scholarly journals Comparative Long-Term Renal Allograft Outcomes of Recurrent Immunoglobulin A with Severe Activity in Kidney Transplant Recipients with and without Rituximab: An Observational Cohort Study

2021 ◽  
Vol 10 (17) ◽  
pp. 3939
Author(s):  
Wiwat Chancharoenthana ◽  
Asada Leelahavanichkul ◽  
Wassawon Ariyanon ◽  
Somratai Vadcharavivad ◽  
Weerapong Phumratanaprapin
Keyword(s):  
Cohort Study ◽  
Kidney Transplant ◽  
Renal Allograft ◽  
Adjunctive Treatment ◽  
Control Group ◽  
Case Group ◽  
Kidney Transplant Recipients ◽  
Allograft Function ◽  
Endocapillary Hypercellularity

Recurrent IgA nephropathy (IgAN) remains an important cause of allograft loss in renal transplantation. Due to the limited efficacy of corticosteroid in the treatment of recurrent glomerulonephritis, rituximab was used in kidney transplant (KT) recipients with severe recurrent IgAN. A retrospective cohort study was conducted between January 2015 and December 2020. Accordingly, there were 64 KT recipients with biopsy-proven recurrent IgAN with similar baseline characteristics that were treated with the conventional standard therapy alone (controls, n = 43) or together with rituximab (cases, n = 21). All of the recipients had glomerular endocapillary hypercellularity and proteinuria (>1 g/d) with creatinine clearance (CrCl) > 30 mL/min/1.73 m2 and well-controlled blood pressure using renin–angiotensin–aldosterone blockers. The treatment outcomes were renal allograft survival rate, proteinuria, and post-treatment allograft pathology. During 3.8 years of follow-up, the rituximab-based regimen rapidly decreased proteinuria within 12 months after rituximab administration and maintained renal allograft function—the primary endpoint—for approximately 3 years. There were eight recipients in the case group (38%), and none in the control group reached a complete remission (proteinuria < 250 mg/d) at 12 months after treatment. Notably, renal allograft histopathology from patients with rituximab-based regimen showed the less severe endocapillary hypercellularity despite the remaining strong IgA deposition. In conclusion, adjunctive treatment with rituximab potentially demonstrated favorable outcomes for treatment of recurrent severe IgAN post-KT as demonstrated by proteinuria reduction and renal allograft function in our cohort. Further in-depth mechanistic studies with the longer follow-up periods are recommended.

scholarly journals Preservation of epoxyeicosatrienoic acid bioavailability prevents renal allograft dysfunction and cardiovascular alterations in kidney transplant recipients

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Thomas Duflot ◽  
Charlotte Laurent ◽  
Anne Soudey ◽  
Xavier Fonrose ◽  
Mouad Hamzaoui ◽  
...  
Keyword(s):  
Endothelial Function ◽  
Kidney Transplant ◽  
Plasma Levels ◽  
Renal Allograft ◽  
Transplant Recipients ◽  
Loss Of Function ◽  
Kidney Transplant Recipients ◽  
Allograft Dysfunction ◽  
Allograft Function ◽  
The Impact

AbstractThis study addressed the hypothesis that epoxyeicosatrienoic acids (EETs) synthesized by CYP450 and catabolized by soluble epoxide hydrolase (sEH) are involved in the maintenance of renal allograft function, either directly or through modulation of cardiovascular function. The impact of single nucleotide polymorphisms (SNPs) in the sEH gene EPHX2 and CYP450 on renal and vascular function, plasma levels of EETs and peripheral blood monuclear cell sEH activity was assessed in 79 kidney transplant recipients explored at least one year after transplantation. Additional experiments in a mouse model mimicking the ischemia–reperfusion (I/R) injury suffered by the transplanted kidney evaluated the cardiovascular and renal effects of the sEH inhibitor t-AUCB administered in drinking water (10 mg/l) during 28 days after surgery. There was a long-term protective effect of the sEH SNP rs6558004, which increased EET plasma levels, on renal allograft function and a deleterious effect of K55R, which increased sEH activity. Surprisingly, the loss-of-function CYP2C9*3 was associated with a better renal function without affecting EET levels. R287Q SNP, which decreased sEH activity, was protective against vascular dysfunction while CYP2C8*3 and 2C9*2 loss-of-function SNP, altered endothelial function by reducing flow-induced EET release. In I/R mice, sEH inhibition reduced kidney lesions, prevented cardiac fibrosis and dysfunction as well as preserved endothelial function. The preservation of EET bioavailability may prevent allograft dysfunction and improve cardiovascular disease in kidney transplant recipients. Inhibition of sEH appears thus as a novel therapeutic option but its impact on other epoxyfatty acids should be carefully evaluated.

