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3.
Clinics (Sao Paulo) ; 75: e1528, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32876110

RESUMO

OBJECTIVES: Many studies indicate that microRNAs (miRNAs) could be potential biomarkers for various diseases. The purpose of this study was to investigate the clinical value of serum exosomal miRNAs in systemic lupus erythematosus (SLE). METHODS: Serum exosomes were isolated from 38 patients with SLE and 18 healthy controls (HCs). The expression of miR-21, miR-146a and miR-155 within exosomes was examined by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Using receiver operating characteristic (ROC) curves, we evaluated the diagnostic value of exosomal miRNAs. RESULTS: Exosomal miR-21 and miR-155 were upregulated (p<0.01), whereas miR-146a expression (p<0.05) was downregulated in patients with SLE, compared to that in HCs. The expression of miR-21 (p<0.01) and miR-155 (p<0.05) was higher in SLE patients with lupus nephritis (LN) than in those without LN (non-LN). The analysis of ROC curves revealed that the expression of miR-21 and miR-155 showed a potential diagnostic value for LN. Furthermore, miR-21 (R=0.44, p<0.05) and miR-155 (R=0.33, p<0.05) were positively correlated with proteinuria. The expression of miR-21 was negatively associated with anti-SSA/Ro antibodies (R=-0.38, p<0.05), and that of miR-146a was negatively associated with anti-dsDNA antibodies (R=-0.39, p<0.05). CONCLUSIONS: These findings suggested that exosomal miR-21 and miR-155 expression levels may serve as potential biomarkers for the diagnosis of SLE and LN.


Assuntos
MicroRNA Circulante , Lúpus Eritematoso Sistêmico , Nefrite Lúpica , MicroRNAs , Biomarcadores , Humanos , Lúpus Eritematoso Sistêmico/diagnóstico , Lúpus Eritematoso Sistêmico/genética , Nefrite Lúpica/diagnóstico , Nefrite Lúpica/genética
4.
Ann Rheum Dis ; 79(10): 1349-1361, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32651195

RESUMO

OBJECTIVE: The goal of these studies is to discover novel urinary biomarkers of lupus nephritis (LN). METHODS: Urine from systemic lupus erythematosus (SLE) patients was interrogated for 1000 proteins using a novel, quantitative planar protein microarray. Hits were validated in an independent SLE cohort with inactive, active non-renal (ANR) and active renal (AR) patients, in a cohort with concurrent renal biopsies, and in a longitudinal cohort. Single-cell renal RNA sequencing data from LN kidneys were examined to deduce the cellular origin of each biomarker. RESULTS: Screening of 1000 proteins revealed 64 proteins to be significantly elevated in SLE urine, of which 17 were ELISA validated in independent cohorts. Urine Angptl4 (area under the curve (AUC)=0.96), L-selectin (AUC=0.86), TPP1 (AUC=0.84), transforming growth factor-ß1 (TGFß1) (AUC=0.78), thrombospondin-1 (AUC=0.73), FOLR2 (AUC=0.72), platelet-derived growth factor receptor-ß (AUC=0.67) and PRX2 (AUC=0.65) distinguished AR from ANR SLE, outperforming anti-dsDNA, C3 and C4, in terms of specificity, sensitivity and positive predictive value. In multivariate regression analysis, urine Angptl4, L-selectin, TPP1 and TGFß1 were highly associated with disease activity, even after correction for demographic variables. In SLE patients with serial follow-up, urine L-selectin (followed by urine Angptl4 and TGFß1) were best at tracking concurrent or pending disease flares. Importantly, several proteins elevated in LN urine were also expressed within the kidneys in LN, either within resident renal cells or infiltrating immune cells, based on single-cell RNA sequencing analysis. CONCLUSION: Unbiased planar array screening of 1000 proteins has led to the discovery of urine Angptl4, L-selectin and TGFß1 as potential biomarker candidates for tracking disease activity in LN.


Assuntos
Proteína 4 Semelhante a Angiopoietina/urina , Biomarcadores/urina , Nefrite Lúpica/diagnóstico , Análise Serial de Proteínas , Fator de Crescimento Transformador beta1/urina , Humanos , Nefrite Lúpica/urina
5.
BMC Infect Dis ; 20(1): 538, 2020 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-32703300

RESUMO

BACKGROUND: The risk of life-threatening complications, such as visceral disseminated varicella zoster virus (VZV) infection, is greater in immunosuppressed individuals, such as systemic lupus erythematosus (SLE) patients. CASE PRESENTATION: Here, a case is reported of a Caucasian woman diagnosed with lupus nephritis and anti-phospholipid syndrome, who was subjected to mycophenolate mofetil and high-dose steroid remission-induction therapy. Two months later she developed abdominal pain followed by a fatal rapid multi-organ failure. As no typical skin rashes were evident, death was initially attributed to catastrophic anti-phospholipid syndrome. However, autopsy and virological examinations on archival material revealed a disseminated VZV infection. CONCLUSIONS: Overall, this case highlights the importance of having a high clinical suspicion of fatal VZV infections in heavily immunosuppressed SLE patients even when typical signs and symptoms are lacking.


