Keywords
IgA nephropathy; silica nephropathy, silicosis, work environment
IgA nephropathy; silica nephropathy, silicosis, work environment
In this new version:
1/ Grammatical errors were corrected.
2/ The term “Renal” is replaced with the term “Kidney”.
3/ NFS was translated to English in the new version and is replaced by complete blood count.
See the authors' detailed response to the review by Imed Helal
See the authors' detailed response to the review by Gisella Vischini
Occupational exposure to crystalline silica dust particles may lead to silicosis, which is the most common pneumoconiosis. Silica crystalline is known to be a trigger of autoimmune and chronic kidney diseases.1 The most common silica nephropathies described to be related to silicosis are crescentic glomerulonephritis, proliferative glomerulonephritis and chronic interstitial nephritis.1 IgA nephropathy (IgA N) is known to be the most frequent glomerulonephritis. However, silicosis-IgA N is a rare association and very few cases have been reported in the literature.2–6 The underlying pathophysiology remains to be elucidated.
Hereby, we report the case of a mason with a coexistent silicosis and IgA nephropathy in order to better understand such association.
A 57-year-old Caucasian man was admitted to our department of nephrology for unexplained kidney failure (serum creatinine 207 μmol/l, eGFR 26 ml/min) that was discovered during routine exams to follow-up his pernicious anemia, including complete blood count and creatinine. The pernicious anemia was diagnosed two years ago and treated by intramuscular injections of vitamin B12.
The patient had a seven pack-year tobacco smoking history that he stopped 5 years ago.
The professional anamneses revealed that the patient worked as a mason for 33 years in several constructions and public work companies. He was responsible for supervising concreting, masonry, foundations, walls and floors covering as well as painting and finishing. During his professional career, he has been exposed to crystalline silica without wearing respiratory protective equipment.
At admission, physical examination revealed a blood pressure of 150/90 mmHg and edema in lower limbs. Urinalysis showed an active urinary sediment with significant proteinuria (2+) and microscopic hematuria (3+). We also noticed bilateral clubbing. The patient was also eupneic. Chest auscultation showed diffuse bilateral crackles.
Biological investigations revealed a kidney failure with a creatinine level at 207 μmol/l, and positive proteinuria at 1.5 g/24 hours (normal range <0.5 g/24 hours), as well as a macrocytic anemia with a hemoglobin level at 11g/dl (anemia shown by level <13g/dl) and an elevated C reactive protein level at 67 mg/l (normal range <5 mg/l).
P anti-neutrophil cytoplamic (p ANCA), c anti-neutrophil cytoplasmic (c ANCA) antibodies and antinuclear antibodies (AAN) were negative. Serum complement level was normal. CT guided percutaneous kidney biopsy as performed using automatic spring loaded needle of 16 gauge under local anesthesia. Thirteen glomeruli were included in the specimen. Five of them were ischemic and sclerotic. The rest of the glomeruli showed focal and segmental mesangial hypercellularity without crescents. There were flocculo-capsular synechiae associated with severe tubular atrophy and interstitial fibrosis. Immunofluorescence revealed granular staining of IgA and C3 in the mesangium. The final pathological diagnosis was IgA nephropathy (Figure 1).
A,B: Light microscopic, hematoxylin and eosin- stained (×200), segmental mesangial hypercellularity. C: Light microscopic, Periodic Acid Schiff (× 200), flocculo-capsular synechiae. D: Immunofluorescence microscopy (×200), Mesangial IgA deposits.
Chest tomography was performed and it revealed fibrosing diffuse interstitial lung disease consisting of bilateral septal thickening, ground-glass opacities and a honeycomb pattern. These aspects predominated at the two bases and on the periphery (Figure 2).
Because of occupational history of prolonged crystalline silica exposure, characteristic radiologic findings and clinical signs, the diagnosis of silicosis was given.
The patient was put on Angiotensin-Converting Enzyme Inhibitors (Ramipril 5 mg/day) because of its antihypertensive and protein-lowering effects and was referred to the pneumology department to complete the respiratory functional exploration and to treat the silicosis. Kidney function was stable after three months of follow-up.
