A novel dosing approach for rituximab in glomerular diseases based on a population pharmacokinetic analysis.

OBJECTIVES: Rituximab is being increasingly prescribed for the treatment of autoimmune glomerular diseases. While it is highly effective for some diseases, the response is less predictable for others, which may be due to differing requirements in terms of the dosing according to the disease type and variations concerning exposure to the drug. METHODS: We compiled novel rituximab dosing schedules according to pharmacokinetic analysis of data gathered from rituximab treated patients in a tertiary referral nephrology centre between May 2020 and June 2023. The population-pharmacokinetic analysis was based on the rituximab dosing, the patients' characteristics, rituximab levels and anti-rituximab antibodies. RESULTS: The analysis, which was based on data from 185 patients, clearly highlighted differing rituximab dosing requirements for patients with ANCA associated vasculitis and minimal change disease compared to those with membranous nephropathy, focal-segmental glomerulosclerosis and lupus nephritis. This corresponded to the good treatment response of the first two diseases and the unreliable efficacy for the others. The model predicts the rituximab pharmacokinetics with high degree of accuracy when body weight, proteinuria, type of glomerulonephritis, treatment length and anti-rituximab antibodies formation are used as covariates. We proposed a dosing schedule with shortened dosing intervals for difficult-to-treat diagnoses with high proteinuria. CONCLUSION: In order to ensure reliable and comparable exposure of rituximab with respect to the full range of glomerular diseases, the dosing schedule should be adjusted for membranous nephropathy, focal-segmental glomerulosclerosis and lupus nephritis. This is largely, but not solely, due to the enhanced level of unselective proteinuria in these diseases.

Clinical Features, Outcomes, and Response to Corticosteroid Treatment of Acute Tubulointerstitial Nephritis: A Single-Centre Retrospective Cohort Study in the Czech Republic.

INTRODUCTION: Acute tubulointerstitial nephritis (ATIN) is a well-recognized cause of acute kidney injury (AKI) due to the tubulointerstitial inflammation. The aim of this study was to explore the clinical features, outcomes, and responses to corticosteroid treatment in patients with ATIN. METHODS: Patients with biopsy-proven ATIN, who were diagnosed between 1994 and 2016 at the Department of Nephrology, Charles University, First Faculty of Medicine, and General University Hospital in Prague, were included in the study. Patient demographics, the aetiological and clinical features, the treatment given, and the outcome at 1 year of follow-up were extracted from patient records. RESULTS: A total of 103 ATIN patients were analysed, of which 68 had been treated with corticosteroids. There was no significant difference in the median serum creatinine 280 (169-569) µmol/L in the conservatively managed group versus 374 (249-558) µmol/L in the corticosteroid-treated group, p = 0.18, and dependence on dialysis treatment at baseline at the time of biopsy (10.3 vs. 8.6%). During the 1 year of follow-up, those ATIN patients who had been treated with corticosteroids did better and showed greater improvement in kidney function, determined as serum creatinine difference from baseline and from 1 month over 1-year period (p = 0.001). CONCLUSIONS: This single-centre retrospective cohort study supports the beneficial role of the administration of corticosteroid therapy in the management of ATIN.

The most common founder pathogenic variant c.868G > A (p.Val290Met) in the NPHS2 gene in a representative adult Czech cohort with focal segmental glomerulosclerosis is associated with a milder disease and its underdiagnosis in childhood.