Assuntos
Síndrome Antifosfolipídica/complicações , Síndrome Antifosfolipídica/diagnóstico , Herpes Zoster/complicações , Herpes Zoster/diagnóstico , Herpesvirus Humano 3/genética , Nefrite Lúpica/complicações , Nefrite Lúpica/diagnóstico , Dor Abdominal , Evolução Fatal , Feminino , Herpes Zoster/patologia , Herpes Zoster/virologia , Herpesvirus Humano 3/isolamento & purificação , Humanos , Hospedeiro Imunocomprometido , Nefrite Lúpica/tratamento farmacológico , Pessoa de Meia-Idade , Ácido Micofenólico/uso terapêutico , Reação em Cadeia da Polimerase em Tempo Real , Esteroides/uso terapêutico
6.
Nat Commun ; 11(1): 2197, 2020 05 04.
Artigo em Inglês | MEDLINE | ID: mdl-32366845

RESUMO

Emerging urinary biomarkers continue to show promise in evaluating lupus nephritis (LN). Here, we screen urine from active LN patients for 1129 proteins using an aptamer-based platform, followed by ELISA validation in two independent cohorts comprised of 127 inactive lupus, 107 active LN, 67 active non-renal lupus patients and 74 healthy controls, of three different ethnicities. Urine proteins that best distinguish active LN from inactive disease are ALCAM, PF-4, properdin, and VCAM-1 among African-Americans, sE-selectin, VCAM-1, BFL-1 and Hemopexin among Caucasians, and ALCAM, VCAM-1, TFPI and PF-4 among Asians. Most of these correlate significantly with disease activity indices in the respective ethnic groups, and surpass conventional metrics in identifying active LN, with better sensitivity, and negative/positive predictive values. Several elevated urinary molecules are also expressed within the kidneys in LN, based on single-cell RNAseq analysis. Longitudinal studies are warranted to assess the utility of these biomarkers in tracking lupus nephritis.


Assuntos
Aptâmeros de Peptídeos/metabolismo , Biomarcadores/urina , Nefrite Lúpica/diagnóstico , Proteínas/análise , Molécula de Adesão de Leucócito Ativado/urina , Adulto , Afro-Americanos/estatística & dados numéricos , Grupo com Ancestrais do Continente Asiático/estatística & dados numéricos , Selectina E/análise , Grupo com Ancestrais do Continente Europeu/estatística & dados numéricos , Feminino , Humanos , Nefrite Lúpica/etnologia , Nefrite Lúpica/urina , Properdina/urina , Sensibilidade e Especificidade , Molécula 1 de Adesão de Célula Vascular/urina , Adulto Jovem
7.
Medicine (Baltimore) ; 99(16): e19875, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32312013

RESUMO

INTRODUCTION: Systemic lupus erythematosus (SLE) is a multisystem, chronic, autoimmune disease which can affect any organ system including the eye. About one-third of the patients can be diagnosed with SLE-related eye involvement which is usually indicative of disease activity. Retinopathy is one of the most vision-threatening complications that can be associated with the disease. PATIENT CONCERNS: An 11-year-old girl was hospitalized with complains of repeated swelling and pain in her extremities for 1 month, chest pain for 24 days, rash for 5 days and proteinuria for 1 day. On the morning of her fourth day in hospital, she suddenly complained of sudden, painless vision loss in the left eye. The ophthalmologist found that she had obstruction of central retinal vein and artery with diffuse retinal hemorrhages and macular edema. DIAGNOSIS: The patient was diagnosed with systemic lupus erythematosus, lupus nephritis, and lupus retinopathy through her clinical manifestations and laboratory tests. INTERVENTIONS: After diagnosis, she received steroid therapy, retinal laser photocoagulation, and intravitreal injection of dexamethasone (OZURDEX, Allergan Pharmaceuticals, Dublin, Ireland) early in her course. OUTCOMES: At the latest follow-up, her vision improved partially. However, she still has the possibility of subsequent neovascular glaucoma and bleeding in the future. CONCLUSIONS: An early diagnosis and the prompt therapeutic measures are necessary to prevent sight-threatening consequences, especially in pediatric patients with SLE.


Assuntos
Lúpus Eritematoso Sistêmico/complicações , Doenças Retinianas/etiologia , Doenças Retinianas/terapia , Transtornos da Visão/etiologia , Criança , Dexametasona/administração & dosagem , Dexametasona/uso terapêutico , Feminino , Glaucoma Neovascular/epidemiologia , Glaucoma Neovascular/etiologia , Glucocorticoides/administração & dosagem , Glucocorticoides/uso terapêutico , Hemorragia , Humanos , Injeções Intravítreas , Fotocoagulação a Laser/métodos , Lúpus Eritematoso Sistêmico/diagnóstico , Lúpus Eritematoso Sistêmico/patologia , Nefrite Lúpica/complicações , Nefrite Lúpica/diagnóstico , Edema Macular , Oclusão da Artéria Retiniana/diagnóstico , Oclusão da Artéria Retiniana/etiologia , Doenças Retinianas/patologia , Oclusão da Veia Retiniana/diagnóstico , Oclusão da Veia Retiniana/etiologia , Resultado do Tratamento
8.
Lupus ; 29(3): 311-323, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32063098

