Interrupción del embarazo en nefritis lúpica: un análisis bioético desde el método integral / Termination of pregnancy in lupus nephritis: A bioethical analysis with the integrative method

Antecedentes y objetivo: La interrupción del embarazo en pacientes con enfermedades reumatológicas es controvertida y pocas veces se realiza un análisis bioético. En este estudio analizamos el caso de una paciente embarazada con nefritis lúpica sin respuesta a tratamiento a quien se le planteó la interrupción del embarazo. Métodos: Se aplicó el modelo integral, incluyendo distintos sistemas normativos para el análisis del dilema. Resultados: Desde el utilitarismo es justificable la interrupción del embarazo, buscando el mayor beneficio para la mayoría de las partes. La deontología justifica tanto continuar como interrumpir el embarazo, centrando la importancia en la acción misma y en la autonomía. Para la ética de la virtud, la importancia de las decisiones recae en la persona que realiza la acción buscando el florecimiento: la interrupción del embarazo sería justificable. Discusión y conclusiones: La interrupción del embarazo sería una solución adecuada según el modelo integral. El análisis bioético de casos paradigmáticos es fundamental para asegurar el mejor actuar posible en casos similares en reumatología.(AU)

Background and objective: Termination of pregnancy in patients with rheumatic diseases is controversial and a bioethical analysis is rarely performed. In this study we analysed the case of a pregnant patient with lupus nephritis unresponsive to treatment, for whom termination of pregnancy is considered. Methods: The integrative model was applied combining different normative ethical theories. Results: From a utilitarian perspective, termination of pregnancy is justifiable, seeking the greatest benefit for the greatest number of stakeholders. Deontology justifies both terminating and continuing the pregnancy, focusing on the action itself and on autonomy. In virtue ethics the importance of decisions rests with the person who performs the action seeking flourishing; termination of pregnancy would be justifiable. Discussion and conclusions: Interruption of pregnancy is a justifiable solution following the integrative model. Bioethical analysis of paradigmatic cases is essential to ensure the best possible action and as a precedent for future similar situations in rheumatology.(AU)

Termination of pregnancy in lupus nephritis: A bioethical analysis with the integrative method.

BACKGROUND AND OBJECTIVE: Termination of pregnancy in patients with rheumatic diseases is controversial and a bioethical analysis is rarely performed. In this study we analysed the case of a pregnant patient with lupus nephritis unresponsive to treatment, for whom termination of pregnancy is considered. METHODS: The integrative model was applied combining different normative ethical theories. RESULTS: From a utilitarian perspective, termination of pregnancy is justifiable, seeking the greatest benefit for the greatest number of stakeholders. Deontology justifies both terminating and continuing the pregnancy, focusing on the action itself and on autonomy. In virtue ethics the importance of decisions rests with the person who performs the action seeking flourishing; termination of pregnancy would be justifiable. DISCUSSION AND CONCLUSIONS: Interruption of pregnancy is a justifiable solution following the integrative model. Bioethical analysis of paradigmatic cases is essential to ensure the best possible action and as a precedent for future similar situations in rheumatology.

Enfermedad relacionada con IgG4 en paciente con antecedente de linfoma MALT gástrico: un gran reto diagnóstico y terapéutico / IgG4 related disease in a patient with a history of gastric MALT lymphoma: a great diagnostic and treatment challenge

We describe a case of a 57-year-old woman with a history of gastric MALT lymphoma and interstitial nephritis attributed to chemotherapy. In the study of chronic diarrhea, we found an atrophic pancreas, with elastase deficiency. Autoimmune pancreatitis is suspected. A significant elevation of serum IgG4 was observed. With these data, a review of the renal biopsy performed 10 months earlier was carried out. Immunohistochemistry reveals a significant number of IgG4-producing plasma cells. In the lungs, the patient has nodules, adenopaties and infiltrates. The diagnosis we arrived at is IgG4-related disease. (AU)

Se presenta el caso de una mujer de 57 años con antecedentes de linfoma MALT gástrico y nefritis intersticial atribuida a la quimioterapia. En el estudio de diarrea crónica encontramos un páncreas atrófico, con deficiencia de elastasa. Se sospecha pancreatitis autoinmune. Se comprueba una elevación importante de IgG4 sérica. Con estos datos, se procede a la revisión de la biopsia renal realizada 10 meses antes. La inmunohistoquímica revela un número significativo de células plasmáticas productoras de IgG4. En los pulmones, la paciente tiene nódulos, adenopatías e infiltrados. El diagnóstico al que llegamos es Enfermedad relacionada con IgG4. (AU)

Tratamiento del lupus eritematoso sistémico: nuevas opciones terapéuticas / Treatment of systemic lupus erythematosus: New therapeutic options

