Hydroxychloroquine blood levels predicts flare in childhood-onset lupus nephritis

Lupus ◽  
2021 ◽  
pp. 096120332110625
Author(s):  
Verena Andrade Balbi ◽  
Clovis Artur Silva ◽  
Tatiana Nascimento Pedrosa ◽  
Rosa Maria Rodrigues Pereira ◽  
Lucia Maria de Arruda Campos ◽  
...  
Keyword(s):  
Lupus Nephritis ◽  
Lupus Erythematosus ◽  
Multiple Logistic Regression Analysis ◽  
Renal Involvement ◽  
Blood Levels ◽  
High Morbidity ◽  
Childhood Onset ◽  
Roc Curve Analysis ◽  
Pharmacy Refill ◽  
Increased Risk

Objective Low hydroxychloroquine (HCQ) blood levels are predictors of flare in adult lupus. Childhood-onset systemic lupus erythematosus (cSLE) has high morbidity with renal involvement in up to 80% of cases. The aim of this study is to determine the HCQ cut-off levels which predicts flare in childhood-onset lupus nephritis (LN). Methods Sixty LN patients on HCQ use for at least 6-months were prospectively evaluated at baseline (BL) and about 6-months later for cSLE flare and HCQ blood levels (ng/mL) measured by liquid chromatography-tandem mass spectrometry. Results There were 19 patients (32%) with flare, during the study with median SLEDAI increase of 4 (0–8). Median (IQR) BL HCQ levels of the flare group were lower compared to stable patients [557.5 (68.6–980.3) vs. 1061.9 (534.8–1590.0 ng/mL); p=0.012]. ROC curve analysis demonstrated that HCQ levels≤1075 ng/mL were associated with a 5.08 (95%CI 1.28-20.13; p=0.021) times increased risk of flare. Six-month HCQ levels revealed that most patients 24/54 (44%) had persistently low levels (≤1075) during follow-up. Among those, 11/24 (46%) had flare. Multiple logistic regression analysis including prednisone use, baseline SLEDAI-2K, adherence based on pharmacy refill and BL HCQ blood levels as possible predictors of flare revealed that only HCQ blood level was independently associated with flare (OR 0.999, 95%CI 0.998-1.0, p=0.013). Conclusions We demonstrated that HCQ blood cut-off level under 1075 ng/mL predicts flare in childhood-onset LN patients under prescribed HCQ dose of 4.0–5.5 mg/kg/day. We further observed that most of these patients have compliance issues reinforcing the need for a close surveillance particularly in those with levels below the defined cut-off.

scholarly journals The presence of lupus nephritis additionally increases the risk of preeclampsia among pregnant women with systemic lupus erythematosus

Lupus ◽  
2021 ◽  
pp. 096120332110047
Author(s):  
Katarina Bremme ◽  
Sonja Honkanen ◽  
Iva Gunnarsson ◽  
Roza Chaireti
Keyword(s):  
Caesarean Section ◽  
Lupus Nephritis ◽  
Pregnant Women ◽  
Lupus Erythematosus ◽  
Premature Birth ◽  
Renal Involvement ◽  
Significant Risk ◽  
Obstetric Outcomes ◽  
Increased Risk ◽  
Renal Lupus

Introduction Pregnant women with systematic lupus erythematosus (SLE) have an increased risk of obstetric complications, such as preeclampsia and premature births. Previous studies have suggested that renal involvement could further increase the risk for adverse obstetric outcomes. Aims: The aim of this study was to compare the obstetric outcomes in a Swedish cohort of patients with SLE with and without lupus nephritis (LN). Patients and methods The study was conducted as a retrospective observational study on 103 women with SLE, who gave birth at the Karolinska University Hospital between the years 2000-2017. Thirty-five women had previous or active LN and 68 women had non-renal lupus. Data was collected from digital medical records. The outcomes that were analysed included infants born small for gestational age (SGA), premature birth, preeclampsia, SLE- or nephritis flare and caesarean section. Results Women with LN, both with previous and with renal flare during pregnancy suffered from pre-eclampsia more often compared to women with non-renal lupus (25.7% vs 2.9%, p = 0.001) and this complication was associated with premature birth (p = 0.021) and caesarean section (p = 0.035). Conclusions Lupus nephritis is a significant risk factor for adverse obstetric outcomes in women with SLE, including preeclampsia. Those patients could benefit from more frequent antenatal controls and more vigorous follow-up.