RESUMO

Lupus nephropathy is a severe and frequent complication of systemic lupus erythematosus. Here, we assessed the biomarkers of oxidative stress, inflammation and disease activity in patients with lupus nephritis. Thirty-four patients with active lupus nephritis, 31 patients with inactive lupus nephritis and 20 lupus patients without renal damage (non-lupus nephritis) were studied. Oxidative stress biomarkers malonyldialdehyde, oxidized-to-total glutathione, catalase, superoxide dismutase and total antioxidant status were assessed, as well as inflammation biomarkers CRP, interleukin 6 and monocyte chemoattractant protein 1. Renal tubular disease biomarkers neutrophil gelatinase-associated lipocalin and ß2-microglobulin were assessed, together with the classic disease activity biomarkers urinary protein/creatinine ratio, anti-dsDNA, anti-C1q antibody and complement proteins C3 and C4. Significant differences were found between active lupus nephritis and inactive lupus nephritis patients and between active lupus nephritis and non-lupus nephritis patients for all the assessed biomarkers (P < 0.05), except for catalase, superoxide dismutase and interleukin 6. There is an imbalance in the redox status in active lupus nephritis patients that would be involved in lipid peroxidation of the glomerular basal membrane that would alter its integrity and could also affect renal tubular function in these patients.


Assuntos
Biomarcadores/sangue , Lúpus Eritematoso Sistêmico/diagnóstico , Nefrite Lúpica/diagnóstico , Estresse Oxidativo/imunologia , Adolescente , Adulto , Quimiocina CCL2/sangue , Complemento C3/análise , Feminino , Humanos , Inflamação/sangue , Inflamação/imunologia , Testes de Função Renal , Lipocalina-2/sangue , Modelos Logísticos , Lúpus Eritematoso Sistêmico/sangue , Lúpus Eritematoso Sistêmico/imunologia , Nefrite Lúpica/sangue , Nefrite Lúpica/imunologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Adulto Jovem
9.
J Immunol ; 204(6): 1448-1461, 2020 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-32060137

RESUMO

Tris (dibenzylideneacetone) dipalladium (Tris DBA), a small-molecule palladium complex, has been shown to inhibit cell growth and proliferation in pancreatic cancer, lymphocytic leukemia, and multiple myeloma. In the current study, we examined the therapeutic effects of Tris DBA on glomerular cell proliferation, renal inflammation, and immune cells. Treatment of accelerated and severe lupus nephritis (ASLN) mice with Tris DBA resulted in improved renal function, albuminuria, and pathology, including measurements of glomerular cell proliferation, cellular crescents, neutrophils, fibrinoid necrosis, and tubulointerstitial inflammation in the kidneys as well as scoring for glomerulonephritis activity. The treated ASLN mice also showed significantly decreased glomerular IgG, IgM, and C3 deposits. Furthermore, the compound was able to 1) inhibit bone marrow-derived dendritic cell-mediated T cell functions and reduce serum anti-dsDNA autoantibody levels; 2) differentially regulate autophagy and both the priming and activation signals of the NLRP3 inflammasome; and 3) suppress the phosphorylation of JNK, ERK, and p38 MAPK signaling pathways. Tris DBA improved ASLN in mice through immunoregulation by blunting the MAPK (ERK, JNK)-mediated priming signal of the NLRP3 inflammasome and by regulating the autophagy/NLRP3 inflammasome axis. These results suggest that the pure compound may be a drug candidate for treating the accelerated and deteriorated type of lupus nephritis.


Assuntos
Inflamassomos/antagonistas & inibidores , Nefrite Lúpica/tratamento farmacológico , Ativação Linfocitária/efeitos dos fármacos , Compostos Organometálicos/farmacologia , Linfócitos T Reguladores/imunologia , Animais , Autofagia/efeitos dos fármacos , Comunicação Celular/efeitos dos fármacos , Comunicação Celular/imunologia , Células Dendríticas/imunologia , Células Dendríticas/metabolismo , Modelos Animais de Doenças , Feminino , Humanos , Inflamassomos/imunologia , Inflamassomos/metabolismo , Glomérulos Renais/imunologia , Glomérulos Renais/metabolismo , Glomérulos Renais/patologia , Nefrite Lúpica/diagnóstico , Nefrite Lúpica/imunologia , Nefrite Lúpica/patologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Sistema de Sinalização das MAP Quinases/imunologia , Camundongos , Proteína 3 que Contém Domínio de Pirina da Família NLR/antagonistas & inibidores , Proteína 3 que Contém Domínio de Pirina da Família NLR/imunologia , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Compostos Organometálicos/uso terapêutico , Índice de Gravidade de Doença , Linfócitos T Reguladores/efeitos dos fármacos
10.
Ren Fail ; 42(1): 166-172, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32054387

