Abstract
Objectives
To characterize a LN cohort over 40 years, assessing its evolution, analysing two major outcomes: the development of end-stage renal disease and mortality rates in the first 5 ...years after LN diagnosis.
Methods
An observational retrospective study of patients with LN, followed up from 1975 at University College Hospital. Patients were divided into four groups, depending on the decade of LN diagnosis: 1975–1985 (D1), 1986–1995 (D2), 1996–2005 (D3) and 2006–2015 (D4). Comparison between groups was performed with respect to demographic, clinical, serological and histological characteristics and outcome.
Results
Two hundred and nineteen patients with LN were studied. There was a change in ethnic distribution, with a decreasing proportion of Caucasians (58.6% in D1 to 31.3% in D4, P = 0.018) and increase in African-ancestry (17.2% in D1 to 39.6% in D4, P = 0.040). Serological and histological patterns changed throughout time, with a reduction in class IV nephritis (51.7% in D1 to 27.1% in D4, P = 0.035), and increase in class II nephritis (10% in D2 to 18.8% in D4, P = 0.01) and anti-extractable nuclear antigen antibody positivity (17.2% in D1 to 83.3% in D4, P = 0.0001). The 5-year mortality rates decreased from D1 (24.1%) to D2 (4%), stabilizing for the next 30 years. The 5-year progression to end-stage renal disease remained stable over the decades.
Conclusion
Despite the changes in treatment of LN in the past 20 years, we have reached a plateau in 5-year mortality and progression to end-stage renal disease rates, suggesting that new therapeutic and management approaches, and strategies to enhance adherence, are needed to improve outcomes further in LN patients.
Membranous glomerulonephritis (MGN) is a common cause of nephrotic syndrome in adults, mediated by glomerular antibody deposition to an increasing number of newly recognised antigens. Previous case ...reports have suggested an association between patients with anti-contactin-1 (CNTN1)-mediated neuropathies and MGN. In an observational study we investigated the pathobiology and extent of this potential cause of MGN by examining the association of antibodies against CNTN1 with the clinical features of a cohort of 468 patients with suspected immune-mediated neuropathies, 295 with idiopathic MGN, and 256 controls. Neuronal and glomerular binding of patient IgG, serum CNTN1 antibody and protein levels, as well as immune-complex deposition were determined. We identified 15 patients with immune-mediated neuropathy and concurrent nephrotic syndrome (biopsy proven MGN in 12/12), and 4 patients with isolated MGN from an idiopathic MGN cohort, all seropositive for IgG4 CNTN1 antibodies. CNTN1-containing immune complexes were found in the renal glomeruli of patients with CNTN1 antibodies, but not in control kidneys. CNTN1 peptides were identified in glomeruli by mass spectroscopy. CNTN1 seropositive patients were largely resistant to first-line neuropathy treatments but achieved a good outcome with escalation therapies. Neurological and renal function improved in parallel with suppressed antibody titres. The reason for isolated MGN without clinical neuropathy is unclear. We show that CNTN1, found in peripheral nerves and kidney glomeruli, is a common target for autoantibody-mediated pathology and may account for between 1 and 2% of idiopathic MGN cases. Greater awareness of this cross-system syndrome should facilitate earlier diagnosis and more timely use of effective treatment.
Introdução: A incidência e prevalência de demência e de Doença de Alzheimer aumentam com a idade, duplicando a cada cinco anos após a sexta década de vida. Portugal é um país envelhecido, ...previsivelmente com um número crescente de casos de demência. No entanto, os dados epidemiológicos são escassos e os estudos sobre os custos da doença praticamente inexistentes. Propomo-nos apresentar uma estimativa actualizada da prevalência de demência/ Doença de Alzheimer em Portugal e inferir, a partir da prescrição específica para demência, o número de diagnósticos efectivos e os encargos financeiros com esses medicamentos.Material e Métodos: À população residente em Portugal (2013), aplicámos os valores de prevalência de demência para a Europa Ocidental (estudo da Alzheimer’s Disease International). A estimativa dos diagnósticos efectivos de Doença de Alzheimer e dos encargos financeiros com medicação específica baseou-se nas informações do Intercontinental Marketing Services Health (IMSH) – 2013.Resultados: O número estimado de Portugueses com mais de 60 anos e com demência foi 160287, o que corresponde a 5,91% deste universo populacional. Sabendo que a Doença de Alzheimer representa 50-70% dos casos, inferimos que existirão entre 80144 e 112201 doentes. Por outro lado, os dados da IMSH indicam que estarão diagnosticados e a receceber anti-demenciais 76250 doentes, representando um encargo financeiro de 37 M€/ano.Conclusão: O envelhecimento da população incrementa o número de casos de demência. Aparentemente, nem todos os doentes com Doença de Alzheimer recebem a medicação aconselhada, sugerindo que esta condição ainda está sub-diagnosticada. A evolução tem sido positiva, com incremento do número de doentes tratados e redução dos custos com fármacos específicos.
