Immunosuppression In Pediatric Renal Transplantation Research Articles

Long‐term experience of steroid‐free pediatric renal transplantation: Effects on graft function, body mass index, and longitudinal growth

Increased focus on the potential negative side effects of steroid usage in pediatric transplantation has led to steroid minimization or steroid-free transplantation. In this study, we report results after complete steroid avoidance in renal transplantation in the period 1994-2009. We evaluate the effects of complete steroid avoidance on allograft function, BMI, and linear growth. The majority of transplanted children were induced with antithymocyte globulin and immunosuppressed with a calcineurin inhibitor and mycophenolate mofetil. Steroids were given only when rejection occurred or due to comorbidities. Anthropometric data were collected from 65 transplantations in 60 children. Patient survival was 93%; graft survival was 81% after five yr (N = 42) and 63% after 10 yr (N = 16). Acute rejection within the first year of transplantation was 9%. The distribution of the children's BMI before transplantation was normal; the mean BMI-SDS was 0.21 before transplantation, and this value remained stable during the next five yr. Post-transplantation the children demonstrated significant improved growth as the mean height-SDS increased significantly from -1.7 to -1.1. Catch-up growth was most pronounced in the youngest (< six yr). Steroid-free immunosuppression in pediatric renal transplantation is safe and protects against steroid-induced obesity and short stature.

Conversion From Tacrolimus/Mycophenolic Acid to Tacrolimus/Leflunomide to Treat Cutaneous Warts in a Series of Four Pediatric Renal Allograft Recipients

The challenge of immunosuppression in pediatric renal transplantation is to balance preventing rejection while avoiding infectious complications. A dermatological complication of immunosuppression is viral warts, which cause significant disfigurement and increase the risk of skin malignancy. We present three pediatric and adolescent renal allograft recipients with multiple, recalcitrant verrucae vulgares lesions and one patient with molluscum contagiosum who were switched from mycophenolate mofetil to leflunomide. Teriflunomide metabolite levels were carefully maintained between 50,000 and 100,000 ng/mL to balance its immunosuppressive and antiviral properties. No adverse events requiring discontinuation of leflunomide were encountered. Switching from mycophenolate mofetil to leflunomide successfully cleared verrucae vulgares and molluscum lesions in all four renal transplant patients. The ability to minimize and even resolve warts can improve quality of life by reducing risk of skin malignancies and emotional distress in solid organ transplant patients. Leflunomide is a potential therapeutic option for posttransplantation patients with skin warts because it serves both as an adjunct to the immunosuppressive regimen and an antiviral agent.

Five‐year experience using sirolimus‐based, calcineurin inhibitor‐free immunosuppression in pediatric renal transplantation

From December 2003 to December 2008, we employed a protocol for withdrawing TAC and converting to SRL in a cohort of low-risk renal pediatric transplant recipients. We report our experience in these children with respect to graft survival, AR episodes, renal function, and adverse events. All patients received basiliximab induction and TAC, MMF, and prednisone. Criteria for conversion to SRL included first transplants without histologic evidence for AR on three-month surveillance biopsies. Patient exclusion criteria included AR prior to or before surveillance biopsies, polyoma (BK) virus nephropathy, a history of nephrotic syndrome, or multiple organ transplants. Fifty-one of 137 patients who received transplants from December 2003 to December 2008 met criteria for withdrawal of TAC and were converted to SRL. SRL was discontinued in 11 children because of adverse events within 12 months after conversion. Among the remaining 40 patients, actuarial graft survival was 91% at five yr. AR occurred in 13% of patients within one yr after conversion. Complications from SRL included aphthous ulcers (30%); viremia with BK virus (20%), EBV (13%), and CMV (3%); proteinuria (7%); elevated cholesterol (7%); diabetes mellitus (2%); thrombocytopenia (2%); erectile dysfunction (2%); and lymph edema (2%). SRL was discontinued in 20%, predominantly for aphthous ulcers. Our experience with SRL-based immunosuppression demonstrates that a CNI-free regimen can be successful in lower-risk patients meeting our selection criteria. Aphthous ulcers and BK virus viremia were the most prevalent adverse events.

