Ten-year trends in epidemiology and outcomes of pediatric kidney replacement therapy in Europe : data from the ESPN/ERA-EDTA Registry

Background For 10 consecutive years, the ESPN/ERA-EDTA Registry has included data on children with stage 5 chronic kidney disease (CKD 5) receiving kidney replacement therapy (KRT) in Europe. We examined trends in incidence and prevalence of KRT and patient survival. Methods We included all children agedPeer reviewe

Clinical relevance of galectin-1 in hematologic malignancies treated with non-myeloablative hemopoietic stem cell transplantation

Non-myeloablative hemopoietic stem cell transplantation (NM-HSCT) is often the only curative treatment option for patients with hematologic malignancies.1 However, the treatment is frequently complicated by significant morbidity and mortality, acute GvHD (aGvHD) and chronic GvHD (cGvHD) being among the major causes.Fil: Petruskevicius, I.. Arhus Universitetshospital; DinamarcaFil: Ludvigsen, M.. University Aarhus; DinamarcaFil: Hjortebjerg, R.. Arhus Universitetshospital; DinamarcaFil: Sorensen, B. S.. Arhus Universitetshospital; DinamarcaFil: Kamper, P.. Arhus Universitetshospital; DinamarcaFil: Vase, M.. Arhus Universitetshospital; DinamarcaFil: Oestgaard, L. G.. Arhus Universitetshospital; DinamarcaFil: Nielsen, B.. Arhus Universitetshospital; DinamarcaFil: Honoré, B.. Arhus Universitetshospital; DinamarcaFil: Bjerre, M.. Arhus Universitetshospital; DinamarcaFil: Rabinovich, Gabriel Adrián. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: D'Amore, F. A.. Arhus Universitetshospital; Dinamarc

Structural Modeling and Electron Paramagnetic Resonance Spectroscopy of the Human Na+/H+ Exchanger Isoform 1, NHE1*

We previously presented evidence that transmembrane domain (TM) IV and TM X-XI are important for inhibitor binding and ion transport by the human Na+/H+ exchanger, hNHE1 (Pedersen, S. F., King, S. A., Nygaard, E. B., Rigor, R. R., and Cala, P. M. (2007) J. Biol. Chem. 282, 19716–19727). Here, we present a structural model of the transmembrane part of hNHE1 that further supports this conclusion. The hNHE1 model was based on the crystal structure of the Escherichia coli Na+/H+ antiporter, NhaA, and previous cysteine scanning accessibility studies of hNHE1 and was validated by EPR spectroscopy of spin labels in TM IV and TM XI, as well as by functional analysis of hNHE1 mutants. Removal of all endogenous cysteines in hNHE1, introduction of the mutations A173C (TM IV) and/or I461C (TM XI), and expression of the constructs in mammalian cells resulted in functional hNHE1 proteins. The distance between these spin labels was ∼15 A, confirming that TM IV and TM XI are in close proximity. This distance was decreased both at pH 5.1 and in the presence of the NHE1 inhibitor cariporide. A similar TM IV·TM XI distance and a similar change upon a pH shift were found for the cariporide-insensitive Pleuronectes americanus (pa) NHE1; however, in paNHE1, cariporide had no effect on TM IV·TM XI distance. The central role of the TM IV·TM XI arrangement was confirmed by the partial loss of function upon mutation of Arg425, which the model predicts stabilizes this arrangement. The data are consistent with a role for TM IV and TM XI rearrangements coincident with ion translocation and inhibitor binding by hNHE1

Growth Patterns After Kidney Transplantation in European Children Over the Past 25 Years

Background. Improved management of growth impairment might have resulted in less growth retardation after pediatric kidney transplantation (KT) over time. We aimed to analyze recent longitudinal growth data after KT in comparison to previous eras, its determinants, and the association with transplant outcome in a large cohort of transplanted children using data from the European Society for Paediatric Nephrology/European Renal Association and European Dialysis and Transplant Association Registry. Methods. A total of 3492 patients transplanted before 18 years from 1990 to 2012 were included. Height SD scores (SDS) were calculated using recent national or European growth charts. We used generalized equation models to estimate the prevalence of growth deficit and linear mixed models to calculate adjusted mean height SDS. Results. Mean adjusted height post-KT was −1.77 SDS. Height SDS was within normal range in 55%, whereas 28% showed moderate, and 17% severe growth deficit. Girls were significantly shorter than boys, but catch-up growth by 5 years post-KT was observed in both boys and girls. Children 12. Conclusions. Catch-up growth post-KT remains limited, height SDS did not improve over time, resulting in short stature in nearly half of transplanted children in Europe