Silica and renal diseases: no longer a problem in the 21st century?

Silicosis and other occupational diseases are still important even in the most developed countries. In fact, at present, silica exposure may be a risk factor for human health not only for workers but also for consumers. Furthermore, this exposure is associated with many other different disorders besides pulmonary silicosis, such as progressive systemic sclerosis, systemic lupus erythematosus, rheumatoid arthritis, dermatomyositis, glomerulonephritis and vasculitis. The relationships between these silica-related diseases need to be clarified, but pathogenic responses to silica are likely to be mediated by interaction of silica particles with the immune system, mainly by activation of macrophages. As regards renal pathology, there is no single specific clinical or laboratory finding of silica-induced nephropathy: renal involvement may occur as a toxic effect or in a context of autoimmune disease, and silica damage may act as an additive factor on an existing, well-established renal disease. An occupational history must be obtained for all renal patients, checking particularly for exposure to silica, heavy metals, and solvents.

The role of metals in autoimmune vasculitis: epidemiological and pathogenic study.

BACKGROUND: A possible relationship between Silica (Si) exposure and antineutrophil cytoplasm antibodies (ANCA)-associated vasculitis has been reported. Furthermore, tuberculosis (TBC) has been frequently described in patients with silicosis, and TBC infection shares with ANCA-associated vasculitis the formation of granulomas. Therefore, an intriguing network including Silica, Vasculitis, TBC and ANCA might be hypothesized. The aim of this work was to further investigate these correlations using both epidemiological and pathogenic approaches. METHODS: Study I--epidemiological study. A case-control study to compare the occupational histories of 31 cases of biopsy proven vasculitis (18 pauci-immune crescentic glomerulonephritis, 9 microscopic polyangitis, 4 Wegener's granulomatosis) with those of 58 age, sex and residence-matched controls (affected by other kidney diseases), was performed. Occupational Health physicians designed an appropriate questionnaire in order to evaluate a wide spread of exposures and calculate their entity by the product of Intensity x Frequency x Duration. Study II--tuberculosis association. A case-control study to evaluate the frequency of a previous history of tuberculosis (TBC) in 45 patients with vasculitis and 45 controls were performed. Study III--ANCA positivity. A case-control study to evaluate the presence of ANCA was performed by testing blood samples of 64 people with previous professional exposure and 65 sex/age matched patients hospitalized in a General Medicine Unit. Furthermore, the same evaluation was made in a pilot study in 16 patients with ongoing or previous TBC. Study IV--experimental study. The oxygen free radicals (OFR) and IL-12 production (both involved in the pathogenesis of vasculitis) from human phagocytic cells stimulated with an amorphous (diatomaceous earth) and a crystalline (quartz) form of Si at the doses of 10 and 100 microg ml(-1) was evaluated. RESULTS: Study I--a positive history of exposure to Si resulted in significantly more present in cases (14/31 = 45%) than in controls (14/58 = 24%, P = 0.04, OR = 2.4) and no other significant exposure association was found (including asbestos, mineral oil, formaldehyde, diesel and welding fumes, grain and wood dust, leather, solvents, fungicides, bitumen, lead and paint). Study II--past TBC infection was significantly more present in patients with vasculitis (12/45 = 26%) than in controls (4/45 = 8%, P < 0.05). Study III--ANCA was present in 2/64 exposed people (vs. 0/65 controls, P = NS) and 0/16 patients with TBC. Study IV--both amorphous and crystalline Si forms represented a stimulus for OFR and IL-12 production, but quartz resulted as a greater inductor. CONCLUSIONS: We conclude that Si exposure might be a risk factor for ANCA-associated vasculitis, possibly enhancing endothelial damage by phagocyte generation of oxygen free radicals and Th1 differentiation by an excessive IL-12 phagocyte production. Frequency of TBC was significantly higher in vasculitis patients. ANCA was not frequent in the preliminary examination of people with previous professional exposure or patients with TBC, but the number of samples evaluated is too small to allow conclusions.

[Correlations between viral serology and different clinical characteristics in patients with lupus nephropathy]. / Correlazioni tra sierologia virale e differenti caratteristiche cliniche dei pazienti con nefropatia lupica.

BACKGROUND: Relationships between viral infections and autoimmune diseases are complex and debated: on the one hand, patients with LES are particularly prone to develop viral infections, on the other, some virus are thought to play a role both in triggering the onset of the immunologic disease and in conferring peculiar clinical features to flare-ups. METHODS: This study has drawn an epidemiologic profile of viral pathology from Epstein Barr virus, Parvovirus B 19 and Cytomegalovirus in 60 patients with LES followed-up for a period ranging from 13 to 340 months (on average 158 months). RESULTS: Cytomegalovirus seropositivity has turned out to be a strong, statistically significant risk factor for vascular accidents and especially for peripheral ones, such as Raynaud phenomenon, ulcers and distal necrosis (OR = 6.5 IC = 0.7-7.9* p = 0.037). CONCLUSIONS: Although Cytomegalovirus seropositivity is associated with an increased frequency of LAC/ACA, its relationship with vascular events does not seem to be mediated through such antibodies, apparently acting as an independent risk factor which also works in LAC/ACA negative patients. Parvovirus B 19 seropositivity has turned out to be the only increased risk factor for the development of anemia, although not reaching statistical significance, whereas Epstein Barr seropositivity does not appear to influence clinical features significantly.

The concept of 'glomerulonephritis'. the fascinating history of evolution and emergence of a specialist's nosology focus on Italy and Torino.

Though the term 'nephritis' first appeared in the 19th century, this word did not bear the same meaning as it does today; indeed, for many years it was used to indicate 'renal diseases' (in the sense of Bright's disease) in a larger sense. This review summarizes the long gestation of the concept of 'glomerulonephritis' from the prehistory of medicine up to the beginning of the second half of the 20th century with emphasis on Italy and, in particular, on Torino, which was the capital of the Kingdom of Italy from 1861 to 1865. To the best of our kowledge, this is the first study reporting an epidemiology survey of Bright's disease in Italy from 1880 up to 1960. Towards the end of the 19th century, Bright's disease accounted for 26 deaths/year/10(5) population (in comparison with more than 200 from tuberculosis) in Italy, roughly paralleling that reported in the USA. At the beginning of the 20th century, Bright's disease was the seventh cause of death (almost 1% of total deaths) in Italy. Furthermore, in Italy, as elsewhere, autopsy studies showed a higher percentage of deaths attributed to Bright's disease (5-7%) in comparison with those obtained from vital statistics. In 1960, just before the beginning of renal replacement therapy, Bright's disease accounted for 15.7 deaths/year/10(5) population (= 1.46% of all deaths), roughly paralleling that reported in the United Kingdom (13.8/10(5) population = 1.25% of deaths). Probably, it was difficult to recognize the real incidence of chronic renal diseases leading to death in the 1960s, and vital statistics were able to furnish only approximate estimates. However, noteworthy is the fact that these values were very close to those estimated as being the annual need for renal replacement therapy (10-20 cases/year/10(5) population).