RESUMO
Proliferative lupus nephritis (PLN) is a serious organ-threatening manifestation of systemic lupus erythematosus (SLE) that is associated with high mortality and renal failure. Here, we analyzed data from 1287 SLE patients with renal manifestations, including 780 of which were confirmed as proliferative or non-proliferative LN patients by renal biopsy, divided into a training cohort (547 patients) and a validation cohort (233 patients). By applying a least absolute shrinkage and selection operator (LASSO) regression approach combined with multivariate logistic regression analysis to build a nomogram for prediction of PLN that was then assessed by receiver operating characteristic (ROC) curves, calibration curves, and clinical decision curves (DCA) in both the training and validation cohorts. The area under the ROC curve (AUC) of the model in the training cohort was 0.921 (95% confidence interval (CI): 0.895-0.946), the AUC of internal validation in the training cohort was 0.909 and the AUC of external validation was 0.848 (95% CI: 0.796-0.900). The nomogram showed good performance as evaluated using calibration and DCA curves. Taken together, our results indicate that our nomogram that comprises 12 significantly relevant variables could be clinically valuable to prognosticate on the risk of PLN in SLE, so as to improve patient prognoses.
Assuntos
Lúpus Eritematoso Sistêmico , Nefrite Lúpica , Nomogramas , Humanos , Feminino , Masculino , Adulto , Lúpus Eritematoso Sistêmico/complicações , Rim/patologia , Curva ROC , Pessoa de Meia-Idade , Prognóstico , Adulto Jovem , Estudos de Coortes , Fatores de RiscoRESUMO
OBJECTIVES: To compare proliferative (PLN) and membranous (MLN) lupus nephritis (LN) regarding clinical and laboratory presentation and long-term outcomes; To investigate predictors of progression to chronic kidney disease (CKD). METHODS: Multicentre observational study, with retrospective analysis of a prospective cohort, using data from the Rheumatic Diseases Portuguese Registry-Reuma.pt. Patients with biopsy-proven PLN, MLN and mixed LN were included. Cox regression survival analysis was used to investigate predictors of CKD. RESULTS: 260 patients were included. Median follow-up was 8 years (IQR 11; minimum 1, maximum 35 years). MLN patients presented with significantly lower serum creatinine (0.70 (IQR 0.20; minimum 0.50, maximum 1.30) mg/dl vs 0.80 (IQR 0.31; minimum 0.26, maximum 2.60) in PLN, p= 0.003). Proteinuria levels did not differ between groups (p= 0.641). Levels of complement were reduced in PLN but nearly normal in MLN patients, and there were fewer patients with positive anti-dsDNA antibodies in the MLN group (p< 0.001). One year after the beginning of treatment, 62% of the patients achieved EULAR/ERA-EDTA complete response, with further 5% achieving partial response. Patients with lower proteinuria at diagnosis were more likely to achieve a complete renal response at one year, however, proteinuria at diagnosis or at one year did not predict long term CKD. Estimated glomerular filtration rate (eGFR) ≤75 mL/min/1.73 m2 at one year was the strongest predictor of progression to CKD (HR 23 [95% CI 8-62], p< 0.001). Other possible predictors included the use of azathioprine for induction of remission, older age at diagnosis and male sex. CONCLUSION: Proteinuria levels did not predict LN histologic class in our cohort. eGFR cutoff of 75 mL/min/1.73 m2 after one year of treatment was strongly predictive of progression to CKD.
RESUMO
OBJECTIVES: To investigate the expression of type I IFN (IFN-I) and neutrophil transcripts in kidney tissue from patients with different classes of LN and their association with distinct clinical and histopathological features. METHODS: Quantitation of IFN-I, defensin-α3 and formyl peptide receptor-like 1 (FPRL-1) transcripts was performed in kidney biopsy tissue from 24 patients with various classes of LN (6 class III, 14 class IV, 4 class V) and 3 control samples. Patient demographics, glomerular filtration rate (eGFR) and histopathological characteristics, including activity and chronicity indices, were analysed. RESULTS: IFNα2 and IFNß transcripts were overexpressed in renal tissues from patients with proliferative forms of LN (III/IV) compared with patients with membranous nephritis and control kidneys. Patients with LN and impaired renal function, attested by eGFR, displayed higher relative expression of IFNα2 transcripts in renal tissues compared with those with normal renal function (23.0 ± 16.2 vs 12.0 ± 14.8, P = 0.04). Defensin-α3, but not FPRL-1, transcripts were overexpressed in LN tissues, particularly those with segmental necrotizing lesions, and were correlated with higher renal pathological activity indices (r = 0.61, P = 0.02), urinary protein levels (r = 0.44, P = 0.048) and IFNα2 expression (r = 0.50, P = 0.01). CONCLUSION: IFN-I transcripts are expressed locally in kidneys from patients with proliferative LN and are associated with impaired renal function. Elevated defensin-α3 transcripts, a neutrophil product associated with neutrophil extracellular traps, may identify a driver of local IFN-I expression. These findings provide insights into the mechanisms of proliferative LN and may inform therapeutic decisions regarding selection of IFN-I pathway inhibitors.
