ABSTRACT
Background: The B-cell activating factor (BAFF) controls the maturation and survival of B cells. An imbalance in this cytokine has been associated with systemic autoimmunity in SLE and lupus nephritis (LN). However, few investigations have evaluated the tissular expression of BAFF in LN. This study aimed to associate BAFF system expression at the tissular level with the proliferative LN classes. Methods: The analysis included eighteen kidney tissues, with sixteen LN (class III = 5, class IV = 6, class III/IV+V = 4, and class V = 1), and two controls. The tissular expression was evaluated with an immunochemistry assay. A Cytation5 imaging reader and ImageJ software were used to analyze the quantitative expression. A p-value < 0.05 was considered significant. Results: The expressions of BAFF, A proliferation-inducing ligand (APRIL), and their receptors were observed in glomerular, tubular, and interstitial zones, with BAFF being the most strongly expressed in the overall analysis. BAFF-Receptor (BR3), transmembrane activator and CALM interactor (TACI), and B-Cell maturation antigen (BCMA) displayed higher expressions in LN class IV in all zones analyzed (p < 0.05). Additionally, a positive correlation was found between APRIL, TACI, and BCMA at the glomerular level; BCMA and APRIL in the interstitial zone; and BR3, TACI, and BCMA in the tubule (p < 0.05). Conclusions: The expression of BAFF and BAFF receptors is mainly associated with LN class IV, emphasizing the participation of these receptors as an essential pathogenic factor in kidney involvement in SLE patients.
ABSTRACT
The optimal duration of maintenance immunosuppressive therapy for patients with lupus nephritis who have achieved clinical remission has not been established. Furthermore, clinical and histologic remissions are often discordant. We postulated that continuing therapy for patients with persistent histologic activity on kidney biopsies done during maintenance and discontinuing therapy only for patients without histologic activity would minimize subsequent lupus nephritis flares. To test this, a cohort of 75 prospectively-followed patients with proliferative lupus nephritis was managed using kidney biopsies performed during maintenance therapy. These patients had been on immunosuppression for at least 42 months, had responded, and had maintained their clinical response for at least 12 months before the kidney biopsy was repeated. Maintenance therapy was withdrawn if the biopsy showed an activity index of zero, but was continued if the biopsy showed an activity index of one or more. A lupus nephritis flare developed in seven patients during the average 50 months from the third biopsy and the final clinic visit for a flare rate of 1.5/year; significantly less than reported flare rates. Baseline clinical parameters (serum creatinine, proteinuria) and serologic parameters (complement C3, C4 and anti-dsDNA) did not predict an activity index of zero on the third biopsy or who would have a lupus nephritis flare. No patients developed end-stage kidney disease. Four patients developed de novo chronic kidney disease. There were no serious adverse events related to biopsy. Thus, at an experienced center, biopsy-informed management of maintenance immunosuppression is safe and may improve the lupus nephritis flare rate compared to conventional clinical management.