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

Given the recent withdrawal of daclizumab (DAC), the safety and efficacy of thymoglobulin (TMG) was tested as an alternative induction agent for steroid-free (SF) immunosuppression in pediatric kidney transplant recipients. Thirteen pediatric renal transplant recipients meeting defined high-risk criteria at transplantation were offered TMG induction and SF immunosuppression with maintenance mycophenolate mofetil and tacrolimus between October 2008 and January 2010. Patients were closely monitored at baseline, 3, 6, 9, and 12 months posttransplant for protocol biopsy and clinical outcomes. Outcomes were compared with 13 consecutively transplanted low-risk patients receiving an established DAC-based SF protocol (Sarwal et al., WA, American Transplant Congress 2003). There was a significant trend for overall decrease in the absolute lymphocyte counts in TMG group (F=5.86, mixed model group effect P=0.02), predominately at 3 months compared with DAC group (0.7±0.6 vs. 2.1±1.0, P=0.0004); however, lymphocyte count was recovered and was back to reference range by 6 months in TMG. There was trend toward more subclinical cytomegalovirus (15% vs. 0%) and BK viremia (17% vs. 0%) in the TMG group, with no differences in the incidence of subclinical Epstein Barr virus viremia (23% vs. 31%) or clinical viral disease. Mean graft function was excellent, and with a minimum follow-up of 6 months, there were no episodes of acute rejection. 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.

Steroid-Free Immunosuppression in Pediatric Renal Transplantation: Rationale Outcomes Following Conversion to Steroid Based Therapy

Background. Short-term outcomes using steroid-free immunosuppression after renal transplantation have been promising. No studies have examined the incidence of and reasons for steroid-avoidance protocol failures. Methods. We present a single-center analysis of steroid-free immunosuppression failures among 129 pediatric renal transplant recipients with mean follow-up of 5 years. We analyzed causes for failure and examined reasons for conversion to steroid-based therapy. We compared actual patient and allograft survival and allograft function in the cohort of patients who required conversion to steroid-based immunosuppression with that of the cohort maintaining steroid-free immunosuppression. Results. A total of 13.2% (17/129) of patients failed steroid-free immunosuppression. Actual patient survival was equivalent in the two cohorts, 96.4% for the cohort maintaining steroid-free immunosuppression and 94.1% for those requiring conversion. Actual allograft survival was lower in patients requiring conversion to a steroid-based protocol, 76.5% vs. 95.5% (P=0.004). Estimated glomerular filtration rates 12-months and 24-months posttransplant were greater in patients maintaining steroid-free immunosuppression (P=0.003). Most patients (52.9%, 9/17) who broke the steroid-free protocol did so because of refractory acute rejection. The second most common reason was recurrence of glomerulonephritis (GN; 35.3%, 6/17). Conclusion. The failure rate of steroid-free immunosuppression among selective pediatric patients undergoing renal transplantation is low. Patients maintaining steroid-free immunosuppression have better allograft survival and function than those requiring conversion to steroid-based therapy. The most common reasons for failure of steroid-free immunosuppression are recalcitrant or recurrent allograft rejection and recurrent GN; the role of conversion to steroid-based immunosuppression after episodes of acute rejection and recurrent GN requires additional analysis.

Is it premature to use calcineurin-inhibitor-free immunosuppression in pediatric renal transplantation?

Is it premature to use calcineurin-inhibitor-free immunosuppression in pediatric renal transplantation?

Tacrolimus vs. cyclosporine A as primary immunosuppression in pediatric renal transplantation: a NAPRTCS study.