Assuntos
Nefrite Lúpica , Humanos , Nefrite Lúpica/tratamento farmacológico , Neutrófilos/metabolismo , Rim/patologia , Biópsia , Defensinas/uso terapêuticoRESUMO
BACKGROUND: Despite progress in the diagnosis and treatment of proliferative lupus nephritis (PLN), the prognosis remains unfavorable. Previous investigations have suggested that the deficiency of regulatory T cells (Tregs) is involved in the pathogenesis of systemic lupus erythematosus (SLE) and lupus nephritis (LN). But the prognostic value of Tregs in PLN remains controversial. This study aimed to investigate the association of Tregs with renal outcomes in patients with PLN. METHODS: The baseline and follow-up data of patients with biopsy-proven PLN were collected in this study. All patients were divided into two groups according to whether the renal endpoint event occurred. Clinicopathologic features and therapeutic responses were compared between the two groups. Cox regression analyses curve fitting and threshold effect analysis were implemented to investigate the relationship between Tregs level and the long-term renal outcomes. The renal endpoint was defined as end-stage kidney disease (ESKD) or doubling the SCr value. RESULTS: A total of 405 PLN patients were included. After a follow-up of 71.53 (53.13-97.47) months, 42 (10.4%) patients reached the renal endpoint. The Treg cell counts (16/µL) in the renal endpoint group were significantly decreased than that in the non-renal endpoint group (p < 0.001). Univariate and multivariate Cox regression analyses showed that the high level of Tregs was an independent protective factor for the long-term renal prognosis of PLN. Smooth curve fitting of the generalized additive mixed model analysis indicated that the risk of renal endpoint first decreased with Tregs and then slightly increased along with Treg cell levels. The segmented linear model revealed that when Treg cell counts <46/µL, the risk of renal endpoint decreased by 6.8% for every 1 µL increase in Treg levels (p = 0.0029). CONCLUSION: Treg cell counts are closely related to the long-term renal outcomes of patients with PLN, and increasing Treg cell levels may play an important role in improving the prognosis of the kidney, but there may be a turning point (i.e., threshold effect) at the Treg cell counts that leads to directional changes in the renal outcomes.
Assuntos
Falência Renal Crônica , Lúpus Eritematoso Sistêmico , Nefrite Lúpica , Humanos , Nefrite Lúpica/tratamento farmacológico , Linfócitos T Reguladores , Lúpus Eritematoso Sistêmico/complicações , Rim/patologia , Falência Renal Crônica/etiologia , Estudos RetrospectivosRESUMO
Childhood-onset systemic lupus erythematosus (SLE) is characterized by increased rates of kidney involvement, termed lupus nephritis. Despite the significant morbidity and mortality associated with this disease, lupus nephritis trials have been plagued by repeated failures to meet clinical endpoints. However, improvements in trial design and the development of targeted approaches have begun to yield promising results, including two new FDA-approved lupus nephritis treatments since 2020. These include belimumab, a monoclonal antibody targeting the B cell survival cytokine BAFF (B cell activating factor), and voclosporin, a cyclosporin analog with improved pharmacokinetic characteristics. In this review, we will summarize the data supporting regulatory approval for these agents in lupus nephritis and highlight ongoing clinical trials targeting the diverse immunologic drivers of renal inflammation in SLE. While pediatric patients remain underrepresented in lupus clinical trials, given the increased severity of childhood-onset SLE and need for long-term protection from kidney damage, we anticipate the need for off-label use of these targeted therapies in the pediatric population. Future studies are needed to define optimal patient selection, drug combinations, and treatment duration in pediatric lupus nephritis.
Assuntos
Lúpus Eritematoso Sistêmico , Nefrite Lúpica , Humanos , Criança , Nefrite Lúpica/tratamento farmacológico , Anticorpos Monoclonais/uso terapêutico , Citocinas , Imunoterapia/métodos , Imunossupressores/uso terapêuticoRESUMO
Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the overproduction of multiple autoantibodies. Lupus nephritis (LN), the most common cause of morbidity and mortality, requires early detection. However, only a limited number of serum biomarkers have been associated with the disease activity of LN. Serum IgE anti-dsDNA autoantibodies are prevalent in patients with SLE and may be associated with the pathogenesis of LN. In this study, serum samples from 88 patients with biopsy-proven proliferative LN were collected along with complete clinical and pathological data to investigate the clinical and pathological associations of anti-dsDNA IgE autoantibodies using ELISA. This study found that the prevalence of IgE anti-dsDNA autoantibodies in patients with proliferative LN was 38.6% (34/88). Patients with anti-dsDNA IgE autoantibodies were more prone to acute kidney injury (17/34 vs. 14/54; p = .025). Levels of anti-dsDNA IgE autoantibodies were associated with interstitial inflammation (r = 0.962, p = .017). Therefore, anti-dsDNA IgE autoantibody levels are associated with tubulointerstitial inflammation in patients with proliferative LN.