Background: Genetic focal segmental glomerulosclerosis (FSGS) is caused by pathogenic variants in a broad spectrum of genes that have a variable representation based on subjects' ethnicity and/or age. The most frequently mutated autosomal recessive gene in FSGS is NPHS2. In this study, we analyzed the spectrum of NPHS2 variants and their associated phenotype in Czech adult FSGS patients. Methods: A representative cohort of 234 adult patients with FSGS, derived from 225 families originating from all regions of Czechia, was analyzed by massively parallel sequencing. In this study, we focused on the comprehensive analysis of the NPHS2 gene. The histological classification of FSGS followed the Columbia classification. Results: We detected seven (3%) cases bearing homozygous or compound heterozygous pathogenic NPHS2 variants. A single pathogenic variant c.868G > A (p.Val290Met) was found in the majority of NPHS2-positive cases (86%; 6 out of 7) in histologically confirmed instances of FSGS. Its allele frequency among unrelated NPHS2-associated FSGS patients was 50% (6/12), and Haplotype analysis predicted its origin to be a result of a founder effect. There is an identical V290M-related haplotype on all V290M alleles spanning a 0,7 Mb region flanking NPHS2 in Central European FSGS populations. The phenotype of the p.Val290Met NPHS2-associated FSGS demonstrated a later onset and a much milder course of the disease compared to other NPHS2 pathogenic variants associated with FSGS. The mean age of the FSGS diagnosis based on kidney biopsy evaluation was 31.2 ± 7.46 years. In 50% of all cases, the initial disease manifestation of proteinuria occurred only in adulthood, with 83% of these cases not presenting with edemas. One-third (33%) of the studied subjects progressed to ESRD (2 out of 6) at the mean age of 35.0 ± 2.82 years. Conclusions: We identified the most prevalent pathogenic variant, p.Val290Met, in the NPHS2 gene among Czech adult FSGS patients, which has arisen due to a founder effect in Central Europe. The documented milder course of the disease associated with this variant leads to the underdiagnosis in childhood. We established the histopathological features of the NPHS2-associated adult FSGS cases based on the Columbia classification. This might improve patient stratification and optimize their treatment.

Anakinra in Paediatric Rheumatology and Periodic Fever Clinics: Is the Higher Dose Safe?

Objective: Anakinra has been increasingly used in off-label indications as well as dosing and mode of administration in a variety of inflammatory conditions. We aimed to review our clinical practice and compare treatment outcomes with published data. Methods: Clinical data from electronic records were retrospectively reviewed for patients treated with anakinra over the past 6 years for autoinflammatory diseases (AID). Results: From 47 eligible patients (27 female patients), 32 were children. Macrophage activation syndrome (MAS) was the indication for anakinra therapy in 42.6% of patients. Systemic juvenile idiopathic arthritis (SJIA) was the most common underlying diagnosis (19/47) followed by the spectrum of AID. Off-label use was noted in 38.3% patients. Recommended dose was exceeded in 21 children (mean induction dose 5.1, highest dose 29.4 mg/kg/day) and two adults; five patients were treated intravenously. The mean treatment duration for SJIA was 1.4 years, that for AID was 2.2 years, and that for patients with higher anakinra dose was 9.7 (19.3) months. The mean follow-up duration was 2.7 (1.7) years. Treatment was effective in the majority of SJIA and cryopyrinopathy patients as well as those with MAS. Anakinra was well-tolerated without any major adverse effects even in patients with long-term administration of higher than recommended doses including two infants treated with a dose of over 20 mg/kg/day. Conclusion: Our results support early use of anakinra in the individually tailored dosing. In patients with hyperinflammation, anakinra may be lifesaving and may even allow for corticosteroid avoidance. Further studies are needed in order to set up generally accepted response parameters and define condition-specific optimal dosing regimen.

Chronic kidney disease and pregnancy outcomes.

Pregnancy complicated by CKD is currently not fully understood topic. Outcome of pregnancy in patients with CKD is related to impaired glomerular filtration rate and the degree of proteinuria. In our study we evaluated the association of serum creatinine level and proteinuria with both maternal and fetal outcomes in the cohort of 84 pregnant patients with CKD. In CKD group we confirmed negative correlation of highest serum creatinine level in pregnancy to fetal weight (p value < 0.001) and gestation period (p value < 0.001). Likewise, negative correlation of preconception serum creatinine to fetal weight (p value < 0.001) and gestation period (p value 0.002). Negative correlation of proteinuria to gestation period (p value < 0.001) and fetal weight (p value < 0.001) was also demonstrated. CKD is serious risk factor for pregnancy outcome. Proteinuria and serum creatinine level should be examined before pregnancy and regularly monitored during pregnancy. Higher serum creatinine levels and higher proteinuria predispose to shorter gestation period and lower birth weight of the neonate.

