Efficacy and Safety of Thymoglobulin Induction as an Alternative Approach for Steroid-Free Maintenance Immunosuppression in Pediatric Renal Transplantation

Li, Li; Chaudhuri, Abanti; Chen, Amery; Zhao, Xinmeng; Bezchinsky, Maria; Concepción, Waldo; Salvatierra, Oscar; Sarwal, Minnie M.

doi:10.1097/tp.0b013e3181fc8937

Cited by 38 publications

(20 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Given the very low incidence of acute tubular necrosis in our transplant program because of a bias toward living donation and a selection of deceased donors with low cold ischemia times, the category of acute tubular necrosis as a transplant injury subtype was not included for analysis because of low sample numbers. The patients included in this study were all on maintenance immunosuppression with tacrolimus, mycophenolate mofetil, and either on maintenance steroids or on a steroid avoidance protocol (24). The study was approved by the Ethics Committee of Stanford University Medical School and California Pacific Medical Center Research Institute (CPMCRI), and all patients/guardians provided informed consent to participate in the research, in full adherence to the Declaration of Helsinki.…”

Section: Methodsmentioning

confidence: 99%

The Identification of Novel Potential Injury Mechanisms and Candidate Biomarkers in Renal Allograft Rejection by Quantitative Proteomics

Sigdel

Salomonis

Nicora

et al. 2014

Molecular & Cellular Proteomics

Self Cite

View full text Add to dashboard Cite

Early transplant dysfunction and failure because of immunological and nonimmunological factors still presents a significant clinical problem for transplant recipients. A critical unmet need is the noninvasive detection and prediction of immune injury such that acute injury can be reversed by proactive immunosuppression titration. In this study, we used iTRAQ -based proteomic discovery and targeted ELISA validation to discover and validate candidate urine protein biomarkers from 262 renal allograft recipients with biopsy-confirmed allograft injury. Urine samples were randomly split into a training set of 108 patients and an independent validation set of 154 patients, which comprised the clinical biopsy-confirmed phenotypes of acute rejection (AR) (n ‫؍‬ 74), stable graft (STA) (n ‫؍‬ 74), chronic allograft injury (CAI) (n ‫؍‬ 58), BK virus nephritis (BKVN) (n ‫؍‬ 38), nephrotic syndrome (NS) (n ‫؍‬ 8), and healthy, normal control (HC) (n ‫؍‬ 10). A total of 389 proteins were measured that displayed differential abundances across urine specimens of the injury types (p < 0.05) with a significant finding that SUMO2 (small ubiquitin-related modifier 2) was identified as a "hub" protein for graft injury irrespective of causation. Sixtynine urine proteins had differences in abundance (p < 0.01) in AR compared with stable graft, of which 12 proteins were up-regulated in AR with a mean fold increase of 2.8. Nine urine proteins were highly specific for AR because of their significant differences (p < 0.01; fold increase >1.5) from all other transplant categories (HLA class II protein HLA-DRB1, KRT14, HIST1H4B, FGG, ACTB, FGB, FGA, KRT7, DPP4). Increased levels of three of these proteins, fibrinogen beta (FGB; p ‫؍‬ 0.04), fibrinogen gamma (FGG; p ‫؍‬ 0.03), and HLA DRB1 (p ‫؍‬ 0.003) were validated by ELISA in AR using an independent sample set. The fibrinogen proteins further segregated AR from BK virus nephritis (FGB p ‫؍‬ 0.03, FGG p ‫؍‬ 0.02), a finding that supports the utility of monitoring these urinary proteins for the specific and sensitive noninvasive diagnosis of acute renal allograft rejection. Molecular & Cellular Proteomics

show abstract

Section: Methodsmentioning

confidence: 99%

The Identification of Novel Potential Injury Mechanisms and Candidate Biomarkers in Renal Allograft Rejection by Quantitative Proteomics

Sigdel

Salomonis

Nicora

et al. 2014

Molecular & Cellular Proteomics

Self Cite

View full text Add to dashboard Cite

show abstract

“…Several studies have shown that both thymoglobulin and basiliximab could significantly decrease the incidence of acute rejection and DGF after a kidney transplant. [7][8][9] However, whether these drugs have similar efficacy and safety in patients who are at high risk for acute rejection and DGF remains to be determined.…”

Section: Introductionmentioning

confidence: 99%

Efficacy and Safety of Thymoglobulin and Basiliximab in Kidney Transplant Patients at High Risk for Acute Rejection and Delayed Graft Function