Assuntos
Anticorpos Antinucleares , Imunoglobulina E , Nefrite Lúpica , Humanos , Autoanticorpos , Imunoglobulina E/sangue , Inflamação , Lúpus Eritematoso Sistêmico , Nefrite Lúpica/sangue , Nefrite Lúpica/patologia , Anticorpos Antinucleares/sangueRESUMO
Renal injury in lupus nephritis (LN) does not manifest as one uniform entity. The clinical presentation, management, and prognosis of membranous LN (MLN) differ from that of the proliferative LN (PLN). Differentiating the molecular mechanisms involved in MLN and PLN and discovering the reliable biomarkers for early diagnosis and target therapy are important. We compared the kidney protein expression patterns of 11 pure MLN and 12 pure PLN patients on formalin-fixed paraffin-embedded (FFPE) kidney tissues using label-free liquid chromatography-mass spectrometry (LC-MS) for quantitative proteomics analysis. FunRich software was used to identify proteins in differentially expressed pathways. Quantitative comparisons of differentially expressed proteins in each patient were further analyzed based on protein intensity levels determined by LC-MS. The protein-protein interaction (PPI) network of the differentially expressed genes (DEGs) was established through Search Tool for the Retrieval of Interacting Genes database (STRING) website, visualized by Cytoscape. A total of 5112 proteins were identified. In total, 12 significantly upregulated (fold change ≥2, p < 0.05) proteins were identified in the MLN group and 220 proteins (fold change ≥2, p < 0.05) were upregulated in the PLN group. Further analysis showed that the most significant upregulated pathway involved in MLN was histone deacetylase (HDAC) class I pathway, and the three most significant upregulated pathways in PLN were interferon signaling, interferon gamma signaling, and the immune system. Next, we selected sirtuin-2 (SIRT2) in MLN, and vascular cell adhesion protein 1 (VCAM1) and Bcl-xl in PLN for further mass spectrometry (MS) intensity and PPI analysis. SIRT2 expression was significantly increased in the MLN group compared with the PLN group, and VCAM1, Bcl-xl expression was significantly increased in the PLN group compared with the MLN group, based on MS intensity. These results may help to improve our understanding of the underlying molecular mechanisms of MLN and PLN and provide potential targets for the diagnosis and treatment of different subclasses of LN.
Assuntos
Lúpus Eritematoso Sistêmico , Nefrite Lúpica , Humanos , Rim , Lúpus Eritematoso Sistêmico/metabolismo , Nefrite Lúpica/metabolismo , ProteômicaRESUMO
OBJECTIVES: Proliferative lupus nephritis (LN) is a crucial complication in systemic lupus erythematosus (SLE). This study evaluated the clinical implications of coexistence of membranous LN in proliferative LN in terms of clinical characteristics and long-term outcome. METHODS: We retrospectively reviewed the medical records of patients with SLE who underwent renal biopsy between 2005 and 2018. Patients with proliferative LN based on the 2003 International Society of Nephrology/Renal Pathology Society classification were subclassified into pure (Class III or IV only) and mixed (Class III or IV + Class V) proliferative LN. The clinical features at the time of renal biopsy, incidence of end-stage renal disease (ESRD), and all-cause mortality were compared between patients with mixed or pure proliferative LN. RESULTS: Of the 171 patients, 30 and 141 were classified into mixed and pure proliferative LN groups, respectively. Patients with pure proliferative LN showed higher anti-dsDNA antibody and lower hemoglobin, platelet, and complement 3 levels than patients with mixed proliferative LN. The SLE disease activity index was also higher in patients with pure proliferative LN (p = 0.047). The pure proliferative LN group showed a higher proportion of Class IV and higher histologic activity index scores (p < 0.001 and p = 0.004, respectively). During the follow-up period of 58.3 months, 18 patients developed ESRD and 15 patients died. ESRD was exclusively observed in patients with pure proliferative LN, although the incidence of ESRD was not statistically different (p = 0.055). All-cause mortality was comparable between the two groups. CONCLUSION: Pure proliferative LN was associated with higher clinical and histological activities and modestly increased risk of ESRD. Active immunosuppressive treatment would be required to control the renal inflammation in patients with proliferative LN, regardless of the coexistence of membranous LN.
