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.

Obesity Alters the Pharmacokinetics of Vincristine in Mice.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1636-1636
Author(s):  
James W Behan ◽  
Vassilios I Avramis ◽  
Jason P Yun ◽  
Anna Butturini ◽  
Steven D Mittelman
Keyword(s):  
Body Weight ◽  
Specific Activity ◽  
Scintillation Counter ◽  
Compartment Model ◽  
Blood Levels ◽  
Obese Patients ◽  
Obese Mice ◽  
Time Points ◽  
Poor Outcome ◽  
Increased Risk

Abstract Obesity has been associated with increased risk of development and poor outcome from a variety of hematological malignancies. There is a lack of consensus as to how to dose chemotherapies in obese patients, and therefore inadequate dosing represents a potential factor contributing to poor outcome. We have previously shown that diet-induced obese mice transplanted with p190BCR/ABL ALL cells and then treated with vincristine (VCR) proportional to body weight (15 mg/kg/wk × 4 wks) have a poorer outcome than non-obese mice (event free survival: Obese = 0.42, Control = 0.75, p=0.07, log rank). The present study was designed to quantify the pharmacokinetic (PK) parameters of vincristine in control and obese mice and determine whether differences in these parameters could explain the poorer outcome in the obese mice. Twenty obese and 20 control mice received tail-vein injections of tritiated vincristine (specific activity 75 mCi/mg; dose 0.5 mg/kg). Blood samples were taken at 5 minutes, and the mice sacrificed at various time-points between 15 minutes and 24 hours post-injection. Whole blood and tissue specimens were solubilized, decolorized, and read on a scintillation counter. Blood vincristine concentrations were fit to a 3-compartment model using the two-stage PK in 3 subsets of VCR concentrations vs. time method. Non-compartmental modeling was used to confirm the results. Due to body weight differences, obese mice received ~ 28% more vincristine per injection than controls. Blood vincristine concentrations in both groups of animals followed a triexponential decay, as has been previously described. Blood levels tended to be higher (by 20±15%) in the obese mice at all time-points tested. While the t1/2α was longer in the obese mice (10.6 vs. 6.0 minutes), the t1/2b and t1/2γ were both shorter (22.7 vs. 27.1 minutes and 114.4 vs. 345.8 hours). Therefore the AUC0 → 24 was higher in the obese mice (3,279 vs. 2,776 ng/ml*hr), while the AUC0 → ∞ was lower in the obese mice (21,705 vs. 53,581 ng/ml*hr). Vincristine concentrations in spleen and bone marrow were similar at all time-points in the obese and control groups. In summary, obesity caused alterations in vincristine pharmacokinetics, characterized by longer initial half-life but shorter terminal half-lives. Thus, it is possible that the decreased AUC0 → ∞ contributed to the poorer outcome in this model. Despite this, blood and tissue concentrations of vincristine were equal or higher in the obese mice during the first 24 hours after injection of the drug when it was dosed proportional to body weight. These data suggest that dosing vincristine in obese patients based on body surface may lead to lower levels in blood and tissue, particularly if the dose is capped. As the prevalence of obesity continues to increase, pharmacokinetics studies should be performed in obese and lean subjects to further optimize chemotherapy dosing regimens in obese patients.

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.

Impact of Weight-Band Dosing of Tinzaparin for Venous Thromboembolism Prophylaxis on Persistent Wound Drainage in Adult Patients Undergoing Hip and Knee Arthroplasty

2021 ◽  
pp. 106002802110242
Author(s):  
Cassandra Cooper ◽  
Ouida Antle ◽  
Jennifer Lowerison ◽  
Deonne Dersch-Mills ◽  
Ashley Kenny
Keyword(s):  
Body Weight ◽  
Venous Thromboembolism ◽  
Knee Arthroplasty ◽  
Total Joint Arthroplasty ◽  
Joint Arthroplasty ◽  
Thromboembolism Prophylaxis ◽  
Wound Drainage ◽  
Increased Risk ◽  
Significant Difference ◽  
The Impact