El lupus eritematoso sistémico (LES) es una enfermedad inflamatoria autoinmune sistémica de causa desconocida, con heterogeneidad en su presentación clínica, así como una variabilidad en su curso clínico y pronóstico. El objetivo actual del tratamiento es conseguir la remisión de la enfermedad o al menos un estado de baja actividad, y por consiguiente mejorar la calidad de vida del paciente. La terapia biológica en el lupus, a diferencia de otras entidades, si bien no ha conseguido instaurarse plenamente, ha irrumpido en los últimos años con novedades terapéuticas importantes. En esta revisión se pretende actualizar las herramientas terapéuticas del tratamiento del LES enfocado a las nuevas moléculas que han conseguido superar los objetivos de sus ensayos clínicos (AU)

Systemic lupus erythematosus (SLE) is a systemic autoimmune inflammatory disease of unknown cause, with heterogeneity in its clinical presentation, as well as variability in its clinical course and prognosis. The current goal of treatment is to achieve disease remission or a state of low activity, and thereby improve the patient's quality of life. Biological therapy in lupus, unlike other entities, although it has not been fully established, in recent years it has burst onto the scene with important therapeutic novelties. This review aims to update the therapeutic tools for the treatment of SLE focusing on the new molecules that have achieved the objectives of their clinical trials (AU)

Anti-C1q como Marcador de Nefritis Lúpica / Anti-C1q as Lupus Nephritis Marker

Introducción: Los autoanticuerpos anti-C1q han sido propuestos como un marcador útil en el lupus eritematoso sistémico por su asociación con la nefritis lúpica. Objetivo: Determinar la prevalencia de anti-C1q en pacientes con lupus eritematoso sistémico y otras enfermedades reumáticas para la evaluar la asociación con la nefropatía lúpica. Métodos: Se incluyeron 179 pacientes con lupus eritematoso sistémico y 82 con otras enfermedades reumáticas. La nefritis lúpica fue diagnosticada en 70 (39 por ciento) de los pacientes con lupus eritematoso sistémico. Los anticuerpos anti-C1q IgG se determinaron por ELISA. Las asociaciones se evaluaron por análisis de regresión logística. Resultados: La prevalencia de anti-C1q fue de 37 poe ciento (66/179) en los pacientes con lupus eritematoso sistémico y de 9 por ciento (7/82) en controles (OR = 6,3; IC 95 por ciento 2,8-14,1; p < 0,001). El anti-C1q fue asociado con proteinuria (OR = 2,6; IC 95 por ciento 1,2-6,0; p < 0,022); eritrosedimentación elevada (OR = 3,2; IC 95 por ciento 1,5-6,7; p < 0,003) y anti-DNAdc (OR = 3,9; IC 95 por ciento 1,7-9,1; p < 0,002). En el modelo de regresión logística ajustado para demografía y anti-DNAdc, aunque la OR del anti-C1q para la nefritis fue 2 veces más alta que en ausencia del anti-C1q, solo se aproximó a la significación estadística. La positividad simultánea de anti-C1q y anti-DNAdc estuvo asociada a la nefritis lúpica (OR = 4,3; IC 95 por ciento 1,9-9,5; p < 0,001). Conclusiones: El anti-C1q se presentó con mayor frecuencia en pacientes con lupus eritematoso sistémico que en los controles. El anti-C1q combinado con anti-DNAdc resultó fuertemente asociado a la nefritis lúpica(AU)

Introducción: Anti-C1q autoantibodies have been proposed as useful marker in systemic lupus erythematosus due to their association with lupus nephritis. Objective: To determine the prevalence of anti-C1q in patients with systemic lupus erythematosus and other rheumatic diseases to evaluate the association with lupus nephropathy. Methods: One hundred seventy-nine patients with systemic lupus erythematosus and 82 with other rheumatic diseases were included. Lupus nephritis was diagnosed in 70 (39percent) of patients with systemic lupus erythematosus. Anti-C1q IgG antibodies were determined by ELISA. Associations were evaluated by logistic regression analysis. Results: The prevalence of anti-C1q was 37percent (66/179) in patients with systemic lupus erythematosus and 9percent (7/82) in controls (OR = 6.3; 95percent CI 2.8-14). .1; p < 0.001). Anti-C1q was associated with proteinuria (OR = 2.6; 95percent CI 1.2-6.0; p < 0.022); elevated erythrocyte sedimentation rate (OR = 3.2; 95percent CI 1.5-6.7; p < 0.003) and anti-dsDNA (OR = 3.9; 95percent CI 1.7-9.1; p < 0.002). In the logistic regression model adjusted for demographics and anti-dsDNA, although the OR of anti-C1q for nephritis was 2-fold higher than in the absence of anti-C1q, it only approached statistical significance. Simultaneous positivity of anti-C1q and anti-dsDNA was associated with lupus nephritis (OR = 4.3; 95percent CI 1.9-9.5; p < 0.001). Conclusions: Anti-C1q occurred more frequently in patients with systemic lupus erythematosus than in controls. Anti-C1q combined with anti-dsDNA was strongly associated with lupus nephritis(AU)

Treatment of systemic lupus erythematosus: new therapeutic options.