RESUMO

Objective: This study analyzed the associations of different crescents' fraction and clinical features in a Chinese lupus nephritis cohort based on the 2018 revision of ISN/RPS classification system.Methods: A total of 288 lupus nephritis patients with complete clinicopathological data and well follow-up was enrolled. The fraction of glomeruli with cellular or fibrocellular crescents based on the new system was reevaluated. The association between crescents fractions and the outcomes were further analyzed.Results: The median follow-up period was 76.5 months. Cellular or fibrocellular crescents were present in 146 (50.7%) of the total individuals. The percentage of crescents were significantly associated with severe clinical renal injury indices and other renal pathological parameter. According to the survival receiver operating characteristic (survival ROC) curve, the optimal cutoff level of cellular or fibrocellular crescents for predicting the composite events was 7.39%. By multivariable Cox hazard analysis, the presence of crescents was predictive of survival from the composite events with a hazard ratio [HR] of 2.5 (95% CI 1.190-5.431; p = .02). Furthermore, when we used absent, present in less than 7.39% of glomeruli, and present in greater than or equal to 7.39% of glomeruli as cutoffs in all the patients, a gradation appeared, with adjusted HRs of 2.9 (95% CI 1.326-6.313; p = .008) for crescents in greater than or equal to 7.39% of glomeruli, in reference to no crescents.Conclusion: We proposed that the crescents were not uncommon and had important clinical significance in lupus nephritis. The cutoff point of crescents as prognosticator might be nearly 7.39%.


Assuntos
Glomérulos Renais/patologia , Nefrite Lúpica/diagnóstico , Nefrite Lúpica/patologia , Nefrologia/métodos , Adulto , Biópsia , China/epidemiologia , Estudos de Coortes , Progressão da Doença , Feminino , Testes Genéticos , Humanos , Nefrite Lúpica/classificação , Nefrite Lúpica/mortalidade , Masculino , Análise Multivariada , Nefrologia/normas , Fatores de Risco , Sociedades Médicas , Análise de Sobrevida , Adulto Jovem
11.
Reumatol. clín. (Barc.) ; 16(1): 17-23, ene.-feb. 2020. tab, graf
Artigo em Espanhol | IBECS | ID: ibc-194255

RESUMO

ANTECEDENTES Y OBJETIVO: El diagnóstico de la nefritis lúpica (NL) se suele hacer con la biopsia renal, que es una técnica invasiva que conlleva múltiples riesgos. Por lo tanto, han surgido diferentes biomarcadores en orina como posibles alternativas para el diagnóstico de la NL. Sin embargo, los estudios de biomarcadores en orina de pacientes latinoamericanos con lupus eritematoso sistémico (LES) son escasos; por lo tanto, el objetivo del presente estudio fue determinar el valor diagnóstico de la transferrina (TF) y la ceruloplasmina (CP) en orina, para diferenciar los pacientes que tienen compromiso renal de aquellos que no. MATERIALES Y MÉTODOS: Se incluyeron prospectivamente pacientes con diagnóstico de LES de acuerdo a los criterios del American College of Rheumatology (ACR). Se excluyeron los pacientes con otra enfermedad autoinmune concomitante, infección activa (de vías urinarias o sistémica), terapia de reemplazo renal, infección por virus de la inmunodeficiencia humana y embarazo. A cada paciente se le tomó una muestra de orina. El diagnóstico de NL se realizó mediante los criterios ACR para la definición de NL. La actividad y la cronicidad de la NL en la biopsia renal fueron medidas con el índice de Austin. La determinación de los niveles de TF y CP se realizó con kits comerciales de ELISA. Se utilizó la prueba t de Student y la prueba U de Mann Whitney para comparar los datos. Para determinar las asociaciones entre las variables se utilizaron los coeficientes de correlación de Spearman. Por último, se construyeron curvas ROC. RESULTADOS: Se incluyeron 120 pacientes con LES, de los cuales el 85% fueron de sexo femenino. El 76% fueron de raza mestiza. Presentaron una edad media de 32,8+/-12,1años, y una media del SLEDAI de 8,4+/-8,9, y un 64% presentaron compromiso renal. Los niveles de ambos biomarcadores fueron significativamente mayores en pacientes con NL comparados con aquellos sin NL. De igual manera, los niveles de ambos biomarcadores fueron significativamente mayores en pacientes con NL activa comparados con aquellos con NL inactiva. Los niveles de TF fueron significativamente mayores en pacientes afro-latinoamericanos. Por otro lado, las concentraciones de TF se correlacionaron con el SLEDAI y el rango de proteinuria, y las concentraciones de TF y CP se correlacionaron entre sí. Las curvas ROC para ambos biomarcadores mostraron un buen valor diagnóstico de la NL. CONCLUSIONES: En nuestra cohorte de pacientes con LES encontramos que la TF y la CP son potenciales biomarcadores para el diagnóstico de la NL e, incluso, de la actividad de la NL