From a medico-legal point of view, silicosis is considered as a compensable occupational disease, according to the Tunisian list table of occupational diseases.7
Occupational silica exposure causes not only lung damages, but also involves many other organs.8 In fact, it was recently noticed that silica exposure is more frequently associated to autoimmune diseases and systemic manifestations such as scleroderma, systemic lupus erythematosus, rheumatoid arthritis or ANCA-associated vasculitis than the general population.8 Little is known about mechanisms, but it has been reported that silica dust triggers autoimmune phenomena.2
Moreover, several authors have reported the association of silicosis with kidney lesions as an occupational disease.9 According to Ghahramani, exposure to silica dust can be associated with tubulointerstitial or glomerulonephritis involvement, which often leads to an important risk of end-stage kidney disease.1 The most common silica nephropathy described in the literature were crescentic glomerulonephritis, proliferative glomerulonephritis and chronic interstitial nephritis.3 IgA nephropathy has been rarely reported even though it is the most common type of glomerulonephritis worldwide.10 Only a few similar cases were described in the literature.2–6 A summary of all cases reported has been presented in Table 1.
Author, Year | Age (Y)/sex | Profession | ABP (mmHg) | Hu | Pr (g/24h) | Serum creatinine | Renal biopsy findings | Treatment |
---|---|---|---|---|---|---|---|---|
Bonnin A et al. 19872 | 69/M | Miner | 200/100 | Yes | 3 | 106 μmol/l | IgA mesangial nephropathy associated to crescents | None |
50/M | Ceramic enamelling | 150/90 | Yes | 1.1 | 165 μmol/l | PE | ||
67/M | Miner | 190/100 | Yes | 3 | 212 μmol/l | None | ||
A R Khan et al 19994 | 45/M | Tunnel construction worker | 160/100 | Yes | 4.2 | 1.2 mg/dl | IgA nephropathy with deposited interstitial nephritis | - |
Fujii Y et al. 20015 | 51/M | Building wrecker | - | Yes | 0.294 | - | Mesangial proliferation with IgA deposition | |
Ricco M et al. 20166 | 68/M | Sandstone cave miner | Yes | 2.8 | 2 mg/dl | Glomerular sclerosis with IgA deposition and tubular atrophy | Immune suppressing therapy | |
Chen F-F et al. 20193 | 43/M | Coal miner | 130/80 | Yes | 3.7 | 2.51 mg/dl | Focal proliferative IgA nephropathy and acute tubulo-interstitial nephritis | Corticosteroids + ACEI |
Our case | 57/M | Mason | 150/90 | Yes | 1.5 | 207 μmol/l | Mesangial proliferation with IgA deposition associated to tubular atrophy and interstitial fibrosis | ACEI |
The underlying mechanism connecting the two entities is probably that silica behaves as an adjuvant to enhance immunologic and inflammatory processes.11 According to the medical history of the association of lung and kidney disease, Endo et al had reported that not only the upper tract, but also the lung or lower respiratory tract is a mucosal site protected by IgA.12 Thus, persistent lung inflammation may stimulate IgA mediated immune mechanisms or activate antibody (IgA) dependent monocytes, which leads to IgA mediated immune abnormalities and mesangial deposition of IgA.12 This process mimics the immunopathologic features of IgA nephropathy and may confirm that this glomerulonephritis may occur secondary to silicosis. Beshir et al revealed serum IgA mean level was significantly higher in the silicosis group compared to the non-silicosis group (315.1 ± 165.3 vs. 154.7 ± 105.1 mg/dl, respectively).13
More interestingly, a recent study may explain the putative link between silicosis and IgA N, which is a NOD-like receptor, pyrin domain-containing 3 (NLRP3). In fact, NLRP3 are the key in the inflammatory process caused by silica: they are involved, in association with alveolar macrophages, in binding and eliminating crystalline silica particles, and thus leading to pulmonary fibrosis in recent studies.3,14
The real mechanism and pathophysiology are still not fully elucidated and need more study to further understand how silica leads to autoimmunity and glomerulonephritis. In our case, simultaneous kidney and pulmonary disease could suggest the hypothesis that Ig A nephropathy might be associated with silica exposure.
