BackgroundPatients with chronic kidney disease (CKD) may have increased plasma concentrations of some tumor markers even when no cancer is present. Previous studies have indicated that plasma concentrations of chromogranin A (CGA), cytokeratin 19 fragments (CYFRA 21-1), cancer antigen 125 (CA 125), cancer antigen 19-9 (CA 19-9) and carcinoembryonic antigen (CEA) are higher in patients with CKD but without cancer, than in healthy individuals, and this can make interpretation of results more complicated. The aim of this study was to establish reference limits for these markers in patients with CKD not receiving dialysis and with no clinical evidence of cancer.MethodsWe measured plasma concentrations in samples from 131 patients with CKD due to various etiologies and studied the association of tumor marker concentrations with estimated glomerular filtration rate (GFR) and other patient characteristics.ResultsEstimated reference limits for plasma CA 125, CA 19-9 and CEA were approximately the same as for healthy populations. Serum concentrations of CGA and CYFRA 21-1 correlated strongly with estimated GFR, and GFR-dependent reference limits were estimated.ConclusionsGFR-dependent reference limits for CGA and CYFRA 21-1 are reported in order to support interpretation of these markers in patients with CKD.

Background Vancomycin-resistant enterococci (VRE) represent several types of transferable vancomycin resistance gene clusters. The vanD type, associated with moderate to high level vancomycin resistance, has only sporadically been described in clinical isolates. The aim of this study was to perform a genetic characterization of the first VanD-type VRE strains detected in Norway. Methods The VanD-type VRE-strains (n = 6) from two patient cases were examined by antimicrobial susceptibility testing and whole genome sequencing (WGS) to uncover Van-phenotype, strain phylogeny, the vanD gene clusters, and their genetic surroundings. The putative transferability of vanD was examined by circularization PCR and filter mating. Results The VanD-type Enterococcus faecium (n = 4) and Enterococcus casseliflavus (n = 2) strains recovered from two cases (A and B), expressed moderate to high level vancomycin resistance (MIC 64—>256 mg/L) and various levels of teicoplanin susceptibility (MIC 2—>256 mg/L). WGS analyses revealed phylogenetically different E. faecium strains (A1, A2, and A3 of case A and B1 from case B) as well as vanD gene clusters located on different novel genomic islands (GIs). The E. casseliflavus strains (B2 and B3 of case B) were not clonally related, but harbored nearly identical novel GIs. The vanD cluster of case B strains represents a novel vanD-subtype. All the vanD-GIs were integrated at the same chromosomal site and contained genes consistent with a Clostridiales origin. Circular forms of the vanD-GIs were detected in all strains except B1. Transfer of vanD to an E. faecium recipient was unsuccessful. Conclusions We describe the first VanD-type E. casseliflavus strains, a novel vanD-subtype, and three novel vanD-GIs with a genetic content consistent with a Clostridiales order origin. Despite temporal occurrence, case A and B E. faecium strains were phylogenetically diverse and harbored different vanD subtypes and vanD-GIs.

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