Systemic lupus erythematosus (SLE) is a systemic autoimmune inflammatory disease of unknown cause, with heterogeneity in its clinical presentation, as well as variability in its clinical course and prognosis. The current goal of treatment is to achieve disease remission or a state of low activity, and thereby improve the patient's quality of life. Biological therapy in lupus, unlike other entities, although it has not been fully established, in recent years it has burst onto the scene with important therapeutic novelties. This review aims to update the therapeutic tools for the treatment of SLE focusing on the new molecules that have achieved the objectives of their clinical trials.

Adverse renal effects of check-point inhibitors (ICI) in cancer patients: Recommendations of the Onco-nephrology Working Group of the Spanish Society of Nephrology.

The most widely used approach in the immunotherapy treatment of cancer is the administration of monoclonal antibodies directed against regulatory molecules of immune control that inhibit the activation of T cells, the so-called check point inhibitors (ICI). ICI nephrotoxicity epidemiology and pathology; its diagnosis with or without kidney biopsy; the type and duration of treatment; the possibility of rechallenging after kidney damage; and its indication in patients with cancer and renal transplantation are certainly controversial. In the absence of definitive studies, this document is intended to specify some recommendations agreed by the group of Onconephrology experts of the Spanish Society of Nephrology in those areas related to ICI nephrotoxicity, in order to help decision-making in daily clinical practice in Onconephrology consultations.

Evolución del diagnóstico y tratamiento de la nefritis lúpica en España / Evolution of diagnosis and treatment for lupus nephritis in Spain

La nefritis lúpica (NL) es una manifestación grave del lupus eritematoso sistémico que puede llevar a una enfermedad renal terminal. La mayor parte de los datos clínicos y pronósticos que manejamos, y sobre los que tomamos decisiones terapéuticas, proceden de cohortes internacionales con importantes diferencias étnicas y relativas al pronóstico renal. Para conocer los datos clínicos y pronósticos de los pacientes con NL en España se realizó una búsqueda bibliográfica de artículos relacionados con la NL publicados por autores españoles en revistas nacionales e internacionales entre 2005 y 2022. Las referencias seleccionadas mostraron que la biopsia no solo es clave en el diagnóstico de la NL, sino que su repetición puede ser útil en el seguimiento. En cuanto al tratamiento el abordaje estándar de la NL consiste en una fase de inducción y una fase de mantenimiento. Sin embargo, la aparición de nuevos fármacos ha motivado que se postule un nuevo paradigma de tratamiento en una sola fase continuada y personalizada (AU)

Lupus nephritis (LN) is a serious manifestation of systemic lupus erythematosus that can lead to end-stage renal disease. Many clinical and prognostic data on which our therapeutic decisions are based come from international cohorts, which have important ethnic and prognostic differences. To identify clinical and prognostic data from patients with LN in Spain, we undertook a bibliographic search of LN-related papers by Spanish authors and published in national and international journals between 2005 and 2022. According to the selected references, renal biopsy is not only essential for LN diagnosis but its repetition can be useful for the follow-up. Regarding LN treatment, standard strategy consists of an induction phase and a maintenance phase. However, as new drugs have been released, a new paradigm of treatment in a single, continuing and personalized phase has been proposed (AU)

Development and validation of a prognostic nomogram for the renal relapse of lupus nephritis / Desarrollo y validación de un nomograma pronóstico para la recaída renal de la nefritis lúpica

Objectives This study aims to assess the risk of relapse after complete remission (CR) and partial remission (PR), and to develop a prognostic nomogram predicting the probability in lupus nephritis (LN) patients. Methods Data from patients with LN who had been in remission were collected as a training cohort. The prognostic factors were analyzed using the univariable and multivariable Cox model for the training group. A nomogram was then developed using significant predictors in multivariable analysis. Both discrimination and calibration were assessed by bootstrapping with 100 resamples. Results A total of 247 participants were enrolled, including 108 in the relapse group and 139 in the no relapse group. In multivariate Cox analysis, Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), erythrocyte sedimentation rate (ESR), complement 1q (C1q), and antiphospholipid (aPL), anti-Sm antibody were found to be significant for predicting relapse rates. The prognostic nomogram including the aforementioned factors effectively predicted 1- and 3-year probability of flare-free. Moreover, a favorable consistency between the predicted and actual survival probabilities was demonstrated using calibration curves. Conclusions High SLEDAI, ESR, and positive aPL, anti-Sm antibody are potential risk factors for LN flare, while high C1q can reduce its recurrence. The visualized model we established can help predict the relapse risk of LN and aid clinical decision-making for individual patients (AU)