scholarly journals The association of two single-nucleotide polymorphisms of the FOXP3 gene (rs3761548 and rs3761547) with renal allograft function and survival in kidney transplant recipients

2020 ◽  
Vol 7 (2) ◽  
pp. e21-e21
Author(s):  
Vahideh Ebrahimzadeh Attari ◽  
Seyed Sadroddin Rasi Hashemi ◽  
Solmaz Oloufi ◽  
Leili Aghebati Maleki ◽  
Dariush Shanehbandi ◽  
...  
Keyword(s):  
Serum Creatinine ◽  
Serum Creatinine Level ◽  
Kidney Transplant ◽  
Creatinine Level ◽  
Kidney Function ◽  
Renal Allograft ◽  
Regulatory Protein ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Allograft Function

Introduction: The FOXP3 protein is an immune regulatory protein that specifically maintains the function and differentiation of regulatory T cells (Tregs) and prevents autoimmunity. Variations in FOXP3 gene may alter its function and also the immune response. Objectives: The present study was conducted to investigate the association of the FOXP3 gene polymorphisms -3499 A/G and -3279 A/C with renal allograft function and survival in kidney transplant recipients. Patients and Methods: In this cross-sectional study, 150 eligible kidney transplant recipients were evaluated. Kidney function was evaluated at three- and five-year post-transplant using serum creatinine level and glomerular filtration rate as indicators. Genotyping of the study participants was performed using the PCR– restriction fragment length polymorphism method. Results: The frequencies of AA, AG, and GG genotypes of the -3499 A/G polymorphism were 62.42%, 29.53%, and 8.05%, respectively. For the -3279 A/C polymorphism, the frequencies of the AA, AC, and CC genotypes were 21.33%, 32%, and 46.67%, respectively. The mean ± SD of serum creatinine level, three and five years after transplantation were 1.70 ± 1.58 and 1.87 ± 1.94, respectively. Serum creatinine level and kidney function did not show any significant association with these polymorphisms. Conclusion: In the present study, only 10% of participants experienced episodes of severe kidney dysfunction and we did not find any significant association between kidney function and the subjects’ genotypes. Further epidemiologic studies with greater sample sizes may be needed to clarify this association.

scholarly journals Comparison of clinical outcome of induction immunosuppressive therapy with thymoglobulin and standard therapy in kidney transplantation; a randomized double-blind clinical trial

2019 ◽  
Vol 9 (1) ◽  
pp. e08-e08
Author(s):  
Heshmatollah Shahbazian ◽  
Ali Ghorbani ◽  
Fatemeh Hayati ◽  
Seyed Seifollah Beladi Mousavi ◽  
Leila Sabetnia ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Kidney Transplantation ◽  
Kidney Transplant ◽  
Induction Therapy ◽  
Allograft Rejection ◽  
Control Group ◽  
Case Group ◽  
Transplant Recipients ◽  
Acute Allograft Rejection ◽  
Kidney Transplant Recipients

