The IPTA Nashville consensus conference on post-transplant lymphoproliferative disorders after solid organ transplantation in children: IV-consensus guidelines for the management of post-transplant lymphoproliferative disorders in children and adolescents.

The International Pediatric Transplant Association convened an expert consensus conference to assess current evidence and develop recommendations for various aspects of care relating to post-transplant lymphoproliferative disorders (PTLD) after pediatric solid organ transplantation. This report addresses the outcomes of deliberations by the PTLD Management Working Group. A strong recommendation was made for reduction in immunosuppression as the first step in management. Similarly, strong recommendations were made for the use of the anti-CD20 monoclonal antibody (rituximab) as was the case for chemotherapy in selected scenarios. In some scenarios, there is uncoupling of the strength of the recommendations from the available evidence in situations where such evidence is lacking but collective clinical experiences drive decision-making. Of note, there are no large, randomized phase III trials of any treatment for PTLD in the pediatric age group. Current gaps and future research priorities are highlighted.

Vesico-ureteric reflux in children and young people undergoing kidney transplantation.

Vesico-ureteric reflux (VUR) into transplanted kidneys in children and young people is a common occurrence, found in 19 to 60% of those who had an anti-reflux procedure and up to 79% in the absence of such a procedure. While VUR is unlikely to be of concern without evidence of symptomatic urinary tract infections, less certainty exists regarding outcomes when the VUR is associated with urinary tract infection (UTI) and transplant pyelonephritis. Issues explored will include additional risk factors that might predispose to UTI, any effect of pyelonephritis on acute and long-term kidney allograft function and practical strategies that may reduce the prevalence of infection.

Three-year outcomes from the CRADLE study in de novo pediatric kidney transplant recipients receiving everolimus with reduced tacrolimus and early steroid withdrawal.

CRADLE was a 36-month multicenter study in pediatric (≥1 to <18 years) kidney transplant recipients randomized at 4 to 6 weeks posttransplant to receive everolimus + reduced-exposure tacrolimus (EVR + rTAC; n = 52) with corticosteroid withdrawal at 6-month posttransplant or continue mycophenolate mofetil + standard-exposure TAC (MMF + sTAC; n = 54) with corticosteroids. The incidence of composite efficacy failure (biopsy-proven acute rejection [BPAR], graft loss, or death) at month 36 was 9.8% vs 9.6% (difference: 0.2%; 80% confidence interval: -7.3 to 7.7) for EVR + rTAC and MMF + sTAC, respectively, which was driven by BPARs. Graft loss was low (2.1% vs 3.8%) with no deaths. Mean estimated glomerular filtration rate at month 36 was comparable between groups (68.1 vs 67.3 mL/min/1.73 m2 ). Mean changes (z-score) in height (0.72 vs 0.39; P = .158) and weight (0.61 vs 0.82; P = .453) from randomization to month 36 were comparable, whereas growth in prepubertal patients on EVR + rTAC was better (P = .050) vs MMF + sTAC. The overall incidence of adverse events (AEs) and serious AEs was comparable between groups. Rejection was the leading AE for study drug discontinuation in the EVR + rTAC group. In conclusion, though AE-related study drug discontinuation was higher, an EVR + rTAC regimen represents an alternative treatment option that enables withdrawal of steroids as well as reduction of CNIs for pediatric kidney transplant recipients. ClinicalTrials.gov: NCT01544491.

European evidence-based recommendations for the diagnosis and treatment of childhood-onset lupus nephritis: the SHARE initiative.