Objetivos Este estudio pretende evaluar el riesgo de recaída tras la remisión completa y la remisión parcial, y desarrollar un nomograma pronóstico que prediga la probabilidad en pacientes con nefritis lúpica (NL). Métodos Se recogieron datos de pacientes con NL que habían estado en remisión como cohorte de entrenamiento. Se analizaron los factores pronósticos utilizando el modelo COX univariable y multivariable para el grupo de entrenamiento. A continuación se desarrolló un nomograma utilizando los predictores significativos en el análisis multivariable. Tanto la discriminación como la calibración se evaluaron mediante bootstrapping con 100 remuestreos. Resultados Se inscribió a un total de 247 participantes, incluidos 108 en el grupo de recaída y 139 en el grupo sin recaída. En el análisis multivariante de Cox, el índice de actividad de la enfermedad lúpica eritematosa sistémica (SLEDAI), la velocidad de sedimentación globular (VSG), el complemento 1q (C1q) y los anticuerpos antifosfolípidos (aPL) y anti-Sm resultaron significativos para predecir las tasas de recaída. El nomograma pronóstico que incluía los factores mencionados predijo eficazmente la probabilidad a 1 y a 3 años de estar libre de reagudizaciones. Además, se demostró una coherencia favorable entre las probabilidades de supervivencia previstas y las reales mediante curvas de calibración. Conclusiones SLEDAI alto, VSG y aPL positivo, anticuerpos anti-Sm son factores de riesgo potenciales de reagudización de la NL, mientras que C1q alto puede reducir su recurrencia. El modelo visualizado que establecimos puede ayudar a predecir el riesgo de recidiva de la NL y ayudar a la toma de decisiones clínicas para pacientes individuales (AU)

Efectos renales adversos por inhibidores del check-point (ICP) en pacientes con cáncer. Recomendaciones del grupo de Onconefrología de la Sociedad Española de Nefrología (SEN) / Adverse renal effects of check-point inhibitors (ICI) in cancer patients: Recommendations of the Onco-nephrology Working Group of the Spanish Society of Nephrology

El enfoque más utilizado en el tratamiento inmunoterápico del cáncer es la administración de anticuerpos monoclonales dirigidos contra moléculas reguladoras del control inmunitario que inhiben la activación de las células T, los llamados inhibidores del check-point (ICP). La epidemiología y patología de la nefrotoxicidad por los ICP, su diagnóstico con o sin biopsia renal, el tipo y la duración del tratamiento, la posibilidad de retratar después del daño renal, y su indicación en pacientes con cáncer y trasplante renal son ciertamente controvertidas. En ausencia de estudios definitivos, este documento está destinado a concretar unas recomendaciones consensuadas por el grupo de expertos de Onconefrología de la SEN en aquellas áreas relacionadas con la nefrotoxicidad por los ICP, con la finalidad de ayudar en la toma de decisiones en la práctica clínica diaria de las consultas de Onconefrología. (AU)

The most widely used approach in the immunotherapy treatment of cancer is the administration of monoclonal antibodies directed against regulatory molecules of immune control that inhibit the activation of T cells, the so-called check point inhibitors (ICI). ICI nephrotoxicity epidemiology and pathology; its diagnosis with or without kidney biopsy; the type and duration of treatment; the possibility of rechallenging after kidney damage; and its indication in patients with cancer and renal transplantation are certainly controversial. In the absence of definitive studies, this document is intended to specify some recommendations agreed by the group of onconephrology experts of the Spanish Society of Nephrology in those areas related to ICI nephrotoxicity, in order to help decision-making in daily clinical practice in onconephrology consultations. (AU)

Development and validation of a prognostic nomogram for the renal relapse of lupus nephritis.

OBJECTIVES: This study aims to assess the risk of relapse after complete remission (CR) and partial remission (PR), and to develop a prognostic nomogram predicting the probability in lupus nephritis (LN) patients. METHODS: Data from patients with LN who had been in remission were collected as a training cohort. The prognostic factors were analyzed using the univariable and multivariable Cox model for the training group. A nomogram was then developed using significant predictors in multivariable analysis. Both discrimination and calibration were assessed by bootstrapping with 100 resamples. RESULTS: A total of 247 participants were enrolled, including 108 in the relapse group and 139 in the no relapse group. In multivariate Cox analysis, Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), erythrocyte sedimentation rate (ESR), complement 1q (C1q), and antiphospholipid (aPL), anti-Sm antibody were found to be significant for predicting relapse rates. The prognostic nomogram including the aforementioned factors effectively predicted 1- and 3-year probability of flare-free. Moreover, a favorable consistency between the predicted and actual survival probabilities was demonstrated using calibration curves. CONCLUSIONS: High SLEDAI, ESR, and positive aPL, anti-Sm antibody are potential risk factors for LN flare, while high C1q can reduce its recurrence. The visualized model we established can help predict the relapse risk of LN and aid clinical decision-making for individual patients.