Renal involvement of a patient with Crohn´s disease: A case report.

Inflammatory bowel disease (IBD) is a group of chronic relapsing intestinal inflammatory processes primarily represented by ulcerative colitis (UC) and Crohn´s disease (CD). Nearly half of IBD cases are followed by extraintestinal complications and renal involvement can occur independatly or along with other complications and are described with the patients sufferring from UC or CD. Most frequent renal involvement is nephrolithiasis, tubulointerstinal nephritis, different kinds of glomerulonephritis and AA amyloidosis. We are presenting an unusal form of renal involvement of a young female patient with a severe form of Crohn´s disease treated with recombinant monoclonal antibodies.

Muckle-Wells Syndrome Across Four Generations in One Czech Family: Natural Course of the Disease.

Background: Muckle-Wells syndrome (MWS) represents a moderate phenotype of cryopyrinopathies. Sensorineural hearing loss and AA amyloidosis belong to the most severe manifestations of uncontrolled disease. Simultaneous discovery of MWS in four generations of one large kindred has enabled us to document natural evolution of untreated disease and their response to targeted therapy. Methods: A retrospective case study, clinical assessment at the time of diagnosis and 2-year prospective follow-up using standardized disease assessments were combined. Results: Collaborative effort of primary care physicians and pediatric and adult specialists led to identification of 11 individuals with MWS within one family. Presence of p.Ala441Val mutation was confirmed. The mildest phenotype of young children suffering with recurrent rash surprised by normal blood tests and absence of fevers. Young adults all presented with fevers, rash, conjunctivitis, and arthralgia/arthritis with raised inflammatory markers. Two patients aged over 50 years suffered with hearing loss and AA amyloidosis. IL-1 blockade induced disease remission in all individuals while hearing mildly improved or remained stable in affected patients as did renal function in one surviving individual with amyloidosis. Conclusions: We have shown that severity of MWS symptoms gradually increased with age toward distinct generation-specific phenotypes. A uniform trajectory of disease evolution has encouraged us to postpone institution of IL-1 blockade in affected oligosymptomatic children. This report illustrates importance of close interdisciplinary collaboration.

Periodic fevers and other autoinflammatory diseases.

Autoinflammatory diseases represent a relatively new and rapidly evolving group of rare disorders associated with mutations of genes encoding proteins with a key regulatory role in inflammatory response. Gradual discovery of mechanisms that link genetic disorder with its biochemical and immunological consequences leading to continuous or episodic inflammatory stimulation has enabled introduction of directed immunotherapies. Periodic fever syndromes belong to the so far best-known entities: familial Mediterranean fever, mevalonate kinase deficiency, cryopyrinopathies and TNF-receptor associated periodic syndrome. These inherited disorders usually manifest in childhood with variably long febrile episodes accompanied with the spectrum of other skin and organ inflammatory features and elevation of laboratory markers of inflammation. Uncontrolled disease may lead to secondary amyloidosis. Directed anti-inflammatory therapy can prevent evolution of organ damage. In children benign syndrome of periodic fever with aphtae, pharyngitis and cervical adenitis is the most common self-limited disorder without clear genetic disposition. Following other autoinflammatory disease groups are described - pyogenic syndromes, disorders with skin and bone manifestations, granulomatous diseases, monogenic vasculopathies and diseases associated with proteasome disorder. Diagnosis of autoinflammatory diseases is often delayed due to their extreme rarity. Increasing efficacy and availability of molecular-genetic testing and centralization of diagnostics and clinical care in a specialized center for children as well as adults can in the future improve quality of care for patients with these rare conditions. Keywords: autoinflammatory diseases (AID), periodic fever syndromes, FMF, CAPS, MKD, TRAPS, PFAPA, NGS.