The influence of obesity on hydroxychloroquine blood levels in lupus nephritis patients

Lupus ◽  
2021 ◽  
pp. 096120332098521
Author(s):  
Tatiana Pedrosa ◽  
Léonard de Vinci Kanda Kupa ◽  
Sandra Gofinet Pasoto ◽  
Nádia Emi Aikawa ◽  
Eduardo Ferreira Borba ◽  
...  
Keyword(s):  
Body Weight ◽  
Lupus Nephritis ◽  
Lupus Erythematosus ◽  
Blood Levels ◽  
Concomitant Treatment ◽  
Obese Patients ◽  
Maximum Daily Dose ◽  
Increased Risk ◽  
Daily Dose ◽  
The Impact

Introduction In 2016 the American Academy of Ophthalmology(2016-AAO) recommended a maximum daily HCQ use of 5.0 mg/kg real body weight(RBW) taking into consideration minimizing eye toxicity. Retinopathy in systemic lupus erythematosus(SLE) patients was recently associated with obesity and this condition is progressively more common in these patients. However, the impact of obesity in HCQ blood levels remains controversial. Objective To determine if the 2016-AAO recommendation based on RBW with and without maximum daily dose restriction results in adequate and safe blood levels in obese lupus nephritis(LN) patients. Methods A cross-sectional study was performed with 108 LN patients under the prescribed 2016-AAO dose for at least 3 months. LN patients were assessed for demographic characteristics, body mass index(BMI), disease parameters, HCQ dose, concomitant treatment and HCQ blood levels measured by liquid chromatography-tandem mass spectrometry. Obesity was defined as BMI ≥30kg/m2. Results Obesity was identified in 35/108(32%) LN patients. The calculation of HCQ daily dosage revealed that obese patients were under a lower prescribed daily dose according to the real body weight (RBW) [4.4(2.9-5.4) vs. 4.9(4-5.5)mg/Kg/day, p < 0.001] due to the maximum limit used. Regardless of that the median of HCQ blood levels was significantly higher in obese compared to non-obese patients (1562 ± 548.6 vs. 1208 ± 448.9 ng/mL, p = 0.002). Further analysis of patients under the 20016-AAO recommendation by RBW without the restriction of maximum daily dose confirmed that in spite of comparable daily dose in 14 obese patients and 61 non-obese patients [4.8 (4.5-5.4) vs. 5.0(4.5-5.5) mg/kg, p = 0.312], the median of HCQ blood levels was significantly higher in obese patients than in non-obese (1734 ± 457.3 vs. 1189 ± 449.4 ng/mL, p < 0.001). Conclusion Obese patients under the 2016-AAO prescribed dose of HCQ based on RBW with and without maximum daily dose restriction have a very high HCQ blood levels compared to non-obese patients, with a potential increased risk of ocular toxicity. The use of 2016-AAO dose of HCQ according to the ideal body weight for this group of patients should be considered.Clinicaltrials.gov #NCT0312243.

scholarly journals Autoantibodies spectrum in lupus nephritis in a cohort of Egyptian patients: relation to disease activity and prognostic value

2020 ◽  
Vol 47 (1) ◽  
Author(s):  
Sahar A. Elsayed ◽  
Omar M M. Mohafez
Keyword(s):  
Lupus Nephritis ◽  
Disease Activity ◽  
Lupus Erythematosus ◽  
Renal Involvement ◽  
High Sensitivity ◽  
Close Monitoring ◽  
Class Iii ◽  
Roc Curve Analysis ◽  
Egyptian Patients ◽  
The Impact

