scholarly journals Tocilizumab Trough Levels Variability in Kidney-Transplant Candidates Undergoing Desensitization

2021 ◽  
Vol 11 (1) ◽  
pp. 91
Author(s):  
Aurélie Truffot ◽  
Thomas Jouve ◽  
Johan Noble ◽  
Béatrice Bardy ◽  
Paolo Malvezzi ◽  
...  
Keyword(s):  
Kidney Transplant ◽  
Trough Concentration ◽  
Hla Antibodies ◽  
Coefficients Of Variation ◽  
Desensitization Therapy ◽  
Liquid Chromatography Tandem Mass ◽  
Interleukin 6 Receptor ◽  
Trough Concentrations ◽  
Transplant Candidates ◽  
The Individual

The presence of anti-HLA antibodies is an increasing challenge in kidney transplantation. Tocilizumab (TCZ), a monoclonal antibody targeting the interleukin-6 receptor (IL-6R), has been proposed to complement conventional desensitization therapy. We aimed to describe TCZ plasma trough concentrations and their variability and to investigate the link between TCZ concentration and the evolution of anti-HLA antibodies. Sensitized kidney-transplant candidates treated monthly with TCZ (8 mg/kg) for desensitization were retrospectively included. TCZ concentrations were determined by liquid chromatography-tandem mass spectrometry. Seventy-four TCZ concentrations from 10 patients were analyzed. The TCZ trough concentration ranged from <1.0 to 52.5 mg·L−1, with a median of 25.6 mg·L−1 [25th–75th percentiles: 13.2–35.3 mg·L−1). The inter- and intra-individual coefficients of variation were 55.0% and 33.0%, respectively. The TCZ trough concentration was not related to IL-6 (rho = −0.46, p = 0.792), soluble IL-6R (rho = −0.81, p = 0.65) concentrations or reduction of anti-HLA antibodies (mixed-effects model adjusting, effect of TCZ trough concentration: rho = −0.004, p = 0.26). The individual median TCZ concentration tended to be associated with the number of antibodies, with an initial MFI > 3000 that dropped to <3000 after TCZ treatment (rho = 0.397, p = 0.083). TCZ trough concentrations in kidney-transplant candidates treated for desensitization were highly variable. Further studies on larger cohorts are needed to study the possible link between TCZ concentrations and the reduction of anti-HLA antibodies.

Analysis of Anti-HLA Antibodies in Sensitized Kidney Transplant Candidates Subjected to Desensitization with Intravenous Immunoglobulin and Rituximab

2013 ◽  
Vol 96 (2) ◽  
pp. 182-190 ◽  
Author(s):  
Andrew L. Lobashevsky ◽  
Nancy G. Higgins ◽  
Kevin M. Rosner ◽  
Muhammad A. Mujtaba ◽  
William C. Goggins ◽  
...  
Keyword(s):  
Intravenous Immunoglobulin ◽  
Kidney Transplant ◽  
Hla Antibodies ◽  
Transplant Candidates

scholarly journals B cell repertoires in HLA-sensitized kidney transplant candidates undergoing desensitization therapy

2017 ◽  
Vol 15 (1) ◽  
Author(s):  
John F. Beausang ◽  
H. Christina Fan ◽  
Rene Sit ◽  
Maria U. Hutchins ◽  
Kshama Jirage ◽  
...  
Keyword(s):  
B Cell ◽  
Kidney Transplant ◽  
Desensitization Therapy ◽  
Transplant Candidates

scholarly journals Plasma Trough Concentrations of Antihypertensive Drugs for the Assessment of Treatment Adherence

Hypertension ◽  
2021 ◽  
Vol 77 (1) ◽  
pp. 85-93
Author(s):  
Eline H. Groenland ◽  
Monique E.A.M. van Kleef ◽  
Michiel L. Bots ◽  
Frank L.J. Visseren ◽  
Kim C.M. van der Elst ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Liquid Chromatography ◽  
Tandem Mass Spectrometry ◽  
Trough Concentration ◽  
Pharmacokinetic Studies ◽  
Tandem Mass ◽  
Chromatography Tandem Mass Spectrometry ◽  
Liquid Chromatography Tandem Mass ◽  
Trough Concentrations ◽  
Biochemical Assessment