Acute interstitial nephritis due to dolutegravir: The first case reported / Nefritis intersticial aguda por dolutegravir: primer caso notificado

Kidney disease is frequent in HIV-patients. We present a case of a 44-year-old woman, with known uncontrolled HIV infection and chronic kidney disease due to HIV-associated nephropathy. After starting dolutegravir, the patient developed eosinophilia and worsening kidney function. A kidney biopsy confirmed the diagnosis of acute interstitial nephritis. Given the time relation with dolutegravir introduction, it was deemed the culprit medication. Dolutegravir was stopped, and corticosteroids were initiated, with moderate improvement in renal function. To our knowledge, this is the first reported case of acute interstitial nephritis to dolutegravir, which should raise awareness of previously undocumented renal effects of antiretroviral therapy. (AU)

La enfermedad renal es frecuente en pacientes con VIH. Presentamos el caso de una mujer de 44 años, con infección por VIH no controlada conocida y enfermedad renal crónica por nefropatía asociada al VIH. Después de comenzar con dolutegravir, el paciente desarrolló eosinofilia y empeoramiento de la función renal. Una biopsia de riñón confirmó el diagnóstico de nefritis intersticial aguda. Dada la relación temporal con la introducción de dolutegravir, se consideró al medicamento el culpable. Se interrumpió el tratamiento con dolutegravir y se iniciaron corticosteroides, con una mejoría moderada de la función renal. Hasta donde sabemos, este es el primer caso notificado de nefritis intersticial aguda por dolutegravir, lo que debería crear conciencia sobre los efectos renales previamente indocumentados de la terapia antirretroviral. (AU)

Enfermedad renal crónica asociada a la exposición a metales pesados y productos agroquímicos en Latinoamérica / Chronic kidney disease associated with heavy metal exposure and agrochemicals in Latin America

Introducción: La Organización Panamericana de la Salud reco-noce a la Enfermedad Renal Crónica de Causas No Tradiciona-les como una forma grave de insuficiencia renal de etiología incierta, la cual ha alcanzado proporciones epidémicas en las comunidades y saturación de los sistemas de salud. La enfer-medad se ha relacionado con infecciones, deshidratación, hi-peruricemia, exposición a agroquímicos o metales pesados y susceptibilidad genética. Objetivo: Realizar una revisión integradora sobre la relación entre la enfermedad renal de causa no tradicional con factores sociodemográficos, exposición agrícola y metales pesados en población latinoamericana. Metodología: Se realizó una revisión sistemática integradora bajo la guía PRISMA en las bases de datos Medigraphic, Bio-Med Central, Wiley Online Library, Web of Science, Science-Direct, PubMed y Scopus. Con las palabras claves: enfermedad renal, nefritis, metales pesados, agroquímicos, factor de riesgo. Se incluyeron 39 estudios después de evaluar la calidad meto-dológica de los mismos. Resultados: El 35,89% de los estudios incluídos tuvo una rigu-rosidad científica alta. Referente a las causas, se encontró que la exposición a agroquímicos fue la causa de mayor frecuencia en el padecimiento de esta enfermedad. Conclusión: Los metales pesados y agroquímicos han demos-trado influir en el desarrollo de la Enfermedad Renal Crónica de causas no tradicionales, no obstante, la mayoría de los re-sultados de los artículos incluidos no tienen resultados genera-lizables ni estadísticamente significativos. Los factores socio-demográficos han sido poco estudiados y se requiere de mayor investigación con rigurosidad científica sobre esta variable.(AU)

ntroduction: The Pan American Health Organization recognizes Chronic Kidney Disease of Nontraditional Causes as a serious form of kidney failure of uncertain etiology, which has reached devastating epidemic proportions in communities and saturation of health systems. Hypotheses related to infections, dehydration, global warming, hyperuricemia, exposure to agrochemicals or heavy metals and genetic susceptibility are mentioned, however, these hypotheses have not been conclusive. Objective: To carry out a systematic review on the relationship between non-traditional kidney disease and sociodemographic factors, agricultural exposure or heavy metals in the Latin American population. Methodology: An integrative systematic review was carried out under the PRISMA guide in the Medigraphic, BioMed Central, Wiley Online Library, Web of Science, ScienceDirect, PubMed and Scopus databases. With the keywords: kidney disease, nephritis, heavy metals, agrochemicals, risk factor. Of which 39 studies were included after evaluating their methodological quality. Results: it was found that 35.89% of the included studies had a high scientific rigor. Regarding the causes, it was found that exposure to agrochemicals was the most frequent cause of this disease. Conclusion: Heavy metals and agrochemicals have been shown to influence the development of Chronic Kidney Disease of Nontraditional Causes, however, most of the results are not generals and doesn ́t demonstrate a statistically significant relationship. Sociodemographic factors have been little studied and more rigorous scientific research on this variable is required.(AU)

Relative CTLA-4, PTPN-22, and interleukin 37 mRNA expressions in patients with lupus nephritis.

