In the past two decades, major progress has been made in our understanding of the pathophysiology and treatment of growth failure in children with chronic kidney disease (CKD). Nevertheless, approximately 40% of children with end-stage renal disease (ESRD) have a reduced final height (below the third percentile) compared with that of healthy age-matched and sex-matched controls 1,2. Short stature impairs quality of life, self-esteem and social rehabilitation and is associated with increased mortality 3-6. The aetiology of growth failure in CKD is multifactorial and includes intrauterine growth restriction, malnutrition, mineral and bone disorder (MBD), metabolic acidosis, loss of electrolytes and disturbances of the somatotropic and gonadotropic hormone axes (Fig. 1). In particular, advanced CKD is a state of growth hormone (GH) insensitivity, characterized by deficiency of functional insulin-like growth factor 1 (IGF1) 7. This GH insensitivity can be overcome by the administration of supraphysiological doses of recombinant human GH (abbreviated to GH hereafter), which stimulates IGF1 synthesis, normalizes somatomedin bioactivity, promotes longitudinal growth and likely improves adult height 8,9. Consequently, GH has been licensed for the treatment of CKD-induced growth failure in Europe, North America and many other high-income countries. However, other than a treatment algorithm proposed by members of a consensus conference held in 2003 (reF. 10) and a brief guidance from the Kidney Disease Outcomes

The number of acute rejections and infections after pediatric kidney transplantation (KTX) could not be reduced in the last years. To reduce these events, we investigated a new immunosuppressive protocol in a prospective trial. After KTX, 20 children (median age 12 years, range 1-17) were initially treated with Basiliximab, ciclosporine A (CsA) (trough-level = C0 200-250 ng/mL) and prednisolone. After 2 weeks, CsA dose was reduced to 50% (C0 75-100 ng/mL, after 6 months: 50-75 ng/mL) and everolimus (1.6 mg/m 2 /day) was started (C0 3-6 ng/mL). Six months after KTX prednisolone was set to alternate dose and stopped 3 months later. All 20 protocol biopsies 6 months after KTX showed no acute rejection or borderline findings. Indication biopsies resulted in no acute rejections and two borderline findings. Mean glomerular filtration rate (GFR) 1 year after KTX was 71 ± 25 mL/min/ 1.73 m 2 . Without cytomegalovirus (CMV)-prophylaxis, only two primary CMV infections were seen despite a donor/recipient-CMV-constellation pos./neg. in 10/ 20 children. In pediatric KTX, de novo immunosuppression with low-dose CsA, everolimus and steroid withdrawal after 9 months led to promising results according to numbers of acute rejections and infections. Further follow up is needed. Future larger trials will have to confirm our findings.

Late steroid withdrawal in selected CsA- and MMF-treated paediatric kidney transplant recipients improves growth, mitigates cardiovascular risk factors and reduces the prevalence of the metabolic syndrome, at no increased risk of acute rejection or unstable graft function.

Background. The renal Fanconi syndrome (FS) is characterized by renal glucosuria, loss of electrolytes, bicarbonate and lactate, generalized hyperaminoaciduria and low-molecular-weight proteinuria. We studied the urinary low-molecular-weight proteome to identify excreted peptides indicative of a pathogenetic mechanism leading to tubular dysfunction. Methods. We established a urinary proteome pattern using capillary electrophoresis mass spectrometry (CE-MS) of 7 paediatric patients with cystinosis and 6 patients with ifosfamide-induced FS as the study group, and 54 healthy volunteers and 45 patients suffering from other renal diseases such as lupus nephritis (n = 8), focal segmental glomerulosclerosis (n = 27), minimal change disease (n = 7) and membranous glomerulonephritis (n = 3) as controls. Consequently, we conducted a blinded study consisting of 11 FS patients and 9 patients with renal disease other than FS. Additionally, we applied this pattern to 294 previously measured samples of patients with different renal diseases. Amino acid sequences of some marker proteins were obtained. Results. Specificity for detecting FS was 89% and sensitivity was 82%. The marker peptides constituting the proteome pattern are fragments derived from osteopontin, uromodulin and collagen alpha-1. Conclusions. CE-MS can be used to diagnose FS in paediatric patients and might be a future tool for the non-invasive diagnosis of FS. The reduced amount of the marker proteins osteopontin and uromodulin indicates loss of function of tubular excretion in all patients suffering from FS regardless of the underlying cause. In addition, the six different fragments of the collagen alpha-1 (I) chain were either elevated or reduced in the urine. This indicates a change of proteases in collagen degradation as observed in interstitial fibrosis. These changes were prominent irrespectively of the stages of FS. This indicates fibrosis as an early starting pathogenetic reason for the development of renal insufficiency in FS patients.

No abstract