Prognostic value of anti-CRP antibodies in lupus nephritis in long-term follow-up.

BACKGROUND: Autoantibodies against monomeric C-reactive protein (anti-CRP-Ab) observed in patients with systemic lupus erythematosus (SLE) and lupus nephritis (LN) were suggested to be associated with active LN and a poor response to therapy during short-term follow-up. The aim of this study was to confirm this finding and to investigate the prognostic value of anti-CRP-Ab in patients with LN during long-term follow-up. METHODS: Sera of 57 SLE patients (47 women, 10 men) with biopsy proven LN and 122 healthy individuals were analyzed for the presence of anti-CRP-Ab by in-house ELISA. Anti-CRP-Ab levels were studied in relation to routine laboratory tests, urine analysis, levels of C3, C4, other immunological markers and the overall disease activity as assessed by Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). The prognostic value of anti-CRP-Ab was tested in a subgroup of 29 newly diagnosed LN patients (median follow-up 5.9 years). Response to therapy at various time points was assessed with respect to baseline anti-CRP-Ab levels. At least partial response in the first/second year of treatment was considered as a "favorable outcome", while non-response, renal flare or end stage renal disease were considered as "unfavorable outcome". RESULTS: Anti-CRP-Ab were only detected in patients with active renal disease and their levels correlated with SLEDAI (rs = 0.165, p = 0.002). The time to response was shorter in patients being anti-CRP-Ab negative at baseline compared to anti-CRP-Ab positive patients, p = 0.037. In the second year of therapy, baseline anti-CRP-Ab positivity was a significant predictor of "unfavorable outcome" (OR [95% CI] = 15.6 [1.2-771]; p = 0.021). The predictive value of "baseline anti-CRP positivity" further increased when combined with "non-response to therapy in the first year". Baseline anti-CRP-Ab positivity was not a predictor of "unfavorable outcome" at the end of follow-up, (OR [95% CI] = 5.5 [0.6-71.1], p = 0.169). CONCLUSIONS: Baseline serum levels of anti-CRP-Ab seem to be a strong risk factor for a composite outcome of non-response, renal flare or end stage renal disease after two years of standard treatment of LN. The response to therapy seems to be delayed in anti-CRP-Ab positive patients.

Nationwide biopsy survey of renal diseases in the Czech Republic during the years 1994-2011.

BACKGROUND: We describe data on 10,472 renal biopsies gathered by the Czech Registry of Renal Biopsies over a period of 18 years. METHODS: We assessed the main demographic, clinical and histological data of individuals who underwent renal biopsies of native kidneys in 31 centers in the Czech Republic (population 10.3 million) during the period 1994-2011. RESULTS: We evaluated 10,472 renal biopsies: males 57.8%, children (≤15 years) 13.6%, elderly (>60 years) 19.1%. The most frequent biopsy-proven diseases were primary (55.7%) and secondary (29.1%) glomerulonephritides (GN). Tubulointerstitial nephritis (TIN) was observed in 3.4 % and vascular diseases in 4.1%. The samples were non-diagnostic in 4.2%. Among primary GN the most frequent diagnoses were IgA nephropathy (IgAN) (37.4%), membranous GN (MGN) (13%) and focal segmental glomerulosclerosis (FSGS) (12.6%). Among secondary GN, systemic lupus erythematosus (SLE) represented 23.2%, hereditary diseases 19.8% and necrotizing vasculitis (NV) 19.4%. Among adults, mild renal insufficiency [serum creatinine (SCr) 111-200 µmol/l] was present in 24.7%, advanced renal insufficiency (SCr 201-400 µmol/l) in 15.3, and 12.3% of patients had SCr > 400 µmol/l. The most common diseases in patients with nephrotic proteinuria were minimal change disease (MCD) (39.7%) among children, IgAN (26.2%) in adults aged 16-60 years and amyloidosis (42.7%) among the elderly. The mean annual incidence (per million population) was: primary GN 30.9, secondary GN 18.1, IgAN 11.6, MGN 4.0, SLE 4.0, FSGS 3.9, MCD 3.4, NV 3.2, diabetic nephropathy 2.3, thin basement membrane glomerulopathy 2.0, mesangioproliferative GN 1.9, and TIN 1.9. Ultrasound needle guidance was used in 66.8%. The frequency of serious complications (symptomatic hematoma, gross hematuria, blood transfusion) was approximately 3.2%. CONCLUSIONS: This report provides representative population-based data on native biopsy-proven renal diseases in the Czech Republic. Over the 18 years of nationwide biopsy survey, we noted an increase of the mean age of renal biopsy cases, an increasing proportion of elderly, and a cardinal change in biopsy technique towards ultrasonography needle guidance.