Gout is currently the most frequent cause of inflammatory arthritis worldwide and is responsible for poor health-related quality of life and loss of work productivity. It is caused by high levels of ...serum urate, leading to the deposition of monosodium urate crystals in joints and soft tissues. This condition is associated with acute flares and, if untreated or refractory, chronic and potentially destructive arthritis and tophi formation. Pegloticase is a recombinant, pegylated uricase used in the treatment of gout patients who fail conventional urate-lowering therapy. In this review, we discuss the impact of pegloticase on patient outcomes in refractory gout. We analyze different parameters, such as plasma uric acid concentration, frequency of flares, tophi reduction, pain, function, quality of life, and safety.
Abstract
Background/Aims
Patients with systemic lupus erythematosus (SLE) have increased mortality compared to age- and sex-matched controls. Lupus nephritis (LN) is a severe manifestation of SLE and ...an important cause of death. Our objective was to carry out a retrospective survival analysis to investigate factors that could influence risk of mortality and LN in a large multi-ethnic cohort of patients with SLE.
Methods
By careful review of medical records, we identified 496 patients with SLE for whom we had complete information regarding period of observation and occurrence of death and nephritis. Patients were stratified into groups according to sex, ethnicity (Caucasian, African/Caribbean, South Asian, East Asian, Other), age at start of follow-up (above and below median) and time-period of diagnosis (1978-89, 1990-99, 2000-5, 2006-11). Kaplan-Meier analysis was used to investigate differences between the groups in survival and LN.
Results
Overall, there were 454 women and 42 men. 91 patients died and 165 developed LN. Mean follow-up was 15.8 ± 8.75 years with a maximum of 40 years. Median age at start of follow-up was 28.0 ± 12.13 years.
Results are shown in Table 1
There were no differences between men and women in mortality or LN.
Caucasian patients were significantly less likely to develop LN (P < 0.0001) than other groups but there was no mortality difference between ethnic groups.
Patients diagnosed below age 28 were more likely to develop LN (P < 0.0001) but less likely to die (P = 0.0039) than those diagnosed above age 28.
Patients diagnosed between 2006 and 2011 were significantly less likely to die than those diagnosed between 1978 and1989 by Cox proportional hazards analysis of survival curves. (P = 0.019)
Conclusion
In this long-term survival analysis of 496 patients, non-Caucasian patients and those diagnosed below the age of 28 years were more likely to develop LN. The latter group were less likely to die than those diagnosed at older ages. Survival curves for groups of patients diagnosed in successive time periods suggested improved survival over time.
Disclosure
W. Luo: None. F. Farinha: None. D.A. Isenberg: None. A. Rahman: None.
Patients with SLE have increased mortality compared with age- and sex-matched controls. LN is a severe manifestation of SLE and an important cause of death. We carried out a retrospective survival ...analysis to investigate factors that could influence the risk of mortality and LN in a large multi-ethnic cohort of patients with SLE.
By careful review of medical records, we identified 496 patients with SLE for whom we had complete information regarding the period of observation and occurrence of death and nephritis. Patients were stratified into groups according to sex, ethnicity, age at start of follow-up and time period of diagnosis. Kaplan-Meier analysis was used to investigate differences between the groups.
Of the 496 patients in the study, 91 (18.3%) died, 165 (33.3%) developed LN and 33 (6.7%) developed end-stage renal failure. There was no difference between men and women in either mortality or development of LN. Caucasian patients were significantly less likely to develop LN than other ethnic groups (P < 0.0001) but not less likely to die. Patients diagnosed before the median age of 28 years were significantly more likely to develop LN (P < 0.0001) but significantly less likely to die (P = 0.0039) during the period of observation. There has been a significant improvement in survival in patients diagnosed between 1978 and 1989 and those diagnosed between 2006 and 2011 (P = 0.019).
In our cohort, non-Caucasian ethnicity and younger age at diagnosis are associated with the risk of developing LN. There is evidence of improvement in survival of patients with SLE over time.
To investigate predictors of sustained complete remission (CR) for 3 and 5 years, minimum.