Lupus nephritis (LN) occurs in 50%-60% of patients with childhood-onset systemic lupus erythematosus (cSLE), leading to significant morbidity. Timely recognition of renal involvement and appropriate treatment are essential to prevent renal damage. The Single Hub and Access point for paediatric Rheumatology in Europe (SHARE) initiative aimed to generate diagnostic and management regimens for children and adolescents with rheumatic diseases including cSLE. Here, we provide evidence-based recommendations for diagnosis and treatment of childhood LN. Recommendations were developed using the European League Against Rheumatism standard operating procedures. A European-wide expert committee including paediatric nephrology representation formulated recommendations using a nominal group technique. Six recommendations regarding diagnosis and 20 recommendations covering treatment choices and goals were accepted, including each class of LN, described in the International Society of Nephrology/Renal Pathology Society 2003 classification system. Treatment goal should be complete renal response. Treatment of class I LN should mainly be guided by other symptoms. Class II LN should be treated initially with low-dose prednisone, only adding a disease-modifying antirheumatic drug after 3 months of persistent proteinuria or prednisone dependency. Induction treatment of class III/IV LN should be mycophenolate mofetil (MMF) or intravenous cyclophosphamide combined with corticosteroids; maintenance treatment should be MMF or azathioprine for at least 3 years. In pure class V LN, MMF with low-dose prednisone can be used as induction and MMF as maintenance treatment. The SHARE recommendations for diagnosis and treatment of LN have been generated to support uniform and high-quality care for all children with SLE.

New immunosuppressants in pediatric solid organ transplantation.

PURPOSE OF REVIEW: This review examines new developments in the prophylaxis and treatment of rejection episodes as there has been a marked improvement in patient and allograft survival in pediatric solid organ transplant recipients over the last 20 years. Improved surgical techniques to allow transplantation of smaller recipients and a wider range of immunosuppressants available to transplant physicians have improved access and reduced the incidence and severity of acute rejection episodes and chronic allograft damage. RECENT FINDINGS: There is increasing knowledge of chronic allograft damage and the role of humorally-mediated rejection, leading to better understanding of the mechanisms involved and potential treatments. There is evidence in the literature of potential targets of B-cell survival factors by inhibiting novel pathways involved in B-cell and plasma cell activation. SUMMARY: There are currently trials underway investigating the use of eculizumab and bortezomib for treatment of antibody-mediated rejection as well as utilising these agents as part of desensitisation protocols. Minimal (or even monotherapy) maintenance immunosuppression regimens include monoclonal antibodies and fusion receptor proteins targeting different pathways (CD40-CD154, CD28-CD80/86, and LFA3-CD2 pathway). Phase III randomised controlled trials in adults are required before embarking on treatment of children.

Successful outcome of renal transplantation in a child with HIV-associated nephropathy.

Classical HIV-associated nephropathy (HIVAN) was first described before the advent of highly active antiretroviral therapy in late stages of HIV disease with high viral load and low CD4 cell count. Renal transplantation has been successful in a large series of carefully selected HIV-infected adults, with patient and renal allograft survival approaching those of non-HIV-infected patients. We report the successful outcome of living related renal transplantation in a vertically transmitted HIV-infected 8-year-old girl with end-stage kidney disease on haemodialysis due to HIVAN. The pretransplant preparations and post-transplant care, with particular emphasis on immunosuppression and avoidance of opportunistic infections, are discussed.

Steroid preservation: the rationale for continued prescribing.

Tailored immunosuppression according to risk stratification for optimal outcome for both immunological and non-immunological risk factors should be the ultimate objective for every child in whom renal transplantation is planned. Renal allograft survival is dependent on the appropriate use of immunosuppressive therapy to prevent acute rejection and chronic allograft nephropathy. Unfortunately, all immunosuppressive therapies, including corticosteroids, have unwanted side effects, including infections, malignancy, nephrotoxicity, hypertension, hyperlipidaemia and diabetes mellitus. However, the most worrying side effects of corticosteroids for children, adolescents and their parents are growth retardation and the cosmetic effects. Consequently, achieving immunosuppressive regimens without corticosteroids would be preferable. The major concern for paediatric nephrologists in the 21st century is no longer acute rejection, as the incidence appears to be decreasing, but infection, particularly EBV and the development of post-transplant lymphoproliferative disease (PTLD). With modern immunosuppressive agents in transplantation, rejection is being traded for infection. The long-term outcome data of PTLD with steroid-free and monoclonal antibody protocols is as yet unknown.