IgA nephropathy in Czech patients--are we able reliably predict the outcome?

BACKGROUND/AIMS: The aim of our study was to retrospectively analyse data of 520 Czech patients with IgA nephropathy (IgAN) and to specify the risk factors affecting renal survival of IgAN patients. METHODS: Cox proportional hazards regression model was used to evaluate the effects of different variables on renal survival during a median follow up of six years. McNemar´s test was used to analyse the progression of renal function according to Bartosik´s formula. RESULTS: In our retrospective analysis of 520 Czech IgAN patients Cox proportional hazards regression model with five variables [hypertension, sex, GFR, proteinuria, age] was used. Significant regression coefficient was found for GFR, hypertension and proteinuria. Using stepwise algorithm GFR (OR = 3.09), hypertension (OR = 2.09) and proteinuria (OR = 1.97) were found as the most important factors for renal survival in our group of IgAN patients. Among patients with CKD 3 we found significantly better renal survival in patients with proteinuria < 1g/day compared to patients with higher proteinuria. We did not find the significant difference between predicted progression of renal function due to Bartosik´s formula and real progression of renal parametres assessed by GFR at the end of the follow up in our group of IgAN patients. CONCLUSION: Our retrospective study of 520 Czech IgAN patients confirmed GFR, hypertension and proteinuria as the most important factors affecting the prognosis of IgAN patients. We validated Toronto Bartosik´s formula to predict prognosis of IgAN patients.

Intracellular cytokine production in ANCA-associated vasculitis: low levels of interleukin-10 in remission are associated with a higher relapse rate in the long-term follow-up.

BACKGROUND AND AIMS: Dysregulation of cell-mediated immune response likely plays a role in the pathogenesis of anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (AAV), but it has not yet been fully established. The aim of this study was to assess the intracellular cytokine production in patients with AAV at different stages of the disease, in particular, in relation to the long-term prognosis. METHODS: We included 69 patients with AAV and 24 healthy controls. Using flow cytometry, the following intracellular cytokines (IC) were measured in all patients: interferon-gamma (IFN-gamma), tumor necrosis factor alpha (TNF-alpha), interleukin-2 and interleukin-4 in CD3+T cells and interleukin-10 (IL-10) and interleukin 12 (IL-12) in monocytes. Patients were then prospectively followed for a median of 43 months and cytokine production was related to the long-term prognosis. RESULTS: When compared to healthy controls, increased IL-12 production was observed in AAV patients, both active (p<0.01) and in remission (p<0.05). In remission, increased IFN-gamma production was also found (p<0.01). IL-10 production was higher in active patients than in patients in remission (p<0.05) but did not differ from controls. Patients in remission who developed a relapse during follow-up had significantly lower IL-10 production than those without relapse (p<0.01). Results of this prospective study of IC production in AAV confirm findings of previous studies measuring circulating cytokine levels. CONCLUSIONS: Activation of the immune system in AAV patients is noticeable even in remission. Patients with AAV display increased IL-12 production, which seems to be counterbalanced by IL-10. Low IL-10 levels in remission are associated with a higher relapse rate in the long-term follow-up.