Abstract Background Specific autoantibodies are considered as an important marker in autoimmune rheumatic diseases and are of great value for the diagnosis and prognosis of systemic lupus erythematosus (SLE) patients. A total of eighteen autoantibodies were analyzed for their positivity in SLE patients and we evaluated the clinical relevance of the five most frequent autoantibodies: anti-dsDNA, anti-nucleosome, anti-histone, anti-Ro60, and anti-Ro52 on disease activity and renal affection in SLE Egyptian patients. Results Immunological profile and correlation of the five autoantibodies with disease activity and histopathological pattern of renal involvement were analyzed for 190 SLE patients. Lupus nephritis (LN) patients showed much worse constitutional and mucocutaneous manifestations than patients without nephritis. Autoantibody profile showed a significant increased frequency of anti-dsDNA, anti-nucleosome, anti-histone, anti-Ro-60, and anti-Ro52 antibodies in LN patients. The impact of the co-positivity of the autoantibodies on the renal function was obvious. Moreover, the disease activity increased by the increased frequency of autoantibodies positivity in LN patients. ROC curve analysis showed that anti-nucleosome had the highest sensitivity; 93% followed by anti-dsDNA 83.3% then anti-histone 73.8%, but anti-Ro60 and anti-Ro52 showed a humble sensitivity. Furthermore, the highest frequency of positivity for the five autoantibodies was found in class-III and class-IV LN patients. Conclusion Detection of anti-dsDNA, anti-nucleosome, anti-histone, and anti-Ro60 in SLE patients may be important for predicting disease progression and kidney affection. Moreover, anti-nucleosome and anti-dsDNA show high sensitivity and specificity for lupus nephritis, thus patients with four to five positive autoantibody panels should be kept under close monitoring as they may warrant considering aggressive therapy to control their disease and prevent renal damage.

scholarly journals The importance of serum neutrophil gelatinase-associated lipocalin level in patients with lupus nephritis

2019 ◽  
Vol 8 (2) ◽  
pp. 133-139
Author(s):  
Mohammad Reza Jafari Nakhjavani ◽  
Sima Abediazar ◽  
Amir Ghorbanihaghjo ◽  
Behnaz Hanafizadeh ◽  
Sepideh Zununi Vahed ◽  
...  
Keyword(s):  
Lupus Nephritis ◽  
Disease Activity ◽  
Lupus Erythematosus ◽  
Activity Index ◽  
Renal Involvement ◽  
Disease Activity Index ◽  
Serum Levels ◽  
Roc Curve Analysis ◽  
Neutrophil Gelatinase Associated Lipocalin ◽  
Neutrophil Gelatinase

Introduction: The neutrophil gelatinase-associated lipocalin (NGAL) has emerged as a biomarker of renal damage. Objectives: The aim of this study was to assess the serum levels of NGAL (sNGAL) as a marker of disease activity in individuals with lupus nephritis (LN). Patients and Methods: This study contained 50 systemic lupus erythematosus (SLE) individuals with (n = 25) and without (n = 25) nephritis, and 39 healthy controls. The sNGAL levels were measured by ELISA. Renal function test, urinary parameters, lupus serology activity, and also calculated SLE disease activity index (SLEDAI) were analyzed to determine their associations with sNGAL. Results: The results revealed that the SLE individuals with or without nephritis had a raised serum NGAL levels as compared to control subjects (P<0.001). Additionally, sNGAL levels in LN individuals were meaningfully higher compared to those in non-LN patients (P<0.001). Serum NGAL showed a significant correlation with the SLEDAI, serum creatinine, and 24-h urinary protein (P<0.05). More importantly, sNGAL had a significant positive correlation with the activity index of LN (r = 0.616, P=0.001). In the ROC curve analysis, the measurement of sNGAL level showed a good diagnostic performance for distinguishing individuals with LN from SLE patients without renal involvement with AUC=0.902 (P<0.001), 72% sensitivity, and 99% specificity. Moreover, sNGAL could identify all of SLE patients from controls with high accuracy, AUC= 0.99, P<0.001, with 99% sensitivity, and 97% specificity. Conclusion: Serum NGAL had an association with clinical parameters and could discriminate LN from SLE patients without renal involvement. Our result suggests that serum NGAL can be used for early diagnosis of LN and identifying active LN.