Retrospective observational study from January 1978 to December 2019, including systemic lupus ...erythmatosus (SLE) patients who attended the Lupus Clinic in a tertiary hospital, for at least 3 years. We used the BILAG score and serological profile to classify patients into CR, serologically active clinically quiescent (SACQ) and serological remission (SR). Multivariable Cox regression analysis was performed to investigate predictors of CR and Kaplan-Meier curves were obtained.
We included 564 patients; 15% achieved CR, 7% SACQ and 15% SR. Some 63% attained no remission. In the CR group, 73% sustained the remission for 5 years or more. Patients who did not reach any kind of sustained remission died significantly earlier (P < 0.001). Cumulative survival figures at 5, 10, 20 and 30 years were 100, 100, 94 and 90%, respectively, for CR patients and 96, 93, 77 and 58%, respectively, for patients in the no-remission group. Significant predictors of CR were White ethnicity adjusted hazard ratio (HR) 2.16 (95% CI 1.30-3.59); P = 0.003; older age at diagnosis (>32 years) HR 1.92 (1.24-2.97); P = 0.003; absence of renal involvement HR 2.55 (1.39-4.67); P = 0.002; and of antiphospholipid syndrome (APS) HR 4.92 (1.55-15.59); P = 0.007.
Patients not achieving any kind of sustained remission have a higher risk of early mortality. White ethnicity, older age at diagnosis, absence of renal involvement and of APS were significantly associated with CR. Predictors for sustained CR do not change whether a 3-year or 5-year period is applied.
Abstract
Objectives
Chronic glucocorticoid use is complicated by osteoporosis and increases the risk of fragility fractures. EULAR guidelines on SLE management recommend reducing chronic ...glucocorticoid dosage to ≤7.5 mg/day to minimize this risk. We examined the relationship of glucocorticoid dose to fragility fracture risk in a cohort of SLE patients.
Methods
Retrospective analysis of SLE patients attending University College Hospital over 28 years was undertaken. Collected data included consecutive steroid dose, dual-energy X-ray absorptiometry scans and fragility fractures.
Results
We collected data on 250 patients with a median of 17 years’ follow-up. Fragility fractures were diagnosed in 28 (11.2%) patients and the mean ± s.d. age of first fracture was 51 ± 16 years. A total of 94% received glucocorticoids, the average dose being 6.20 mg/day. Patients with fragility fractures had a lower average daily dose (5.36 vs 6.23 mg/day) but a higher median cumulative dose (25.19 vs 20.96 g). These differences were not significant (P = 0.127 and 0.229, respectively). Some 93% of patients received vitamin D, and 85% received calcium. Cox regression analysis showed older age at SLE diagnosis, osteoporosis and secondary hyperparathyroidism were associated with fragility fractures. Glucocorticoid dose was not significantly associated with the occurrence of fragility fractures. Twenty-two patients with fractures were treated with bisphosphonates, two with denosumab and two with teriparatide.
Conclusions
We found no significant association between glucocorticoid treatment and fragility fractures in our group of patients; however, a prospective study including more patients not treated with CS would be necessary to confirm these results.
Objectives
Patients with SLE have an increased risk of developing cardiovascular disease (CVD). Multiple studies have shown that these patients have increased numbers of carotid plaques and greater ...intima-media thickness (IMT) than healthy controls. Measures such as total plaque area (TPA) and plaque echogenicity may be more sensitive and more relevant to cardiovascular risk than presence of plaque and IMT alone. Our objective was to produce the first report of TPA and echogenicity in a population of patients with SLE.
Methods
One hundred patients with SLE and no history of clinical CVD were recruited. Clinical, serological and treatment variables were recorded and serum was tested for antibodies to apolipoprotein A-1 and high-density lipoprotein. Both carotid and both femoral artery bifurcations of each patient were scanned to determine IMT, TPA and echogenicity of plaques. Univariable and multivariable statistical analyses were carried out to define factors associated with each of these outcomes.
Results
Thirty-six patients had carotid and/or femoral plaque. Increasing age was associated with presence of plaque and increased IMT. Triglyceride levels were associated with presence of plaque. Mean (s.d.) TPA was 60.8 (41.6) mm2. Patients taking prednisolone had higher TPA. Most plaques were echolucent, but increased echogenicity was associated with prednisolone therapy and persistent disease activity.
Conclusion
TPA and plaque echogenicity in patients with SLE are associated with different factors than those associated with presence of plaque and IMT. Longitudinal studies may show whether these outcome measures add value in the management of cardiovascular risk in SLE.
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