Assuntos
Lúpus Eritematoso Sistêmico , Nefrite Lúpica , Anticorpos Antinucleares , Biópsia , Humanos , Rim/patologia , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/patologia , Nefrite Lúpica/complicações , Nefrite Lúpica/epidemiologia , Estudos RetrospectivosRESUMO
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.
Assuntos
Imunossupressores/administração & dosagem , Falência Renal Crônica/prevenção & controle , Rim/patologia , Nefrite Lúpica/tratamento farmacológico , Conduta do Tratamento Medicamentoso , Adulto , Biópsia/normas , Progressão da Doença , Feminino , Seguimentos , Humanos , Imunossupressores/efeitos adversos , Rim/efeitos dos fármacos , Rim/imunologia , Falência Renal Crônica/imunologia , Nefrite Lúpica/complicações , Nefrite Lúpica/diagnóstico , Nefrite Lúpica/imunologia , Quimioterapia de Manutenção/efeitos adversos , Quimioterapia de Manutenção/métodos , Masculino , Exacerbação dos Sintomas , Adulto JovemRESUMO
BACKGROUND: Children presenting with proliferative lupus nephritis (LN) are treated with intensified immunosuppressive protocols. Data on renal outcome and treatment toxicity is scare. METHODS: Twelve-month renal outcome and comorbidity were assessed in 79 predominantly Caucasian children with proliferative LN reported to the Lupus Nephritis Registry of the German Society of Paediatric Nephrology diagnosed between 1997 and 2015. RESULTS: At the time of diagnosis, median age was 13.7 (interquartile range 11.8-15.8) years; 86% showed WHO histology class IV, nephrotic range proteinuria was noted in 55%, and median estimated glomerular filtration rate amounted to 75 ml/min/1.73 m2. At 12 months, the percentage of patients with complete and partial remission was 38% and 41%, respectively. Six percent of patients were non-responders and 15% presented with renal flare. Nephrotic range proteinuria at the time of diagnosis was associated with inferior renal outcome (odds ratio 5.34, 95% confidence interval 1.26-22.62, p = 0.02), whereas all other variables including mode of immune-suppressive treatment (e.g., induction treatment with cyclophosphamide (IVCYC) versus mycophenolate mofetil (MMF)) were not significant correlates. Complications were reported in 80% of patients including glucocorticoid toxicity in 42% (Cushingoid appearance, striae distensae, cataract, or osteonecrosis), leukopenia in 37%, infection in 23%, and menstrual disorder in 20%. Growth impairment, more pronounced in boys than girls, was noted in 78% of patients. CONCLUSIONS: In this cohort of juvenile proliferative LN, renal outcome at 12 months was good irrespectively if patients received induction treatment with MMF or IVCYC, but glucocorticoid toxicity was very high underscoring the need for corticoid sparing protocols. Graphical abstract.
Assuntos
Ciclofosfamida/administração & dosagem , Inibidores Enzimáticos/administração & dosagem , Imunossupressores/administração & dosagem , Nefrite Lúpica/tratamento farmacológico , Ácido Micofenólico/administração & dosagem , Adolescente , Criança , Ciclofosfamida/efeitos adversos , Inibidores Enzimáticos/efeitos adversos , Feminino , Alemanha , Glucocorticoides/efeitos adversos , Humanos , Imunossupressores/efeitos adversos , Masculino , Ácido Micofenólico/efeitos adversos , Estudos Prospectivos , Sistema de Registros , Indução de Remissão , Estudos Retrospectivos , Resultado do TratamentoRESUMO
OBJECTIVES: Favourable long-term prognosis in proliferative lupus nephritis (LN) is associated with the achievement of complete renal response (CR), which is defined as a urine protein/creatinine ratio (UPCR) of < 0.5. However, it is unclear whether a more stringent cut-off for proteinuria (normal value of proteinuria; UPCR < 0.15) is better than CR. We aimed to evaluate the effect of stringent CR, defined as a UPCR of <0.15, on long-term renal outcomes in proliferative LN. METHODS: We included 87 patients with class III or IV LN who achieved CR at one year after induction therapy. Clinical and laboratory data were compared between the stringent and non-stringent CR groups. Logistic regression analysis was performed to identify factors associated with achievement of stringent CR. Cox analysis was performed to analyse the risk factors for renal flare and development of chronic kidney disease (CKD). RESULTS: The stringent and non-stringent CR groups included 58 and 29 patients, respectively. The two groups showed no significant baseline differences in terms of the clinical, laboratory and pathological classification. The sustained CR rates during five years were 91.3% and 50.0% (p = 0.014) in the stringent and non-stringent CR groups, respectively. In Cox analyses, the achievement of stringent CR was associated with a lower risk of five-year renal flare rate (hazard ratio (HR) = 0.161, 95% confidence interval (CI) 0.063-0.411, p < 0.01) and development of CKD (HR = 0.189, 95% CI 0.047-0.752, p = 0.018). Mycophenolate mofetil induction therapy was associated with achievement of stringent CR at a borderline level of significance (HR = 7.268, 95% CI 0.894-59.089, p = 0.064). CONCLUSION: Achievement of stringent CR predicted lower risk of renal flare and development of CKD in proliferative LN. These findings suggest that stringent CR is a valuable treatment target in proliferative LN.
