The value of repeat kidney biopsy in lupus nephritis. A systematic review / La utilidad de la biopsia renal repetida en nefritis lúpica. Una revisión sistemática

ABSTRACT A renal biopsy is the 'gold standard' for diagnosis and classification of lupus nephritis (LN). The role of repeat renal biopsy in lupus nephritis (LN) to guide treatment or predict prognosis has been controversial. A systematic literature review was conducted based on retrospective and prospective studies. The studies were identified using English electronic scientific databases, including MEDLINE PUBMED, published between January 1990 and August 2020. The eligibility criteria were studies including adult LN patients with at least one follow-up renal biopsy with appropriate longitudinal information. Case reports, studies with incomplete information or including duplicate patients were excluded. Based on the inclusion and exclusion criteria, a total of 73 publications were identified. This study included a total of 1167 repeat biopsies in LN patients from 15 studies. The primary indication for a repeat biopsy was relapse in 44-78% of the cases, and lack of response in 13-51%. Additionally, several repeat biopsies were done according to the protocol, after induction and maintenance therapy. In terms of histopathological class switches, there was a higher frequency of changes from nonproliferative to proliferative lesions. Only two studies provide a definition of histological response. There were often changes in the therapeutic approach after a repeat biopsy. Repeat kidney biopsies are helpful in patients with LN flare/relapse, and in patients with poor treatment response. Histological transformation was a common finding. The histologic and clinical responses are discordant. A repeat biopsy could be of prognostic value for therapeutic decision-making.

RESUMEN La biopsia renal es el «estándar de oro¼ para el diagnóstico y la clasificación de la nefritis lúpica (NL). El papel de la biopsia renal repetida en nefritis lúpica para orientar el tratamiento o predecir el pronóstico ha sido controversial. Se llevó a cabo una revisión sistemática de la literatura basada en estudios retrospectivos y prospectivos. Los estudios se identificaron a través de bases de datos científicas electrónicas en inglés, incluyendo Medline PubMed, de publicaciones entre enero de 1990 y agosto del 2020. Los criterios de elegibilidad fueron estudios que incluyeran a pacientes adultos con NL, quienes tuvieran al menos una biopsia renal de seguimiento, con información longitudinal apropiada. Se excluyeron informes de casos, estudios con información incompleta o con pacientes duplicados. Basándose en los criterios de inclusión y exclusión, se identificaron 73 publicaciones. En la presente revisión se analizaron un total de 1.167 biopsias repetidas en pacientes con NL en 15 estudios. Las principales indicaciones para la biopsia repetida fueron: recidiva en 44-78% de los casos, y falta de respuesta en 13-51%. Adicionalmente, varias biopsias repetidas se hicieron conforme al protocolo, luego de la terapia de inducción y de mantenimiento. Con respecto a los cambios de clase histopatológica, hubo una mayor frecuencia de cambios de lesiones no proliferativas a lesiones proliferativas. Solamente dos estudios ofrecen una definición de respuesta histológica. Con frecuencia hubo cambios en el abordaje terapéutico después de realizar la biopsia repetida. Las biopsias renales repetidas son útiles en pacientes con exacerbación/recidiva y en pacientes con falta de respuesta a tratamiento. La transformación histológica fue un hallazgo frecuente; las respuestas histológicas y clínicas son discordantes. Una biopsia repetida puede ser de valor pronóstico para la toma de decisiones terapéuticas.

Systemic lupus erythematosus and pregnancy: Strategies before, during and after pregnancy to improve outcomes / Lupus eritematoso sistémico y embarazo: estrategias antes, durante y después del embarazo para mejorar los desenlaces

ABSTRACT Systemic lupus erythematosus is a multisystemic autoimmune disorder that predominantly affects women in reproductive years. Pregnancy in women with SLE is still considered a high-risk condition although several strategies may improve maternal and fetal outcomes. Preconception counseling is fundamental and should include identification of risk factors for adverse pregnancy outcomes, explanation of potential maternal and obstetric complications and timely planning of pregnancy. Risk stratification must consider end-organ damage, comorbidities, disease activity and autoantibodies profile in order to implement an individual-risk pregnancy monitoring plan by a multidisciplinary team. Hydroxychloroquine and low dose aspirin have shown to lower the risk of disease flares and preeclampsia with a good safety profile, so its use during pregnancy in all SLE patients is recommended. Lupus nephritis and preeclampsia share clinical and laboratory features hindering differentiation between both entities. Novel angiogenic markers and fetal ultrasound findings could be helpful in the differential diagnosis, especially after 20 weeks of gestation. Antiphospholipid antibodies, particularly lupus anticoagulant, are closely associated with obstetric complications. Therapy with low dose aspirin and heparin, according to risk profile, may improve live birth rates. Anti-Ro/La antibodies confer risk for neonatal lupus, and therefore preventive therapy and special fetal surveillance should be instituted.