Using the North American Renal Transplant Cooperative Study (NAPRTCS) database, we performed a retrospective cohort study of 986 pediatric renal transplant recipients (index transplant 1997-2000) who were treated either with Cyclosporine A (CSA), Mycophenolate Mofetil (MMF) and steroids (n = 766) or tacrolimus (TAC), MMF and steroids (n = 220) to examine potential difference in clinical outcomes between these two groups. In the first year post-transplant, time to first rejection (29.1% vs. 29%, p = 0.840), risk for rejection [Adjusted Relative Risk (aRR) 1.01, 95% Confidence Interval (CI) 0.77, 1.323], graft survival (96.8% vs. 97.9%, p = 0.607) and risk for graft failure (aRR 0.988, 95% CI 0.64, 1.928) were not significantly different in TAC and CSA-treated patients. At 2 yr post-transplant, there was also no difference in risk for rejection (aRR 0.918, 95% CI 0.669, 1.259), graft survival (91.4% vs. 95.1%, p = 0.152) and risk for graft failure (aRR 0.702, 95% CI 0.461, 1.762) in the subset of 391 CSA-treated patients and 77 TAC-treated patients on whom 2 yr follow data were available in the database. TAC-treated patients were significantly less likely to require antihypertensive medication at 1 yr [aRR 0.74 (95% CI 0.454, 0.637)] and 2 yr post-transplant [aRR 0.67 (95% CI 0.56, 0.793)]. At 1 yr post-transplant, TAC-treated patients enjoyed a higher mean GFR as estimated by the Schwartz formula [89.1 mL/min/1.73 m(2) (SE 2.64) vs. 78.6 mL/min/1.73 m(2) (SE 1.07), p = 0.0003]. In addition, in the subset of patients with 2 yr of follow-up, TAC patients had a higher mean GFR at both 1 yr [98.6 mL/min/1.73 m(2) (SE 3.83) vs. 78.0 mL/min/1.73 m(2) (SE 1.44), p = 0.0003] and 2 yr post-transplant [96.7 mL/min/1.73 m(2) (SE 3.33) vs. 73.2 mL/min/1.73 m(2) (SE 1.48), p < 0.0001]. In summary, TAC and CSA, in combination with MMF and steroids, produce similar rejection rates and graft survival in pediatric renal transplant recipients. However, TAC is associated with improved graft function at 1 and 2 yr post-transplant. Further analysis as more patient data are obtained will be necessary to determine if this difference in graft function persists and translates into improved graft survival.

Tacrolimus-based immunosuppression in pediatric renal transplantation

Tacrolimus has been shown to be a safe and effective immunosuppressive agent in adult renal transplantation with significant advantages, including the ability to taper corticosteroids in up to 65% of recipients.1–4 The use of this agent in the pediatric population is less well described. We and others have previously reported that its use in pediatric patients is associated with excellent patient and graft survival results in a relatively small number of patients.5–9 Here we report our expanded experience on the use of tacrolimus in pediatric renal transplantation.

Comparison between mycophenolate mofetil and azathioprine based immunosuppression in pediatric renal transplantation from living related donors

Comparison between mycophenolate mofetil and azathioprine based immunosuppression in pediatric renal transplantation from living related donors

Mycophenolate mofetil as maintenance immunosuppression in pediatric renal transplantation

Mycophenolate mofetil as maintenance immunosuppression in pediatric renal transplantation

Low-Bose Cyclosporine Therapy Combined With Standard Immunosuppression in Pediatric Renal Transplantation

Low-Bose Cyclosporine Therapy Combined With Standard Immunosuppression in Pediatric Renal Transplantation

Low-dose cyclosporine therapy combined with standard immunosuppression in pediatric renal transplantation

A new immunosuppressive regimen combining anti-lymphocyte globulin, azathioprine, prednisone, and low doses of cyclosporine was used in 28 children aged 9 months to 17 years (mean 5.8 years) who received primary renal allografts between July 1, 1984, and September 25, 1986. After a mean follow-up of 17.3 months, the patient and graft survival is 100% (18 of 18) for mismatched related kidneys, and 90% (nine of 10) for cadaver kidneys. The single graft failure was the result of a death from technical complications. Serum creatinine concentration after transplantation ranged from 0.3 to 1.7 mg/dL (mean 0.85 mg/dL). The probability of a rejection episode in the first year was 45% and 60% for mismatched-related and cadaver kidneys, respectively. Cyclosporine nephrotoxicity was recognized in only one (3.7%) of 27 children, and was rapidly reversed after cyclosporine was discontinued. An initial group of nine children was weaned from cyclosporine therapy 6 to 12 months after transplantation, but two (22%) had rejection episodes. Our preliminary experience suggests that the use of a quadruple immunosuppressive regimen for both living related and cadaver renal transplants in children is associated with an improved graft function rate and a low incidence of complications.