Assuntos
Imunossupressores/administração & dosagem , Nefrite Lúpica/fisiopatologia , Ácido Micofenólico/administração & dosagem , Proteinúria/epidemiologia , Adulto , Feminino , Humanos , Nefrite Lúpica/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Prognóstico , Proteinúria/etiologia , Indução de Remissão , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: Few data are available about the rate of short-term remission and its impact on the long-term outcomes of proliferative lupus nephritis in the Middle East. METHODS: An observational study was carried out involving 96 adult patients with biopsy-proven focal or diffuse proliferative lupus nephritis (PLN) from four different hospitals. Data on induction, remission and long-term outcomes were collected and analyzed. RESULTS: Among the 96 patients with biopsy-proven PLN (median age 27 (IQR: 21,34) years, 85% women and median duration of systemic lupus erythematosus (SLE) prior to diagnosis 27 (IQR: 11, 55) months), 67% developed remission at 6 months (proportion 0.67; 95% CI 0.57, 0.76). Mycophenolate mofetil (MMF) was used in 45/96 (47%), CYC in 41/95 (43%) and other agents in 10/96 (10%). The choice of MMF as induction agent has increased in recent years. Among baseline characteristics, only histologic activity was found to have a significant association with remission, with active lesions more likely to remit than active/chronic and chronic lesions (AOR 6.5, 95% CI 1.44-29.39, p = 0.015). Based on Kaplan-Meier analysis, the 5-year renal survival rate without doubling serum creatinine was 73.8%. Compared to patients with complete remission, lower long-term renal survival rates were observed in patients with no remission (89.7 versus 43%, p = 0.001) and partial remission (89.7 versus 77.6%, p = 0.256). The cumulative rate of doubling serum creatinine, dialysis, relapse and death was 23%, 11%, 10% and 5%, respectively, at 48-month median follow up. CONCLUSION: Approximately two-thirds of patients with PLN develop remission in response to standard induction therapy. Remission was negatively associated with the presence of chronic changes in renal biopsy. Overall, MMF is the most commonly used agent to induce remission; however, with more severe disease CYC, is used more frequently. PLN is associated with significant long-term renal outcomes including a 26% cumulative rate of doubling of serum creatinine at 5 years. Initial remission predicts this long-term renal survival.
Assuntos
Creatinina/sangue , Imunossupressores/uso terapêutico , Lúpus Eritematoso Sistêmico/complicações , Nefrite Lúpica/tratamento farmacológico , Adulto , Ciclofosfamida/uso terapêutico , Feminino , Humanos , Nefrite Lúpica/diagnóstico , Nefrite Lúpica/fisiopatologia , Masculino , Ácido Micofenólico/uso terapêutico , Indução de Remissão , Estudos Retrospectivos , Arábia Saudita , Fatores de Tempo , Resultado do Tratamento , Adulto JovemRESUMO
OBJECTIVE: This study aimed to evaluate long-term efficacy of low dose cyclosporine A (CsA) in the treatment of resistant proliferative lupus nephritis. METHODS: In this retrospective study, patients with biopsy proven proliferative lupus nephritis who were unresponsive to combination therapy with steroid plus mycophenolate mofetil (MMF) or cyclophosphamide (CYC) and had been treated with CsA were included. Efficacy monitoring was based on the systemic lupus erythematosus (SLE) disease activity index, dose of prednisolone, serum complement, anti-double stranded DNA (anti-dsDNA) titration, urine analysis, proteinuria, creatinine clearance, remission of the renal disease, renal survival and involvement of other organs. RESULTS: This study included 27 consecutive patients (22 females, 5 males) with resistant proliferative lupus nephritis. Mean duration of follow up and treatment with CsA were 40.7 ± 24.9 and 35.2 ± 19.1 months, respectively. Complete and partial renal remission occurred in 66.9% and 25.7% patients, respectively. Creatinine clearance was stable, proteinuria and anti-dsDNA titer decreased, and C3 and C4 increased significantly during the treatment with CsA. Severe complications such as death, dialysis, kidney transplantation and severe infection did not occur in the studied patients during the follow-up period. CONCLUSIONS: Low-dose CsA could induce renal remission and ameliorate the SLE disease activity in patients with resistant proliferative lupus nephritis and it would be a safe drug for treatment of these patients.