RESUMEN El lupus eritematoso sistémico es un trastorno autoinmune multisistémico que afecta primordialmente a mujeres en edad reproductiva. El embarazo en mujeres con LES aún se considera una condición de alto riesgo, a pesar de que diversas estrategias pueden mejorar los desenlaces maternos y fetales. La asesoría preconcepción es fundamental, y debe incluir la identificación de factores de riesgo de desenlaces adversos del embarazo, una explicación de las posibles complicaciones maternas y obstétricas, así como la planificación oportuna del embarazo. La estratificación de riesgos debe considerar el daño orgánico terminal, las comorbilidades, la actividad de la enfermedad y el perfil de autoanticuerpos, a fin de llevar a cabo un plan de monitoreo de los riesgos individuales del embarazo por parte de un equipo multidisciplinario. La hidroxicloroquina y la aspirina a bajas dosis han demostrado reducir el riesgo de exacerbaciones de la enfermedad y de preeclampsia, con un buen perfil de seguridad, por lo cual se recomienda su uso en todas las pacientes con LES durante el embarazo. La nefritis lúpica y la preeclampsia comparten características clínicas y de laboratorio, obstaculizando la diferenciación entre las 2 entidades. Nuevos marcadores angiogénicos y hallazgos ecográficos fetales pudieran ser de utilidad para el diagnóstico diferencial, especialmente después de las 20 semanas de gestación. Los anticuerpos antifosfolípidos, en particular el anticoagulante lúpico, tiene una estrecha asociación con las complicaciones obstétricas. El tratamiento con aspirina a bajas dosis y heparina, según el perfil de riesgos, puede mejorar las tasas de nacimientos vivos. Los anticuerpos anti-Ro/La representan un riesgo de lupus neonatal, por lo cual debe instituirse tratamiento preventivo y vigilancia fetal especial.

Classification of ANCA-associated vasculitis: differences based on ANCA specificity and clinicopathologic phenotype.

The classification of vasculitis according to a schema with universal acceptance is challenging, given the heterogeneous and protean nature of these diseases. Formal nomenclature and classification criteria for anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) have suffered several changes since their first description; none provides comprehensive diagnostic and classification criteria. Different factors account for the difficulties in the classification of vasculitis, including the incomplete understanding of the pathogenesis, the multisystemic nature of the disease, the non-specific patterns of vascular involvement, the overlap between entities, and the presence of various classification systems. The present article reviews the classification of AAV considering different points of view, including clinical, serologic, pathogenetic, organ predilection, therapeutic, and prognostic factors, and provides perspectives on future challenges in the understanding of AAV. There is an unmet need for a unifying view of the disease spectrum that considers the constantly evolving paradigms.

Asymptomatic Coronary Artery Calcifications in Men with Systemic Lupus Erythematosus.

OBJECTIVE: To determine whether the prevalence and extent of asymptomatic coronary artery atherosclerosis are increased in men with systemic lupus erythematosus (SLE) compared with age- and sex-matched controls, and to define the associated risk factors. METHODS: Ninety-five patients with SLE (mean ± SD age, 34.7 ± 10.1 yrs) and 100 control subjects (age 34.8 ± 9.7 yrs) with no history of coronary artery disease were screened for coronary artery calcification using multidetector computed tomography. The extent of calcification was measured using the Agatston score. The frequency of risk factors for calcification was compared between patients and controls, and the relationship between clinical and immunological characteristics and the presence of coronary artery calcification was investigated. RESULTS: Coronary artery calcification was more frequent in patients than controls [18% vs 7%, respectively (OR 2.89, 95% CI 1.07-8.65)]. These factors were independently associated with the presence of calcifications: age (OR 1.12, 95% CI 1.04-1.20), SLE diagnosis (OR 3.38, 95% CI 1.07-10.64), diabetes mellitus (OR 6.88, 95% CI 1.50-31.62), Framingham risk score (OR 1.12, 95% CI 1.00-1.23), and glomerular filtration rate (OR 0.98, 95% CI 0.96-1.00). Among patients with SLE, coronary artery calcifications were observed starting at age 32 years, within 2.3 years of diagnosis. Increasing age (OR 1.18, 95% CI 1.06-1.31), Systemic Lupus International Collaborating Clinics score (OR 2.85, 95% CI 1.21-6.73), and cumulative dose of prednisone (OR 1.04, 95% CI 1.01-1.08) were independent risk factors. CONCLUSION: Men with SLE are at an increased risk of coronary artery calcifications than age- and sex-matched controls. Among patients with SLE, the increased risk is associated to older age, increasing chronic damage, and cumulative dose of corticosteroids.