BACKGROUND AND OBJECTIVE: Diagnosis of lupus nephritis (LN) is usually based on renal biopsy, which is an invasive technique that involves multiple risks. Therefore, different biomarkers have emerged as alternatives for the diagnosis of LN. Nonetheless, studies regarding urinary biomarkers in Latin American patients are limited. The objective of this study was to assess the diagnostic value of urinary transferrin and ceruloplasmin to differentiate patients who have renal involvement from those who do not. MATERIALS AND METHODS: Systemic lupus erythematosus (SLE) patients that met the revised American College of Rheumatology (ACR) classification criteria were recruited. Patients with another autoimmune disease, active infection (urinary tract or systemic infection), renal replacement therapy, human immunodeficiency virus infection or pregnancy were excluded. A urine sample was collected from each patient. LN was diagnosed according to ACR criteria. The activity and chronicity of LN were measured using the Austin indices. Urinary transferrin and ceruloplasmin levels were measured using commercial enzyme-linked immunosorbent assay (ELISA) kits. Mann-Whitney U test and Student's t-test were used to compare data. Spearman's rank correlation was used to determine associations. Lastly, receiver operating characteristic (ROC) curves were created. RESULTS: The study involved 120 SLE patients. In all, 85% were female, 76% mestizo, the mean age was 32.8+/-12.1years and mean systemic lupus erythematosus disease activity index (SLEDAI) was 8.4+/-8.9; 64% had renal involvement. Urinary levels of the two biomarkers were significantly higher in patients with LN compared to those without LN. Similarly, urinary levels of both biomarkers were significantly higher in patients with active LN compared to those with inactive LN. Furthermore, urinary transferrin levels were significantly higher in Afro-Latin American patients. On the other hand, urinary transferrin levels correlated with SLEDAI and proteinuria, and transferrin and ceruloplasmin levels correlated with each other. The diagnostic value of ROC curves for these urinary biomarkers for LN were good. CONCLUSIONS: In our cohort of SLE patients, we found that transferrin and ceruloplasmin were potential biomarkers for LN, and can even differentiate active LN


Assuntos
Humanos , Feminino , Adulto Jovem , Adulto , Transferrinas/urina , Lúpus Eritematoso Sistêmico/diagnóstico , Lúpus Eritematoso Sistêmico/urina , Nefrite Lúpica/diagnóstico , Biomarcadores/urina , Ceruloplasmina/urina , Estudos Prospectivos , Curva ROC , Técnica Indireta de Fluorescência para Anticorpo/métodos , Ensaio de Imunoadsorção Enzimática
12.
Lupus ; 29(3): 248-255, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31996111

RESUMO

BACKGROUND: Despite improved survival of patients with lupus nephritis (LN), some require kidney transplantation because of progression to end-stage renal disease (ESRD). However, the transplant outcomes of these patients and other recipients have not been thoroughly compared. METHODS: In total, 1848 Korean kidney recipients who underwent transplantation from 1998 to 2017 at two tertiary referral centers were evaluated retrospectively. Among them, 28 recipients with LN, and 50 control recipients matched by age, sex, and donor type, were compared with respect to graft and patient survival. We pooled our data with 17 previous cohort studies in which the graft survival of recipients with LN was described in detail. RESULTS: During the median follow-up period of 9.5 years (maximum 21 years), graft failure (GF) occurred in 10.7% and 16.0% of LN and control recipients, respectively. No differences were found in the rates of GF and death-censored graft failure or patient survival between the two groups. The risks of acute T cell-mediated and antibody-mediated rejection were also similar between the two groups. The pooled analysis showed similar 1- and 5-year graft survival rates between LN and control recipients. CONCLUSIONS: Kidney transplantation is an acceptable option in patients with concurrent LN and ESRD.


Assuntos
Falência Renal Crônica/cirurgia , Transplante de Rim/efeitos adversos , Transplante de Rim/mortalidade , Nefrite Lúpica/cirurgia , Adulto , Progressão da Doença , Feminino , Rejeição de Enxerto/epidemiologia , Sobrevivência de Enxerto , Humanos , Falência Renal Crônica/diagnóstico , Falência Renal Crônica/mortalidade , Nefrite Lúpica/diagnóstico , Nefrite Lúpica/mortalidade , Masculino , Pessoa de Meia-Idade , Segurança do Paciente , Complicações Pós-Operatórias/epidemiologia , República da Coreia/epidemiologia , Estudos Retrospectivos , Taxa de Sobrevida , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
13.
Clin Rheumatol ; 39(2): 401-405, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31637610

RESUMO

The objective of this study is to assess the usefulness of the stand-alone renal SLICC criterion in patients with childhood systemic lupus erythematosus (cSLE) and report their disease course, treatment response, and outcome. This study included children who were followed regularly in our lupus clinic with proved full house glomerular immune deposits nephritis and antinuclear (ANA), or anti-double-stranded DNA (dsDNA). They were compared with patients who diagnosed with cSLE with and without biopsy proven nephritis, based on Systemic Lupus International Collaborating (SLICC). The comparative group selected by systematic sampling from our cSLE database; the first patient was chosen randomly, and the subsequent patients chosen at intervals of three. The two groups were compared in respect to demographic data, clinical and laboratory findings, and disease course including response to treatment and outcome using urine protein/creatinine ratio, eGFR, and urine sediments. A total of 37 patients were assessed, six patients met the stand-alone renal SLICC criterion, 18 patients had cSLE with biopsy proven nephritis, and 13 cSLE patients without biopsy proven nephritis. Age of onset and time to diagnosis were comparable. However, patients with stand-alone renal criterion had significantly higher baseline serum creatinine, urine protein/creatinine ratio, and lower ANA titer (p < 0.05). Furthermore, none of the patients had other lupus manifestations. Four patients showed partial response to treatment. Two patients had renal impairment and one patient developed end-stage renal disease. Patients with full house glomerular immune deposits nephritis and ANA, or anti-dsDNA reflect a different disease spectrum with severe renal manifestations and worse outcome. Further large prospective study is required to revisit the validity of the stand-alone renal SLICC criterion in cSLE. KEY POINTS : • There is no definite diagnostic tool for SLE. Furthermore, to date there are no specific classification criteria for cSLE. • It seems that patients who met the stand-alone renal SLICC criterion might represent a distinct disease spectrum with severe renal involvement.


