Coorte de validação de instrumento preditor de classe histológica proliferativa em pacientes com nefrite lúpica: estudo LUCAS (Lupus Nephritis Class Assessment System)
Data
2024-09-12
Autores
Araújo Júnior, Antônio Silaide de 
Orientadores
Reis Neto, Edgard Torres dos
Tipo
Tese de doutorado
Título da Revista
ISSN da Revista
Título de Volume
Resumo
Introdução: A nefrite lúpica (NL) é uma das principais causas de morbimortalidade em pacientes com lúpus eritematoso sistêmico (LES), sendo a biópsia renal o padrão ouro para o diagnóstico e para guiar o tratamento. Estudos apontam discordância entre parâmetros clínicos e laboratoriais e classe histológica da NL. Assim, o desenvolvimento e validação de instrumentos de predição de classe histológica são importantes, especialmente quando a biópsia renal não estiver disponível ou houver alguma contraindicação ao procedimento. Objetivos: Validação de instrumento de predição de classe histológica da NL classe III ou IV(±V) versus classe V, baseado em parâmetros clínicos e laboratoriais, previamente desenvolvido. Secundários: Avaliar a sensibilidade, especificidade, acurácia e valores preditivos positivo e negativo do instrumento, com diferentes pontos de corte para a contagem de hemácias na urina; em primeiro episódio versus recidiva de NL; e, em classes III ou IV sem classe V associada versus classe V; correlacionar os parâmetros clínicos e laboratoriais com índices de atividade (IA) e cronicidade (IC) na biópsia renal. Pacientes e métodos: Estudo retrospectivo, transversal, com análise de prontuário de 196 pacientes com LES submetidos a biópsia renal entre janeiro de 2010 e janeiro de 2024. A validação do instrumento foi realizada através da análise da sensibilidade, especificidade, valores preditivos positivo e negativo, acurácia, razão de verossimilhança positiva e negativa. Análise estatística: associações entre duas variáveis categóricas através dos testes de Qui-Quadrado ou exato de Fisher; normalidade dos dados pelo teste de Kolmogorov-Smirnov; e, comparação de média entre os grupos através do teste t de Student ou Mann-Whitney. P<0,05 foi considerado significante. Resultados: Entre os 196 pacientes incluídos, 81,6% eram do sexo feminino, 60,2% não caucasianos e a idade média no momento da biópsia era de 31,2±10,4 anos. Trinta pacientes apresentaram classe III, 104 classe IV, 36 classe V e 26 classes mistas (7 classe III+V e 19 classe IV+V). Os valores médios de creatinina sérica e proteinúria foram de 1,8±1,5 mg/dL (TFG 71,3±42,2 mL/1,73 m²) e de 3,4±2,7g/24horas, respectivamente, e o SLEDAI de 16,3±7,0. Sexo, idade, etnia e tempo de doença foram semelhantes nas coortes de desenvolvimento e validação. Na coorte de validação encontramos sensibilidade de 90,6%, especificidade de 66,7 %, valor preditivo positivo de 92,4 % com acurácia de 86,2%, em predizer a classe histológica III ou IV(±V) versus classe V, sendo a especificidade pouco inferior à coorte de desenvolvimento (80,0% versus 66,7%). Não houve diferença no desempenho do instrumento, quando considerados os valores de hemácias > 5.000/mL, > 10.000 /mL ou > 20.000 /mL; primeiro episódio versus recidiva de nefrite e classes III ou IV sem classe V associada. Encontramos maior IA histológica renal naqueles com presença de hemácias na urina. Houve fraca correlação negativa do IA com TFG (rS= -0,302; p=0,001) e fraca correlação positiva com creatinina (rS= 0,300; p=0,001) e uma correlação moderada positiva do IC com a creatinina (rS= 0,477; p<0,001) e correlação moderada negativa com a TFG (rS= -0,475; p<0,001). Conclusões: A validação do instrumento de predição de classe histológica proliferativa demonstrou desempenho semelhante ao encontrado na coorte de desenvolvimento, sem diferença da acurácia do instrumento com diferentes pontos de corte de hemácias na urina e na avaliação de primeiro episódio de nefrite ou recidiva. A presença de hemácias na urina se correlacionou com índices de atividade, enquanto os índices de cronicidade apresentaram correlação fraca negativa com a TFG e creatinina sérica.