Assuntos
Ciclosporina/uso terapêutico , Imunossupressores/uso terapêutico , Nefrite Lúpica/tratamento farmacológico , Adulto , Ciclosporina/administração & dosagem , Ciclosporina/efeitos adversos , Feminino , Humanos , Imunossupressores/administração & dosagem , Imunossupressores/efeitos adversos , Masculino , Pessoa de Meia-Idade , Indução de RemissãoRESUMO
BACKGROUND: proliferative lupus nephritis (LN) has higher prevalence and worse prognosis than non-proliferative LN. Renal biopsy plays an important role in diagnosis and therapy of LN, but there are some obstacles in its implementation. A diagnostic scoring system for proliferative LN is necessary, especially for cases in which renal biopsy cannot be performed. This study aimed to develop a diagnostic scoring system of proliferative LN based on its diagnostic determinants including hypertension, proteinuria, hematuria, eGFR, anti-dsDNA antibody, and C3 levels. METHODS: a cross-sectional study with total sampling method was conducted. Our subjects were adult LN patients who underwent renal biopsy in Cipto Mangunkusumo Hospital between January 2007 and June 2017. RESULTS: from a total of 191 subjects with biopsy-proven LN in this study, we found a proportion of proliferative LN of 74.8%. There were 113 subjects included for analysis of proliferative LN determinants. The multivariate analysis demonstrated that determinants for proliferative LN were hypertension (OR 3.39; 95% CI 1.30-8.84), eGFR <60ml/min/1.73m2 (OR 9.095; 95% CI 1.11-74.68), and low C3 levels (OR 3.97; 95% CI 1.41-11.17). After further analysis, we found that hypertension, eGFR <60ml/min/1.73m2, low C3 levels, and hematuria were essential components of the diagnostic scoring system on proliferative LN. The scoring system was tested with ROC curve and an AUC of 80.4% was obtained (95% CI 71.9-89). CONCLUSION: the proportion of proliferative LN in biopsy-proven LN patients of Cipto Mangunkusumo Hospital is 74.8%. Components of scoring system for proliferative LN consist of hypertension, eGFR <60ml/min/1.73m2, low C3 levels, and hematuria.
Assuntos
Complemento C3/análise , Hipertensão/complicações , Rim/patologia , Nefrite Lúpica/diagnóstico , Nefrite Lúpica/fisiopatologia , Proteinúria/complicações , Adolescente , Adulto , Estudos Transversais , Feminino , Taxa de Filtração Glomerular , Humanos , Indonésia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Curva ROC , Estudos Retrospectivos , Adulto JovemRESUMO
Background Repeat renal biopsies in patients with lupus nephritis are usually done to guide treatment or to establish disease chronicity. Their value is not clear from available literature. There are also no available data in Africa to guide clinicians. Methods This was a retrospective study of patients undergoing a repeat renal biopsy between January 2003 and December 2014 from a single centre in Cape Town, South Africa. Relevant demographic, clinical and histological records of patients with repeat renal biopsies were documented. Comparison of data from first and second renal biopsy was performed. Results Forty-four patients had at least two biopsies done during the study period. Most patients were females (81.8%). The mean biopsy interval was 2.8 ± 1.8 (range 0.38-9.4) years. Proteinuria was the main indication for the repeat biopsy (36.1%). The glomerular filtration rate and proteinuria worsened between the two biopsies ( p = 0.001 and 0.019, respectively) suggesting disease progression. Most patients (65.4%) with a non-proliferative class of lupus nephritis at first biopsy progressed into a proliferative class, whereas patients with initial proliferative lupus nephritis at first biopsy (77.8%) remained as proliferative at repeat biopsy. Treatment was changed in 85% of patients at second biopsy. Conclusion Repeat renal biopsies in patients with lupus nephritis presents a useful means of assessing disease progression and provides guidance regarding modification of treatment. More studies are, however, required to evaluate the value of repeat biopsies and perhaps the need for protocol renal biopsies in patients with lupus nephritis.