scholarly journals AB0750 FUNCTIONAL CONDITION OF KIDNEYS IN THE LONG-TERM COURSE OF SLE IN ADOLESCENTS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1403.2-1403
Author(s):  
L. Bohmat ◽  
N. Shevchenko ◽  
I. Bessonova
Keyword(s):  
Renal Function ◽  
Lupus Nephritis ◽  
Lupus Erythematosus ◽  
Disease Duration ◽  
Renal Involvement ◽  
Clinical Manifestations ◽  
Clinical Analysis ◽  
Average Dose ◽  
One Year

Background:Lupus nephritis is the most severe and adverse systemic lupus erythematosus (SLE) syndrome. According to modern recommendations, the clinical manifestations of active nephritis should be taken under medical control in 6 months after the start of the disease’s treatment1.Objectives:The aim of this study was to examine the functional status of the kidneys in children with SLE in the course of the disease for more than one year.Methods:The analysis included case histories of 43 patients with SLE, mostly females (41), aged 7 to 18 years (mean age 14.4 years) with disease duration of 4.75 ± 0.58 years of whom 22 were less than three years, 21 - more than three years. All children received corticosteroid therapy, at the time of the examination the average dose was 13.85 ± 1.86 mg per day in terms of prednisolone. The second component of therapy was azathioprine (average dose 97.61 ± 2.11 mg). All children received hydroxychloroquine (5 mg/kg per day).To determine the functional state of the kidneys a clinical analysis of urine, a study of the scope of specific gravity of urine during the day (Zymnytsky test), the content of creatinine and urea in serum to determine the glomerular filtration rate (GFR), the level of microalbuminuria per day were evaluated.Results:Renal involvement in the developed SLE occurred in 73.08% of patients. Among them, therapy during the first 6 months was considered quite effective in 58.06% of patients. It was found that in children with disease duration from one to three years proteinuria was registered in 68.18%, a decrease in GFR in 4.45% and hyperfiltration in 9.09%. In the group of children with duration of SLE more than three years revealed deeper changes in renal function; there was proteinuria in 90.47%, the frequency of GFR decreased was in 19.04%, a decrease of renal concentration function was in 14.28% of cases.Indicators of renal function in children with SLE depending on the duration of the disease (M ± m)IndicatorDuration of the diseasefrom 1 year to 3 years n = 22over 3 yearsn = 21Creatinine, mmol/l0,080 ± 0,0140,090 ± 0,018Мочевина, mmol/l5,66 ± 1,425,63 ± 1,61GFR, ml/min117,05 ± 19,68100,20 ± 18,98 *Microalbuminuria, mg/day24,41 ± 13,1334,73 ± 24,76Density min1,007 ± 0,0051,006 ± 0,005Density max1,024 ± 0,0051,019 ± 0,005 ***р<0,03;**р<0,01 the probability of differences when comparing between groupsConclusion:Long-term follow-up of children with SLE over one year reveals a prolongation of renal dysfunction, which worsens after three years, and is the basis for the development of irreversible renal impairment.References:[1]European evidence-based recommendations for the diagnosis and treatment of childhood-onset lupus nephritis: the SHARE initiative /Noortje Groot, Nienke de Graeff, Stephen D Marks et all. //Ann Rheum Dis. 2017 Dec;76(12):1965-1973.Disclosure of Interests:None declared

Higher sRAGE Levels Predict Mortality in Frail Older Adults with Cardiovascular Disease