Background: Lupus nephritis (LN) is one of the main causes of morbidity and mortality in Systemic Lupus erythematosus (SLE) patients and kidney biopsy is considered the gold standard for its diagnosis and useful to guiding therapy. However, there is a discordance between clinical and laboratory parameters and histological class of LN. Development and validation of histological class prediction tools are important when kidney biopsy is not available or there is a contraindication to the procedure. Objectives: To validate an instrument for predicting LN histological class, based on clinical and laboratory parameters. Secondary: To evaluate the sensitivity, specificity, accuracy, and positive and negative predictive values of different cutoff points for red blood cells in urine; in first flare versus recurrence of LN; and, in classes III or IV without class V versus class V; to correlate clinical and laboratory parameters with activity indices (AI) and chronicity (CI) in kidney biopsy. Patients and methods: Retrospective study, based on analysis of medical records of 196 SLE patients who underwent kidney biopsy between January 2010 and January 2024. Statistical analysis: Associations between two categorical variables were evaluated using the Chi-Square or Fisher's exact tests, normality of data distribution was assessed by Kolmogorov-Smirnov test and Student's t or Mann-Whitney test was used to compare means between groups. Validation of the histological class prediction instrument was carried out by evaluating the performance of the development cohort model in the validation sample regarding sensitivity, specificity, positive and negative predictive values, accuracy, positive and negative likelihood ratio. P < 0.05 was considered significant. Results: Among the 196 patients included in the study, 81.6% were female, 60.2% were non-Caucasian and the mean age at the time of biopsy was 31.2±10.4 years. Thirty patients presented class III, 104 class IV, 36 class V, and 26 mixed classes (7 class III+V and 19 class IV+V). The mean serum creatinine value was 1.8±1.5 mg/dL (GFR 71.3±42.2 mL/1.73 m²), proteinuria was 3.4±2.7g/24 hours and the SLEDAI was 16.3±7.0. Sex, age, ethnicity, and disease duration were similar in the development and validation cohorts. In the validation cohort, we found a sensitivity of 90.6%, specificity of 66.7%, positive predictive value of 92.4% with an accuracy of 86.2%, in predicting histological class III or IV (±V) versus class V, with lower specificity than the development cohort (80,0% versus 66,7%). There was no difference when considering the red blood cell values > 5.000/mL, > 10,000/mL, or > 20,000/mL; first episode versus recurrence of nephritis; and classes III or IV without associated class V in the instrument performance. We found higher renal histological AI in those with the presence of red blood cells in the urine. There was a weak negative correlation of AI with GFR (rS= -0.302; p=0.001) and a weak positive correlation with creatinine (rS= 0.300; p=0.001) and a moderate positive correlation of CI with creatinine (rS= 0.477; p<0.001) and a moderate negative correlation with GFR (rS= -0.475; p<0.001). Conclusions: The validation of the proliferative histological class prediction tool demonstrated similar performance to that found in the development cohort, without difference in the accuracy of the instrument with different cut-off points for red blood cells in urine as well as first first flare or recurrence of LN. The presence of red blood cells in the urine, at different cutoff points, correlated with activity indices, while chronicity indices showed a weak negative correlation with GFR.
Background: Lupus nephritis (LN) is one of the main causes of morbidity and mortality in Systemic Lupus erythematosus (SLE) patients and kidney biopsy is considered the gold standard for its diagnosis and useful to guiding therapy. However, there is a discordance between clinical and laboratory parameters and histological class of LN. Development and validation of histological class prediction tools are important when kidney biopsy is not available or there is a contraindication to the procedure. Objectives: To validate an instrument for predicting LN histological class, based on clinical and laboratory parameters. Secondary: To evaluate the sensitivity, specificity, accuracy, and positive and negative predictive values of different cutoff points for red blood cells in urine; in first flare versus recurrence of LN; and, in classes III or IV without class V versus class V; to correlate clinical and laboratory parameters with activity indices (AI) and chronicity (CI) in kidney biopsy. Patients and methods: Retrospective study, based on analysis of medical records of 196 SLE patients who underwent kidney biopsy between January 2010 and January 2024. Statistical analysis: Associations between two categorical variables were evaluated using the Chi-Square or Fisher's exact tests, normality of data distribution was assessed by Kolmogorov-Smirnov test and Student's t or Mann-Whitney test was used to compare means between groups. Validation of the histological class prediction instrument was carried out by evaluating the performance of the development cohort model in the validation sample regarding sensitivity, specificity, positive and negative predictive values, accuracy, positive and negative likelihood ratio. P < 0.05 was considered significant. Results: Among the 196 patients included in the study, 81.6% were female, 60.2% were non-Caucasian and the mean age at the time of biopsy was 31.2±10.4 years. Thirty patients presented class III, 104 class IV, 36 class V, and 26 mixed classes (7 class III+V and 19 class IV+V). The mean serum creatinine value was 1.8±1.5 mg/dL (GFR 71.3±42.2 mL/1.73 m²), proteinuria was 3.4±2.7g/24 hours and the SLEDAI was 16.3±7.0. Sex, age, ethnicity, and disease duration were similar in the development and validation cohorts. In the validation cohort, we found a sensitivity of 90.6%, specificity of 66.7%, positive predictive value of 92.4% with an accuracy of 86.2%, in predicting histological class III or IV (±V) versus class V, with lower specificity than the development cohort (80,0% versus 66,7%). There was no difference when considering the red blood cell values > 5.000/mL, > 10,000/mL, or > 20,000/mL; first episode versus recurrence of nephritis; and classes III or IV without associated class V in the instrument performance. We found higher renal histological AI in those with the presence of red blood cells in the urine. There was a weak negative correlation of AI with GFR (rS= -0.302; p=0.001) and a weak positive correlation with creatinine (rS= 0.300; p=0.001) and a moderate positive correlation of CI with creatinine (rS= 0.477; p<0.001) and a moderate negative correlation with GFR (rS= -0.475; p<0.001). Conclusions: The validation of the proliferative histological class prediction tool demonstrated similar performance to that found in the development cohort, without difference in the accuracy of the instrument with different cut-off points for red blood cells in urine as well as first first flare or recurrence of LN. The presence of red blood cells in the urine, at different cutoff points, correlated with activity indices, while chronicity indices showed a weak negative correlation with GFR.
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Citação
ARAÚJO JÚNIOR, Antônio Silaide de. Coorte de validação de instrumento preditor de classe histológica proliferativa em pacientes com nefrite lúpica: estudo LUCAS (Lupus Nephritis Class Assessment System). 2024. 48 f. Tese (Doutorado em Reumatologia) - Escola Paulista de Medicina, Universidade Federal de São Paulo (UNIFESP). São Paulo, 2024.