Prevalence and risk of hypertension in renal disease--data from the Czech Registry of Renal Biopsies.

BACKGROUND/AIMS: We intended to compare the risk and prevalence of hypertension in patients undergoing renal biopsy with those of the general population and to investigate the possible effects of various independent factors (age, sex and degree of renal insufficiency) on the prevalence of hypertension. METHODS: Data obtained within the Czech Registry of Renal Biopsies over an 8-year period (1995-2002) were statistically evaluated and compared with those of the general population obtained within the Post-MONICA Study conducted in 2000/2001. RESULTS: Hypertension was present in 1,839 out of a total of 3,601 renal patients (51.1%). The risk of hypertension in the patients with renal disease was increased in all age groups compared with the general population (OR = 1.3-5.3). The prevalence of hypertension increased significantly with age, serum creatinine and proteinuria (p < 0.001). Male sex was identified as an independent risk factor for the presence of hypertension (p < 0.01). Sex, age and glomerular filtration rate were shown to be more important determinants of the risk of hypertension than the underlying biopsy-proven diagnosis itself. CONCLUSION: Hypertension occurs as a common complication of renal disease, even in its early stages, and irrespective of the histological finding.

Mycophenolate mofetil in low doses stabilizes and improves antineutrophil cytoplasmic antibody-associated vasculitis and lupus nephritis.

BACKGROUND: Clinical experience with mycophenolate mofetil (MMF) in glomerulonephritis still remains limited. METHODS: In order to assess the experience of one center with the efficacy and tolerability of MMF in patients with glomerulonephritis, we performed a retrospective 6-year analysis of 68 patients treated by MMF for glomerular disease, mainly anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV: n=34) and systemic lupus erythematosus and lupus nephritis (SLE: n=24). Indications were maintenance treatment in 40% of patients, induction treatment in patients not tolerating cyclophosphamide in 27%, and disease relapse in 33%. Mean treatment duration was 11.5 months. RESULTS: Efficacy endpoints were serum creatinine, urinary protein excretion, and steroid dose. In AAV patients, MMF was associated with significant improvement in 18%, partial improvement in 26%, stabilization in 29%, and disease progression in 12%; adverse event dropouts totalled 15%. In SLE, the respective figures were 30, 22, 9, and 22%, with 17% adverse event dropouts. The most frequent side effects were gastrointestinal events (n=7) and infections (n=3). None was life-threatening and there were no deaths. CONCLUSIONS: MMF, in the relatively low doses used, was safe and effective, stabilizing or improving AAV in 73% of patients and SLE in 61%. Further prospective randomized controlled trials with MMF in renal vasculitis and lupus nephritis are clearly warranted.

Treatment of lupus nephritis with cyclosporine - an outcome analysis.

BACKGROUND: The optimal therapy for lupus nephritis (LN), including the role of cyclosporine (CsA), still lacks scientifically valid clinical experience. We evaluated the efficacy of CsA in the induction and maintenance treatment of patients with biopsy-proven LN. PATIENTS AND METHODS: A total of 31 patients (25 women, 6 men, mean age 29.5 years) were enrolled in the study. The majority had proliferative LN. The mean follow-up was 85.6 +/- 24.7 months. RESULTS: CsA was used as first-line treatment in 38.7% of patients and as second-line treatment in 61.3% of patients. Complete remission was achieved in 93.5% of patients. The relapse rate was 45.2%. The mean disease-free interval was 33 months. At the end of follow-up, a total of 67.9% of the patients were in remission. The treatment led to significant improvement in proteinuria (p = 0.001) and stabilization of renal function. CONCLUSION: CsA might be an appropriate and a less toxic alternative drug for LN both as a first-choice and rescue therapy.

