OBJECTIVE To analyse the morphological appearance of horseshoe kidneys (HKs) and crossed fused ectopia (CFE) and to assess the frequency and clinical significance of associated anomalies and diseases. PATIENTS AND METHODS The findings and images of 209 patients with fused kidneys (FKs) were reviewed; in all, 244 scans from computed tomography (CT), 233 ultrasonograms and 89 micturition cysto‐urethrograms, urograms, magnetic resonance images and angiograms were taken. RESULTS HKs (found in one of 474 abdominal CT scans) and CFEs (found in one of 3078 CT scans) showed a high variability of vasculature that could not be classified. However, some generalized conclusions were possible about the renal vasculature (430 arteries in 103 kidneys). Variants of the most cephalad artery of both sides were rare. The second artery on the right had a pre‐caval course. The origins of vessels located further caudal were more ventral. CFEs were anatomically different from HKs with respect to lower position, greater axial rotation, smaller pelvic width, more caudal origin, and fewer vessels, but not in accompanying anomalies. Severe anomalies or malformations were found in 23% of patients, with half of them in the urogenital system. Malformations were found considerably more often in children than in adults. There was no increased incidence of diseases such as stones or inflammation of the renal pelvis. CONCLUSION Concomitant anomalies and diseases were equally frequent for HK and CFE, but less frequent than generally assumed. Individual cases of complex anatomical situations require special examination strategies, and CT appears to be the most reliable imaging method.

Hepcidin levels in stable haemodialysis patients appear to reflect systemic iron load, but not inflammation. Due to the negative association between reticulocyte counts and hepcidin, the reduction of circulating hepcidin concentrations by dialysis and/or rhEpo treatment may positively affect erythropoiesis.

SummaryAlthough chronological donor age is the most potent predictor of long-term outcome after renal transplantation, it does not incorporate individual differences of the agingprocess itself. We therefore hypothesized that an estimate of biological organ age as derived from markers of cellular senescence in zero hour biopsies would be of higher predictive value. Telomere length and mRNA expression levels of the cell cycle inhibitors CDKN2A (p16INK4a) and CDKN1A (p21WAF1) were assessed in pre-implantation biopsies of 54 patients and the association of these and various other clinical parameters with serum creatinine after 1 year was determined. In a linear regression analysis, CDKN2A turned out to be the best single predictor followed by donor age and telomere length. A multiple linear regression analysis revealed that the combination of CDKN2A values and donor age yielded even higher predictive values for serum creatinine 1 year after transplantation. We conclude that the molecular aging marker CDKN2A in combination with chronological donor age predict renal allograft function after 1 year significantly better than chronological donor age alone.

The nephrotoxic potential of the widely used immunosuppressive agent cyclosporine A (CsA) is well recognized. However, the mechanism of renal tubular toxicity is not yet fully elucidated. Chronic CsA nephropathy and renal organ aging share some clinical features, such as renal fibrosis and tubular atrophy, raising the possibility that CsA may exert some of its deleterious effects via induction of a stress-induced senescent phenotype. We investigated this hypothesis in HK-2 cells and primary proximal tubular cells in vitro. CsA induced the production of H2O2, caused cell cycle arrest in the G0/G1 phase, and inhibited DNA synthesis. Furthermore, CsA exposure lead to a reduction of telomere length, increased p53 serine 15 phosphorylation, and caused an upregulation of the cell cycle inhibitor p21(Kip1) (CDKN1A) mRNA levels. CsA caused an increase in p16(INK4a) (CDKN2A) expression after a 13-day exposure in primary proximal tubular cells but not in HK-2 cells. Coincubation of cells with CsA and catalase was able to prevent telomere shortening and partially restored DNA synthesis. In summary, CsA induces cellular senescence in human renal tubular epithelial cells, which can be attenuated by scavenging reactive oxygen species.

Objective. Juvenile idiopathic arthritis (JIA) is an autoimmune disease of the young. The pathogenesis is not completely understood. Premature aging, associated thymic involution, and compensatory autoproliferation could play important roles in the pathogenesis of autoimmunity. We undertook this study to determine whether patients with JIA demonstrate premature immunosenescence.Methods. To test this hypothesis, we measured 3 indicators of aging: the percentages and total counts of peripheral blood naive T cells, the frequency of T cell receptor excision circles (TRECs) in naive T cells, and telomeric erosion and Ki-67 expression as estimates of the replicative history of homeostatic proliferation.Results. JIA patients showed an accelerated loss of CD4؉,CD45RA؉,CD62L؉ naive T cells with advancing age and a compensatory increase in the number of CD4؉,CD45RO؉ memory T cells. JIA patients demonstrated a significantly decreased frequency of TRECs in CD4؉,CD45RA؉ naive T cells compared with agematched healthy donors (P ‫؍‬ 0.002). TREC numbers correlated with age only in healthy donors (P ‫؍‬ 0.0001).Telomeric erosion in CD4؉,CD45RA؉ naive T cells was increased in JIA patients (P ‫؍‬ 0.01). The percentages of Ki-67-positive CD4؉,CD45RA؉ naive T cells were increased in JIA patients (P ‫؍‬ 0.001) and correlated with disease duration (P ‫؍‬ 0.003), which was also an independent factor contributing to telomeric erosion (P ‫؍‬ 0.04).Conclusion. Our findings suggest that ageinappropriate T cell senescence and disturbed T cell homeostasis may contribute to the development of JIA. In patients with JIA, dysfunction in the ability to reconstitute the T cell compartment should be considered when exploring new therapeutic strategies.