Introduction: Thymoglobulin is a lymphocyte-depleting polyclonal antibody, administered for induction therapy at the time of kidney transplantation to reduce the risk of acute allograft rejection. The appropriate dosage and duration of therapy is controversial. The higher dosages are associated with infection and malignancy. Objectives: In this study efficacy and safety of lower dosage (in comparison with previous studies) of thymoglobulin in kidney transplant recipients was evaluated. Patients and Methods: In this clinical trial, 106 adult kidney transplant recipients, were randomized before transplantation in two groups (case and control). The case group (53 patients) were received induction therapy with thymoglobulin (1.5 mg/kg/d for 3 days) and the control group (53 patients) were received non-induction regiment. Delayed graft function (DGF), glomerular filtration rate (GFR), acute allograft rejection and thymoglobulin complications were evaluated during the first post-transplantation year. Results: Around 106 kidney transplant recipients were enrolled (71 or 66.98% deceased donor) to the study. No significant statistical differences were found in GFR at the time of discharge from hospital (P=0.399) and at 1 year (P=0.851) and acute allograft rejection (P= 0.304) between two groups. Graft survival (73.5% in case group versus 81.1% in control group, P=0.392) at month 12th was similar among groups. Additionally, no significant differences of acute allograft rejection in recipient from deceased or living donor between two groups were detected. There was a higher incidence of DGF in the control group (26.4%) than the thymoglobulin group (5.8%) and the difference was statistically significant (P= 0.004). Thrombocytopenia (17% versus 49.1%, P<0.001) and leukopenia (11.3% versus 50.9%, P<0.001) were also significantly higher in the case group. Conclusion: While the incidence of DGF was reduced in thymoglobulin group, the short-term acute allograft rejection rate was not reduced compared to the control group. However, our results require further consideration with larger samples

scholarly journals Early and Late Post-Kidney Transplant Weight Changes and Renal Allograft Outcome (P21-036-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Ekamol Tantisattamo ◽  
Possawat Vutthikraivit ◽  
Siroj Dejhansathit
Keyword(s):  
Weight Loss ◽  
Weight Gain ◽  
Kidney Transplant ◽  
Renal Allograft ◽  
Statistical Significance ◽  
Potential Effect ◽  
Weight Changes ◽  
Kidney Transplant Recipients ◽  
Number Of Patients ◽  
Allograft Function

Abstract Objectives Post-Transplant weight gain is associated with poor renal allograft function. Association between pattern of weight gain at different period after kidney transplantation (KTx) especially during late transplantation and renal allograft function is unclear. We aim to address to potential effect of weight changes on renal allograft function. Methods Seventy kidney transplant recipients from a single center were stratified into 4 groups based on weight gain (+) and/or weight loss (−) compared to weight at the time of KTx both at 1 and 6 months post-KTx (Gr1 (−, −), Gr2 (−, +), Gr3 (+ , −), Gr4 (+, +)). Decline in renal allograft function defined by dropped in eGFR from baseline eGFR at 1-month post-KTx during 24 months of follow-up in different 4 groups is examined by multivariable Cox proportional hazard regression analysis. Results Mean ± SD age was 52.66 ± 11.97 years and 59% was male. Mean ± SD body mass index (BMI) at the time of KTx was 27.64 ± 5.64 kg/m2. Distribution of patients in 4 groups of Gr1, 2, 3, and 4 were 34, 36, 10, and 20%, respectively and mean BMI of all 4 groups at the time of KTx were not statistically significant (p 0.0981). Mean weight changes among 4 groups based on weight change both at 1- and 6-month post-KTx were summarized in the Table 1. Baseline renal allograft function with a mean eGFR of 50.86 ± 18.90 ml/min/1.73 m2 were not different among all 4 groups (Table 1). Among 70 patients, 43 patients (61%) had a decline in eGFR between 1 and 24 months post-KTx and contributed to the incidence rate of 0.056 person-months. The number of patients with dropped eGFR in Gr1, 2, 3 and 4 were 14 (58%), 14 (56%), 4 (57%), and 11 (79%) patients, respectively. Compared to Gr1, Gr2 had lower, but Gr 3 and 4 had higher the risk for declining eGFR but no statistical significance (HR(95% CI) :0.84 (0.40–1.76); 1.18 (0.39–3.60); 1.31 (0.60–2.90)). After adjusted for age, gender, race, types of KTx, systolic and diastolic blood pressure and BMI at the time of KTx, the association remains the same. (HR(95% CI) :0.78 (0.34–1.81); 1.66 (0.46–6.04); 1.32 (0.53–3.34)). Conclusions Weight loss at very early (1 month) post-KTx appears protective for a decline in renal allograft function during 24 months post-KTx; whereas, weight gain at later time post-KTx (6 months) after initial early weight loss was even associated with better renal allograft outcomes. Factors associated with early post-KTx weight gain may contribute to pathophysiology of poorer renal allograft function. Funding Sources None. Supporting Tables, Images and/or Graphs