Gerontology ◽  
2021 ◽  
pp. 1-9
Author(s):  
Lee Butcher ◽  
Jose Antonio Carnicero ◽  
Karine Pérès ◽  
Marco Colpo ◽  
David Gomez Cabrero ◽  
...  
Keyword(s):  
Older Adults ◽  
Cox Regression ◽  
Population Based ◽  
Blood Levels ◽  
Roc Curve Analysis ◽  
Baseline Serum ◽  
Frailty Status ◽  
Risk Of Death ◽  
Survival Difference ◽  
Increased Risk

<b><i>Introduction:</i></b> The evidence that blood levels of the soluble receptor for advanced glycation end products (sRAGE) predict mortality in people with cardiovascular diseases (CVD) is inconsistent. To clarify this matter, we investigated if frailty status influences this association. <b><i>Methods:</i></b> We analysed data of 1,016 individuals (median age, 75 years) from 3 population-based European cohorts, enrolled in the FRAILOMIC project. Participants were stratified by history of CVD and frailty status. Mortality was recorded during 8 years of follow-up. <b><i>Results:</i></b> In adjusted Cox regression models, baseline serum sRAGE was positively associated with an increased risk of mortality in participants with CVD (HR 1.64, 95% CI 1.09–2.49, <i>p</i> = 0.019) but not in non-CVD. Within the CVD group, the risk of death was markedly enhanced in the frail subgroup (CVD-F, HR 1.97, 95% CI 1.18–3.29, <i>p</i> = 0.009), compared to the non-frail subgroup (CVD-NF, HR 1.50, 95% CI 0.71–3.15, <i>p</i> = 0.287). Kaplan-Meier analysis showed that the median survival time of CVD-F with high sRAGE (&#x3e;1,554 pg/mL) was 2.9 years shorter than that of CVD-F with low sRAGE, whereas no survival difference was seen for CVD-NF. Area under the ROC curve analysis demonstrated that for CVD-F, addition of sRAGE to the prediction model increased its prognostic value. <b><i>Conclusions:</i></b> Frailty status influences the relationship between sRAGE and mortality in older adults with CVD. sRAGE could be used as a prognostic marker of mortality for these individuals, particularly if they are also frail.

scholarly journals Predictors of mortality in children with lupus nephritis

2014 ◽  
Vol 54 (6) ◽  
pp. 338
Author(s):  
Lukman Oktadianto ◽  
Risky Vitria Prasetyo ◽  
Ninik Asmaningsih Soemyarso ◽  
Mohammad Sjaifullah Noer
Keyword(s):  
Lupus Nephritis ◽  
Lupus Erythematosus ◽  
Renal Involvement ◽  
Hypertensive Crisis ◽  
Clinical Signs ◽  
Clinical Manifestations ◽  
Predictors Of Mortality ◽  
Cox Proportional Hazard ◽  
Kaplan Meier ◽  
Mean Time

Background Renal involvement during the clinical course ofsystemic lupus erythematosus (SLE) is generally considered to bethe most important factor influencing disease prognosis in termsof morbidity and mortality. Various factors have been reported toinfluence the prognosis of lupus nephritis (LN).Objective To analyze clinical signs and laboratory parameters thatmight serve as predictors associated with mortality in pediatricLN.Methods Retrospectively, medical records of children with LNat Soetomo Hospital from 1998 to 2011 were studied. Diagnosisof SLE was based on Revised American Rheumatism Associationcritera, while patients with clinical manifestations of hypertension,abnormal urinalysis, and serum creatinin > 1 mg/dL wereconsidered as lupus nephritis. Cox proportional hazard modelingwas used to assess for associations of clinical signs and laboratoryparameters with mortality. Kaplan-Meier survival analysis wasused to assess the cumulative survival from the time of diagnosisto the outcome.Results There were 57 children with LN of whom 43 (75%) weregirls. The female-to-male ratio was 3:1. Subjects’ mean age was 10.6(SD 6.87) years. The mean time of observation was 51 (SD 74.54)months and 23 (40%) children died. Age, gender, hypertension,hematuria, proteinuria, and anemia were not significant aspredictors for mortality. However, hypertensive crisis (HR=2.79;95%CI 1.16 to 6.75; P=0.02) and initial glomerular filtration rate(GFR) of <75 mL/min/1.73m2 (HR=3.01; 95%CI 1.23 to 7.34;P=0.01) were significant predictors of mortality in children with LN.The mean survival time of LN with hypertensive crisis and initialGFR <75 mL/min/1.73m2 was 36.9 (SD 12.17) months.Conclusion Hypertensive crisis and GFR <75 mL/min/1.73m2 aresignificant predictors of mortality in children with LN.