Assuntos
Taxa de Filtração Glomerular , Nefrite Lúpica/diagnóstico , Proteinúria/etiologia , Adolescente , Adulto , Biópsia/métodos , Progressão da Doença , Feminino , Humanos , Nefrite Lúpica/fisiopatologia , Nefrite Lúpica/terapia , Masculino , Estudos Retrospectivos , África do Sul , Adulto JovemRESUMO
Proteinuria is a well-known risk factor for the progression of renal dysfunction in chronic kidney disease; however, its importance for estimating the prognosis of lupus nephritis requires verification. Korean adult patients with renal biopsy-diagnosed diffuse proliferative lupus nephritis who had undergone three or more consecutive urine protein to creatinine ratio or urine dipstick tests within six months after renal biopsy were enrolled. The cumulative risks, predictors, and outcomes of proteinuric remission and flare were evaluated. This study included 26 men and 167 women with a mean age at renal biopsy of 31.2 ± 9.8 years. Eighty-two (42.5%) patients experienced proteinuric remission during the follow-up period. During a mean follow-up of 157.9 ± 69.5 months, among patients who achieved proteinuric remission, one died, one developed end-stage renal disease (ESRD), and two had composite outcomes; among patients without remission, nine died, 24 developed ESRD, and 30 had composite outcomes. Patients who achieved proteinuric remission had a 0.089-fold risk (95% CI: 0.011-0.736) of mortality, 0.110-fold risk (95% CI: 0.013-0.904) of incident ESRD, and 0.210-fold risk (95% CI: 0.048-0.920) of a composite outcome compared to patients without remission. Among the 82 patients who achieved proteinuric remission, 59 (72.0%) experienced at least one proteinuria flare; however, relapse did not correlate with the incidence of outcomes. In conclusion, proteinuric remission is an independent predictive prognostic marker of good renal survival and mortality, regardless of the interval from biopsy to remission, recurrence of proteinuria after remission, renal function status at remission, or hematuria remission.
Assuntos
Nefrite Lúpica/complicações , Proteinúria/etiologia , Adulto , Biópsia , Bases de Dados Factuais , Progressão da Doença , Feminino , Humanos , Imunossupressores/uso terapêutico , Estimativa de Kaplan-Meier , Falência Renal Crônica/diagnóstico , Falência Renal Crônica/etiologia , Nefrite Lúpica/diagnóstico , Nefrite Lúpica/tratamento farmacológico , Nefrite Lúpica/mortalidade , Masculino , Modelos de Riscos Proporcionais , Proteinúria/diagnóstico , Proteinúria/tratamento farmacológico , Proteinúria/mortalidade , Recidiva , Indução de Remissão , República da Coreia , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Urinálise , Adulto JovemRESUMO
We have previously reported the one-year outcomes of 16 children with severe proliferative lupus nephritis (LN) who were treated using a multi-targeted induction protocol based on intravenous (IV) pulse methylprednisolone (MP), mycophenolate mofetil (MMF) and cyclosporine (CSA). This study examined the long-term renal outcomes of these 16 children, followed up for a median duration of 9.2 years (range 5.8-14.2 years). Primary treatment outcome was complete renal remission. Secondary outcomes included patient and renal survival as well as relapse-free and event-free survival. All patients achieved complete renal remission within 24 months (median 8.7 months, range 4.0-24.0 months). Comparing clinical and laboratory parameters at induction and last follow-up, respectively, Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score (25.4 ± 8.7 vs. 0.4 ± 0.8), serum complement C3 (47 ± 21 vs. 107 ± 27 mg/dL), estimated glomerular filtration rate (eGFR) (72 ± 57 vs. 109.7 ± 43 ml/min/1.73 m2) and urine protein (6.97 ± 7.09 vs. 0.2 ± 0.02 g/day/1.73 m2) improved significantly (p < 0.05). Kaplan-Meier survival analysis showed a cumulative ten-year renal relapse-free survival of 73.3% when considering relapses with severe proteinuria >1 g/day/1.73 m2. Cumulative probability that hospitalization would not be required was 93.8% at one year, and 71.4% at ten years. Our multi-targeted protocol for induction and maintenance therapy in Asian children with severe proliferative LN resulted in good long-term patient survival and renal preservation, with a good safety profile.