Chen

Gu²,

Qiu³

et al. 2013

Exp Clin Transplant

View full text Add to dashboard Cite

Objectives: To compare the efficacy and safety of thymoglobulin compared with basiliximab in patients who had kidney transplants and are at high risk for acute rejection and delayed graft function. Materials and Methods: A retrospective review of patients who had 1 or more risk factors for acute rejection and delayed graft function and who were given either thymoglobulin or basiliximab for induction therapy. Incidences of acute rejection, antibody-treated acute rejection, delayed graft function, chronic rejection, cancer, infection, leucopenia, and thrombocytopenia were compared between thymoglobulin and basiliximab groups. Serum creatinine levels within 1 year and long-term graft and patient survival also were compared. Results: A total of 327 patients were included. Incidences of acute rejection, antibody-treated acute rejection, delayed graft function, and chronic rejection were significantly lower in the thymoglobulin group than in the basiliximab group (P < .05). Serum creatinine levels were lower in the thymoglobulin group on postoperative days 7, 14, and 30 (P < .05). There were no statistically significant differences regarding long-term graft and patient survival, cancer, or total infection rate between the groups. Incidences of Cytomegalovirus infection, leucopenia, and thrombocytopenia were significantly higher in the thymoglobulin group (P < .05). Conclusions:Thymoglobulin may improve shortterm outcomes, compared with basiliximab, in patients who had kidney transplants and are at high risk for acute rejection and delayed graft function. However, long-term outcomes are similar with thymoglobulin and basiliximab.

show abstract

“…Previous pediatric protocols for steroid avoidance have specified various exclusion criteria, including increased panel reactive antibody (PRA) levels, repeat transplant, African‐American race, and previous steroid use . Moreover, induction therapy has differed significantly: Some protocols have included lymphocyte‐depleting agents (LDAs) , while others have used standard or extended dosing of IL‐2 receptor blockers . The use of steroid‐avoidance protocols in pediatric kidney transplantation involves a combination of center‐specific policies and patient‐level immunologic risk factors.…”

Section: Introductionmentioning

confidence: 99%

Clinical Practice of Steroid Avoidance in Pediatric Kidney Transplantation

Nehus

Liu

Hooper

et al. 2015

American Journal of Transplantation

View full text Add to dashboard Cite

Steroid‐avoidance protocols have recently gained popularity in pediatric kidney transplantation. We investigated the clinical practice of steroid avoidance among 9494 kidney transplant recipients at 124 transplant centers between 2000 and 2012 in the Organ Procurement and Transplantation Network database. The practice of steroid avoidance increased during the study period and demonstrated significant variability among transplant centers. From 2008 to 2012, 39% of transplant centers used steroid avoidance in <10% of all discharged transplant recipients. Twenty‐one percent of transplant centers practiced steroid avoidance in 10–40% of transplant recipients, and 40% of transplant centers used steroid avoidance in >40% of discharged patients. Children receiving steroid avoidance more frequently received induction with lymphocyte‐depleting agents. Repeat kidney transplants were the least likely to receive steroid avoidance. Children who received a deceased donor kidney, underwent pretransplant dialysis, were highly sensitized, or had glomerular kidney disease or delayed graft function were also less likely to receive steroid avoidance. The variation in practice between centers remained highly significant (p < 0.0001) after adjustment for all patient‐ and center‐level factors in multivariate analysis. We conclude that significant differences in the practice of steroid avoidance among transplant centers remain unexplained and may reflect uncertainty about the safety and efficacy of steroid‐avoidance protocols.

show abstract

Efficacy and Safety of Thymoglobulin Induction as an Alternative Approach for Steroid-Free Maintenance Immunosuppression in Pediatric Renal Transplantation

Abstract: TMG seems to be a safe alternative induction strategy in patients for SF immunosuppression in pediatric renal transplantation. Extended follow-up and greater enrollment are necessary to fully explore the impact of TMG dosing on viral replication posttransplantation.

Cited by 38 publications

References 17 publications

The Identification of Novel Potential Injury Mechanisms and Candidate Biomarkers in Renal Allograft Rejection by Quantitative Proteomics

The Identification of Novel Potential Injury Mechanisms and Candidate Biomarkers in Renal Allograft Rejection by Quantitative Proteomics

Efficacy and Safety of Thymoglobulin and Basiliximab in Kidney Transplant Patients at High Risk for Acute Rejection and Delayed Graft Function

Clinical Practice of Steroid Avoidance in Pediatric Kidney Transplantation

Contact Info

Product

Resources

About