OBJECTIVES: Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by T-cell immune-dysregulation and loss of tolerance to self-antigens. CTLA-4 and PTPN-22 are involved in the inhibition of T-lymphocytes activation. IL-37 is an anti-inflammatory cytokine that suppresses innate immunity. The relative expression of CTLA-4, IL-37 and PTPN-22 were evaluated as negative regulators of immune response in SLE patients, lupus nephritis (LN) and disease activity. METHODS: Real-Time PCR was performed to determine relative CTLA-4, IL-37, and PTPN-22 mRNA expressions in fifty-eight SLE patients, who were divided into two groups: 29 SLE patients without nephritis and 29 patients with LN, versus fifty controls. RESULTS: There was a significantly high-expression of CTLA-4 and IL-37 genes in SLE patients compared to controls (p=0.005; 0.018 respectively). There was no difference in relative PTPN-22 mRNA expression between the SLE patients and controls. Relative CTLA-4 mRNA expression decreased in LN patients (p=0.044), however, relative IL-37 mRNA over-expressed in LN patients (p=0.001) compared to those without LN. There was a significant over-expression of relative IL-37 andPTPN-22 mRNA in active SLE patients. But, there was a non-significant difference in CTLA-4 expression with disease activity. Regression analysis revealed patients with relative IL-37 mRNA over-expression had two times more to develop lupus nephritis (OR=1.906, 95% CI=1.218-2.983, p=0.005). CONCLUSIONS: Relative IL-37mRNA expression was elevated in SLE patients and associated with renal involvement and disease activity. It could be considered as a new promising predicting tool for LN. Relative PTPN-22 mRNA expression was correlated with disease activity only in SLE patients.

Relative CTLA-4, PTPN-22, and interleukin 37 mRNA expressions in patients with lupus nephritis / Expresiones relativas de ARNm de CTLA-4, PTPN-22 e interleucina 37 en pacientes con nefritis lúpica

Objectives: Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by T-cell immune-dysregulation and loss of tolerance to self-antigens. CTLA-4 and PTPN-22 are involved in the inhibition of T-lymphocytes activation. IL-37 is an anti-inflammatory cytokine that suppresses innate immunity. The relative expression of CTLA-4, IL-37 and PTPN-22 were evaluated as negative regulators of immune response in SLE patients, lupus nephritis (LN) and disease activity. Methods: Real-Time PCR was performed to determine relative CTLA-4, IL-37, and PTPN-22 mRNA expressions in fifty-eight SLE patients, who were divided into two groups: 29 SLE patients without nephritis and 29 patients with LN, versus fifty controls. Results: There was a significantly high-expression of CTLA-4 and IL-37 genes in SLE patients compared to controls (p=0.005; 0.018 respectively). There was no difference in relative PTPN-22 mRNA expression between the SLE patients and controls. Relative CTLA-4 mRNA expression decreased in LN patients (p=0.044), however, relative IL-37 mRNA over-expressed in LN patients (p=0.001) compared to those without LN. There was a significant over-expression of relative IL-37 andPTPN-22 mRNA in active SLE patients. But, there was a non-significant difference in CTLA-4 expression with disease activity. Regression analysis revealed patients with relative IL-37 mRNA over-expression had two times more to develop lupus nephritis (OR=1.906, 95% CI=1.218–2.983, p=0.005). Conclusions: Relative IL-37mRNA expression was elevated in SLE patients and associated with renal involvement and disease activity. It could be considered as a new promising predicting tool for LN. Relative PTPN-22 mRNA expression was correlated with disease activity only in SLE patients.(AU)

Objetivos: El lupus eritematoso sistémico (LES) es una enfermedad autoinmune caracterizada por la desregulación inmune de las células T, y la pérdida de tolerancia a los antígenos propios. CTLA-4 y PTPN-22 están involucrados en la inhibición de la activación de los linfocitos T. IL-37 es una citocina antiinflamatoria que suprime la inmunidad innata. La expresión relativa de CTLA-4, IL-37 y PTPN-22 se evaluó como reguladores negativos de la respuesta inmune en pacientes con LES, nefritis lúpica (NL) y actividad de la enfermedad. Métodos: Se realizó PCR en tiempo real para determinar las expresiones relativas de ARNm de CTLA-4, IL-37 y PTPN-22 en 58 pacientes con LES, que se dividieron en 2 grupos: 29 pacientes con LES sin nefritis y 29 pacientes con NL frente a 50 controles. Resultados: Hubo una expresión significativamente alta de los genes CTLA-4 e IL-37 en pacientes con LES en comparación con los controles (p=0,005; 0,018, respectivamente). No hubo diferencia en la expresión relativa del ARNm de PTPN-22 entre los pacientes con LES y los controles. La expresión relativa de ARNm de CTLA-4 disminuyó en pacientes con LN (p=0,044); sin embargo, la expresión relativa de ARNm de IL-37 se sobreexpresó en pacientes con LN (p=0,001) en comparación con aquellos sin LN. Hubo una sobreexpresión significativa de ARNm relativo de IL-37 y PTPN-22 en pacientes con LES activo. Pero hubo una diferencia no significativa en la expresión de CTLA-4 con la actividad de la enfermedad. El análisis de regresión reveló que los pacientes con sobreexpresión relativa de ARNm de IL-37 tenían el doble de riesgo de desarrollar nefritis lúpica (OR: 1,906; IC 95%: 1,218-2,983; p=0,005). Conclusiones: La expresión relativa de ARNm de IL-37 fue elevada en pacientes con LES y se asoció con compromiso renal y actividad de la enfermedad. Podría considerarse como una nueva herramienta de predicción prometedora para LN. La expresión relativa del ARNm de PTPN-22 se correlacionó con la actividad de la...(AU)

