The Preliminary Results of Bortezomib Used as A Primary Treatment for An Early Acute Antibody-Mediated Rejection after Kidney Transplantation—A Single-Center Case Series

Proteasome inhibitor bortezomib has been used in the treatment of refractory cases of acute and chronic antibody-mediated rejection (AMR) in kidney transplant recipients. However, its efficacy and safety as a primary treatment for early AMR has been scarcely investigated. We herein present our preliminary experience with bortezomib- and plasmapheresis-based primary treatment for early AMR. Thirteen patients transplanted between October 2015 and September 2019 were treated (starting at median 19th post-transplant day) with bortezomib/plasmapheresis protocol for early biopsy-proven AMR. Twelve out of thirteen patients received 4 doses and one patient recieved 3 doses of bortezomib (1.3 mg/m2 per dose). In 11/13 patients, 4–7 concomitant plasmapheresis sessions were performed, with or without intravenous immunoglobulin (IVIG). Of note, rituximab was not used in all study patients. The kidney graft and patient survival were 100%. The mean 3-month estimated glomerular filtration rate (eGFR) was 55.3 (95%CI: 44.9–65.8) mL/min/1.73m2, 8/13 patients completed 12-month follow-up with mean eGFR 60.4 (45.4–75.4) mL/min/1.73m2, and 6/13 patients completed a 24-month follow-up period with mean eGFR 73.9 (56.7–91.1) mL/min/1.73m2. Neutropenia < 1 G/L was observed in one patient, third or fourth grade thrombocytopenia in two patients, and eleven patients needed a blood transfusion (median: 2 units/patient). The mid-term results of a primary bortezomib-based treatment for kidney AMR showed its non-inferiority as compared to preceding regimens and acceptable safety. However, our data should be validated in a multicenter randomized trial

Genotypes of renin-angiotensin system and plasma adiponectin concentration in kidney transplant patients

Background: Low plasma adiponectin concentration was recently recognized as a novel risk factor for new-onset diabetes after transplantation. Pharmacological modulation of the renin-angiotensin system activity and genetic predisposition were shown to have an influence on plasma adiponectin level. Therefore the aim of this study is to analyze the association between angiotensin-converting enzyme (ACE) I/D, angiotensin II type 1 receptor (AT 1 R) A1166C and angiotensinogen (AGT) M235T genotypes and plasma adiponectin concentration as well as insulin resistance in a cohort of kidney transplant patients. Material/Methods: AGT M235T, ACE I/D and AT 1 R A1166C genotyping and plasma adiponectin and insulin concentrations assessment were performed in 372 patients with functioning kidney allograft (eGFR >20 ml/min/1.73 m(2)) from 2 transplant centres. Results: Females with II ACE I/D genotype had a significantly higher plasma adiponectin concentration than the ID+DD subgroup, which could partially be explained by a lower BMI in the II subgroup. Males with TT genotype of the AGT M235T gene polymorphism (and higher BMI) had higher plasma concentration of insulin and HOMA-IR values than those in the MT+MM subgroup. A multiple regression analysis revealed that only female sex (beta=0.239), BMI (beta=-0.208) and ACE II genotype (beta=0.129) were significantly associated with plasma adiponectin concentration variability. A similar analysis for HOMA-IR showed that its variability was associated with BMI (beta=0.333), eGFR (beta=-0.115) and plasma adiponectin concentration (beta=-0.064) irrespective of any of the analyzed genotypes. Conclusions: Plasma adiponectin concentration, but not insulin resistance, seems to be modulated only by ACE I/D polymorphism in kidney transplant patients. Polymorphisms of the other renin-angiotensin system components do not influence plasma adiponectin concentration or insulin resistance in these patients

The Relationship between Initial Tacrolimus Metabolism Rate and Recipients Body Composition in Kidney Transplantation

There are several premises that the body composition of kidney transplant recipients may play a role in tacrolimus metabolism early after transplantation. The present study aimed at analyzing the relationship between the body composition parameters assessed by bioimpedance analysis (BIA) and initial tacrolimus metabolism. Immediately prior to transplantation, BIA using InBody 770 device was performed in 122 subjects. Tacrolimus concentration-to-dose (C/D) ratio was calculated based on the first blood trough level measurement. There was no difference in phase angle, visceral fat area, lean body mass index (LBMI) and the proportion of lean mass as a percentage of total body mass between the subgroups of slow and fast metabolizers. However, subjects with LBMI ≥ median value of 18.7 kg/m2, despite similar initial tacrolimus dose per kg of body weight, were characterized by a significantly lower tacrolimus C/D ratio (median 1.39 vs. 1.67, respectively; p < 0.05) in comparison with the subgroup of lower LBMI. Multivariate regression analysis confirmed that age (rpartial = 0.322; p < 0.001) and LBMI (rpartial = −0.254; p < 0.01) independently influenced the tacrolimus C/D ratio. A LBMI assessed by BIA may influence the tacrolimus metabolism in the early post-transplant period and can be a useful in the optimization of initial tacrolimus dosing

Tonsillectomy in a European Cohort of 1,147 Patients with IgA Nephropathy

BACKGROUND: Tonsillectomy has been considered a treatment for IgA nephropathy (IgAN). It is aimed at removing a source of pathogens, reducing mucosa-associated lymphoid tissue and decreasing polymeric IgA synthesis. However, its beneficial effect is still controversial. In Asia, favorable outcomes have been claimed mostly in association with corticosteroids. In Europe, small, single-center uncontrolled studies have failed to show benefits. METHODS: The European validation study of the Oxford classification of IgAN (VALIGA) collected data from 1,147 patients with IgAN over a follow-up of 4.7 years. We investigated the outcome of progression to end-stage renal disease (ESRD) and/or 50% loss of estimated glomerular filtration rate (eGFR) and the annual loss of eGFR in 61 patients who had had tonsillectomy. RESULTS: Using the propensity score, which is a logistic regression model, we paired 41 patients with tonsillectomy and 41 without tonsillectomy with similar risk of progression (gender, age, race, mean blood pressure, proteinuria, eGFR at renal biopsy, previous treatments and Oxford MEST scores). No significant difference was found in the outcome. Moreover, we performed an additional propensity score pairing 17 patients who underwent tonsillectomy after the diagnosis of IgAN and 51 without tonsillectomy with similar risk of progression at renal biopsy and subsequent treatments. No significant difference was found in changes in proteinuria, or in the renal end point of 50% reduction in GFR and/or ESRD, or in the annual loss of eGFR. CONCLUSION: In the large VALIGA cohort of European subjects with IgAN, no significant correlation was found between tonsillectomy and renal function decline. © 2015 S. Karger AG, Basel