Assuntos
Anticorpos Antinucleares/sangue , Glomérulos Renais/imunologia , Nefrite Lúpica/diagnóstico , Criança , Estudos de Coortes , Feminino , Humanos , Nefrite Lúpica/sangue , Nefrite Lúpica/imunologia , Nefrite Lúpica/terapia , Masculino
14.
Mod Rheumatol ; 30(1): 125-131, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30557058

RESUMO

AbstractsBackground: Recent studies have identified the significance of proteinuria levels after initial induction therapies on the renal outcomes in patients with proliferative lupus nephritis, but the issue has not been evaluated in Japanese patients.Methods: Based on the ISN/RPS classification, only patients diagnosed with lupus nephritis class III or IV were included. The remission of proteinuria 12 months after diagnosis, as well as the clinicopathological features at diagnosis, on renal outcomes was examined retrospectively. Renal progression was defined as a 50% decrease in the estimated glomerular filtration rate or the development of end-stage renal disease.Results: This study included 82 Japanese patients with a median follow-up period of seven years. Although all patients received intensive induction therapy, 15 patients (18%) showed progression. Proteinuric remission 12 months after diagnosis predicted a good renal outcome by multivariate analysis. A receiver-operating characteristic analysis of 38 patients whose quantitative urinary protein excretion levels at 12 months were available for analysis showed that a cut-off value of 0.8 g/day predicted renal progression most effectively. Neither the renal function nor proteinuria level at diagnosis were associated with the renal outcomes.Conclusion: In Japanese patients with lupus nephritis class III or IV, proteinuria levels after 12 months under intensive therapy predicted renal outcomes more accurately than did factors identified at diagnosis.


Assuntos
Glucocorticoides/uso terapêutico , Imunossupressores/uso terapêutico , Rim/patologia , Nefrite Lúpica/terapia , Proteinúria/terapia , Indução de Remissão/métodos , Adolescente , Adulto , Idoso , Biópsia , Criança , Progressão da Doença , Feminino , Taxa de Filtração Glomerular , Humanos , Incidência , Japão/epidemiologia , Rim/fisiopatologia , Nefrite Lúpica/complicações , Nefrite Lúpica/diagnóstico , Masculino , Pessoa de Meia-Idade , Proteinúria/epidemiologia , Proteinúria/etiologia , Curva ROC , Estudos Retrospectivos , Adulto Jovem
15.
Arthritis Care Res (Hoboken) ; 72(7): 888-896, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-31058460

RESUMO

OBJECTIVE: We examined quality measures for screening, diagnosis, and treatment of lupus nephritis (LN) among participants of the California Lupus Epidemiology Study across 25 different clinical sites to identify gaps in quality of care. METHODS: Data from 250 participants with lupus were analyzed across 3 sources (medical records, physician examination, and patient interviews). Overall performance on 8 quality measures was calculated separately for participants with and without LN. We used generalized estimating equations in which the outcome was performance on measures, adjusting for participant demographics, lupus disease severity, and practice characteristics. RESULTS: Of 148 patients without LN, 42% underwent screening laboratory tests for nephritis, 38% underwent lupus activity serum studies, and 81% had their blood pressure checked every 6 months. Of 102 LN patients, 67% had a timely kidney biopsy, at least 81% had appropriate treatment, and 78% achieved target blood pressure within 1 year of diagnosis. Overall performance in participants across quality measures was 54% (no LN) and 80% (LN). Significantly higher overall performance for screening measures for LN was seen at academic (63.4-73%) versus community clinics (37.9-38.4%). Similarly, among those with LN, higher performance in academic (84.1-85.2%) versus community clinics (54.8-60.2%) was observed for treatment measures. CONCLUSION: In this quality-of-care analysis across 25 diverse clinical settings, we found relatively high performance on measures for management of LN. However, future work should focus on bridging the gaps in lupus quality of care for patients without nephritis, particularly in community settings.


Assuntos
Nefrite Lúpica/diagnóstico , Nefrite Lúpica/terapia , Garantia da Qualidade dos Cuidados de Saúde , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
16.
Arthritis Care Res (Hoboken) ; 72(5): 622-629, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-31115180

