harvesting may be of particular importance in the southeastern United States. Interval of time since last exposure did not influence development of ANCA-SVV.
PMCID: PMC4049534  PMID: 17699427
2.  Positive association of renal insufficiency with agriculture employment and unregulated alcohol consumption in Nicaragua 
Renal failure  2010;32(7):766-777.
Background and objectives
Endemic renal insufficiency (RI) of unknown etiology is a major public health issue with high mortality in the Pacific coastal regions of Central America. We studied RI in León and Chinandega, Nicaragua, evaluating associations with known risk factors and hypothesized exposures.
A cross-sectional survey was conducted with assessment of medical, social, and occupational history and exposures in conjunction with measurement of serum creatinine. Cases were defined by an estimated glomerular filtration rate (eGFR) ≤60 mL/min/1.73 m2 using the modified four-variable Modification of Diet in Renal Disease (MDRD) study equation for non-African Americans. Logistic regression models controlling for known risk factors of kidney disease were used to evaluate associations between exposures and RI.
A total of 124 RI cases were compared to 873 persons without RI. Cases had no significant differences in the odds of having a systolic blood pressure (SBP) > 140 or diastolic blood pressure (DBP) > 90 mmHg, or in reporting diabetes. Agricultural labor was associated with RI (OR = 2.48, 95%CI: 1.59, 3.89, p < 0.0001). There was no association with agricultural non-field work (OR = 0.91, 95%CI: 0.60, 1.38, p = 0.65). Consumption of unregulated alcohol (“lija”) was associated with RI (OR = 2.10, 95%CI: 1.31, 3.39, p = 0.0023), as was drinking 5 L or more of water per day (OR = 3.59 vs. 1 L 95%CI: 1.52, 4.46, p = 0.0035).
Agricultural field labor and lija consumption were associated with RI in this region. Water intake may also be important. Identifying specific risk factors for RI within these exposures, such as individual pesticides or lija ingredients, may facilitate prevention in a setting where dialysis and transplantation are limited.
PMCID: PMC3699859  PMID: 20662688
chronic kidney disease; Nicaragua; alcohol; pesticides; renal failure
3.  Pre-Dialysis Chronic Kidney Disease: Evaluation of Quality of Life in Clinic Patients Receiving Comprehensive Anemia Care 
Anemia is common in chronic kidney disease (CKD), and suboptimal management of anemia can lead to serious health complications and poor quality of life.
1) To describe health-related and overall quality of life among patients entering a clinic focused on anemia management; 2) to compare their baseline quality of life with other relevant populations; 3) to explore predictors of quality of life prior to anemia management; and 4) to explore changes in quality of life over 1 year for patients managed in the clinic.
The Kidney Disease Quality of Life questionnaire – short form (KDQOL™-SF) was used to measure kidney disease specific and overall quality of life in a cohort of pre-dialysis CKD patients (n=79) enrolled in the clinic from January 2003 to September 2004. Baseline measures were compared to previously published measurements. The influence of demographic and clinical characteristics on baseline quality of life was explored. Changes in quality of life were evaluated over time.
Patients with CKD entering the clinic had lower overall quality of life compared with estimates from the general US population (physical composite 35.7 vs. 48.4 and mental composite 46.0 vs. 50.2, respectively). Clinic patients had better kidney disease specific scores than patients with end stage kidney disease. General quality of life scores were similar regardless of kidney disease severity, with the exception of physical functioning which was lowest for patients with end-stage disease. Hemoglobin was the only factor predictive of quality of life. Over time, quality of life improved among patients managed in the CKD clinic, with statistically significant improvements in sleep (change of 6.2 ± 15.2; p < 0.05) and social function (change of 11.6 ± 27.7; p < 0.05).
Patients with anemia of chronic kidney disease reported reduced quality of life compared to populations without kidney disease, but better quality of life compared to populations with end stage kidney disease on dialysis. Quality of life generally improved among patients managed in the multidisciplinary anemia clinic.