Background: Persistent wound drainage and venous thromboembolism (VTE) are potential complications of total joint arthroplasty, and these risks can be challenging to balance in clinical practice. Anecdotal observation has suggested that following joint arthroplasty, persistent wound drainage occurs more frequently with higher body weight and higher doses of tinzaparin when compared with lower body weight and lower doses of tinzaparin. Objective: The overall purpose of this study was to describe the impact of a tinzaparin weight-band dosing table for VTE prophylaxis on wound healing, thrombosis, and bleeding outcomes in patients undergoing total joint arthroplasty. Methods: This retrospective chart review included patients who underwent total hip or knee arthroplasty and received tinzaparin for thromboprophylaxis per their weight-banding category. The primary outcome was the incidence of persistent wound drainage. Secondary outcomes include the occurrence of VTE and clinically important bleeding during hospital admission. Results: A total of 231 patients were included in the analysis. There was no significant difference in persistent wound drainage between the 3 weight categories, and there were no differences in rates of VTE or clinically important bleeding. Concurrent use of low-dose acetylsalicylic acid was associated with a 3-fold increased risk of persistent wound drainage (risk ratio = 3.35; 95% CI = 2.14-5.24; P = 0.00003). Conclusion and Relevance: In joint arthroplasty patients, we observed no significant difference in rates of persistent wound drainage between various weight categories receiving different weight-banded doses of tinzaparin. Our results do not suggest that the current weight-band dosing table for tinzaparin needs to be adjusted to optimize patient outcomes.

The effect of acenocoumarol on the antiplatelet effect of clopidogrel

2015 ◽  
Vol 114 (10) ◽  
pp. 708-716 ◽  
Author(s):  
Thomas Bergmeijer ◽  
Johannes Kelder ◽  
Christian Hackeng ◽  
Jurriën ten Berg ◽  
Willem Dewilde ◽  
...  
Keyword(s):  
Platelet Reactivity ◽  
Multivariable Analysis ◽  
Coumarin Derivative ◽  
Concomitant Treatment ◽  
Confounding By Indication ◽  
Increased Risk ◽  
Percutaneous Coronary ◽  
Propensity Matching ◽  
Multivariable Analyses ◽  
The Impact

SummaryPatients exhibiting high on-clopidogrel platelet reactivity (HPR) are at an increased risk of atherothrombotic events following percutaneous coronary interventions (PCI). The use of concomitant medication which is metabolised by the hepatic cytochrome P450 system, such as phenprocoumon, is associated with HPR. We assessed the level of platelet reactivity on clopidogrel in patients who received concomitant treatment with acenocoumarol (another coumarin derivative). Patients scheduled for PCI were included in a prospective, single centre, observational registry. Patients who were adequately pre-treated with clopidogrel were eligible for this analysis, which included 1,582 patients, of whom 104 patients (6.6 %) received concomitant acenocoumarol treatment. Platelet reactivity, as measured with the VerifyNow P2Y12 assay and expressed in P2Y12 Reaction Units (PRU), was significantly higher in patients on concomitant acenocoumarol treatment (mean PRU 229 ± 88 vs 187 ± 95; p< 0.001). In patients with concomitant acenocoumarol use, the proportion of patients with HPR was higher, defined as PRU > 208 (57.7 % vs 41.1 %; p=0.001) and PRU236 (49.0 % vs 31.4 %; p< 0.001). In multivariable analysis, concomitant acenocoumarol use was independently associated with a higher PRU and the occurrence of HPR defined as PRU236 (OR 2.00, [1.07–3.79]), but not with HPR defined as PRU > 208 (OR 1.37, [0.74–2.54]). PRU also was significantly increased after 1:1 propensity matching (+28.2; p< 0.001). As this was an observational study, confounding by indication cannot be excluded, although multivariable analyses and propensity matching were performed. The impact of the findings from this hypothesis-generating study on clinical outcome requires further investigation.