P1638EARLY RENAL FUNCTION TRAJECTORIES, CYTOMEGALOVIRUS SEROSTATUS AND LONG-TERM GRAFT OUTCOMES IN KIDNEY TRANSPLANT RECIPIENTS: A BAYESIAN ANALYSIS STUDY

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Jonathan Law ◽  
Richard Borrows ◽  
David McNulty ◽  
Adnan Sharif ◽  
Charles Ferro
Keyword(s):  
Kidney Transplant ◽  
Graft Loss ◽  
Smooth Curve ◽  
Rapid Progression ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Short Term ◽  
Allograft Function

Abstract Background and Aims Despite significant improvements in short-term kidney transplant survival, long-term graft survival has not improved to the same degree with transplant failure being a top four cause of end-stage renal disease. We previously showed in a prevalent kidney transplant population that most patients do not experience linear renal function trajectories1. Many, instead, have periods of stability whilst others experience rapid progression. We also showed that episodes of rapid progression are associated with graft loss. Understanding trajectories of kidney allograft function is, therefore, key to defining the mechanisms underpinning allograft dysfunction. In this study, we evaluated the allograft function trajectories and associated factors, in an unselected, incident population of kidney allograft recipients in the early period post-transplantation. We also investigate whether episodes of rapid progression or non-progression are associated with graft loss in an extended follow-up period Method Demographic and clinical data were obtained from electronic health records. We used Bayesian smoothing techniques1 to create 10,000 Monte Carlo sample curves for 310 kidney transplant recipients for estimated glomerular filtration rates from 3-27 months after transplantation. This technique produces a smooth curve for each patient that reflects the gradual, longer term changes in eGFR values, rather than the rapid, short-term changes because of clinical and biologic variation as well as other interference including measurement error. The estimated trajectory is a smooth curve, allowing its slope to be calculated month by month. The probability of having an episode of rapid progression (decline greater than 5 ml/min/1.73m2/year in any 1-month period) and non-progression (decline no greater than -1ml/min/1.73m2/year) were calculated. Overall follow-up period was 8 years. Factors associated with having an episode of rapid progression, non-progression, and associations with long-term graft loss were explored. Results A median of 54 eGFR measurements per patient were available from 3-27 months for analysis. 65 patients (21%) had a probability of rapid progression greater than 0.8. During the follow-up period, 34 patients (11%) lost their graft. In multivariable Cox Proportional Hazard analysis, a probability greater than 0.8 of rapid progression was associated with long-term death-censored graft loss (Hazard ratio, 2.17; 95% CI, 1.04-4.55). In separate multivariable logistic regression models, cytomegalovirus serostatus donor positive to recipient positive (Odds ratio [OR], 3.82; 95% CI 1.63-8.97), CMV donor positive (OR 2.06; 95% CI 1.15-3.68), and CMV recipient positive (OR 2.03; 95% CI 1.14-3.60) were associated with having a greater than 0.8 probability of an episode of rapid progression. Having a probability greater than 0.8 of non-progression was not associated graft loss. Conclusion Early episodes of rapid progression are associated with long-term death-censored graft loss and are associated with cytomegalovirus seropositivity. Possible mechanisms include adverse cytomegalovirus-related immunomodulatory effects resulting in increased infections, glomerular injury and allograft vasculopathy. Further investigation into these factors may yield potentially modifiable risk factors and improve graft survival.