PMCID: PMC2722114  PMID: 19524862
Quality of life; chronic kidney disease; anemia; SF-36; KDQOL; multidisciplinary
4.  ANCA patients have T cells responsive to complementary PR-3 antigen 
Kidney international  2008;74(9):1159-1169.
Some patients with proteinase 3 specific anti-neutrophil cytoplasmic autoantibodies (PR3-ANCA) also have antibodies that react to complementary-PR3 (cPR3), a protein encoded by the antisense RNA of the PR3 gene. To study whether patients with anti-cPR3 antibodies have cPR3-responsive memory T cells we selected conditions that allowed cultivation of memory cells but not naïve cells. About half of the patients were found to have CD4+TH1 memory cells responsive to the cPR3138-169-peptide; while only a third of the patients had HI-PR3 protein responsive T cells. A significant number of T cells from patients responded to cPR3138-169 peptide and to HI-PR3 protein by proliferation and/or secretion of IFN-γ, compared to healthy controls while there was no response to scrambled peptide. Cells responsive to cPR3138-169-peptide were not detected in MPO-ANCA patients suggesting that this response is specific. The HLADRB1* 15 allele was significantly overrepresented in our patient group and is predicted to bind cPR3138-169 peptide with high affinity. Regression analysis showed a significant likelihood that anti-cPR3 antibodies and cPR3-specific T cells coexist in individuals, consistent with an immunological history of encounter with a PR3-complementary protein. We suggest that the presence of cells reacting to potential complementary protein pairs might provide an alternative mechanism for auto-immune diseases.
PMCID: PMC2754720  PMID: 18596726
ANCA; PR-3; complementary PR-3; autoantigen complementarity; memory T-cells; autoimmune disease
5.  Predictors of Treatment Resistance and Relapse in Antineutrophil Cytoplasmic Antibody–Associated Small-Vessel Vasculitis 
Arthritis and rheumatism  2008;58(9):2908-2918.
Predictors of treatment resistance and relapse have been identified in patients with antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis in the Glomerular Disease Collaborative Network (GDCN) in the southeastern US. This study was undertaken to evaluate the applicability of those predictors in an independent cohort followed up by the French Vasculitis Study Group.
Predictors of treatment resistance were evaluated using logistic regression models and reported as odds ratios (ORs) with 95% confidence intervals (95% CIs). Predictors of relapse were evaluated using Cox proportional hazards models and reported as hazard ratios (HRs) with 95% CIs. Models were controlled for age, sex, race, baseline serum creatinine level, and cyclophosphamide therapy.
The French cohort (n = 434) and the GDCN cohort (n = 350) had similar median followup periods (44 months versus 45 months) and initial percentages of patients taking cyclophosphamide (82% versus 78%). The French cohort included more patients with proteinase 3 (PR3) ANCA (58% versus 40%), lung involvement (58% versus 49%), and upper respiratory tract involvement (62% versus 31%). Of the predictors of treatment resistance in the GDCN cohort (female sex, African American race, presence of myeloperoxidase ANCA, elevated creatinine level, and age), only age predicted treatment resistance in the French cohort (OR 1.32 per 10 years [95% CI 1.05–1.66]). Predictors of relapse in the GDCN cohort were PR3 ANCA (HR 1.77 [95% CI 1.11–2.82]), lung involvement (HR 1.68 [95% CI 1.10–2.57), and upper respiratory tract involvement (HR 1.58 [95% CI 1.00–2.48]), while predictors in the French cohort were PR3 ANCA (HR 1.66 [95% CI 1.15–2.39]) and lung involvement (HR 1.56 [95% CI 1.11–2.20]), but not upper respiratory tract involvement (HR 0.96 [95% CI 0.67–1.38]).
Our findings indicate that older age is a predictor of treatment resistance, and that PR3 ANCA and lung involvement are predictors of relapse in both cohorts. Discrepancies in predictors of treatment tract resistance may reflect differences in access to care, and differences in predictors of relapse may reflect variations in disease expression.
PMCID: PMC2754705  PMID: 18759282

Results 1-5 (5)