MICHELLE REMIAO UGOLINI LOPES
Projetos de Pesquisa
Unidades Organizacionais
Instituto Central, Hospital das Clínicas, Faculdade de Medicina
LIM/17 - Laboratório de Investigação em Reumatologia, Hospital das Clínicas, Faculdade de Medicina
LIM/17 - Laboratório de Investigação em Reumatologia, Hospital das Clínicas, Faculdade de Medicina
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- Early proteinuria response: a valid real-life situation predictor of long-term lupus renal outcome in an ethnically diverse group with severe biopsy-proven nephritis?(2017) UGOLINI-LOPES, Michelle R.; SEGURO, Luciana Parente C.; CASTRO, Maite Xavier F.; DAFFRE, Danielle; LOPES, Alex C.; BORBA, Eduardo F.; BONFA, EloisaObjective Two recent important lupus nephritis trials reported that proteinuria was a good predictor of renal outcome in Caucasians, but data on real-life situation, other races and severe nephritis are lacking to substantiate this finding as a simple test to guide clinical practice. The aim of this study was to validate proteinuria as a predictor of long-term renal outcome in real-life situation in a racially diverse group of patients with severe nephritis. Methods Proteinuria, serum creatinine (SCr) and urine red blood cells were assessed at baseline and after 3, 6 and 12 months, as early predictors of long-term renal outcome (SCr <1.5 mg/dL at 7 years), in 94 patients with biopsy-proven lupus nephritis. The parameter performance and cut-off values were computed by receiver operating characteristic curves. Kaplan-Meier curves were used to validate the parameter. Results A proteinuria <0.8 g/24 hours at 12 months was the best single predictor of long-term renal outcome (sensitivity 90%, specificity 78%, positive predictive value 67%, negative predictive value (NPV) 94% and area under the curve 0.86; p<0.001). Addition of other variables to proteinuria such as SCr and haematuria at 12 months did not improve its performance. The proteinuria cut-aft value of <0.8 g/24 hours at 12 months was a good predictor of 7-year renal survival (years free of dialysis) for patients with pure membranous (p=0.005) and proliferative nephritis (p=0.043), as well as black (p=0.002) and white race (p=0.001), anti-dsDNA positive (p=0.001) and anti-dsDNA negative (p=0.04) and male (p=0.028) and female (p=0.003) patients. Conclusion We provided novel evidence that, in a real-life situation, proteinuria at 12 months of follow-up was the single best predictor of renal outcome at 7 years for an ethnically diverse group of patients with severe nephritis and a valid parameter for distinct histological classes, races, genders and anti-dsDNA profiles. The remarkably high NPV obtained reinforces its recommendation as the ideal predictor for clinical practice, since it is of low cost, easy to interpret, non-invasive and widely available.
- Antiphospholipid syndrome damage index (DIAPS): distinct long-term kinetic in primary antiphospholipid syndrome and antiphospholipid syndrome related to systemic lupus erythematosus(2020) TORRICELLI, A. Kuhl; UGOLINI-LOPES, M. Remiao; BONFA, E.; ANDRADE, D.Background Antiphospholipid syndrome (APS) is an acquired thrombophilia that affects young productive individuals, with permanent damage and negative impact on quality of life. Recently, a damage index specific for APS (DIAPS) was developed. There are, however, no data regarding the comparison of its performance and long-term damage in primary antiphospholipid syndrome (PAPS) and APS related to systemic lupus erythematosus (SLE; APS + SLE). The primary purpose of this study was therefore to compare the long-term damage in patients with these conditions. Methods This is a retrospective analysis of a single tertiary center cohort followed for approximately 10 years using a standardized prospective electronic chart database. Fifty consecutive PAPS patients age matched with 50 APS+SLE patients were consecutively selected for the study, and DIAPS was calculated once a year during follow-up. Long-term damage and damage kinetics in both groups were compared. Results PAPS and APS + SLE had comparable age (47.10 +/- 12.4 vs. 44.04 +/- 10.80 years; p = 0.19) and time of follow-up (9.40 +/- 3.60 vs. 10.94 +/- 4.50 years; p = 0.06). At diagnosis, PAPS had higher DIAPS than APS + SLE (1.72 +/- 1.17 vs. 0.82 +/- 0.96; p < 0.001). At the end of the 10-year follow-up, both groups presented comparable mean damage scores (2.04 +/- 1.50 vs. 2.24 +/- 1.61; p = 0.52). The damage increment throughout the observation period for PAPS was solely 35%, whereas for APS + SLE it was gradual, persistent and reached 139% at the end of follow-up, with a total damage increment for PAPS lower than APS + SLE (0.43 +/- 0.30 vs. 1.22 +/- 1.24; p < 0.001). Of note, the frequency of individuals who acquired damage was lower in PAPS than in APS + SLE (32% vs. 71%; p < 0.001). PAPS also had a longer delay in diagnosis than APS + SLE (4.00 +/- 4.20 vs. 2.54 +/- 3.05 years; p = 0.04). This delay was positively correlated with a higher damage score at diagnosis (r = 0.36, p < 0.001) in all groups. Conclusion We identified a distinct pattern of damage in PAPS and APS related to SLE. Damage in PAPS is an early event, while APS+SLE is associated with higher long-term damage, with a striking increment of damage along the follow-up. A diagnosis delay is correlated with higher damage scores. Damage surveillance therefore requires different approaches for these two conditions.
