Tacrolimus‐based immunosuppression with steroid withdrawal in pediatric kidney transplantation – 4‐year experience at a moderate‐volume center

Jensen, Sena; Jackson, Elizabeth; Riley, L. P.; Reddy, Sudhakar; Goebel, Jens

doi:10.1034/j.1399-3046.2003.00027.x

Cited by 21 publications

(20 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…With the advent of tacrolimus, improved graft outcomes and decreased rates of rejection have been demonstrated both in adult and pediatric populations (16,17). This heralded the successful implementation of steroid withdrawal in clinically stable pediatric kidney transplant recipients (18,19) followed by the development of steroid-avoidance protocols (5-9). Furthermore, a recent Cochrane meta-analysis of adult randomized controlled trials demonstrated that there was no increased risk of acute rejection or graft loss in steroidsparing regimens that used tacrolimus for baseline maintenance immunosuppression (20).…”

Section: Discussionmentioning

confidence: 99%

Outcomes of Steroid-Avoidance Protocols in Pediatric Kidney Transplant Recipients

Nehus

Goebel

Abraham

2012

American Journal of Transplantation

View full text Add to dashboard Cite

show abstract

Section: Discussionmentioning

confidence: 99%

Outcomes of Steroid-Avoidance Protocols in Pediatric Kidney Transplant Recipients

Nehus

Goebel

Abraham

2012

American Journal of Transplantation

View full text Add to dashboard Cite

show abstract

“…Reliable prevention of acute rejection resulted, as well as reduction in the use of steroids. [8][9][10][11][12][13] However, the drastic weaning from immunosuppression accomplished in the early cases was almost never accomplished. Efforts to improve the complex protocols were frustrated for many years because the mechanisms of organ engraftment, and the effect of immunosuppression on these mechanisms, were unknown.…”

Section: Discussionmentioning

confidence: 99%

Antilymphoid antibody preconditioning and tacrolimus monotherapy for pediatric kidney transplantation

Shapiro

Ellis

Tan

et al. 2006

The Journal of Pediatrics

View full text Add to dashboard Cite

Objective-Heavy post-transplant immunosuppression may contribute to long-term immunosuppression dependence by subverting tolerogenic mechanisms; thus, we sought to determine if this undesirable consequence could be mitigated by pretransplant lymphoid depletion and minimalistic post-transplant monotherapy.Study design-Lymphoid depletion in 17 unselected pediatric recipients of live (n = 14) or deceased donor kidneys (n = 3) was accomplished with antithymocyte globulin (ATG) (n = 8) or alemtuzumab (n = 9). Tacrolimus was begun post-transplantation with subsequent lengthening of intervals between doses (spaced weaning). Maintenance immunosuppression, morbidity, graft function, and patient/graft survival were collated.Results-Steroids were added temporarily to treat rejection in two patients (both ATG subgroup) or to treat hemolytic anemia in two others. After 16 to 31 months (mean 22), patient and graft survival was 100% and 94%, respectively. The only graft loss was in a nonweaned noncompliant recipient. In the other 16, serum creatinine was 0.85 ± 0.35 mg/dL and creatinine clearance was 90.8 ± 22.1 mL/1.73 m 2 . All 16 patients are on monotherapy (15 tacrolimus, one sirolimus), and 14 receive every other day or 3 times per week doses. There were no wound or other infections. Two patients developed insulin-dependent diabetes.Conclusion-The strategy of lymphoid depletion and minimum post-transplant immunosuppression appears safe and effective for pediatric kidney recipients.Until the late 1960s, renal transplantation in pediatric patients was a controversial service that was systematically provided in only a few centers. 1-4 Numerous ethical issues were raised at the outset, including risk to live donors, effects on family unity, mental health of well siblings, and doubts about the long-term prognosis.5 Some of these anxieties have been relieved with the passage of time. For example, complications associated with heavy steroid use have been progressively circumvented with better adjunct6 and/or baseline drugs7 -13 However, chronic immunodepression per se and drug-specific side effects (eg, nephrotoxicity) have remained the principal threats to the quality and duration of life of the pediatric recipient. 14 We report here an experience in 17 pediatric kidney recipients in whom the burden of longterm immunosuppression was lightened with a treatment regimen designed to avoid acute rejection while interfering minimally with natural tolerogenic mechanisms. 17 One principle of the strategy consisted of lymphoid depletion before renal allograft revascularization. In the first eight patients, the lymphoid depletion was done with antithymocyte globulin (ATG; Thymoglobulin R ). 18 In the next nine patients, alemtuzumab (Campath-1H ® )19 -23 was used. The second therapeutic principle consisted of the use of the least amount of post-transplant immunosuppression consistent with stable graft function. This was accomplished by beginning the postoperative course on tacrolimus monotherapy with subsequent attempts to reduce ...

show abstract

“…Tacrolimusbased immunosuppression has proven efficacy in reducing graft rejection and minimizing adverse events in pediatric patients undergoing renal transplantation (2)(3)(4)(5)(6). In an effort to expand the options for effective and safe prophylaxis against early rejection, there has been investigation into new adjunctive immunosuppressants such as the interleukin-2 receptor antagonists (IL-2 Ra).…”

Section: Introductionmentioning

confidence: 99%

A Prospective, Randomized, Multicenter Trial of Tacrolimus-Based Therapy with or without Basiliximab in Pediatric Renal Transplantation

Grenda

Watson

Vondrák

et al. 2006

American Journal of Transplantation

107

View full text Add to dashboard Cite

In a 6-month, multicenter, randomized, controlled, open-label, parallel-group trial, we investigated the efficacy and safety of adding basiliximab to a standard tacrolimus-based regimen in pediatric renal transplant recipients. Patients <18 years received tacrolimus/azathioprine/steroids (TAS, n = 93) or tacrolimus/azathioprine/steroids/basiliximab (TAS + B, n = 99). Target tacrolimus levels were 10-20 ng/mL between days 0-21 and 5-15 ng/mL thereafter. Steroid dosing was identical in both groups. Basiliximab was administered at 10 mg (patients <40 kg) or 20 mg (patients ≥40 kg) within 4 h of reperfusion; the same dose was repeated on day 4. Biopsy-proven acute rejection rates were 20.4% (TAS) and 19.2% (TAS + B); steroid-resistant acute rejection rates were 3.2% and 3.0%, respectively. Patient survival was 100%; graft survival rates were 95% in both arms. The nature and incidence of adverse events were similar in both arms except toxic nephropathy and abdominal pain, which were significantly higher in the TAS + B arm (14.1% vs. 4.3%; p = 0.03 and 11.1% vs. 2.2%; p = 0.02; respectively). Median serum creatinine concentrations at 6 months were 86 lmol/L in the TAS and 91 lmol/L in the TAS + B arm; glomerular filtration rate was 79.4 and 77.6 (mL/min/1.73 m 2 ), respectively. Adding basiliximab to a tacrolimus-based regimen is safe in pediatric patients, but does not improve clinical efficacy.

show abstract

Tacrolimus‐based immunosuppression with steroid withdrawal in pediatric kidney transplantation – 4‐year experience at a moderate‐volume center

Cited by 21 publications

References 22 publications

Outcomes of Steroid-Avoidance Protocols in Pediatric Kidney Transplant Recipients

Outcomes of Steroid-Avoidance Protocols in Pediatric Kidney Transplant Recipients

Antilymphoid antibody preconditioning and tacrolimus monotherapy for pediatric kidney transplantation

A Prospective, Randomized, Multicenter Trial of Tacrolimus-Based Therapy with or without Basiliximab in Pediatric Renal Transplantation

Contact Info

Product

Resources

About