scholarly journals Renal allograft function in kidney transplant recipients infected with SARS-CoV 2: An academic single center experience

PLoS ONE ◽  
2021 ◽  
Vol 16 (6) ◽  
pp. e0252979
Author(s):  
Skylar L. Nahi ◽  
Aneesha A. Shetty ◽  
Sajal D. Tanna ◽  
Joseph R. Leventhal
Keyword(s):  
Kidney Transplant ◽  
Renal Allograft ◽  
Severe Disease ◽  
Kidney Injury ◽  
Transplant Recipients ◽  
Single Center ◽  
Kidney Transplant Recipients ◽  
P Values ◽  
Mild Disease ◽  
Allograft Function

Background Kidney transplant recipients are a unique cohort in regard to SARS-CoV 2 susceptibility and clinical course, owing to their immunosuppressed state and propensity for kidney injury. The primary purpose of this study is to ascertain if, in kidney transplant recipients, SARS-CoV 2 infection impacts long term renal allograft function. Methods This retrospective, single-center study reviewed 53 kidney transplant recipients with a positive SARS-CoV-2 PCR at NMH from January 1, 2020 to June 30, 2020. Results Change in eGFR from baseline kidney function prior to infection to 90 days after the first positive SARS-CoV 2 test was +1.76%, -17.5% and -23.16% the mild, moderate and severe disease groups respectively. There was a significant decline in kidney function in the moderate and severe disease cohorts as compared to the mild disease cohort, with respective p values of p = 0.0002 and p = 0.021. Relative to the mild disease cohort, the moderate and severe disease cohorts also demonstrated significantly increased risk of developing AKI (66%, 85%), both with p values of P = 0.0001. Conclusions Clinically severe SARS-CoV 2 infection is associated with greater risk of acute kidney injury and greater decline in renal allograft function at 90 days post infection, compared to mild disease.

scholarly journals Indicators of monocyte-derived component of the immune system in patients with satisfactory renal graft function

2020 ◽  
Vol 22 (2) ◽  
pp. 53-62
Author(s):  
S. V. Zybleva ◽  
S. L. Zyblev
Keyword(s):  
Kidney Transplant ◽  
Negative Correlation ◽  
Graft Function ◽  
Control Group ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Post Transplant ◽  
Long Term Follow Up