In addition, data about silicosis-IgA N treatment is poor and inconclusive, because there are no clinical trials or controlled studies, but only sporadic cases have been reported. According to Ghahramani, there is no specific treatment.1 However, vasculitis and immune-mediated disease required steroids and cytotoxic agents in addition to reducing exposure to silica crystalline dust.8
In our case, steroids or immunosuppressant agents were not required because of the absence of active lesions on kidney biopsy. Thus, only antihypertensive treatment with a nephroprotective effect was initiated in association with a withdrawal from occupational exposure. Moreover, chronic lesions, such as tubular atrophy and interstitial fibrosis might explain the degree of kidney insufficiency and the uselessness of immunosuppressive agents.
Moreover, there is no evident data regarding the course of the association of silicosis and IgA nephropathy. Some authors reported that occupational exposure to silica is associated with an elevated risk of end stage renal disease and thus with high mortality,1 while others had reported that kidney disease or progression is associated with a worsening lung involvement.11
Silicosis-IgA N is a very rarely reported association in the literature. It seems to be far more than an incidental association. The pathogenesis is still not fully understood, and the paucity of information makes a significant barrier to confirm such a link. Nevertheless, according to many authors, the main underlying mechanism is a triggering of autoimmunity with a mal-adaptive immune response. In addition, it is necessary to be particularly vigilant with these rare associations and to think systematically about environmental and occupational exposure.
All data underlying the results are available as part of the article and no additional source data are required.
Written informed consent for publication of his clinical details and clinical images was obtained from the patient.
Views | Downloads | |
---|---|---|
F1000Research | - | - |
PubMed Central
Data from PMC are received and updated monthly.
|
- | - |
Competing Interests: No competing interests were disclosed.
Competing Interests: No competing interests were disclosed.
Reviewer Expertise: clinical nephrology , dialysis
Is the background of the case’s history and progression described in sufficient detail?
Yes
Are enough details provided of any physical examination and diagnostic tests, treatment given and outcomes?
No
Is sufficient discussion included of the importance of the findings and their relevance to future understanding of disease processes, diagnosis or treatment?
No
Is the case presented with sufficient detail to be useful for other practitioners?
Yes
Competing Interests: No competing interests were disclosed.
Reviewer Expertise: Renal pathology, glomerulonephritis
Is the background of the case’s history and progression described in sufficient detail?
Yes
Are enough details provided of any physical examination and diagnostic tests, treatment given and outcomes?
Yes
Is sufficient discussion included of the importance of the findings and their relevance to future understanding of disease processes, diagnosis or treatment?
Yes
Is the case presented with sufficient detail to be useful for other practitioners?
Partly
Competing Interests: No competing interests were disclosed.
Reviewer Expertise: clinical nephrology , dialysis
Alongside their report, reviewers assign a status to the article:
Invited Reviewers | ||
---|---|---|
1 | 2 | |
Version 2 (revision) 10 Jan 22 |
read | read |
Version 1 11 Nov 21 |
read | read |
Provide sufficient details of any financial or non-financial competing interests to enable users to assess whether your comments might lead a reasonable person to question your impartiality. Consider the following examples, but note that this is not an exhaustive list:
Sign up for content alerts and receive a weekly or monthly email with all newly published articles
Already registered? Sign in
The email address should be the one you originally registered with F1000.
You registered with F1000 via Google, so we cannot reset your password.
To sign in, please click here.
If you still need help with your Google account password, please click here.
You registered with F1000 via Facebook, so we cannot reset your password.
To sign in, please click here.
If you still need help with your Facebook account password, please click here.
If your email address is registered with us, we will email you instructions to reset your password.
If you think you should have received this email but it has not arrived, please check your spam filters and/or contact for further assistance.
Comments on this article Comments (0)