High prevalence of anti-C1q antibodies in biopsy-proven active lupus nephritis.

BACKGROUND: Anti-C1q antibodies (anti-C1q) have been shown to correlate positively with systemic lupus erythematosus (SLE) nephritis. Several clinical studies indicated a high negative predictive value, suggesting that active lupus nephritis is rarely seen in patients with no anti-C1q. However, the true prevalence of anti-C1q at the time of active lupus nephritis has not been well established. The aim of this study was to determine prospectively the prevalence of anti-C1q in proven active lupus nephritis at the time of the renal biopsy. METHODS: In this prospective multi-centre study, we investigated adult SLE patients undergoing renal biopsy for suspected active lupus nephritis. Serum samples were taken at the time of the biopsy and analysed for the presence of anti-C1q in a standardized way. The activity of lupus nephritis was classified according to the renal histology. Biopsies were also analysed for the presence of glomerular IgG, C1q and C3 deposition. RESULTS: A total of 38 patients fulfilling at least 4/11 American College of Rheumatology (ACR) criteria for the diagnosis of SLE were included. Out of this, 36 patients had proliferative (class II, III or IV) and two had class V lupus nephritis. All but one patient with proliferative lupus nephritis were positive for anti-C1q (97.2%) compared with the 35% of control SLE patients with inactive lupus nephritis and 25% of SLE patients without lupus nephritis ever. All patients were positive for glomerular C1q (36/36) and 37/38 patients had glomerular IgG deposits. Anti-C1q strongly decreased during successful treatment. CONCLUSIONS: Anti-C1q have a very high prevalence in biopsy-proven active lupus nephritis, thus a negative test result almost excludes active nephritis. The data support the hypothesis of a pathogenic role of anti-C1q in lupus nephritis.

Silica and asbestos exposure in ANCA-associated vasculitis with pulmonary involvement.

Silica and asbestos exposure are thought to belong to the triggering factors of antineutrophil cytoplasm antibodies (ANCA)-associated vasculitis. We carried out a study to find out whether patients with pulmonary involvement attributable to ANCA-associated vasculitis (AAV) have been exposed to silicon-containing materials. Thirty-one patients (12 women, 19 men, median age 51 years) were interviewed using a structured questionnaire. Occupational exposure to silicon-containing chemicals was reported by 22.6% of the patients (12.9% to SiO2, 9.7% to asbestos), compared with 0% of control subjects (p<0.05). Our findings support the pathophysiologic role of silica in AAV.

Secondary membranous nephropathy--one center experience.

INTRODUCTION: Secondary membranous nephropathy (MN) is most commonly seen in the setting of autoimmune disease, infection, and neoplasia, and with certain therapeutic agents. The aim of our study was to analyze the presenting features and outcome of the patients with secondary MN. PATIENTS AND METHODS: We retrospectively studied patients with secondary MN diagnosed between the years 1991-2002. In this period, we performed a total of 1874 renal biopsies. MN was diagnosed in 129 cases. RESULTS: In 40 patients (31%), an underlying primary cause was verified (70% women, 30% men, median age 49.5 years). In 18 patients (45%), the disease was drug induced, 11 patients (27.5%) had autoimmune disease, seven patients (17.5%) solid tumors, three patients (7.5%) hepatitis B, and one patient was diagnosed with both hepatitis B and prostate carcinoma. At presentation, median proteinuria was 4.09 g/24 h; 60% were nephrotic. Most of the patients had normal renal function with a median serum creatinine 79 micromol/L and a median GFR 1.285 ml/s. The patients were treated according to the underlying disease. At the end of the follow-up, the patients with drug-induced MN were in complete remission after the discontinuation of the drug. The patients with autoimmune disease were treated with immunosuppression, most of them with very good results. The outcome of the patients with neoplasia was much worse. CONCLUSION: A thorough and repeated exclusion of secondary forms of MN has significant prognostic and therapeutic implications, especially in drug-induced and autoimmune MN.