Assuntos
Ciclosporina/administração & dosagem , Imunossupressores/administração & dosagem , Nefrite Lúpica/tratamento farmacológico , Metilprednisolona/administração & dosagem , Ácido Micofenólico/administração & dosagem , Administração Intravenosa , Adolescente , Fatores Etários , Criança , Pré-Escolar , Intervalo Livre de Doença , Quimioterapia Combinada , Feminino , Seguimentos , Hospitalização , Humanos , Estimativa de Kaplan-Meier , Modelos Logísticos , Nefrite Lúpica/diagnóstico , Nefrite Lúpica/imunologia , Masculino , Pulsoterapia , Recidiva , Indução de Remissão , Fatores de Risco , Índice de Gravidade de Doença , Singapura , Fatores de Tempo , Resultado do TratamentoRESUMO
OBJECTIVES: Mycophenolate mofetil (MMF) is used as one of the standard induction/maintenance protocols for lupus nephritis (LN). However, MMF has not been approved for treating LN in any country, resulting in worldwide off-label use of this immunosuppressant. In order to clarify the real-world use of MMF as a treatment for LN in Japan, Japan College of Rheumatology surveyed the use of MMF in daily clinical practice. METHODS: Adult patients with LN who visited enrolled hospitals from October 2008 to September 2013 were surveyed for the initial, maximum, and maintenance doses of MMF. The safety and efficacy of MMF were retrospectively evaluated. RESULTS: One hundred and thirty-seven LN patients including 116 females were enrolled. The median of initial, maximum, and maintenance doses of MMF were 1.0 g/day, 1.5 g/day, and 1.0 g/day, respectively. Sixty-one adverse events were reported in 39 patients during the follow-up period. Median urine protein level decreased from 1.89 g/gCr to 0.21 g/gCr, meanC3 level increased from 66.4 mg/dl to 80.3 mg/dl, and median anti-DNA antibody titer decreased from 40.6 IU/ml to 10.6 IU/ml. CONCLUSION: MMF was commonly used for the treatment of adult LN patients with acceptable efficacy and safety in Japan.
Assuntos
Imunossupressores/uso terapêutico , Nefrite Lúpica/tratamento farmacológico , Ácido Micofenólico/análogos & derivados , Uso Off-Label , Adulto , Idoso , Feminino , Humanos , Imunossupressores/administração & dosagem , Imunossupressores/efeitos adversos , Japão , Masculino , Pessoa de Meia-Idade , Ácido Micofenólico/administração & dosagem , Ácido Micofenólico/efeitos adversos , Ácido Micofenólico/uso terapêutico , Indução de Remissão , Estudos Retrospectivos , Reumatologia , Resultado do TratamentoRESUMO
Objective: This study aims to develop and validate machine learning models to predict proliferative lupus nephritis (PLN) occurrence, offering a reliable diagnostic alternative when renal biopsy is not feasible or safe. Methods: This study retrospectively analyzed clinical and laboratory data from patients diagnosed with SLE and renal involvement who underwent renal biopsy at West China Hospital of Sichuan University between 2011 and 2021. We randomly assigned 70% of the patients to a training cohort and the remaining 30% to a test cohort. Various machine learning models were constructed on the training cohort, including generalized linear models (e.g., logistic regression, least absolute shrinkage and selection operator, ridge regression, and elastic net), support vector machines (linear and radial basis kernel functions), and decision tree models (e.g., classical decision tree, conditional inference tree, and random forest). Diagnostic performance was evaluated using ROC curves, calibration curves, and DCA for both cohorts. Furthermore, different machine learning models were compared to identify key and shared features, aiming to screen for potential PLN diagnostic markers. Results: Involving 1312 LN patients, with 780 PLN/NPLN cases analyzed. They were randomly divided into a training group (547 cases) and a testing group (233 cases). we developed nine machine learning models in the training group. Seven models demonstrated excellent discriminatory abilities in the testing cohort, random forest model showed the highest discriminatory ability (AUC: 0.880, 95% confidence interval(CI): 0.835-0.926). Logistic regression had the best calibration, while random forest exhibited the greatest clinical net benefit. By comparing features across various models, we confirmed the efficacy of traditional indicators like anti-dsDNA antibodies, complement levels, serum creatinine, and urinary red and white blood cells in predicting and distinguishing PLN. Additionally, we uncovered the potential value of previously controversial or underutilized indicators such as serum chloride, neutrophil percentage, serum cystatin C, hematocrit, urinary pH, blood routine red blood cells, and immunoglobulin M in predicting PLN. Conclusion: This study provides a comprehensive perspective on incorporating a broader range of biomarkers for diagnosing and predicting PLN. Additionally, it offers an ideal non-invasive diagnostic tool for SLE patients unable to undergo renal biopsy.
Assuntos
Nefrite Lúpica , Aprendizado de Máquina , Humanos , Nefrite Lúpica/diagnóstico , Nefrite Lúpica/patologia , Feminino , Masculino , Adulto , Estudos Retrospectivos , Pessoa de Meia-Idade , Biomarcadores , Adulto JovemRESUMO
We report the case of a 19-year-old woman with progressive proliferative lupus nephritis (LN) class III after induction and maintenance therapy with mycophenolate mofetil (MMF). Despite a satisfying clinical improvement proteinuria progressed under this medication. We treated the patient with additional belimumab after discussing other options. Following treatment with belimumab, proteinuria rapidly improved to almost normal levels and clinical remission lasted. Belimumab might hold promise for this indication.