scholarly journals An uncommon cause of diffuse alveolar hemorrhage in a young male

2019 ◽  
Vol 89 (2) ◽  
Author(s):  
Anshul Mittal ◽  
Jagdish Chander Suri ◽  
Shibdas Chakrabarti ◽  
Pranav Ish
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Nephritis ◽  
Lupus Erythematosus ◽  
Renal Involvement ◽  
Young Male ◽  
Diffuse Alveolar Hemorrhage ◽  
Alveolar Hemorrhage ◽  
Systemic Lupus ◽  
Threatening Condition ◽  
Life Threatening

It is uncommon for Systemic lupus erythematosus (SLE) to present with diffuse alveolar hemorrhage (DAH) as the initial presentation. To diagnose this in a young male with no renal involvement is further uncommon. We report a case of a 16-year-old boy, who presented with hemoptysis and was eventually diagnosed as DAH with underlying SLE. Treatment with steroids and immunosuppressant helped in rapid recovery from this potentially life-threatening condition. This case highlights the need of defining diagnostic criteria for SLE in patients presenting as DAH and formulating guidelines for treatment of the same, especially in absence of co-existing lupus nephritis.

Cell-free DNA profiling in patients with lupus nephritis

Lupus ◽  
2020 ◽  
Vol 29 (13) ◽  
pp. 1759-1772
Author(s):  
Anna Truszewska ◽  
Agnieszka Wirkowska ◽  
Kamila Gala ◽  
Piotr Truszewski ◽  
Łucja Krzemień-Ojak ◽  
...  
Keyword(s):  
Lupus Nephritis ◽  
Lupus Erythematosus ◽  
Copy Number ◽  
Severe Disease ◽  
Renal Involvement ◽  
Mtdna Copy Number ◽  
Cell Free Dna ◽  
Free Dna ◽  
Mitochondrial Fractions ◽  
Kidney Involvement

Background Increased level of cell-free DNA (cf-DNA) is associated with systemic lupus erythematosus (SLE) and might be related to disease activity. The aim of this study was to evaluate whether cfDNA integrity, size distribution and concentration of different cfDNA fractions is associated with lupus activity and kidney involvement. Methods Blood samples were collected from 43 SLE patients and 50 healthy controls. Nuclear and mitochondrial fractions of cfDNA and intracellular DNA were quantified by real-time qPCR. Sizing and quantification of total cfDNA level was performed on Bioanalyzer. Results We determined four parameters that characterized cfDNA profile: fragmentation index, ratio of intra- to extracellular mtDNA copy number, cfDNA concentration, and presence of 54–149 bp and 209–297 bp fragments. Patients with healthy-like cfDNA profile had higher eGFR ( P = 0.009) and more often no indications for kidney biopsy or less advanced lupus nephritis (LN) ( P = 0.037). In contrary, SLE patients with distinct cfDNA profile (characterized by increased cfDNA concentration and fragmentation, higher discrepancy between intra- to extracellular mtDNA copy number, and the presence of 54–149 bp and 209–297 bp fragments) had lower eGFR ( P = 0.005) and more often advanced LN or history of renal transplantation ( P = 0.001). Conclusions We showed that cfDNA profiling may help to distinguish SLE patients with renal involvement and severe disease course from patients with more favorable outcomes. We suggest cfDNA profile a promising SLE biomarker.

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