RESUMO

OBJECTIVE: The California Lupus Surveillance Project (CLSP) is a population-based registry of individuals with systemic lupus erythematosus (SLE) residing in San Francisco County, California from 2007 to 2009, with a special focus on Asian/Pacific Islander and Hispanic patients. We used retrospective CLSP data to analyze racial and ethnic differences in lupus manifestations and in the timing and risk of developing severe manifestations. METHODS: A total of 724 patients with SLE were retrospectively identified. Prevalence ratios (PRs) of SLE manifestations were calculated using Poisson regression models stratified by race/ethnicity and adjusted for sex, age at SLE diagnosis, and disease duration. We studied onset of severe SLE manifestations after SLE diagnosis using Kaplan-Meier methods to examine time-to-event and Cox proportional hazards regression models to estimate hazard ratios (HRs). White patients were the referent group in all analyses. RESULTS: African Americans, Asian/Pacific Islanders, and Hispanic patients had increased prevalence of renal manifestations (PR 1.74 [95% confidence interval (95% CI) 1.40-2.16], PR 1.68 [95% CI 1.38-2.05], and PR 1.35 [95% CI 1.05-1.74], respectively). Furthermore, African Americans had increased prevalence of neurologic manifestations (PR 1.49 [95% CI 1.12-1.98]), and both African Americans (PR 1.09 [95% CI 1.04-1.15]) and Asian/Pacific Islanders (PR 1.07 [95% CI 1.01-1.13]) had increased prevalence of hematologic manifestations. African Americans, Asian/Pacific Islanders, and Hispanic patients, respectively, had higher risk of developing lupus nephritis (HR 2.4 [95% CI 1.6-3.8], HR 4.3 [95% CI 2.9-6.4], and HR 2.3 [95% CI 1.4-3.8]) and thrombocytopenia (HR 2.3 [95% CI 1.1-4.4], HR 2.3 [95% CI 1.3-4.2], and HR 2.2 [95% CI 1.1-4.7]). Asian/Pacific Islander and Hispanic patients had higher risk of developing antiphospholipid syndrome (HR 2.5 [95% CI 1.4-4.4] and HR 2.6 [95% CI 1.3-5.1], respectively). CONCLUSION: This is the first epidemiologic study comparing lupus manifestations among 4 major racial and ethnic groups. We found substantial differences in the prevalence of several clinical SLE manifestations among racial/ethnic groups and discovered that African Americans, Asian/Pacific Islanders, and Hispanic patients are at increased risk of developing several severe manifestations following a diagnosis of SLE.


Assuntos
Grupos de Populações Continentais , Grupos Étnicos , Disparidades nos Níveis de Saúde , Lúpus Eritematoso Sistêmico/etnologia , Adolescente , Adulto , California/epidemiologia , Progressão da Doença , Feminino , Humanos , Lúpus Eritematoso Sistêmico/diagnóstico , Nefrite Lúpica/diagnóstico , Nefrite Lúpica/etnologia , Vasculite Associada ao Lúpus do Sistema Nervoso Central/diagnóstico , Vasculite Associada ao Lúpus do Sistema Nervoso Central/etnologia , Masculino , Pessoa de Meia-Idade , Vigilância da População , Prevalência , Prognóstico , Fatores Raciais , Sistema de Registros , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Adulto Jovem
17.
Pan Afr Med J ; 37: 228, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33520067

RESUMO

Primary hyperparathyroidism (PHP) is the most common cause of hypercalcemia. Patients with systemic lupus erythematosus (SLE) can develop hypercalcemia but it is exceptionally due to PHP. There are only few cases of concurrent SLE and primary hyperparathyroidism (PHP) described in the literature. We report a case of a 31-year-old patient having SLE with lupus nephritis class III and anti-phospholipid syndrome, complicated by pulmonary embolism associated to primary hyperparathyroidism causing severe hypercalcemia and osteoporosis. Even if there is no evidence for potential pathogenic association between PHP and SLE, the recognition of this association is very important because of therapeutic and prognostic impact. Early detection of PHP leads to avoid severe complications and significant morbidity.


Assuntos
Hipercalcemia/diagnóstico , Hiperparatireoidismo Primário/diagnóstico , Lúpus Eritematoso Sistêmico/complicações , Embolia Pulmonar/diagnóstico , Adulto , Síndrome Antifosfolipídica/diagnóstico , Feminino , Humanos , Hipercalcemia/etiologia , Hiperparatireoidismo Primário/complicações , Nefrite Lúpica/diagnóstico , Osteoporose/etiologia , Embolia Pulmonar/etiologia
18.
Iran J Kidney Dis ; 13(6): 389-397, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31880585

RESUMO

INTRODUCTION: Kidney involvement is a hallmark of systemic lupus erythematosus (SLE) and evaluation of its inflammatory response is demanding. It was the aim of the present study to evaluate the levels of CXCL10 and vitamin D in serum samples of cases with active lupus nephritis (LN). METHODS: Fifty lupus patients were enrolled in our study, 25 patients had lupus nephritis and 25 patients were without evidence of LN. Thirty-nine healthy subjects were also participated as a control group. Complete biochemical and serological parameters were measured and their correlation with serum levels of vitamin D and CXCL10 were assessed in the studied groups. RESULTS: Serum levels of CXCL10 were significantly elevated (P≤ 0.020), while vitamin D were diminished in SLE group and active LN as compared with healthy controls and SLE patients without nephritis, respectively. CXCL10 correlated with SLE disease activity index (SLEDAI) and renal activity (P < .05), while vitamin D correlated with C3 and anti-dsDNA antibody (P < .05). Based on the receiver operator characteristic (ROC) curve analysis, CXCL10 and vitamin D levels were not better than conventional biomarkers for discriminating LN patients from non-nephritis SLE patients; however, they could differentiate most of SLE cases from healthy individuals with area under the curve (AUC) ≥ 0.703 (P < .05). CONCLUSION: Results indicated the importance of elevated levels of CXCL10 and deficiency of vitamin D on the pathogenesis of active LN disease.


