Development and Internal Validation of a Prediction Model to Estimate the Probability of Needing Aggressive Immunosuppressive Therapy With Cytostatics in de Novo Lupus Nephritis Patients

Restrepo-Escobar, Mauricio; Granda-Carvajal, Paula A; Jaimes, Fabián

doi:10.1016/j.reuma.2017.05.010

Cited by 6 publications

(2 citation statements)

References 33 publications

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“…31 In the present study, abnormal urinary analysis was a significant predictor of proliferative LN; this association was also observed in a retrospective study involving Latin American patients in which patients with hematuria and leukocyturia presented a higher risk of having histological Class III or IV than the other LN classes. 32 The authors also found that serum creatinine levels above 0.9 mg/dL conferred a high risk of proliferative classes in kidney biopsy, similar to our findings. 33 In another cohort, anti-dsDNA antibodies, abnormal urinary sediment, and increased serum creatinine were associated with higher activity levels in kidney biopsy, and the presence of anti-dsDNA antibody was the most relevant factor for proliferative LN.…”

Section: Discussionsupporting

confidence: 90%

Development of an instrument to predict proliferative histological class in lupus nephritis based on clinical and laboratory data

Júnior

Sato

Souza

et al. 2022

Lupus

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Objectives To compare the correlations of histological class inferences based on clinical manifestations and laboratory tests between rheumatologists and nephrologists, to determine the associations of clinical and laboratory data with histological classes and to develop an instrument that can assist histological class identification in lupus nephritis (LN). Methods Retrospective study based on medical records of 80 systemic lupus erythematosus patients (SLICC criteria classification, 2012) who underwent kidney biopsy between 2010 and 2017. Two rheumatologists and two nephrologists received clinical and laboratory data and answered questions regarding which histological class was expected on kidney biopsy. Kappa (K) coefficient was used to assess agreement between evaluators. A decision tree was constructed using the chi-square interaction detector and logistic regression was performed for the development of the proliferative histological class predictor instrument . Results The mean age and disease duration were 33 ± 10.3 years and 11.5 ± 6.7 years, respectively. The level of agreement between the evaluators and kidney biopsy was poor (global K 0.364 ± 0.029; p < .001). Analyzing clinical and laboratory variables as predictors of proliferative histological class, patients with abnormal urinary sediment and positive anti-dsDNA antibodies presented 13.96 and 4.96 times higher risks of presenting class III or IV, respectively ( p < 0.001). Our instrument has a sensitivity of 87.8% and specificity of 80%, using abnormal urinary sediment, anti-dsDNA antibodies, and serum creatinine as variables. Conclusions Rheumatologists and nephrologists with experience in treating LN generated evaluations that correlated weakly with kidney biopsy. When kidney biopsy is unavailable or is contraindicated for medical reasons, instruments based on clinical and laboratory predictors may be helpful.

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Section: Discussionsupporting

confidence: 90%

Development of an instrument to predict proliferative histological class in lupus nephritis based on clinical and laboratory data

Júnior

Sato

Souza

et al. 2022

Lupus

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“…[ 22 , 23 ] This is especially important for those with class III, IV, V, or a combination (III + V or IV + V) who need aggressive immunosuppressive therapy to achieve remission of the active inflammatory process and reduce the probability of relapses and long-term renal failure. [ 24 ] Beginning in the 1970s, the National Institutes of Health (NIH) [ 25 – 27 ] carried out a series of clinical RCTs on CTX treatment of SLE. The results showed that the intermittent intravenous infusion CTX pulse therapy was superior to a single application of prednisone in controlling the progress of kidney diseases inducing remission and protecting renal function.…”

Section: Discussionmentioning

confidence: 99%

Systematic evaluation of different doses of cyclophosphamide induction therapy for lupus nephritis

et al. 2017

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Objective:This study systemically evaluated the efficacy and safety of intermittent intravenous pulse therapy with different doses of cyclophosphamide (CTX) for the treatment of lupus nephritis (LN).Methods:We screened the Chinese Journal Full-text Database (CNKI, 1994–present), China Biology Medicine (CBMdisc, 1978–present), VIP Database for Chinese Technical Periodicals (1989–present), PubMed (1948–present), MEDLINE (Ovid SP, 1946–present), Embase (1947–present), and the Cochrane controlled trials register (13, 2017). Literature reports were selected according to the inclusion and exclusion criteria, effective data were extracted, research quality was evaluated, and RevMan5.2 was used for meta-analysis.Results:Seven randomized controlled studies were included, consisting of 655 patients. The meta-analysis results showed no significant differences between the low- and high-dose cyclophosphamide groups in partial, complete, and total remission rates as well Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). Furthermore, there were no significant differences between the 2 groups in hematologic toxicity and gastrointestinal reaction, but the risk of infection (risk ratio [RR] = 0.74, 95% confidence interval [CI], 0.56–0.98, total effect inspection Z = 2.12, P = .03), and menstrual disorder (RR = 0.46, 95% CI, 0.31–0.69, total effect inspection Z = 3.83, P = .0001) decreased in the low-dose cyclophosphamide group.Conclusions:There was no obvious difference between the low- and high-dose cyclophosphamide groups in efficacy in the treatment of lupus nephritis, but the risk of infection and menstrual disorder significantly decreased in the low-dose group.

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Virtual screening to identify Leishmania braziliensis N-myristoyltransferase inhibitors: pharmacophore models, docking, and molecular dynamics

et al. 2018

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Leishmaniasis is caused by several protozoa species belonging to genus Leishmania that are hosted by humans and other mammals. Millions of new cases are recorded every year and the drugs available on the market do not show satisfactory efficacy and safety. A hierarchical virtual screening approach based on the pharmacophore model, molecular docking, and molecular dynamics was conducted to identify possible Leishmania braziliensis N-misristoyltransferase (LbNMT) inhibitors. The adopted pharmacophore model had three main features: four hydrophobic centers, four hydrogen-bond acceptor atoms, and one positive nitrogen center. The molecules (n=15,000) were submitted to alignment with the pharmacophore model and only 27 molecules aligned to model. Six molecules were submitted to molecular docking, using receptor PDB ID 5A27. After docking, the ZINC35426134 was a top-ranked molecule (- 64.61 kcal/mol). The molecule ZINC35426134 shows hydrophobic interactions with Phe82, Tyr209, Val370, and Leu391 and hydrogen bonds with Asn159, Tyr318, and Val370. Molecular dynamics simulations were performed with the protein in its APO and HOLO forms for 37 ns in order to assess the stability of the protein-ligand complex. Results showed that the HOLO form was more stable than the APO one, and it suggests that the ZINC35426134 binding stabilizes the enzyme. Therefore, the selected molecule has the potential to meet the herein proposed target.

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Development and Internal Validation of a Prediction Model to Estimate the Probability of Needing Aggressive Immunosuppressive Therapy With Cytostatics in de Novo Lupus Nephritis Patients

Cited by 6 publications

References 33 publications

Development of an instrument to predict proliferative histological class in lupus nephritis based on clinical and laboratory data

Development of an instrument to predict proliferative histological class in lupus nephritis based on clinical and laboratory data

Systematic evaluation of different doses of cyclophosphamide induction therapy for lupus nephritis

Virtual screening to identify Leishmania braziliensis N-myristoyltransferase inhibitors: pharmacophore models, docking, and molecular dynamics

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