- Cognitive dysfunction and serum levels of brain-derived neurotrophic factor (BDNF) in primary anti-phospholipid syndrome (PAPS)(2021) ROSA, Renata F.; UGOLINI-LOPES, Michelle Remiao; GANDARA, Ana Paula Rossi; VENDRAMINI, Margarete B. G.; CAMPANHOLO, Kenia Repiso; DUTRA, Livia; ANDRADE, Danieli Castro Oliveira deObjectives. Cognitive dysfunction (CD) is a poorly understood non-stroke central neurological manifestation in anti-phospholipid syndrome (APS). Brain-derived neurotrophic factor (BDNF) is a neurotrophin that plays an important role in neural plasticity and could potentially be a biomarker of CD in primary APS (PAPS). The aim of the study is to assess CD in PAPS patients and to evaluate its association with clinical data, anti-phospholipid antibodies and serum BDNF levels. Methods. This cross-sectional study compared 44 PAPS patients and 20 healthy controls matched for age, gender and education. PAPS patients and controls underwent a standardized cognitive examination. The demographic, clinical and laboratory characteristics of patients were recorded. Serum BDNF was measured by Enzyme Linked Immunosorbent. Results. Fourteen (31.8%) of the 44 patients with PAPS had CD compared with only one (5%) healthy control (P =0.019). PAPS patients presented lower serum BDNF levels when compared with controls (P =0.007). Lower levels of BDNF were associated with CD in PAPS patients (P =0.032). In the univariate analysis, a positive association was found between CD and livedo reticularis, deep vein thrombosis, stroke, seizure, smoking as well as a negative association with Mini Mental State Examination and serum BDNF. According to multivariate analysis, the only independent predictor of CD in PAPS was stroke (OR 137.06; 95% CI: 4.73, 3974.32; P =0.004). Conclusions. CD is commonly reported in PAPS patients; however, its assessment lacks in standards and objective screening tests. The association between CD and low serum BDNF suggests that this neurotrophin can be a promising biomarker for PAPS cognitive impairment.
- Short- and Long-Term Outcome of Systemic Lupus Erythematosus Peripheral Neuropathy Bimodal Pattern of Onset and Treatment Response(2021) FARGETTI, Simone; UGOLINI-LOPES, Michelle R.; PASOTO, Sandra G.; SEGURO, Luciana P. C.; SHINJO, Samuel K.; BONFA, Eloisa; BORBA, Eduardo F.Background/Objective: Our aim was to describe the short- and long-term outcome of peripheral neuropathy (PN) attributed exclusively to systemic lupus erythematosus (SLE). Methods: Systemic lupus erythematosus patients with defined PN (clinical and electroneuromyography) were retrospectively evaluated at onset, 1-year, and 5-year follow-up using a standardized electronic chart database that started in 2000. Exclusion criteria were comorbidities, drugs, and infections. Age-, sex-, and disease duration-matched SLE patients without PN were selected as controls. Results: Lupus PN was identified in 38 (1.8%) of 2074 patients, and almost two thirds had PN onset in the first 5 years of SLE (63.2%). Peripheral neuropathy SLE had higher frequencies of cutaneous vasculitis (50% vs 21.1%, p = 0.002), lymphopenia (60.5% vs 36.8%, p = 0.027), anti-Sm (52.6% vs 27.6%, p = 0.013), and higher SLEDAI-2K scores (11.5 +/- 10.5 vs 4.9 +/- 6.7, p < 0.001) compared with controls. The most common type was polyneuropathy (71.1%) with sensory-motor pattern (68.4%). At PN diagnosis, all patients received glucocorticoid and 97.4% started immunosuppressive therapy (50% intravenous cyclophosphamide, 42.1% azathioprine). After 1-year follow-up, 92.1% had a favorable outcome with complete (36.8%) or partial remission (55.2%), in parallel with a decrease in prednisone dose (48.3 +/- 17.9 vs 15.3 +/- 13.4 mg/d, p < 0.001), symptomatic therapy (57.9% vs 29.7%, p = 0.02), and SLEDAI-2K score (11.5 +/- 10.5 vs 1.7 +/- 3.7, p < 0.001). SLEDAI-2K scores were higher in patientswho had PN onsetwith less than 1 year of SLE duration, compared with those with more than 5 years of disease (21.3 +/- 9.1 vs 3.9 +/- 5.3, p < 0.001). Early-PN-onset group had a better response to treatment (complete remission at 1-year follow-up 61.5% vs 25%, p = 0.039). At 5-year follow-up, 89.3% remained with complete/partial remission. Conclusions: Peripheral neuropathy attributed to SLE itself is a rare manifestation with a bimodal pattern, characterized by a predominant early-onset group associated with high disease activity and a higher rate of complete remission, and a late-onset group with low disease activity and a partial therapy response.