Subject(s)
Immunosuppressive Agents/administration & dosage , Kidney Failure, Chronic/prevention & control , Kidney/pathology , Lupus Nephritis/drug therapy , Medication Therapy Management , Adult , Biopsy/standards , Disease Progression , Female , Follow-Up Studies , Humans , Immunosuppressive Agents/adverse effects , Kidney/drug effects , Kidney/immunology , Kidney Failure, Chronic/immunology , Lupus Nephritis/complications , Lupus Nephritis/diagnosis , Lupus Nephritis/immunology , Maintenance Chemotherapy/adverse effects , Maintenance Chemotherapy/methods , Male , Symptom Flare Up , Young AdultABSTRACT
INTRODUCCIÓN: La nefritis lúpica proliferativa (NPL) con proliferación extra capilar focal (PECF) es una entidad frecuente en las biopsias renales, pero poco se conoce acerca de su evolución. Este estudio se realizó para investigar la correlación clínica, histológica y de laboratorio en la evolución de estos pacientes. OBJETIVO: Analizar las biopsias de nefritis lúpicas proliferativas focales o difusas (clases III y IV de la OMS), y su evolución de acuerdo al grado de proliferación extracapilar en un período de 10 años, en el Hospital de Clínicas "José de San Martín". MATERIAL Y MÉTODOS: Estudio observacional retrospectivo, se incluyeron 147 pacientes con GN clase III o IV, estudiados en un período de 10 años. Se subdividieron en base al compromiso extracapilar en: grupo 1 (5- <25% de semilunas, n=33), grupo 2 (25- 50% semilunas, n=34) y grupo 3 (>50% semilunas, n= 20) o proliferación extracapilar difusa (PECD). Los pacientes con nefritis lúpica III y IV, sin compromiso extra capilar, se denominó grupo control (n=60); las características clínicas, laboratorios y evolución en cuanto alcanzar remisión completa al año fueron comparadas entre los subgrupos y el grupo de control. Remisión completa se definió según normas KDIGO 2012. Se realizó un análisis univariado y posteriormente un multivariado, ambos con regresión logística. RESULTADOS: Hubo 124 mujeres (84,35%) y 23 hombres (15,65%) con una edad media de 35±10 años. Edad media en el grupo control, 32±10 años. El univariado mostro mayor remisión completa en el grupo control con odds ratio 0.05 (0.02.-0.12) p=0.001, y menor remisión completa en los 3 subgrupos con proliferación extra capilar, inclusive el grupo I con un odds ratio 7.61 (2,42-23.9) y valor de p=0.001 en dicho grupo. El análisis multivariado evidenció que la persistencia de la proteinuria a los 6 meses tenía significación estadística para no alcanzar la remisión completa, con un odd ratio 2.81 (1.58-5.0), valor de p=0.001. CONCLUSIÓN: La presencia de distintos grados de semilunas en la histología de las NL proliferativas (NPL), clase III y IV, y la persistencia de la proteinuria a los 6 meses, son marcadores independiente para no alcanzar la remisión completa al año
IINTRODUCTION: Although focal lupus nephritis (FLN) with extracapillary proliferation (ECP) is usually found in renal biopsies, little is known about its course. This study was carried out to investigate the correlation of clinical, histological and laboratory findings in these patients' progress. OBJECTIVE: To analyze focal or diffuse proliferative lupus nephritis biopsies (class III and IV, according to WHO) and their development regarding the level of extracapillary proliferation throughout a period of 10 years at Hospital de Clínicas 'José de San Martín'. METHODS: In this retrospective observational study, 147 patients with class III or IV GN were observed for 10 years. According to the degree of extracapillary proliferation, they were divided into the following groups: group 1 (5% <25% of crescents, n=33), group 2 (25% 50% of crescents, n=34) and group 3 [>50% of crescents, i.e. diffuse proliferative nephritis (DPN), n=20]. Patients suffering from class III and IV lupus nephritis with no extracapillary proliferation formed the control group (n=60). After one year, clinical and laboratory findings as well as the development of the condition among the four groups were compared to assess their level of remission. Complete remission was considered as defined in KDIGO 2012 Guideline. A univariate logistic regression analysis and a subsequent multivariate one were performed. RESULTS: There were 124 women (84.35%) and 23 men (15.65%) with an average age of 35±10. The average age in the control group was 32±10. The univariate analysis showed a greater number of patients who achieved complete remission in the control group with an odds ratio of 0.05 (0.02 0.12) p=0.001, whereas in the 3 groups with extracapillary proliferation fewer patients reached this state, even in group 1, which had an odds ratio of 7.61 (2.42 23.9) and p=0.001. The multivariate analysis revealed that the persistent protein in the urine after 6 months was statistically significant for not achieving complete remission, the odds ratio being 2.81 (1.58 5.0) and p=0.001. CONCLUSION: The presence of various degrees of crescent formation in class III and IV proliferative lupus nephritis (PLN) shown in the histological findings and the persistent protein in the urine at 6 months constitute independent factors for not achieving complete remission after one year