The Impact of Dietician Support and Behavioural Therapy in Addition to Concomitant Treatment with Intragastric Balloon in Obese Patients

2019 ◽  
Vol 30 (2) ◽  
pp. 612-617
Author(s):  
Salvatore Francesco Vadalà di Prampero ◽  
Sonia Solito ◽  
Giacomo Faleschini ◽  
Nikola Panic ◽  
Luigi Castriotta ◽  
...  
Keyword(s):  
Intragastric Balloon ◽  
Behavioural Therapy ◽  
Concomitant Treatment ◽  
Obese Patients ◽  
The Impact

scholarly journals Impact of Birth Weight and Length on Primary Hypertension in Children

2019 ◽  
Vol 16 (23) ◽  
pp. 4649
Author(s):  
Aneta Weres ◽  
Joanna Baran ◽  
Ewelina Czenczek-Lewandowska ◽  
Justyna Leszczak ◽  
Artur Mazur
Keyword(s):  
Body Weight ◽  
Birth Weight ◽  
Gestational Age ◽  
Primary Schools ◽  
Body Height ◽  
Primary Hypertension ◽  
Increased Risk ◽  
Appropriate For Gestational Age ◽  
The Impact ◽  
Hypertension In Children

Background: A child’s birth parameters not only enable assessment of intrauterine growth but are also helpful in identifying children at risk of developmental defects or diseases occurring in adulthood. Studies show that children born with a body weight that is small for their gestational age (SGA) are at a greater risk of hypertension though the inverse relation between excessive birth weight and the risk of primary hypertension in children is discussed less frequently. Purpose: To assess the impact of both birth weight and length on hypertension occurring in children aged 3–15 years. Methods: A total of 1000 children attending randomly selected primary schools and kindergartens were examined. Ultimately, the analyses took into account n = 747 children aged 4–15; 52.6% boys and 47.4% girls. The children’s body height and weight were measured; their blood pressure was examined using the oscillometric method. Information on perinatal measurements was retrieved from the children’s personal health records. Results: Compared to the children with small for gestational age (SGA) birth weight, the children with appropriate for gestational age birth weight (AGA) (odds ratio (OR) 1.31; 95% confidence interval (CI) 0.64–2.65) present greater risk for primary hypertension. Infants born with excessive body weight >4000 g irrespective of gestational age, compared to infants born with normal body weight, show increased risk of primary hypertension (OR 1.19; 95% CI 0.68–2.06). Higher risk of hypertension is observed in infants born with greater body length (OR 1.03; 95% CI 0.97–1.08). Conclusions: The problem of hypertension may also affect children with birth weight appropriate for gestational age. The prevalence of hypertension in children with AGA birth weight decreases with age. Birth length can be a potential risk factor for hypertension in children and adolescents.

scholarly journals High Bodyweight Variability Increases Depression Risk in Patients With Type 2 Diabetes Mellitus: A Nationwide Cohort Study in Korea

2021 ◽  
Vol 12 ◽  
Author(s):  
Ji Hyun An ◽  
Kyung-do Han ◽  
Jin-Hyung Jung ◽  
Juhwan Yoo ◽  
Maurizio Fava ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Body Weight ◽  
Obese Patients ◽  
Type 2 Dm ◽  
Increased Risk ◽  
Quartile Group ◽  
New Onset

Objectives: Although obesity is associated with increased risk for depression in patients with type 2 diabetes mellitus (DM), the relationship between body weight variability (BWV) and depression remains poorly studied. This study was to investigate the incidence of depression in patients with type 2 DM according to their BWV.Methods: Intraindividual variation in body weight were measured in the nationwide, population-based retrospective cohort of 540,293 patients with type 2 DM from the Korean national health insurance system between 2009 and 2010. The diagnoses of new-onset depression occurring until the end of 2017 were ascertained. Risk of new-onset depression was examined using multivariate-adjusted Cox proportional hazards regression analysis by BWV quartile.Results: 93,149 (17.2%) patients developed new-onset depression for the follow up. BWV was significantly associated with an increased risk of depression after adjusting for confounding factors. The highest BWV quartile group had a hazard ratio (HR) of 1.17 (95% CI 1.15–1.19) compared to the lowest BWV quartile group as a reference. Obese patients in the highest BWV quartile group showed 12% increased risk of depression (HR 1.12, 95% CI 1.09–1.15) while non-obese patients in the highest BWV quartile group showed 20% increased risk of depression (HR: 1.20, 95% CI: 1.17–1.23) compared to their respective lowest BWV quartile groups.Conclusion: A higher BWV was significantly associated with an increased risk of depression in patients with type 2 DM. Thus, BWV may serve as an indicator for early detection of depression in type 2 DM patients.