Objective: to study the indicators of the monocyte-derived component of the immune system in kidney transplant recipients with satisfactory early and delayed renal transplant function. Materials and methods. The study involved 76 kidney transplant recipients. Concentrations of serum creatinine (sCr), serum urea (sUr) and serum cystatin C (sCysC) were measured. CD14+mid/high and CD14+low were isolated from CD14+ monocytes. CD64- and CD86-expressing cell counts were determined for each subpopulation. Immunological examination was performed before surgery, as well as at days 1, 3, 7, 30, 90, 180 and 360 after surgery. Results. There was significant imbalance between the two monocyte subpopulations before transplantation and in the early post-transplant period (first 3 months). By the end of a 6-month follow-up period, the percentage of CD14+ cells had normalized. The dynamics of the subclasses of CD86-expressing monocytes in the post-transplant period is somewhat different from the dynamics of the total count for these monocytes. However, by the end of a 6-month follow-up period, these biomarkers returned to normal for the group of healthy individuals (CD14+mid/highCD86+ p180 = 0.079; CD14+lowCD86+ p180 = 0.789). CD14+lowCD64+ level was significantly higher in the kidney transplant group than in the control group during the entire follow-up period (p0 = 0.0006, p1 = 0.0001, p7 = 0.005, p30 = 0.005, p90 = 0.007, p180 = 0.0002, p360 = 0.001). On the other hand, CD14+mid/highCD64+ count for up to 180 days was not significantly different from that of the control group (p0 = 0.561, p1 = 0.632, p7 = 0.874, p30 = 0.926, p90 = 0.912), with subsequent significant increase by day 360 of follow-up (p180 = 0.01, p360 = 0.003). We observed a negative correlation between CD14+lowCD86+ level at day 0 and sCr levels at day 7 (r = –0.4; p = 0.008) and day 360 (r = –0.34; p = 0.042) and sCysC level at day 7 (r = –0.57; p = 0.014). A negative correlation was also found between CD14+lowCD86+ at day 1 and sCr levels at day 7 (r = –0.4; p = 0.005) and day 360 (r = –0.39; p = 0.02). There was positive correlation between the CD14+lowCD64+ subpopulation index at day 0 and sCr (r = 0.54; p = 0.008) and sCysC (r = 0.6; p = 0.008) levels at day 7, and also between the CD14+lowCD64+ count at day 1 and sCr (r = 0.55; p < 0.0001) and sCysC (r = 0.58; p = 0.004) levels at day 7. CD14+mid/highCD64+ at day 0 negatively correlated with sCysC level at day 360 (r = –0.85; p = 0.015), while CD14+mid/highCD64+ at day 7 positively correlated with sCysC level at day 360 (r = 0.50; p = 0.016). Conclusion. Before transplant surgery, CD14+mid/high, CD14+mid/highCD86+ , and CD14+lowCD86+ counts were reduced, while those of CD14+low, CD14+mid/highCD64+ and CD14+lowCD64+ were increased. By the 6-month follow-up, all these subpopulations except CD14+mid/highCD64+ had reached values for healthy people. Positive correlation between CD14+mid/high, CD14+lowCD64+ , CD14+mid/highCD86+ , CD14+mid/highCD64+ counts in the early post-transplant period and sCr/sCysC levels in long-term follow-up, as well as negative correlation between CD14+low, CD14+lowCD86+ counts in the early post-transplant period and sCr/sCysC levels in long-term follow-up can serve as a predictor of renal graft function.

scholarly journals Study of Lophomonas blattarum Infection in Kidney Transplant Patients in Mashhad City, Iran

2020 ◽  
Vol 2020 ◽  
pp. 1-5
Author(s):  
Zahra Gheisari ◽  
Fariba Berenji ◽  
Fatemeh Nazemian ◽  
Seyed Ali Akbar Shamsian ◽  
Lida Jarahi ◽  
...  
Keyword(s):  
Kidney Transplant ◽  
Organ Transplant ◽  
Immunosuppressive Drugs ◽  
Control Group ◽  
Case Group ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Transplant Patients ◽  
Mashhad City ◽  
Lophomonas Blattarum

Background. Lophomonas blattarum is a flagellate protozoan which is known as an emerging parasite in the human respiratory system. Organ transplant recipients are considered as immunocompromised patients due to prescription of immunosuppressive drugs. This group of patients is susceptible to opportunistic infection as well as lophomoniasis. This study aims to investigate the prevalence and clinical manifestation of pulmonary infections caused by L. blattarum in kidney transplant recipients. Methods. This is a case-control study including 50 kidney transplant recipients and 50 controls. The sputum samples were collected from 50 kidney transplant recipients with bronchopulmonary infection signs suspected to lophomoniasis admitted in Montaserieh and Imam Reza hospitals, Mashhad, Iran. 50 healthy individuals as the control group were matched for sex and age with case ones. The consent form, checklist, and required information were provided for each patient. All samples were microscopically examined for the flagellated protozoan, L. blattarum, using direct smear. Results. Among 50 kidney transplant recipients suspected to lophomoniasis, L. blattarum was identified in sputum samples of 4 (8%) participants of the case group including one female and three males. None of the samples were positive among the control group. Symptoms in patients of this study were high fever (4 out of 4 patients), cough (3 out of 4 patients), and dyspnea (2 out of 4 patients). Three patients showed a positive response to metronidazole treatment. Conclusion. The results of this study suggest that L. blattarum should be considered as a pathogenic agent in kidney transplant recipients. It is necessary to examine sputum samples in posttransplant pneumonia patients, especially in those resistant to antibacterial therapy.

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