Growth hormone axis in chronic kidney disease

Chronic kidney disease (CKD) in children is associated with dramatic changes in the growth hormone (GH) and insulin-like growth factor (IGF-1) axis, resulting in growth retardation. Moderate-to-severe growth retardation in CKD is associated with increased morbidity and mortality. Renal failure is a state of GH resistance and not GH deficiency. Some mechanisms of GH resistance are: reduced density of GH receptors in target organs, impaired GH-activated post-receptor Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling, and reduced levels of free IGF-1 due to increased inhibitory IGF-binding proteins (IGFBPs). Treatment with recombinant human growth hormone (rhGH) has been proven to be safe and efficacious in children with CKD. Even though rhGH has been shown to improve catch-up growth and to allow the child to achieve normal adult height, the final adult height is still significantly below the genetic target. Growth retardation may persist after renal transplantation due to multiple factors, such as steroid use, decreased renal function and an abnormal GH–IGF1 axis. Those below age 6 years are the ones to benefit most from transplantation in demonstrating acceleration in linear growth. Newer treatment modalities targeting the GH resistance with recombinant human IGF-1 (rhIGF-1), recombinant human IGFBP3 (rhIGFBP3) and IGFBP displacers are under investigation and may prove to be more effective in treating growth failure in CKD

Perception, diagnosis and management of BK polyomavirus replication and disease in paediatric kidney transplant recipients in Europe

BACKGROUND: BK polyomavirus (BKPyV)-associated nephropathy remains a challenge to the success of kidney transplantation, but its impact varies in different transplant programmes. METHODS: We investigated current practice through a web-based questionnaire made available by the European Society for Paediatric Nephrology (ESPN). RESULTS: A total of 90 physicians (23% of 391 active members) from 27 countries participated in the study. BKPyV-associated nephropathy is seen in 1-5% of patients annually with treatment success in 30-60%, and graft loss in 10%. Quantitative BKPyV load testing is available to <90% of physicians. Screening is performed in urine alone in 26%, in urine and blood in 37% and in blood alone in 37%. Most physicians (47%) screen at month 1, 2, 3, 6, 9 and 12 post-transplant. For patients with baseline renal function and plasma BKPyV loads of 10 000-1 000 000 copies/mL, 50% report performing renal biopsies prior to intervention. Intervention consists of reducing immunosuppression first with mycophenolate (Myc) in 40%, first with calcineurin inhibitors (CNI) in 29% or with both in 31%. Changing immunosuppressive drugs is considered mainly for biopsy-proven nephropathy consisting of discontinuation of Myc in 75%, and switching from CNI to mTOR inhibitors (52%). Cidofovir, intravenous immunoglobulin G, leflunomide and fluoroquinolones are used in less than one-third of this group. Furthermore, 66% of participants see a need for new antiviral drugs and new immmunosuppressive strategies, and almost 90% are willing to participate in future observational and interventional trials. CONCLUSION: This ESPN survey suggests that prompt translation of a positive screening test into reducing immunosuppression could improve outcomes

Comparison of MMF efficacy and safety in paediatric vs. adult renal transplantation: subgroup analysis of the randomised, multicentre FDCC trial

Background. Mycophenolate mofetil (MMF) is widely used for immunosuppressive therapy in renal transplantation, but comparative data regarding efficacy and safety in paediatric vs. adult kidney allograft recipients in one and the same study are lacking. Methods. We therefore performed this subgroup analysis of the FDCC trial, a 12-month, prospective, randomised study, comparing fixed-dose (FD) with concentration-controlled (CC) MMF dosing in paediatric and adult renal transplant recipients. Sixty-two paediatric and 839 adult de novo patients in 19 countries were randomised 1: 1 to receive fixed-dose or concentration-controlled MMF therapy in combination with calcineurin inhibitors and corticosteroids. Results. Both patient and allograft survival proved to be excellent in paediatric patients (98.4% and 90.3%) and adults (96.8% and 95.0%). The rates of biopsy-proven acute rejections (BPAR) and treated acute rejection episodes (ARE) were comparable between paediatric (12.9% and 17.7%) and adult patients (15.5% and 20.7%). Transplant function at 12 months post-transplant was similar in paediatric (67.8 +/- 45.6 mL/min/1.73 m(2)) and adult recipients (64.7 +/- 23.3 mL/min/1.73 m(2)). Children < 6 years (n = 10) exhibited a numerically higher frequency of leucocytopaenia (20%), diarrhoea (40%) and weight loss (10%) than older children (6-18 years; 5.8%, 28.8% and 1.9%) and adults (16.1%, 24.7% and 1.5%). On the whole, the percentage of patients who experienced adverse events causing interruption of MMF therapy were numerically lower in children (4.8%) than in adults (12.5%). Conclusions. The overall efficacy and tolerability of MMF appear to be comparable between paediatric and adult patients. Further studies are needed to validate these results