Toru Takatani

Circulating Aminoterminal Propeptide of Type III Procollagen as a Biomarker of Cardiovascular Events in Patients Undergoing Hemodialysis

Aim: Type III collagen abundantly exists in the cardiovascular system, including the aorta and heart. We prospectively investigated whether serum levels of aminoterminal propeptide of type III procollagen (PIIINP), a circulating biomarker of cardiovascular fibrosis, could predict cardiovascular events in patients undergoing hemodialysis. Methods: Serum PIIINP concentrations were measured in 244 patients undergoing maintenance hemodialysis (men, 126; women, 118; mean age, 64 ± 11 years; dialysis duration, 11.5 ± 7.8 years) by immunoradiometric assay in February 2005. The endpoint was cardiovascular events, and the patients were followed up until the endpoint was reached, or until January 31, 2011. Results: During the follow-up for 4.7 ± 1.8 years, cardiovascular events occurred in 78 (30.3%) of 244 patients. Stepwise Cox hazard analysis revealed that cardiovascular events were associated with increased serum PIIINP concentration (1 U/mL; hazard ratio, 1.616; P = 0.0001). The median serum PIIINP concentrations were higher in patients with cardiovascular events than in those without (2.30 ± 0.19 U/mL vs 1.30 ± 0.03 U/mL; P < 0.0001). When the patients were assigned to subgroups based on serum PIIINP cut-off value for cardiovascular events of 1.75 U/mL, defined by receiver operating characteristic analysis, cardiovascular event-free survival rates at 5 years were lower (P = 0.0001) in the subgroup of serum PIIINP ≥ 1.75 U/mL than in that of serum PIIINP < 1.75 U/mL (31.9% vs 88.2%). Conclusions: Serum PIIINP could be a new biomarker for predicting the cardiovascular events in patients undergoing hemodialysis.

Possible Inhibitory Effect of Erythropoiesis-Stimulating Agents at the Predialysis Stage on Early-Phase Coronary Events after Hemodialysis Initiation

Background: We examined whether the use of erythropoiesis-stimulating agents (ESAs) to correct anemia at the predialysis stage could inhibit early-phase coronary events after hemodialysis initiation. Methods: We enrolled 242 patients with chronic kidney disease who had received continued medical treatments and initiated maintenance hemodialysis from 1 September 2000 to 31 December 2014 at Toujinkai Hospital. Patients with a previous history of blood transfusion or any cardiovascular events or interventions were excluded. The coronary events were followed for 1 year after initiation of hemodialysis. Results: Coronary events occurred in 51 of 242 patients: 10 patients had acute coronary syndrome [9 with percutaneous coronary intervention (PCI), 1 without intervention], and 41 had elective coronary revascularization (38 PCI and 3 coronary artery bypass graft). ESA was administered in 118 of 242 patients (48.8%). In stepwise logistic analysis, coronary events were positively associated with nonuse of ESA at the predialysis stage (odds ratio 2.66, p = 0.005) and diabetes mellitus (odds ratio 5.33, p < 0.001). When dividing the patients into 4 subgroups by blood hemoglobin (Hb) level (8.5 g/dl) and the use/nonuse of ESA, coronary event-free survival rates were higher (p = 0.005) in those with Hb ≥8.5 g/dl, ESA+ (86.6%, n = 82) and tended to be higher (p = 0.055) in those with Hb <8.5 g/dl, ESA+ (86.1%, n = 36) than in patients with Hb <8.5 g/dl, ESA- (68.6%, n = 86) in a Kaplan-Meier analysis. Conclusions: The use of ESA to correct anemia at the predialysis stage may inhibit early-phase coronary events after hemodialysis initiation.

Quantitative and qualitative analysis of tonsillar IgA in IgA nephropathy patients

There are many reports of the presence of an incompletely glycosylated O-linked oligosaccharides in the IgA1 hinge region in some IgA nephropathy patients. Meanwhile, there are also some reports on the relationship of tonsillectomy and IgA nephropathy. In this experiment, immunoglobulins in the extract of tonsillectomized tissue and other sources were analysed by the isoelectoric focusing (IEF) and enzymelinked immunosorbent assay (ELISA). The IEF profile of the tonsillar IgA differed from that in the pooled serum and it was enriched in cationic IgA. The profiles were very similar in the extracts from chronic tonsillitis controls and IgA nephropathy patients. Similarly, the IEF profiles of serum IgA from controls and IgA nephropathy patients were also similar. Enzymatic removal of sialic acid induced a shift of the cathode side. Both the profiles of IgA from the treated tonsillar extract and the treated serum were approximately overlapped. On the other hand, the presence of asialo Galβ1,3GalNAc in the cationic IgA from tonsillar extract and aberrant IgA1 prepared from serum (IgA1 binding protein,) became clear with the enzymatic transfer of sialic acid to IgA1. Serum IgA also contained partly sialylated IgA1. Quantitative analysis of IgA and IgG in the extracts indicated that the IgA was significantly higher, but the IgG was significantly lower in IgA nephropathy patients. It was found that the IgA1 produced in tonsillar tissue differed from the serum IgA1. Furthermore, overproduction of asialo IgA1 due to the disordered balance between IgAand IgG-producing cells in the tonsil from the IgA nephropathy patient became obvious. Although the transfer of such an asialo IgA1 from tonsil tissue to the serum is still not completely clear, there is a possibility of a tonsillar source of a few micrograms of the aberrant IgA1 in the serum. REFERENCE