Biochemical drug screening by liquid chromatography-tandem mass spectrometry in plasma is an accurate method for the quantification of plasma concentrations of antihypertensive medications in patients with hypertension. Trough concentrations could possibly be used as drug-specific cutoff values in the biochemical assessment of (non-)adherence. We performed a literature review and meta-analysis of pharmacokinetic studies to determine plasma trough concentrations of amlodipine, hydrochlorothiazide, and valsartan. PubMed was searched for pharmacokinetic studies up to September 2020. Eligible studies reported steady-state mean trough concentration and their variance. Pooled trough concentrations were estimated using a three-level random effects meta-analytic model. Moderator analyses were performed to explore sources of heterogeneity. One thousand three hundred eighteen potentially relevant articles were identified of which 45 were eligible for inclusion. The pooled mean trough concentration was 9.2 ng/mL (95% CI, 7.5–10.8) for amlodipine, 41.0 ng/mL (95% CI, 17.4–64.7) for hydrochlorothiazide, and 352.9 ng/mL (95% CI, 243.5–462.3) for valsartan. Substantial heterogeneity was present for all 3 pooled estimates. Moderator analyses identified dosage as a significant moderator for the pooled trough concentration of amlodipine (β 1 =0.9; P <0.05), mean age, and mean body weight for the mean trough concentration of hydrochlorothiazide (β 1 =2.2, P <0.05, respectively, β 1 =−4.0, P <0.05) and no significant moderators for valsartan. Plasma trough concentrations of amlodipine, hydrochlorothiazide, and valsartan, measured with liquid chromatography-tandem mass spectrometry, are highly heterogeneous over the different studies. Use of the pooled trough concentration as a cutoff in the biochemical assessment of adherence can result in inaccurate diagnosis of (non-)adherence, which may seriously harm the patient-physician relationship, and is therefore not recommended.

scholarly journals Effect of high-dose intravenous immunoglobulin on anti-HLA antibodies in sensitized kidney transplant candidates

2012 ◽  
Vol 26 (3) ◽  
pp. E261-E268 ◽  
Author(s):  
Vinay Nair ◽  
Deirdre Sawinski ◽  
Enver Akalin ◽  
Rex Friedlander ◽  
Zeynep Ebcioglu ◽  
...  
Keyword(s):  
Intravenous Immunoglobulin ◽  
Kidney Transplant ◽  
High Dose ◽  
Hla Antibodies ◽  
Transplant Candidates

scholarly journals To screen or not to screen? The development of a prediction model for aorto‐iliac stenosis in kidney transplant candidates

2021 ◽  
Author(s):  
Elsaline Rijkse ◽  
Hongchao Qi ◽  
Shabnam Babakry ◽  
Diederik C. Bijdevaate ◽  
Hendrikus J.A.N. Kimenai ◽  
...  
Keyword(s):  
Prediction Model ◽  
Kidney Transplant ◽  
Transplant Candidates

scholarly journals Abdominal Panniculectomy Can Simplify Kidney Transplantation in Obese Patients

2021 ◽  
pp. 1-8
Author(s):  
Dominik Promny ◽  
Theresa Hauck ◽  
Aijia Cai ◽  
Andreas Arkudas ◽  
Katharina Heller ◽  
...  
Keyword(s):  
Wound Healing ◽  
Kidney Transplantation ◽  
Postoperative Complications ◽  
Kidney Transplant ◽  
Interdisciplinary Approach ◽  
Wound Complications ◽  
Obese Patients ◽  
Patient Cohort ◽  
Transplant Candidates ◽  
Stage Renal Disease