Neurorretinitis bilateral y nefritis lúpica membranosa: dos manifestaciones infrecuentes en el lupus juvenil / Bilateral neuroretinitis and membranous lupus nephritis: 2 infrequent manifestations in juvenile lupus

Joven de 15 años, previamente sana, se presentó con dolor abdominal, vómitos, diarrea, eritema malar, edema palpebral y en miembros inferiores, artralgias, rigidez matinal y visión borrosa bilateral. Estudios de laboratorio y por imágenes junto con la clínica permitieron realizar el diagnóstico de síndrome nefrótico secundario a lupus eritematoso sistémico. Al examen oftalmológico se constató 8/10 de visión en ambos ojos y edema de papila bilateral con estrella macular parcial, hallazgos compatibles con una neurorretinitis bilateral. La biopsia renal estableció el diagnóstico de nefritis lúpica membranosa. Se inició tratamiento inmunosupresor, con mejoría clínica gradual. Si bien el lupus eritematoso sistémico con nefritis lúpica membranosa y neurorretinitis es una asociación muy infrecuente, frente a un paciente con neurorretinitis bilateral debemos considerar el lupus eritematoso sistémico dentro de los diagnósticos diferenciales (AU)

Fifteen-year-old female patient, previously healthy, referred to our center for presenting abdominal pain, vomiting, diarrhea, malar erythema, palpebral and lower limb edema, arthralgia, morning stiffness and bilateral blurred vision. Laboratory and imaging studies together with the clinic allowed the diagnosis of nephrotic syndrome secondary to systemic lupus erythematosus. Ophthalmology examination revealed a visual acuity of 8/10 in both eyes and bilateral disc edema with partial macular star, findings compatible with bilateral neuroretinitis. Renal biopsy established the diagnosis of membranous lupus nephritis. Immunosuppressive treatment was started, obtaining gradual clinical improvement. Although systemic lupus erythematosus with membranous lupus nephritis and neuroretinitis is a very infrequent association, when faced with a patient with bilateral neuroretinitis, we must consider systemic lupus erythematosus within the differential diagnoses (AU)

Bilateral neuroretinitis and membranous lupus nephritis: 2 infrequent manifestations in juvenile lupus.

Fifteen-year-old female patient, previously healthy, referred to our center for presenting abdominal pain, vomiting, diarrhea, malar erythema, palpebral and lower limb edema, arthralgia, morning stiffness and bilateral blurred vision. Laboratory and imaging studies together with the clinic allowed the diagnosis of nephrotic syndrome secondary to systemic lupus erythematosus. Ophthalmology examination revealed a visual acuity of 8/10 in both eyes and bilateral disc edema with partial macular star, findings compatible with bilateral neuroretinitis. Renal biopsy established the diagnosis of membranous lupus nephritis. Immunosuppressive treatment was started, obtaining gradual clinical improvement. Although systemic lupus erythematosus with membranous lupus nephritis and neuroretinitis is a very infrequent association, when faced with a patient with bilateral neuroretinitis, we must consider systemic lupus erythematosus within the differential diagnoses.

Documento de consenso del Grupo de Estudio de Enfermedades Glomerulares de la Sociedad Española de Nefrología (GLOSEN) para el diagnóstico y tratamiento de la nefritis lúpica / Consensus document of the Spanish Group for the Study of the Glomerular Diseases (GLOSEN) for the diagnosis and treatment of lupus nephritis

Un número importante de pacientes con lupus eritematoso sistémico (entre 20 a 60%, según diferentes series) desarrolla nefritis lúpica en el curso de su evolución, lo que influye directamente en su calidad de vida y pronóstico vital. En años recientes, el mayor conocimiento sobre la patogénesis del lupus sistémico y de la nefritis lúpica ha permitido avances relevantes en el abordaje diagnóstico y en el tratamiento de estos pacientes, lográndose desarrollar fármacos dirigidos específicamente a bloquear vías patogénicas claves de la enfermedad. Alentadoramente estos agentes inmunomoduladores han demostrado en ensayos clínicos aleatorizados, y bien ponderados, buena eficacia clínica a mediano plazo, definida como remisión de proteinuria y preservación de la función renal, con un aceptable perfil de seguridad y buena tolerabilidad del paciente. Todo esto ha permitido reducir el uso de corticoides y de otras terapias potencialmente más tóxicas, así como incrementar el uso de terapias combinadas. El presento documento de consenso realizado por el Grupo de Trabajo de Enfermedades Glomerulares de la Sociedad Española de Nefrología (GLOSEN) recoge de manera práctica y resumida, pero rigurosa, la mejor evidencia actual disponible acerca del diagnóstico, tratamiento y seguimiento del paciente con nefritis lúpica, incluyendo casos de situaciones especiales, con el objetivo principal de brindar información actualizada y recomendaciones clínicas bien fundamentadas a los médicos tratantes, para mejorar el enfoque diagnóstico y terapéutico a nuestro pacientes. (AU)