Assuntos
Quimiocina CXCL10/sangue , Nefrite Lúpica/sangue , Deficiência de Vitamina D/sangue , Vitamina D/sangue , Adulto , Biomarcadores/sangue , Feminino , Humanos , Testes de Função Renal , Lúpus Eritematoso Sistêmico/diagnóstico , Nefrite Lúpica/diagnóstico , Nefrite Lúpica/fisiopatologia , Masculino , Pessoa de Meia-Idade , Curva ROC , Índice de Gravidade de Doença
19.
Arthritis Res Ther ; 21(1): 267, 2019 12 04.
Artigo em Inglês | MEDLINE | ID: mdl-31801580

RESUMO

BACKGROUND: The information concerning non-invasive, easily obtainable, and accurate biomarkers for diagnosis of lupus nephritis (LN) is extremely limited. The aim of this study was to evaluate the diagnostic performance of cystatin C (CysC) and complement component 1q (C1q) for LN. METHODS: A case-control study that included 905 patients with systemic lupus erythematosus (SLE) without LN (group SLE), 334 patients with active lupus nephritis (group LNA), 255 patients with inactive lupus nephritis (group LNI), and 497 healthy individuals (group HC) was performed in Mianyang Central Hospital from March 2017 to December 2018. The serum levels of CysC, C1q, urea (Urea), and creatinine (Creat) were measured, and 2 estimated glomerular filtration rates (eGFRCysC and eGFRCreat) were calculated by equations which were based on serum CysC established by our group and the modification of diet in renal disease (MDRD), respectively. ANOVA analysis or Kruskal-Wallis test was used for comparing the differences among the groups, and receiver operating characteristic (ROC) curve was applied to identify the diagnostic efficiencies of individual or combined multiple indicators. RESULTS: Significantly elevated CysC and decreased C1q were observed in the LNA and LNI groups, which was in contrast to their levels in the SLE and HC groups. CysC (AUC = 0.906) or eGFRCysC (AUC = 0.907) assessed the highest diagnostic performance on LNA when detected individually, followed by C1q (AUC = 0.753). Joint utilization of C1q and CysC achieved very good performance (AUC = 0.933) which approximated to the best one observed in the combinations of C1q, Urea, CysC, eGFRCreat, and Creat (AUC = 0.975). CONCLUSION: The separately detected CysC (eGFRCysC) and C1q were superior to the conventional biomarkers Urea, Creat, and eGFRCreat in the diagnosis of LNA. Moreover, although the combined detection of Urea, Creat, C1q, CysC, and eGFRCreat had the greatest diagnostic performance, the joint utilization of CysC and C1q could be prioritized for rapid discrimination of LNA if the economic burden is taken into consideration.


Assuntos
Biomarcadores/sangue , Complemento C1q/análise , Cistatina C/sangue , Nefrite Lúpica/sangue , Nefrite Lúpica/diagnóstico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
20.
Lupus ; 28(14): 1669-1677, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31718467

RESUMO

OBJECTIVE: To examine longitudinal associations of active lupus nephritis with organ damage accrual in patients with systemic lupus erythematosus (SLE). METHODS: This study was performed using data from a large multinational prospective cohort. Active lupus nephritis at any visit was defined by the presence of urinary casts, proteinuria, haematuria or pyuria, as indicated by the cut-offs in the SLE Disease Activity Index (SLEDAI)-2K, collected at each visit. Organ damage accrual was defined as a change of SLICC-ACR Damage Index (SDI) score >0 units between baseline and final annual visits. Renal damage accrual was defined if there was new damage recorded in renal SDI domains (estimated glomerular filtration rate <50%/proteinuria >3.5 g per 24 h/end-stage kidney disease). Time-dependent hazard regression analyses were used to examine the associations between active lupus nephritis and damage accrual. RESULTS: Patients (N = 1735) were studied during 12,717 visits for a median (inter-quartile range) follow-up period of 795 (532, 1087) days. Forty per cent of patients had evidence of active lupus nephritis at least once during the study period, and active lupus nephritis was observed in 3030 (24%) visits. Forty-eight per cent of patients had organ damage at baseline and 14% accrued organ damage. Patients with active lupus nephritis were 52% more likely to accrue any organ damage compared with those without active lupus nephritis (adjusted hazard ratio = 1.52 (95% confidence interval (CI): 1.16, 1.97), p < 0.02). Active lupus nephritis was strongly associated with damage accrual in renal but not in non-renal organ domains (hazard ratios = 13.0 (95% CI: 6.58, 25.5) p < 0.001 and 0.96 (95% CI: 0.69, 1.32) p = 0.8, respectively). There was no effect of ethnicity on renal damage accrual, but Asian ethnicity was significantly associated with reduced non-renal damage accrual. CONCLUSION: Active lupus nephritis measured using the SLEDAI-2K domain cut-offs is associated with renal, but not non-renal, damage accrual in SLE.


Assuntos
Rim/patologia , Lúpus Eritematoso Sistêmico/fisiopatologia , Nefrite Lúpica/diagnóstico , Nefrite Lúpica/epidemiologia , Adolescente , Adulto , Idoso , Progressão da Doença , Feminino , Taxa de Filtração Glomerular , Humanos , Internacionalidade , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Prospectivos , Índice de Gravidade de Doença , Adulto Jovem
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