<b><i>Background:</i></b> Obesity is frequently present in patients suffering from end-stage renal disease (ESRD). However, overweight kidney transplant candidates are a challenge for the transplant surgeon. Obese patients tend to develop a large abdominal panniculus after weight loss creating an area predisposed to wound-healing disorders. Due to concerns about graft survival and postoperative complications after kidney transplantation, obese patients are often refused in this selective patient cohort. The study aimed to analyze the effect of panniculectomies on postoperative complications and transplant candidacy in an interdisciplinary setting. <b><i>Methods:</i></b> A retrospective database review of 10 cases of abdominal panniculectomies performed in patients with ESRD prior to kidney transplantation was conducted. <b><i>Results:</i></b> The median body mass index was 35.2 kg/m<sup>2</sup> (range 28.5–53.0 kg/m<sup>2</sup>) at first transplant-assessment versus 31.0 kg/m<sup>2</sup> (range 28.0–34.4 kg/m<sup>2</sup>) at panniculectomy, and 31.6 kg/m<sup>2</sup> (range 30.3–32.4 kg/m<sup>2</sup>) at kidney transplantation. We observed no major postoperative complications following panniculectomy and minor wound-healing complications in 2 patients. All aside from 1 patient became active transplant candidates 6 weeks after panniculectomy. No posttransplant wound complications occurred in the transplanted patients. <b><i>Conclusion:</i></b> Abdominal panniculectomy is feasible in patients suffering ESRD with no major postoperative complications, thus converting previously ineligible patients into kidney transplant candidates. An interdisciplinary approach is advisable in this selective patient cohort.

scholarly journals Coronary microvascular dysfunction is associated with degree of anaemia in end‐stage renal disease

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Ashwin Radhakrishnan ◽  
Luke C. Pickup ◽  
Anna M. Price ◽  
Jonathan P. Law ◽  
Kirsty C. McGee ◽  
...  
Keyword(s):  
Confidence Interval ◽  
Renal Disease ◽  
Kidney Transplant ◽  
End Stage Renal Disease ◽  
Microvascular Dysfunction ◽  
Left Ventricular ◽  
Coronary Microvascular Dysfunction ◽  
Transplant Candidates ◽  
Stage Renal Disease ◽  
End Stage

Abstract Background Coronary microvascular dysfunction (CMD) is common in end-stage renal disease (ESRD) and is an adverse prognostic marker. Coronary flow velocity reserve (CFVR) is a measure of coronary microvascular function and can be assessed using Doppler echocardiography. Reduced CFVR in ESRD has been attributed to factors such as diabetes, hypertension and left ventricular hypertrophy. The contributory role of other mediators important in the development of cardiovascular disease in ESRD has not been studied. The aim of this study was to examine the prevalence of CMD in a cohort of kidney transplant candidates and to look for associations of CMD with markers of anaemia, bone mineral metabolism and chronic inflammation. Methods Twenty-two kidney transplant candidates with ESRD were studied with myocardial contrast echocardiography, Doppler CFVR assessment and serum multiplex immunoassay analysis. Individuals with diabetes, uncontrolled hypertension or ischaemic heart disease were excluded. Results 7/22 subjects had CMD (defined as CFVR < 2). Demographic, laboratory and echocardiographic parameters and serum biomarkers were similar between subjects with and without CMD. Subjects with CMD had significantly lower haemoglobin than subjects without CMD (102 g/L ± 12 vs. 117 g/L ± 11, p = 0.008). There was a positive correlation between haemoglobin and CFVR (r = 0.7, p = 0.001). Similar results were seen for haematocrit. In regression analyses, haemoglobin was an independent predictor of CFVR (β = 0.041 95% confidence interval 0.012–0.071, p = 0.009) and of CFVR < 2 (odds ratio 0.85 95% confidence interval 0.74–0.98, p = 0.022). Conclusions Among kidney transplant candidates with ESRD, there is a high prevalence of CMD, despite the absence of traditional risk factors. Anaemia may be a potential driver of microvascular dysfunction in this population and requires further investigation.

scholarly journals Daratumumab for Desensitization Therapy in Lung Transplant Candidates

2021 ◽  
Vol 40 (4) ◽  
pp. S335
Author(s):  
G. Magda ◽  
A.L. Ramsey ◽  
R. Saggar ◽  
M.Y. Shino ◽  
S.S. Weigt ◽  
...  
Keyword(s):  
Lung Transplant ◽  
Desensitization Therapy ◽  
Transplant Candidates
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