A significant number of patients with systemic lupus erythematosus (between 20% to 60% according to different reported series) develop lupus nephritis in the course of its evolution, which directly influences their quality of life and vital prognosis. In recent years, the greater knowledge about the pathogenesis of systemic lupus and lupus nephritis has allowed relevant advances in the diagnostic approach and treatment of these patients, achieving the development of drugs specifically aimed at blocking key pathogenic pathways of the disease. Encouragingly, these immunomodulatory agents have shown in well-powered, randomized clinical trials good clinical efficacy in the medium-term, defined as proteinuria remission and preservation of kidney function, with an acceptable safety profile and good patient tolerability. All this has made it possible to reduce the use of corticosteroids and other potentially more toxic therapies, as well as to increase the use of combined therapies. The present consensus document carried out by the Glomerular Diseases Working Group of the Spanish Society of Nephrology (GLOSEN), collects in a practical and summarized, but rigorous way, the best currently available evidence about the diagnosis, treatment, and follow-up of lupus nephritis patients, including cases of special situations, with the main objective of providing updated information and well-founded clinical recommendations to treating physicians, to improve the diagnostic and therapeutic approach to our patients. (AU)

Acute interstitial nephritis due to dolutegravir: The first case reported.

Kidney disease is frequent in HIV-patients. We present a case of a 44-year-old woman, with known uncontrolled HIV infection and chronic kidney disease due to HIV-associated nephropathy. After starting dolutegravir, the patient developed eosinophilia and worsening kidney function. A kidney biopsy confirmed the diagnosis of acute interstitial nephritis. Given the time relation with dolutegravir introduction, it was deemed the culprit medication. Dolutegravir was stopped, and corticosteroids were initiated, with moderate improvement in renal function. To our knowledge, this is the first reported case of acute interstitial nephritis to dolutegravir, which should raise awareness of previously undocumented renal effects of antiretroviral therapy.

Hipoacusia Neurosensorial en el síndrome de Alport: Una revisión Sistemática / Sensorineural hearing loss in Alport syndrome: A systematic review

El Síndrome de Alport (SA) es un desorden genético originado por mutaciones en el colágeno tipo IV que es el constituyente principal de las membranas basales. Clínicamente, se caracteriza por nefropatía hereditaria progresiva. En el oído interno, el colágeno IV se encuentra ubicado en la membrana basilar y en el ligamento espiral, por lo que las mutaciones en los genes codificadores provocan hipoacusia de tipo neurosensorial. La presente investigación tiene por objetivo caracterizar el comportamiento de la pérdida de audición en personas diagnosticadas con SA, mediante la revisión de estudios de la literatura. Se realizó una búsqueda en bases de datos con los criterios de inclusión establecidos, incorporando un total de siete artículos para su análisis. Teniendo en cuenta los hallazgos de las diversas investigaciones recopiladas, se concluye que la pérdida auditiva secundaria al SA es heterogénea. No hay un patrón común de presentación pues depende del modo de herencia y del tipo de mutación de la enfermedad, además su grado de severidad y progresión va paralelo a la función renal. Sin embargo, independientemente del momento en que se manifieste el deterioro auditivo, es de vital importancia una intervención audiológica oportuna, con el fin de detectar la hipoacusia lo más temprano posible, hacer un seguimiento riguroso de la funcionalidad auditiva y, en caso de ser necesario, adaptar ayudas auditivas de acuerdo con las necesidades comunicativas del paciente

Alport Syndrome (AS) is a genetic disorder originated by mutations in the collagen type IV which is the main constituent of the basal membranes. Clinically, is characterized by progressive hereditary nephropathy. In the inner ear, the collagen IV is ubicated in the basilar membrane and in the spiral ligament, whereby the mutations in the codifier gens, cause neurosensorial hearing loss. The aim of this investigation is to characterize how hearing loss behaves in people diagnosed with AS, by presenting a reviewing of reported studies in the literature. A database search was performed with the established criteria of inclusion and a total of seven articles were incorporated for its analysis. Considering the findings by the several investigations collected the conclusion is that the secondary hearing loss to AS is heterogenous. There is no a common pattern of presentation as it depends on the mode of heredity and the type of mutation of the disease, and besides of the degree of severity and progression that goes along with the renal function. Nevertheless, regardless of the moment that the auditive impair appears, it is of vital importance an opportune audiological intervention, aiming at detecting an alteration as soon as possible, make a rigorous tracking of the auditive functionality and, if necessary, incorporate hearing aids in accordance with the communicative needs of the patients