scholarly journals Case Report on Pregnancy with Lupus Nephritis Type IV with Hypothyroidism – A Clinical Vignette

2021 ◽  
Vol 8 (05) ◽  
pp. 272-274
Author(s):  
Abirbhab Pal
Keyword(s):  
Lupus Nephritis ◽  
Lupus Erythematosus ◽  
First Trimester ◽  
The Body ◽  
Fetal Mortality ◽  
Thyroid Disorder ◽  
Multisystem Disease ◽  
Mortality And Morbidity ◽  
Multiple Systems ◽  
Increased Risk

Lupus is a multisystem disease affecting almost all systems including the immune system of our body. Its aetiology is not known. Lupus involving kidneys causes lupus nephritis and adds more complications in the multisystem disease. Lupus or systemic lupus erythematosus (SLE) is a multifactorial chronic disease involving multiple systems of the body. It is autoimmune1 in nature. There is increase in maternal and fetal risk of mortality and morbidity in lupus with pregnancy. The rate of pregnancy loss is 1.7 %2 in active SLE during initial first trimester and the most common adverse morbidity causing factor of fetomaternal side.3 There can be an increase in fetal mortality and morbidity associated with lupus nephritis.4,5 There is increased risk of intrauterine growth restriction (IUGR) / neonatal lupus / gestational diabetes mellitus / osteoporosis / HELLP syndrome / preeclampsia. Associated thyroid disorder is increased with preterm pregnancy.

scholarly journals Early breast cancer: why does obesity affect prognosis?

2018 ◽  
Vol 77 (4) ◽  
pp. 369-381 ◽  
Author(s):  
A. Heetun ◽  
R. I. Cutress ◽  
E. R. Copson
Keyword(s):  
Breast Cancer ◽  
Body Composition ◽  
Treatment Effectiveness ◽  
Management Strategies ◽  
Age Groups ◽  
Obese Patients ◽  
Chemotherapy Drugs ◽  
Increased Risk ◽  
The Impact ◽  
High Bmi

High BMI is associated with an increased risk of breast cancer in post-menopausal women but poorer outcomes in all age groups. The underlying mechanism is likely to be multi-factorial. Patients with a high BMI may present later due to body habitus. Some studies have also indicated an increased incidence of biologically adverse features, including a higher frequency of oestrogen receptor (ER negative) tumours, in obese patients. Obese patients have a higher frequency of surgical complications, potentially delaying systemic therapies, and reports suggest that chemotherapy and endocrine therapy are less effective in patients with BMI ≥30 kg/m2.High BMI is generally interpreted as excess adiposity and a World Cancer Research Fund report judged that the associations between BMI and incidence of breast cancer were due to body fatness. However, BMI cannot distinguish lean mass from fat mass, or characterise body fat distribution. Most chemotherapy drugs are dosed according to calculated body surface area (BSA). Patients with a similar BSA or BMI may have wide variations in their distribution of adipose tissue and skeletal muscle (body composition); however, few studies have looked at the effect of this on chemotherapy tolerance or effectiveness. Finally, adjuvant treatments for breast cancer can themselves result in body composition changes.Research is required to fully understand the biological mechanisms by which obesity influences cancer behaviour and the impact of obesity on treatment effectiveness and tolerance so that specific management strategies can be developed to improve the prognosis of this patient group.

Sign in / Sign up

Export Citation Format

Share Document